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3,5,6,7,8,3′,4′-heptamethoxyflavone
Foam cell formation is the hallmark of the development and progression of Atherosclerosis. The aim of this study was to investigate the regulatory effects of three polymethoxyflavones (PMFs), namely, tangeretin (TAN), 5,6,7,3′,4′,5′-hexamethoxyflavone (HxMF), and 3,5,6,7,8,3′,4′-heptamethoxyflavone (HpMF) on macrophage-derived foam cell formation and to further explore the molecular mechanisms. The RAW264.7 macrophage-derived foam cell model was successfully induced by oxidized low-density lipoprotein (ox-LDL) (80 μg/ml). It showed that TAN, HxMF, and HpMF alleviated ox-LDL-induced NO release while also inhibiting the expression of IL-1β, IL-6, and TNF-α in RAW264.7 cells. Uptake of excess ox-LDL was inhibited by TAN, HxMF, and HpMF, resulting in the reduction of its foam cell formation. Moreover, TAN, HxMF, and HpMF promoted HDL-mediated cholesterol efflux. Western blot experiment showed that TAN, HxMF, and HpMF inhibited the expression of scavenger receptor class A type I (SRA1) and cluster of differentiation 36 (CD36), while upregulating peroxisome proliferator-activated receptor γ (PPARγ), liver X receptor α (LXRα), phospholipid ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SRB1) expression. Together, our findings suggested that PMFs inhibited foam cell formation might inhibit lipid uptake via downregulating SRA1/CD36 expression and promote cholesterol efflux from foam cells via upregulating PPARγ/LXRα/ABCG1/SRB1 expression. This Antiatherosclerotic activity is expected to provide new insights into the development of healthcare uses for PMFs.
Inhibitory effect of foam cell formation
Oil Red O staining was used to observe the accumulation of lipids and foam cell formation. As shown in Figure 3A, the number of red lipid droplets was significantly increased, and the lipid droplets were distributed in a ring-like pattern within the ox-LDL-induced RAW264.7 cells, which indicated that the foam cell model was successfully established. Incubation with TAN, HxMF, and HpMF significantly reversed such consequences. In addition, the contents of Triglyceride and TC were quantitatively tested. As expected, the levels of Triglyceride and TC were significantly increased by ox-LDL stimulation (Figures 3B,C). TAN (12, 25, and 50 μM) significantly reduced Triglyceride levels in a dose-dependent manner. The Triglyceride content was significantly reduced by HxMF (25 and 50 μM) and HpMF (50 μM) treatments. All three PMFs showed significant inhibition of TC levels in ox-LDL-induced RAW264.7 cells.
5,6,7,3′,4′,5′-hexamethoxyflavone
Foam cell formation is the hallmark of the development and progression of Atherosclerosis. The aim of this study was to investigate the regulatory effects of three polymethoxyflavones (PMFs), namely, tangeretin (TAN), 5,6,7,3′,4′,5′-hexamethoxyflavone (HxMF), and 3,5,6,7,8,3′,4′-heptamethoxyflavone (HpMF) on macrophage-derived foam cell formation and to further explore the molecular mechanisms. The RAW264.7 macrophage-derived foam cell model was successfully induced by oxidized low-density lipoprotein (ox-LDL) (80 μg/ml). It showed that TAN, HxMF, and HpMF alleviated ox-LDL-induced NO release while also inhibiting the expression of IL-1β, IL-6, and TNF-α in RAW264.7 cells. Uptake of excess ox-LDL was inhibited by TAN, HxMF, and HpMF, resulting in the reduction of its foam cell formation. Moreover, TAN, HxMF, and HpMF promoted HDL-mediated cholesterol efflux. Western blot experiment showed that TAN, HxMF, and HpMF inhibited the expression of scavenger receptor class A type I (SRA1) and cluster of differentiation 36 (CD36), while upregulating peroxisome proliferator-activated receptor γ (PPARγ), liver X receptor α (LXRα), phospholipid ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SRB1) expression. Together, our findings suggested that PMFs inhibited foam cell formation might inhibit lipid uptake via downregulating SRA1/CD36 expression and promote cholesterol efflux from foam cells via upregulating PPARγ/LXRα/ABCG1/SRB1 expression. This Antiatherosclerotic activity is expected to provide new insights into the development of healthcare uses for PMFs.
6-Gingerol
Gingerols including 6-gingerol, 8-gingerol and 10-gingerol are the pungent ingredients in ginger. Ginger extract and 6-gingerol have been reported to possess hypocholesterolemic activity. However, cholesterol–lowering activity of 8-gingerol and 10-gingerol has not been well investigated. The present study was to investigate effect of 8-gingerol and 10-gingerol on cholesterol level in HepG2 cells compared with 6-gingerol. HepG2 cells were incubated with 40 μM cholesterol and 4 μM 25-hydroxycholeterol with various concentrations of 6-gingerol, 8-gingerol or 10-gingerol, ranging from 0 to 100 μM for 24 h. It was found that 10-gingerol at 75 and 100 μM was more effective in decreasing cholesterol levels compared with 6-gingerol and 8-gingerol. Furthermore, 10-gingerol increased the expression of LDLR with a dose–response manner through up-regulating SREBP-2 and down-regulating PCSK9. 10-Gingerol also enhanced the expression of genes related to cholesterol efflux and bile acid expression including ABCG5/8 and ABCA1 through LXRα, PPARγ and CYP7A1 in HepG2 cells.
Gingerols, the pungent ingredients in ginger, are reported to possess a cholesterol–lowering activity. However, the underlying mechanism remains unclear. The present study was to investigate how 6-gingerol (6-GN), the most abundant gingerol in fresh ginger, regulates hepatic cholesterol metabolism. HepG2 cells were incubated with various concentrations of 6-GN ranging from 50 to 200 μM for 24 h. Results showed that both cellular total cholesterol and free cholesterol decreased in a dose-dependent manner. Besides, 6-GN ranging from 100 to 200 μM increased the LDLR protein and uptake of fluorescent-labeled LDL. Moreover, the mRNA and protein expressions of cholesterol metabolism-related genes were also examined. It was found that 6-GN regulated cholesterol metabolism via up-regulation of LDLR through activation of SREBP2 as well as up-regulation of cholesterol efflux-related genes LXRα and ABCA1.
Excessive synthesis of Triglycerides and cholesterol accelerates the progression of hepatic steatosis in metabolic-associated fatty liver disease (MAFLD). However, the precise mechanism by which 6-gingerol mitigates hepatic steatosis in MAFLD model mice has yet to be fully understood. The present study observed that 6-gingerol administration exhibited significant protective effects against obesity, insulin resistance, and hepatic steatosis in mice subjected to a high-fat diet (HFD), and mitigated lipid accumulation in HepG2 cells treated with palmitate (PA). Following the hepatic lipidomic analysis, we confirmed that the AMPK-SREBPs signaling pathway as the underlying molecular mechanism by which 6-gingerol inhibited Triglyceride and cholesterol biosynthesis, both in vivo and in vitro, through Western blot and immunofluorescence assay. Additionally, the application of an AMPK agonist/inhibitor further validated that 6-gingerol promoted AMPK activation by increasing the phosphorylation level of AMPK in vitro. Notably, the inhibitory effect of 6-gingerol on cholesterol biosynthesis, rather than Triglyceride biosynthesis, was significantly diminished after silencing SREBP2 using a lentiviral plasmid shRNA in HepG2 cells. Our study demonstrates that 6-gingerol mitigates hepatic Triglyceride and cholesterol biosynthesis to alleviate hepatic steatosis by activating the AMPK-SREBPs signaling pathway, indicating that 6-gingerol may be a potential candidate in the therapy of MAFLD.
We investigated the effects of 6-gingerol on adiposity and obesity-induced inflammation by focusing on the regulation of adipogenesis and adipokines in white adipose tissue (WAT) of diet-induced obese mice. C57BL/6 mice were fed a high-fat diet (HFD) containing 0.05% 6-gingerol for 8 weeks. 6-Gingerol supplementation significantly reduced body weight, WAT mass, serum Triglyceride , leptin and insulin levels, and HOMA-IR in HFD-fed mice. Additionally, the size of adipocytes in epididymal fat pads was reduced in HFD-fed mice by 6-gingerol supplementation. 6-Gingerol reduced the mRNA and protein levels of adipogenesis-related transcription factors, such as SREBP-1, PPARγ, and C/EBPα in WAT. Furthermore, 6-gingerol suppressed the expression of lipogenesis-related genes, such as fatty acid synthase and CD36 in WAT. Adiponectin expression was significantly increased, whereas inflammatory adipokines (leptin, resistin, TNF-α, MCP-1, and PAI-1) and the macrophage marker F4/80 were significantly reduced in the WAT of HFD-fed mice by 6-gingerol supplementation. In conclusion, 6-gingerol effectively contributed to the alleviation of adiposity and inflammation in WAT, which is associated with the regulation of adipokines in diet-induced obese mice.
Acacia senegal Seeds
Acacia senegal L. (Fabaceae) seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored Antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced Atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil) for 15 days. Circulating total cholesterol (TC), HDL-cholesterol (HDL-C), LDL–cholesterol (LDL-C), Triglycerides , and VLDL–cholesterol (VLDL-C) levels; atherogenic index (AI); cardiac lipid peroxidation (LPO); planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed. Apart from reduced atherosclerotic plaques in aorta () and increased lumen volume (), administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o.) for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, Triglyceride , and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced Atherosclerosis and could be considered as lead in the development of novel therapeutics.
Effect of Gum Arabic (Acacia senegal, L. Willd) on lipid profile and performance of Laying Hens
Objective: This experiment studied effect of Gum Arabic as a supplementary diet and its effect on lipid profile (serum, egg yolk and meat) and performance of Laying Hen. Methodology and results: One hundred and fifty commercial laying hens (29 weeks age/ white lohmann) were used. The 150 laying hens are divided into five groups randomly G1, G2, G3, G4 and G5, where each group contained 30 laying hens kept in separated battery house. G1(Control) was fed basal layers diet while G2, G3, G4 and G5 were fed basal diet supplemented with Gum Arabic concentration at 1, 3, 5 and 7% respectively. The study revealed that in serum, there was a significant decrease in cholesterol, Triglyceride , but no significant difference in High Density protein (HDP) – cholesterol at P≤ 0.05, in egg yolk. There was a significant decrease in cholesterol for G5 compared with G1, also there was a significant decrease Triglyceride in G4 and G5 compared with G1 indicated that there was a decrease in phospholipids in G5 compared with G1. Lipid profile of meat for treated groups (G2, G3, G4 and G5) showed no significant difference at P≤ 0.05 compared with non- treated group (G1). The performance (body weight, egg weight and daily egg production) of laying hens showed significant increase at P≤ 0.05, but there was an increase in body and egg weight. Finally, there was no significant difference in daily egg production at P≤ 0.05. The addition of Gum Arabic as supplement of laying hens diet indicated there was no significant difference in serum cholesterol and daily egg production. Whereas, it is showed significant decrease in Triglyceride , total lipid and phospholipids, but indicated significant increase in egg and body weight. Application of Gum Arabic as supplement in the diet of poultry production should be done because Gum Arabic is rich in highly soluble fiber.
The prevailing strategy for the management of hypercholesterolemia is the use of HMG-CoA reductase inhibitors which work by inhibiting cholesterol synthesis by HMG-CoA reductase in the liver and removal of excess cholesterol level in peripheral circulation by several mechanisms of reverse cholesterol transport [47, 48]. Excess cholesterol in the circulatory system is indicated by biomarker indices of dyslipidaemia and abnormal lipoproteins ratios, which can be regulated by proper fractional esterication of cholesterol and reverse cholesterol transport (RCT) [49, 50]. Cholesterol present in the intestine is rst absorbed in the form of chylomicron (Triglyceride rich complex) and is then modied and packaged as high-density lipoprotein (HDL) cholesterol. Therefore, the ratio of Triglyceride to HDL is indicative of the levels of peripheral cholesterol in circulation. Abnormal cholesterol esterication rates in apoB-lipoprotein- depleted plasma (fractional esterication) and lipoprotein particle size result in dyslipidaemia [49, 51]. In animal model, specically hypercholesteraemic rabbits, exhibit elevated levels of the biomarker indices of dyslipidaemia, such as the logarithm of the TG/HDL ratio, total cholesterol/ HDL (Castelli risk index -I (CRI-I)) and LDL-cholesterol/HDL-cholesterol (Castelli risk index-II (CRI-II)). In the present study, the treatment of hypercholesterolemic rabbits with an aqueous seed extract of Acacia senegal (L.) Willd. caused a signicant reduction in the atherogenic index and CRI – I&II, indicating improved fractional esterication of cholesterol and reverse cholesterol transport.
Achillea millefolium L.extract
Background
Recent studies have reported that herbal extracts may have some protective effect against the complications of diabetes mellitus. This study aimed to investigate the effects of Achillea millefolium hydroalcoholic extract in comparison to metformin on liver damage, lipid abnormality, and glycemic control in diabetic rats.
Methods
Rats were randomly assigned to 7 groups of 10 animals. Diabetes was induced by injection of streptozotocin (STZ) to 4 groups of rats. Three groups of diabetic rats were given 250 mg/kg/day metformin, 25 mg/kg/day Achillea millefolium hydroalcoholic extract, or 100 mg/kg/day of this extract. Two non-diabetic groups were also given either 25 mg/kg/day or 100 mg/kg/day Achillea millefolium extract. Normal control and diabetic control rats received 1 mL/day of normal saline. Treatments were administered through oral gavage for 28 days. At the end, rats were anesthetized with ether and their serum samples were separated in order to measure blood glucose, serum total protein, lipids, and liver enzymes.
Results
There was a significant reduction in blood glucose, serum liver enzymes, Triglycerides , and total- and LDL–cholesterol levels of the Achillea millefolium extract-treated groups compared to the other groups. In addition, there was a significant increment in body weight and HDL-cholesterol serum level in the Achillea millefolium-treated groups.
Conclusion
Achillea millefolium extract compared to metformin reduces lipid abnormality, blood glucose and liver enzymes in STZ-induced diabetic rats. Future clinical studies are warranted to confirm our experimental findings in humans.
Background
Recent studies have reported that herbal extracts may have some protective effect against the complications of diabetes mellitus. This study aimed to investigate the effects of Achillea millefolium hydroalcoholic extract in comparison to metformin on liver damage, lipid abnormality, and glycemic control in diabetic rats.
Methods
Rats were randomly assigned to 7 groups of 10 animals. Diabetes was induced by injection of streptozotocin (STZ) to 4 groups of rats. Three groups of diabetic rats were given 250 mg/kg/day metformin, 25 mg/kg/day Achillea millefolium hydroalcoholic extract, or 100 mg/kg/day of this extract. Two non-diabetic groups were also given either 25 mg/kg/day or 100 mg/kg/day Achillea millefolium extract. Normal control and diabetic control rats received 1 mL/day of normal saline. Treatments were administered through oral gavage for 28 days. At the end, rats were anesthetized with ether and their serum samples were separated in order to measure blood glucose, serum total protein, lipids, and liver enzymes.
Results
There was a significant reduction in blood glucose, serum liver enzymes, Triglycerides , and total- and LDL-cholesterol levels of the Achillea millefolium extract-treated groups compared to the other groups. In addition, there was a significant increment in body weight and HDL-cholesterol serum level in the Achillea millefolium-treated groups.
Conclusion
Achillea millefolium extract compared to metformin reduces lipid abnormality, blood glucose and liver enzymes in STZ-induced diabetic rats. Future clinical studies are warranted to confirm our experimental findings in humans.
Acorus calamus L.extract
hypolipidemic activity of Acorus calamus L. in rats
The rhizomes of Acorus calamus are empirically used in the treatment of a wide variety of human diseases. Administration of the 50% ethanolic extract (100 and 200 mg/kg) as well as saponins (10 mg/kg) isolated from the extract demonstrated significant hypolipidemic activity. On the contrary, the aqueous extract showed hypolipidemic activity only at a dose of 200 mg/kg.
Hypolipidemic Effect of Methanol Fraction of Acorus calamus Linn. in Diet-Induced Obese Rats
Acorus calamus Linn. is a traditional medicinal plant included in “lekhaneyagana” (which means “reduce excess fat”), a pharmacological classification mentioned by Charaka in Charakasamhita. Traditionally, this plant has been prescribed as a first-line treatment for many ailments such as digestive problems, diabetes, obesity, and related problems. The purpose of the present study was to check the effect of methanolic fraction of A. calamus on serum lipids, Lecithin-cholesterol acyltransferase (LCAT) enzyme, and apolipoproteins. We found that treatment of A. calamus at concentrations of 200 and 400 mg/kg body weight was able to reduce total cholesterol (T-c), Triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) levels and increase high-density lipoprotein cholesterol (HDL-c) levels compared to model control group. A. calamus treatment results in activation of LCAT enzyme, which helps in the maturation of HDL-c. ApoA1 level was found to be increased considerably by the administration of A. calamus extract, and the Apo B level was decreased. GCMS analysis of the A. calamus extract showed the presence of compound, Friedelan-3-one. The result suggests the use of methanol fraction of A .calamus, as a potential drug for controlling the cholesterol level.
Agaricus blazei Mur ill extract
Atheroprotective effect of the Agaricus blazei Mur ill extract in high Fat diet-Induced Mice
The purpose of the present study was to provide evidence of the potential of Agaricus blazei Murill extract as atheroprotective agent. The study was conducted with 25 male mice (Mus musculus) divided into f ive groups consisting of f ive mice in each group. Three doses of Agaricus blazei Murill extract: D1 (100 mg/kg body weight), D2 (200 mg/kg body weight), and D3 (400 mg/kg body weight) was used. All treatment groups, except for normal mice were induced to high fat diet (HFD) and given A. blazei extract for 12 weeks. The activation of T regulatory cells, the production of anti-inflammatory cytokines TGF-?, and the number of LpPLA2-expressing cells in spleen were analyzed using flow cytometry. Results showed that administration of A. blazei extract was able to induce activation of T regulatory cells, increased the production of anti-inflammatory cytokines TGF-β, and decreased the number of LpPLA2-expressing cells in the spleen signif icantly. Our results revealed that A. blazei extract is a good candidate as atheroprotective agent by reducing inflammation in atheroschlerosis.
This study was performed to investigate the effects of liquid culture of Agaricus blazei on the lipid metabolism and enzyme activities in growing male rats. Sprague-Dawley rats were given four different types of diets for a succeeding period of 5 weeks, respectively a normal diet group (7% corn oil), a high fat diet group (7% com oil + 15% lard), a 20 or 30% Agaricus diet groups (high fat diet + 20 or 30% Agaricus in water) according to the levels of Agaricus supplementation. The body weight gains, food intake, food efficiency ratios, and hepatic, kidney, spleen and pancreas weights of the rats fed 20 or 30% Agaricus diets were similar to those of the rats fed high fat diet. The epididymal fat pad weight of the rats fed high fat diet and 20 or 30% Agaricus diets were significantly higher than that of the rats fed normal diet. The concentrations of serum Triglyceride , total cholesterol, LDL-cholesterol and HDL-cholesterol, and the activity of glutamic pyruvic transaminase in the rats fed 30% Agaricus diet were significantly lower than those in the rats 114 high fat diet. But the concentrations of hepatic total cholesterol and Triglyceride of rats fed the 20 or 30% Agaricus diets were similar to those of rats fed the high fat diet. The HDL-oholesterol/total-cholesterol ratio of the rat fed 30% Agaricus diet was significantly higher than that of the rats fed high fat diet, The activity of glutamic oxaloacetic transaminase in the rats fed 20 or 30% Agaricus diets were similar to those in the rats fed high fat diet. There were no differences in the concentrations of total protein, hemoglobin and glucose, and the activities of alkaline phosphatase, and the atherogenic index in the serum among the experimental groups. These results showed that the 30% Agaricus diet feeding decreased the total cholesterol, the Triglyceride and the LDL-cholesterol, and increased the HDL-oholesterol/total cholesterol ratio in serum of rats.
Obesity and diabetes mellitus are associated with common pathogenic mechanism, and ${\beta}-glucan$ of Agaricus blazei Murill is potent inhibitor of intestinal ${\alpha}-glycosidase$ and inhibit the digestion of starch and sucrose in the small intestine. In this studies, there was observed the anti-hyperglycemic effect in obese diabetic mice(C57BLKsJ db/db), which were supplied Agaricus and Acarbose for 5 weeks. In db/db mice, food intake and body weight gain were decreased significantly in Agaricus groups(p<0.05). Also these group exhibited lower fasting serum glucose level compared with control group. HbA1c level, Triglyceride level, total cholesterol level, HDL cholesterol level, LDL cholesterol level and VLDL cholesterol level were lowered in db/db mice. The activity of disaccharidases on proximal and distal segments of small intestine was decreased. In conclusion, it was assumed that ${\beta}-glucan$ of Agaricus blazei Murill has anti-hyperglycemic and anti-obesitic effects by reducing food intake and body weight gain, and also decreasing serum glucose and lipid level through inhibiting the activity of small intestinal disaccharidases.
Ajuga iva extract
Objectives
The aim of this study was to determine the effects of Ajuga iva aqueous extract on lecithin : cholesterol acyltransferase (LCAT) activity and amount and composition of high-density lipoprotein (HDL)2 and (HDL)3, in streptozotocin (STZ)-induced diabetic rats.
Methods
Diabetes was induced in male Wistar rats by intraperitoneal injection of STZ (60 mg/kg body weight). Diabetic rats (n = 12) were divided into two groups. The diabetic control group (D) received a 20% casein diet and the diabetic treated group received the same diet supplemented with A. iva aqueous extract (0.5 g/100 g diet) (DAi), for 4 weeks.
Key findings
Total cholesterol and HDL3-C were respectively decreased by 32% and 55% in the DAi group compared with the D group, whereas HDL2-C was increased by 30%. The amounts of HDL2 and HDL3, which were the sum of apolipoproteins, unesterified cholesterol (UC), cholesteryl esters (CEs), triacylglycerols (TGs) and phospholipids (PLs), showed no significant difference. A. iva treatment increased LCAT by 33% and its cofactor-activator, apolipoprotein A-I, by 58%. HDL3-PL (enzyme substrate) and HDL3-UC (acyl group acceptor) were respectively decreased by 70% and 57%, whereas HDL2-CE (product of LCAT reaction) was enhanced by 30%.
Conclusions
In STZ-induced diabetic rats, A. iva improves reverse cholesterol transport by enhancing LCAT activity, leading to anti-atherogenic effects.
The present study was designed to explore the possible antioxidant and hypolipidemic effects of the aqueous extract of Ajuga iva (0.5% in the diet) in rats fed a high-cholesterol (1%) diet (HCD). The results indicated that the HCD-Ai versus HCD treatment led to many changes in biochemical parameters. They showed a decrease of plasma total cholesterol (TC) and VLDL-cholesterol but an increase of HDL2-cholesterol. The triacylglycerol contents were reduced in plasma and in VLDL. The lipid peroxidation determined by TBARS was decreased by 75% in plasma. TBARS in liver, heart and kidneys were highly reduced excepted in the adipose tissue. Ajuga iva treatment enhanced superoxide dismutase activity in liver and kidney. Glutathione reductase activity was lowered in adipose tissue but increased in liver and in kidney. A significant increase was noted in glutathione peroxidase activity in liver, heart and kidney but a low value in adipose tissue was observed. In conclusion, the present study demonstrates that in addition to its potent TG and TC-lowering effects, Ajuga iva is effective in improving the antioxidant status by reducing lipid peroxidation in plasma and tissues and enhancing the antioxidant enzymes in rats fed high-cholesterol diet. Furthermore, Ajuga iva may reduce intestinal cholesterol absorption.
Alisma orientalis (Sam.) Juzep.extract
Alisma orientale (Sam.) Juzep (A. orientale) is a traditional herb that is often used to treat disease including edema and hyperlipidemia. However, the molecular mechanism by which Alisma orientale (Sam.) Juzep exerts its hypolipidemic effects remains unclear. In this study, a diabetic rat model was established by feeding a high-fat and high-sugar diet combined with a low-dose streptozotocin injection (HFS). Then the rats were treated with an A. orientale water extract (AOW), an A. orientale ethanolic extract (AOE) or metform (MET). The gut microflora and liver transcriptome were analyzed by high-throughput next-generation sequencing. Ultra-performance liquid chromatography-triple quadrupole-mass spectrometry was employed to analyze the major compounds in the AOE. The results showed that the serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in rats of the AOE group (2.10 g/kg/day, 14 days) were significantly lower than those in the HFS group (p<0.01). Moreover, AOE treatment altered the gut microecology, particularly modulating the relative abundance of gut microflora involved in lipid metabolism compared with the HFS group. Furthermore, compared with the HFS group, the mRNA expression levels of Fam13a, Mapk7, Mpp7, Chac1, Insig1, Mcpt10, Noct, Greb1l, Fabp12 and Hba-a3 were upregulated after the administration of AOE. In contrast, the mRNA expression levels of Lox, Mybl1, Arrdc3, Cyp4a2, Krt20, Vxn, Ggt1, Nr1d1 and S100a9 were downregulated. Moreover, AOE treatment for two weeks markedly promoted the relative abundance of Lachnospiraceae (p = 0.0013). The triterpenoids contents in AOE were alisol A, alisol A 24-acetate, alisol B, alisol B 23-acetate, alisol C 23-acetate, alisol F, alisol F 24-acetate, and alisol G. Our findings above illustrated that the hypolipidemic effect of the triterpenoids of A. orientale is mediated mainly through alteration of the gut microecology and the regulation of genes involved in cholesterol metabolism, especially Insig1.
Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging hepatic manifestation of metabolic syndrome. However, its unrevealed mechanism and complicated comorbidities have led to no specific medication, except for weight loss and lifestyle modification. Alisma orientale (Sam.) Juzep (A. orientale, Alismataceae) has been increasingly reported on therapeutic effects of A. orientale against NAFLD and metabolic syndrome such as insulin resistance, hyperlipidemia, and obesity. Therefore, this study aimed to review the preclinical efficacy of A. orientale and its chemical constituents including Alisol A 24-acetate, Alisol B 23-acetate, Alisol F, and Alismol against NAFLD and metabolic syndrome. A. orientale prevented hepatic Triglyceride accumulation through suppressing de novo lipogenesis and increasing lipid export. In addition, it controlled oxidative stress markers, lipoapoptosis, liver injury panels, and inflammatory and fibrotic mediators, eventually influencing steatohepatitis and liver fibrosis. Moreover, it exhibited pharmacological activities against hyperlipidemia, obesity, and hyperglycemia as well as appetite. These biological actions of A. orientale might contribute to adiponectin activation or a role as a farnesoid X receptor agonist. In particular, Alisol A 24-acetate and Alisol B 23-acetate could be expected as main compounds. Taken together, A. orientale might be an effective candidate agent for the treatment of NAFLD and its comorbidities, although further assessment of its standardization, safety test, and clinical trials is consistently required.
The treatment of cardiovascular diseases and obesity, two diseases posing a major risk to human health, has been plagued by the scarcity of potent and effective medication with fewer side effects. To address this problem, numerous efforts, and some progress, have been made. Among possible treatments are some medicinal herbs; particularly promising is Alisma orientale (AO). In the last decade, an increasing amount of research has shown that AO has some desirable therapeutic effects on cardiovascular diseases and obesity. Because of its efficacy, natural origin, and minimal adverse effects, AO has aroused great attention. Based on this, this review provides an overview of the latest progress from the last decade regarding the pharmacological and therapeutic effects, molecular mechanisms, and related effective constituents of AO in the treatment of cardiovascular diseases and obesity. Results from the research currently available reveal that active constituents of AO, such as alisol B 23-acetate, alisol A 24-acetace, and alisol A, have been proven to be effective for treating cardiovascular diseases by modulating the lipid metabolism of macrophages, improving the biological behavior of vascular smooth muscle cells (VSMCs), and enhancing anti-inflammatory effects. Moreover, the active constituents of AO can also intervene in obesity by modulating abnormal glucose and lipid metabolism and fat decomposition of the body by activating the AMPK- and PPAR-related signaling pathways. In summation, based upon our research of available literature, this review reveals that AO and its active constituents have a great potential to be used as drugs for treating cardiovascular diseases and ameliorating obesity.
Allium cepavar. aggregatum G. Don extract
effect of the polyphenol-rich extract from Allium cepa on hyperlipidemic sprague-dawley rats
Allium cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as Atherosclerosis in the folk. This study was mainly aimed at investigating the effects of A. cepa extract (ACE) enriched in polyphenols on hyperlipidemia Sprague-Dawley (SD) experiment rat models. The levels of total cholesterol (TC), Triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), and superoxide dismutase (SOD) activity in serum and liver were measured using ELISA kits. In addition, hematoxylin-eosin (HE) technique was used to observe the liver and the aortic arch pathology. Moreover, western blotting (WB) method was applied to analyze LDL receptor (LDLR) and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HMGCR) in liver. As a result, quercetin (2.42 mg/g DW) and isoquercitrin (4.60 mg/g DW) were the main constituents of ACE using HPLC analysis. Furthermore, ACE reduced the levels of TC, TG, LDL-C, and MDA, and increased HDL levels and elevated SOD activity both in serum and liver in hyperlipidemic SD rats (p < .05). HE results showed that liver fat drops of the rats in ACE group were obviously decreased, and the lipid and foam cells of the aortic arch of the rats in ACE group were markedly ameliorated. WB results showed that ACE promoted the degradation of HMGCR and increased LDLR expression in liver (p < .05). In conclusion, ACE alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR. PRACTICAL APPLICATIONS: Atherosclerosis, a major cardiovascular disease, is the leading cause of mortality and morbidity in the developed countries. Moreover, accumulating data indicate that, during Atherosclerosis development, hyperlipidemia is an important risk factor. To date, hyperlipidemia is mainly treated with hyperlipidemic agents including statins, in spite of the side effects and poor tolerance in some patients. In addition, Allium cepa is a medicinal and edible plant. Furthermore, A. cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as Atherosclerosis in the folk. But the underlying mechanism is still unclear. In fact, this research showed that A. cepa extract (ACE) alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR, suggesting that ACE might be a potential option for hyperlipidemia as non-statin lipid–lowering agent.
Studies on Antihyperliperlipemic and Antioxidant Activity of Allium cepa L.
This Study was attempted to investigate the effect of Allium cepa L. (onion) on the activities of GOT and GPT, the levels total lipids, Triglyceride , total cholesterol, phospholipid and ${\beta}-lipoprotein$ in the serum and the increase ratio of body and liver weight in the experimentally induced hyperlipemic rats. The activities of S-GOT and S-GPT were significantly decreased in dose of onion juice 3 ml and 5 ml/head as compared to the high lipid-diet control group. The levels of total lipids. Triglyceride , total cholesterol and phospholipids were significantly decreased in dose of onion juice 3 ml and 5 ml/head as compared to the control group, respectively. However, the level of ${\beta}-lipoprotein$ was significantly decreased in dose of onion juice 3 ml/head. The levels of Triglyceride and total cholesterol in the liver were significanatly decreased in dose of onion juice 3 ml/head. Increase ratio of the body and liver weight were significantly decreased in dose of onion juice 3 ml/head. Anti-fatigue activity of onion juice were studied in mice using the swimming performance method. The potencies of anti-fatigue acti-vities was significantly found in 1.2 ml/head. p.o. of onion juice. The methanol extract and juice extract of onion was significantly found to have an antioxidative activity on the air oxidation of linoleic acid as compared to the 3-butyl-4-hydroxyanisole and ${\alpha}-tocopherol$.
Allium sativum extract
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
cholesterol lowering property of garlic (Allium sativum) on patients with hypercholesterolemia
Background: Cardiovascular disease especially atherosclerotic coronary heart disease (CHD) accounts for a large population of all deaths and disability worldwide. Elevated lipid levels have a strong association with cardiovascular events. Objectives: Study aim is to reduce cholesterol levels with garlic supplementation. Materials and Methods: It is a prospective, interventional open-label study to see the effect of garlic on serum cholesterol levels. Study was conducted in the Department of Pharmacology and Therapeutics, Rajendra Institute of Medical Sciences, Ranchi. Fifty Healthy subjects with elevated cholesterol levels between 240 and 330 mg/dL were enrolled. Subjects were given 3 g of raw garlic daily for a total period of 90 days. Follow-up was done on 30th, 60th, and 90th day after starting treatment. Results: In male patients, the serum cholesterol level showed significant decrease of 13% (P < 0.001) from mean baseline of 269.30 mg/dL to 233.93 mg/dL at 90th day. In female patients, the decrease was 10% (P < 0.001) from mean baseline of 260.30 mg/dL to 233.90 mg/dL at 90th day. Conclusion: Garlic has a role in cholesterol management as an adjunctive therapy in most cases of significant hypercholesterolemia thereby reducing risk of Atherosclerosis and cardiovascular events.
A review on the effects of Allium sativum (Garlic) in metabolic syndrome
The metabolic syndrome is a common problem world-wide and includes abdominal obesity, hypertension, dyslipidemia, and hyperglycemia disorders. It leads to insulin resistance and the development of diabetes mellitus or cardiovascular disease. Allium sativum (garlic) has been documented to exhibit anti-diabetic, hypotensive, and hypolipidemic properties. This suggests a potential role of A. sativum in the management of metabolic syndrome; however, more studies should be conducted to evaluate its effectiveness. In this review, we discussed the most relevant articles to find out the role of A. sativum in different components of metabolic syndrome and cardiovascular disease risk factors. Because human reports are rare, further studies are required to establish the clinical value of A. sativum in metabolic syndrome.
alpha-Linolenic acid
Alpha-linolenic acid (ALA) reduces cardiovascular disease (CVD) risk, possibly by favorably changing vascular inflammation and endothelial dysfunction. Inflammatory markers and lipids and lipoproteins were assessed in hypercholesterolemic subjects (n = 23) fed 2 diets low in saturated fat and cholesterol, and high in PUFA varying in ALA (ALA diet) and linoleic acid (LA diet) compared with an average American diet (AAD). The ALA diet provided 17% energy from PUFA (10.5% LA; 6.5% ALA); the LA diet provided 16.4% energy from PUFA (12.6% LA; 3.6% ALA); and the AAD provided 8.7% energy from PUFA (7.7% LA; 0.8% ALA). The ALA diet decreased C-reactive protein (CRP, P < 0.01), whereas the LA diet tended to decrease CRP (P = 0.08). Although the 2 high-PUFA diets similarly decreased intercellular cell adhesion molecule-1 vs. AAD (-19.1% by the ALA diet, P < 0.01; -11.0% by the LA diet, P < 0.01), the ALA diet decreased vascular cell adhesion molecule-1 (VCAM-1, -15.6% vs. -3.1%, P < 0.01) and E-selectin (-14.6% vs. -8.1%, P < 0.01) more than the LA diet. Changes in CRP and VCAM-1 were inversely associated with changes in serum eicosapentaenoic acid (EPA) (r = -0.496, P = 0.016; r = -0.418, P = 0.047), or EPA plus docosapentaenoic acid (r = -0.409, P = 0.053; r = -0.357, P = 0.091) after subjects consumed the ALA diet. The 2 high-PUFA diets decreased serum total cholesterol, LDL cholesterol and Triglycerides similarly (P < 0.05); the ALA diet decreased HDL cholesterol and apolipoprotein AI compared with the AAD (P < 0.05). ALA appears to decrease CVD risk by inhibiting vascular inflammation and endothelial activation beyond its lipid–lowering effects.
This meta-analysis aimed to investigate the impact of low-ratio linoleic acid/alpha-linolenic acid (LA/ALA) supplementation on the blood lipid profiles in adults. We conducted a systematic search for relevant randomized controlled trials (RCTs) assessing the effects of low-ratio LA/ALA using databases including PubMed, Embase, Cochrane, and Web of Science, as well as screened related references up until February 2023. The intervention effects were analyzed adopting weighted mean difference (WMD) and 95% confidence interval (CI). The meta-analysis indicated that low-ratio LA/ALA supplementation decreased total cholesterol (TC, WMD: −0.09 mmol/L, 95% CI: −0.17, −0.01, p = 0.031, I2 = 33.2%), low-density lipoprotein cholesterol (LDL-C, WMD: −0.08 mmol/L, 95% CI: −0.13, −0.02, p = 0.007, I2 = 0.0%), and Triglycerides (TG, WMD: −0.05 mmol/L, 95% CI: −0.09, 0.00, p = 0.049, I2 = 0.0%) concentrations. There was no significant effect on high-density lipoprotein cholesterol concentration (HDL-C, WMD: −0.00 mmol/L, 95% CI: −0.02, 0.02, p = 0.895, I2 = 0.0%). Subgroup analysis showed that low-ratio LA/ALA supplementation significantly decreased plasma TC, LDL-C, and TG concentrations when the intervention period was less than 12 weeks. In the subgroup analysis, a noteworthy decrease in both TC and LDL-C levels was observed in individuals receiving low-ratio LA/ALA supplementation in the range of 1–5. These findings suggest that this specific range could potentially be effective in reducing lipid profiles. The findings of this study provide additional evidence supporting the potential role of low-ratio LA/ALA supplementation in reducing TC, LDL-C, and TG concentrations, although no significant impact on HDL-C was observed.
Amaranthus viridis leaf extract
Hypercholesterolemia is one of the main causes for coronary heart disease, which occurs due to high levels of serum cholesterol. oxidized LDL accumulation leads to atherosclerotic plaque formation, which contributes to myocardial infarction and cardiovascular diseases. Consumption of statins leads to adverse health effects such as liver and muscle toxicity; thus attention is now focused on alternative treatments using chemicals of plant origin. This study is designed to investigate the phytochemical components, hypocholesterolemic and Antiatherosclerotic effects of Amaranthus viridis (A. viridis) using hypercholesterolemic rabbits. Gas Chromatography Mass Spectrometry (GC-MS/MS) analysis revealed 30 compounds, while reverse Phase-high Performance Liquid Chromatography (RP-HPLC) detected the presence of ascorbic acid, rutin, quercetin and catechin. An animal model study was performed on twenty New Zealand white rabbits that were randomly divided into 5 groups and fed with normal diet, 2% high cholesterol diet (HCD), 2% HCD + 10 mg kg−1 simvastatin, 2% HCD + 100 mg kg−1 A. viridis extract and 2% HCD + 200 mg kg−1 A. viridis extract, respectively. The supplementation with A. viridis extract significantly reduced total cholesterol, LDL and Triglyceride levels, and increased the levels of HDL and antioxidant enzymes (SOD and GPx). The elevated levels of AST, ALT and creatine kinase indicate liver and muscle injuries. Treatment with A. viridis extract also diminished the development of aortic plaques and decreased the intima : media ratio, as observed in simvastatin-treated rabbits. The phytocomponents of A. viridis have been reported to have therapeutic effects in treating hypercholesterolemia and Atherosclerosis, and the in vivo study on A. viridis further confirms its potential as an alternative therapeutic agent.
Hypercholesterolemia is one of the main causes for coronary heart disease, which occurs due to high levels of serum cholesterol. Oxidized LDL accumulation leads to atherosclerotic plaque formation, which contributes to myocardial infarction and cardiovascular diseases. Consumption of statins leads to adverse health effects such as liver and muscle toxicity; thus attention is now focused on alternative treatments using chemicals of plant origin. This study is designed to investigate the phytochemical components, hypocholesterolemic and antiatherosclerotic effects of Amaranthus viridis (A. viridis) using hypercholesterolemic rabbits. Gas Chromatography Mass Spectrometry (GC-MS/MS) analysis revealed 30 compounds, while Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) detected the presence of ascorbic acid, rutin, quercetin and catechin. An animal model study was performed on twenty New Zealand white rabbits that were randomly divided into 5 groups and fed with normal diet, 2% high cholesterol diet (HCD), 2% HCD + 10 mg kg−1 simvastatin, 2% HCD + 100 mg kg−1 A. viridis extract and 2% HCD + 200 mg kg−1 A. viridis extract, respectively. The supplementation with A. viridis extract significantly reduced total cholesterol, LDL and Triglyceride levels, and increased the levels of HDL and antioxidant enzymes (SOD and GPx). The elevated levels of AST, ALT and creatine kinase indicate liver and muscle injuries. Treatment with A. viridis extract also diminished the development of aortic plaques and decreased the intima : media ratio, as observed in simvastatin-treated rabbits. The phytocomponents of A. viridis have been reported to have therapeutic effects in treating hypercholesterolemia and atherosclerosis, and the in vivo study on A. viridis further confirms its potential as an alternative therapeutic agent.
To investigate the antihyperglycemic and hypolipidemic effects of methanolic extract of leaves of Amaranthus viridis (MEAV) in normal and Streptozotocin (STZ) induced diabetic rats. The anti-hyperglycemic and hypolipidemic activity of methanolic extract of leaves of Amaranthus viridis was evaluated by using normal and STZ induced diabetic rats at dose of 200 mg/kg and 400 mg/kg by mouth per day for 21 days. Blood glucose levels and body weight was monitored at specific intervals, and different biochemical parameters, serum cholesterol, serum Triglyceride , high density lipoprotein, low density lipoprotein, very low density lipoprotein were also assessed in the experimental animals. Histology of pancreas was performed. The statistical data indicated a significant increase in the body weight, decrease in the blood glucose, total cholesterol and serum Triglycerides after treatment with MEAV. High density lipoprotein (HDL) cholesterol level was significantly increased when treated with extract. Histologically, focal necrosis was observed in the diabetic rat pancreas; however, was less obvious in treated groups. The MEAV has beneficial effects in reducing the elevated blood glucose level and body weight changes, and improves the lipid profile of STZ induced rats.
Amomum subulatum seeds (Family Zingiberaceae)
In the present study, hypolipidemic activity of fraction (50:50; CHCl3:CH3OH) of Amomum subulatum (Zingiberaceae) seeds was evaluated in cholesterol-fed rabbits. Hyperlipidemia induced by feeding atherogenic diet for 120 days resulted in a significant increase in serum total cholesterol, phospholipid and Triglyceride levels when compared with control group. The levels of LDL and VLDL–cholesterol were increased significantly, but the HDL-cholesterol ratio was decreased. The changes in the antioxidant parameters were accompanied by an increase in lipid peroxidation and reduction in glutathione (GSH) and catalase activity. The level of lipid peroxidation was reduced whereas GSH content and catalase activity were elevated after the treatment with A. subulatum fraction at the dose level of 100 mg/kg.b.wt/day. A significant reduction was observed in total cholesterol, Triglyceride , phospholipid, LDL and VLDL cholesterol where as HDL-cholesterol ratio was increased after administration of A. subulatum. The results of the present study indicate that fraction of A. subulatum possesses lipid–lowering and antioxidant activity and could be beneficial in the treatment of hyperlipidemia.
In the present study, hypolipidemic activity of fraction (50:50; CHCl3:CH3OH) of Amomum subulatum (Zingiberaceae) seeds was evaluated in cholesterol-fed rabbits. Hyperlipidemia induced by feeding atherogenic diet for 120 days resulted in a significant increase in serum total cholesterol, phospholipid and Triglyceride levels when compared with control group. The levels of LDL and VLDL-cholesterol were increased significantly, but the HDL-cholesterol ratio was decreased. The changes in the antioxidant parameters were accompanied by an increase in lipid peroxidation and reduction in glutathione (GSH) and catalase activity. The level of lipid peroxidation was reduced whereas GSH content and catalase activity were elevated after the treatment with A. subulatum fraction at the dose level of 100 mg/kg.b.wt/day. A significant reduction was observed in total cholesterol, Triglyceride , phospholipid, LDL and VLDL cholesterol where as HDL-cholesterol ratio was increased after administration of A. subulatum. The results of the present study indicate that fraction of A. subulatum possesses lipid-lowering and antioxidant activity and could be beneficial in the treatment of hyperlipidemia.
Ananas comosus
Background
Pineapple peel is a waste component of pineapple with valuable source of metabolites as phytoactive compounds in ameliorating metabolic-related disorders. This study investigated the atheroprotective and neuroprotective effects of peel extract of Ananas comosus fruit (PEAC) in normal diet (ND) and high-fat diet (HFD) fed rats.
Methods
Male Wistar rats were fed ND or HFD for 9 weeks, and beginning from the 6th week animals were also orally treated with PEAC (200 mg/kg). Memory performance was assessed using Y-maze test (YMT) and novel object recognition test (NORT) while anxiolytic-like effect was assessed on the elevated plus maze (EPM). serum cholesterol, Triglycerides and HDL-C were determined, while LDL-C and atherogenic risk calculated. serum and brain tissue malondialdehyde, reduced glutathione, catalase were determined. Brain acetylcholinesterase activity and interleukin-6 level were also determined.
Results
PEAC significantly attenuated HFD-induced reduction in correct alternation in YMT, and discrimination index in NORT. Also, PEAC demonstrated anxiolytic-like activity in EPM test. PEAC significantly improved lipid profile and decreased risk of atherogenicity in ND and HFD-fed rats. In addition, PEAC improves serum and brain antioxidant status by decreasing malondialdehyde and increasing GSH and catalase. PEAC significantly impaired HFD-induced brain acetylcholinesterase activity and IL-6 levels.
Conclusion
These findings suggest that peel extract of Ananas comosus fruit may protect against diet-induced behavioral disturbances via atheroprotective, antioxidants and anti-inflammatory activities.
In this study, we investigated hypolipidemic mechanisms of the ethanolic extract of Ananas comosus L. leaves (AC) in mice and then determined its activities in related enzymes. The results showed that AC (0.40 g/kg) significantly inhibited the increase in serum Triglycerides by 40% in fructose-fed mice. In mice induced by alloxan and high-fat diets, serum total cholesterol remained at a high level (180 – 220 mg/dl) within 7 days of removing high-fat diets but reached normal level (120 – 140 mg/dl) after AC (0.40 g/kg per day) treatment. Also, AC (0.40 and 0.80 g/kg) significantly inhibited serum lipids from the increase in Triton WR-1339-induced hyperlipidemic mice. AC (0.01 – 100 µg/ml) selectively activated lipoprotein lipase (LPL) activity by 200% – 400% and significantly inhibited 3-hydroxyl-methyl glutaryl coenzyme A (HMGCoA) reductase activity by 20% – 49% in vitro. Furthermore, 2 months of fenofibrate (0.20 g/kg) administration particularly increased mice liver weights (0.0760 ± 0.0110 g/g) while AC (0.40 g/kg) had no effect (0.0403 ± 0.0047). Taken together, these results suggest that AC will be a new potential natural product for the treatment of hyperlipidemia that exerts its actions through mechanisms of inhibiting HMGCoA reductase and activating LPL activities. Its action mechanisms differentiate from those with fibrates but may be partly similar to those with statins. It is hopeful that AC may serve as the adjuvant for fibrates.
Angelica sinensis (Oliv.) Diels.extract
Background: Angelica root is the dry root of the Umbelliferae plant Angelica sinensis (oliv) Diels. Angelica organic acid (OA) is the main active ingredient in Angelica sinensis, and it exerts potential Anti-atherosclerotic effects by preventing oxidized low-density lipoprotein (Ox-LDL) induced endothelial injury. To study the protective effects of OA on ox-LDL-induced HUVECs autophagic flux dysfunction and inflammatory injury.
Methods: OA were isolated by water extraction and alcohol precipitation, and then the content of ferulic acid (FA) in the OA was determined by high performance liquid chromatography. The ox-LDL-induced endothelial injury model was established. The effect of ferulic acid on the survival of Human umbilical vein endothelial cells (HVUECs) was detected by CCK-8 assay. HUVECs were pretreated with different concentrations of OA (20 μmol/L, 40 μmol/L, and 80 μmol/L), and Western Blot was used to detect the expressions of LC3II, p62, MCP-1, VCAM-1 and LOX-1. The autophagosomes in HUVECs were observed by transmission electron microscopy (TEM).
Results: 20 μmol/L OA could increase the expression of LC3II and decrease the expression of p62, MCP-1, VCAM-1 and LOX-1. The results of TEM showed that angelica organic acids promoted cell organelle degradation in autolysosomes.
Conclusion: OA could reduce inflammation, protect endothelial cells and play an Anti-atherosclerotic role by enhancing the autophagy flux of damaged endothelial cells, in which FA the major active ingredient of OA played a major role.
Nonalcoholic fatty liver disease (NAFLD) is one of the prevalent and typical chronic liver diseases. In this study, we extracted a novel Angelica sinensis polysaccharide (ASP) with low molecular weight (MW) of 3.2 kDa through optimized “one-step” purification process. The major monosaccharide components of ASP were mannose, rhamnose, glucuronic acid, galactose, arabinose, and xylose with weight ratio of 0.23:0.17:14.41:0.39:1.68:0.87, respectively. Herein, “small” ASP could serve as an effective therapeutic option for NAFLD both in free fatty acid-induced L02 models and in high-fat diet-induced mice models. Results revealed that low MW ASP dose-dependently decreased TG, TC in vitro and TG, TC, ALT, HDL-C, and LDL-C in vivo. Oil Red O-positive area and Nile red fluorescence intensity decreased in ASP treatment groups both in vitro and in vivo which suggested ASP could reduce lipid accumulation and fatty regeneration. Hematoxylin–eosin staining results shown a decrease in hepatocytes ballooning indicating that ASP could ameliorate liver lipid degeneration. Briefly, a novel polysaccharide with low MW was successfully obtained which can prospectively act as NAFLD therapy.
Annurca Apple Polyphenols
Background: Angelica root is the dry root of the Umbelliferae plant Angelica sinensis (oliv) Diels. Angelica organic acid (OA) is the main active ingredient in Angelica sinensis, and it exerts potential Anti-atherosclerotic effects by preventing oxidized low-density lipoprotein (Ox-LDL) induced endothelial injury. To study the protective effects of OA on ox-LDL-induced HUVECs autophagic flux dysfunction and inflammatory injury.
Methods: OA were isolated by water extraction and alcohol precipitation, and then the content of ferulic acid (FA) in the OA was determined by high performance liquid chromatography. The ox-LDL-induced endothelial injury model was established. The effect of ferulic acid on the survival of Human umbilical vein endothelial cells (HVUECs) was detected by CCK-8 assay. HUVECs were pretreated with different concentrations of OA (20 μmol/L, 40 μmol/L, and 80 μmol/L), and Western Blot was used to detect the expressions of LC3II, p62, MCP-1, VCAM-1 and LOX-1. The autophagosomes in HUVECs were observed by transmission electron microscopy (TEM).
Results: 20 μmol/L OA could increase the expression of LC3II and decrease the expression of p62, MCP-1, VCAM-1 and LOX-1. The results of TEM showed that angelica organic acids promoted cell organelle degradation in autolysosomes.
Conclusion: OA could reduce inflammation, protect endothelial cells and play an Anti-atherosclerotic role by enhancing the autophagy flux of damaged endothelial cells, in which FA the major active ingredient of OA played a major role.
Aim:
Cardiovascular disease (CVD) are among the main causes of death worldwide and dyslipidemias account for one of the risk factors for these diseases. Habitual apple consumption appears to be inversely associated with reduced cardiovascular risk. Then, this systematic review aims to investigate the effect of chronic apple consumption on the lipid profile of adults with dyslipidemia.
Methods:
A systematic search was performed in electronic databases, including PubMed, Embase, Web of Science and Scopus, without restriction of year of publication. Inclusion criteria were randomized clinical trials in humans that investigated the effect of chronic consumption of whole fresh or dried apple, for a period longer than two weeks of intervention on the lipid profile.
Results:
Based on the methodology used and following the pre-established search strategies, 4,468 articles were found. After applying the inclusion and exclusion criteria, five articles were selected for qualitative evaluation, covering 522 adult participants of both sexes. Three randomized controlled trials included in this review demonstrated that there was a decrease in plasma total cholesterol (TC), Triglyceride and low-density lipoprotein cholesterol (LDL-c) concentrations, in addition to an increase in high-density lipoprotein cholesterol (HDL-c) concentration. Two other studies found different results. Low risk of bias was identified in three studies.
Conclusions:
The analysis of the studies indicates that the consumption of fresh and/or dried apples with the peel has a beneficial effect on the lipid profile of adults, with a decrease in TC and LDL-c. These effects may be related to polyphenols and soluble fibers, among other functional compounds present in this fruit.
Antrodia Camphorata
effects of Antrodia Camphorata Mycelia Extract Containing Antroquinonol on lowering Low-Density Lipoprotein cholesterol:
A Randomized Double-Blind Study
Objective: Antrodia camphorata is a type of true fungus that grows only on Cinnamomum camphora trees,
also known as Cinnamomum kanehirae (“kashi”) in Taiwan. Antroquinonol is a characteristic component of A.
camphorata mycelia extract and was previously shown to exhibit antitumor action and lower blood cholesterol (total
cholesterol and low-density lipoprotein [LDL] cholesterol) in cellular and animal models. So, This study examined the
ability of A. camphorata mycelia extract to reduce LDL cholesterol in humans.
Methods: We conducted a randomized double-blind trial in 26 subjects with either borderline LDL cholesterol (120–139
mg/dL; n = 11) or miLDLy elevated LDL cholesterol (140–159 mg/dL; n = 15). Participants ingested tablets containing
either 25 mg of A. camphorata mycelia extract (antroquinonol: 0.68 mg; n = 14) or a placebo (n = 12) for 12 weeks.
Results: The test group showed a significant reduction in LDL cholesterol when compared with the placebo group after
12 weeks of tablet ingestion (p < 0.05), demonstrating the effects of A. camphorata mycelia extract on LDL cholesterol.
A. camphorata mycelia extract also tended to reduce total cholesterol when compared with the placebo (p < 0.10). The
borderline LDL cholesterol and miLDLy elevated LDL cholesterol subgroups showed a significant reduction in LDL
cholesterol in subjects who ingested A. camphorata mycelia extract compared with those who ingested the placebo,
again demonstrating the LDL cholesterol–lowering effect of the extract.
Conclusion: A. camphorata mycelia extract lowers LDL cholesterol in individuals with somewhat high LDL cholesterol
levels.
This study investigated the potential effects of dehydroeburicoic acid (TT), a triterpenoid compound from Antrodia camphorata, in vitro and examined the effects and mechanisms of TT on glucose and lipid homeostasis in high-fat-diet (HFD)-fed mice. The in vitro study examined the effects of a MeOH crude extract (CruE) of A. camphorata and Antcin K (AnK; the main constituent of fruiting body of this mushroom) on membrane glucose transporter 4 (GLUT4) and phospho-Akt in C2C12 myoblasts cells. The in vitro study demonstrated that treatment with CruE, AnK and TT increased the membrane levels of glucose transporter 4 (GLUT4) and phospho-Akt at different concentrations. The animal experiments were performed for 12 weeks. Diabetic mice were randomly divided into six groups after 8 weeks of HFD-induction and treated with daily oral gavage doses of TT (at three dose levels), fenofibrate (Feno) (at 0.25 g/kg body weight), metformin (Metf) (at 0.3 g/kg body weight) or vehicle for another 4 weeks while on an HFD diet. HFD-fed mice exhibited increased blood glucose levels. TT treatment dramatically lowered blood glucose levels by 34.2%~43.4%, which was comparable to the antidiabetic agent-Metf (36.5%). TT-treated mice reduced the HFD-induced hyperglycemia, hyperTriglyceride mia, hyperinsulinemia, hyperleptinemia, and hypercholesterolemia. Membrane levels of GLUT4 were significantly higher in CruE-treated groups in vitro. Skeletal muscle membrane levels of GLUT4 were significantly higher in TT-treated mice. These groups of mice also displayed lower mRNA levels of glucose-6-phosphatase (G6 Pase), an inhibitor of hepatic glucose production. The combination of these agents produced a net hypoglycemic effect in TT-treated mice. TT treatment enhanced the expressions of hepatic and skeletal muscle AMP-activated protein kinase (AMPK) phosphorylation in mice. TT-treated mice exhibited enhanced expression of hepatic fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor α (PPARα) and increased mRNA levels of carnitine palmitoyl transferase Ia (CPT-1a). These mice also exhibited decreased expression levels of lipogenic fatty acid synthase (FAS) in liver and adipose tissue and reduced mRNA levels of hepatic adipocyte fatty acid binding protein 2 (aP2) and glycerol-3-phosphate acyltransferase (GPAT). These alterations resulted in a reduction in fat stores within the liver and lower Triglyceride levels in blood. Our results demonstrate that TT is an excellent therapeutic approach for the treatment of type 2 diabetes and hyperTriglyceride mia.
The aim of this study was to examine the effects of dehydroeburicoic acid (TT) on type 1 diabetes mellitus and dyslipidemia in streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were randomly divided into six groups and given orally by gavage TT (at three dosages), metformin (Metf), fenfibrate (Feno), or vehicle for 4 weeks. STZ-induced diabetic mice showed elevations in blood glucose levels (P < 0.001). TT treatment markedly decreased blood glucose levels by 42.6–46.5%. Moreover, STZ-induced diabetic mice displayed an increase in circulating Triglyceride (TG) and total cholesterol (TC) levels (P < 0.001 and P < 0.01, respectively) but a decrease in blood insulin and adiponectin levels (P < 0.01 and P < 0.05, respectively). These substances are also reversed by TT treatment, indicating TT ameliorated diabetes and dyslipidemia. Membrane skeletal muscular expression levels of glucose transporter 4 (GLUT4) and expression levels of AMPK phosphorylation (phospho-AMPK) in both liver and skeletal muscle were reduced in STZ-induced diabetic mice, which normalized upon TT treatment and correction of hyperglycemia accompanied with a decrease in mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6 Pase), which was related to the inhibition of hepatic glucose production and attenuating diabetic state. In addition, TT also showed hypolipidemic effect by increasing hepatic expression levels of peroxisome proliferator-activated receptor α (PPARα) and mRNA levels of carnitine palmitoyl transferase Ia (CPT-1a) but decreasing expression levels of fatty acid synthase (FAS), which further contributed to a decrease in circulating TG levels. TT-treated mice displayed decreased SREBP2 mRNA levels and reduced blood TC levels. These findings strongly support that TT prevents diabetic and dyslipidemic states in STZ-induced diabetic mice evidenced by regulation of GLUT4, PPARα, FAS, and phosphorylation of AMPK.
The present study was designed to evaluate the protective effect of sulphurenic acid (SA), a pure compound from Antrodia camphorata, on diabetes and hyperlipidemia in an animal model study and to clarify the underlying molecular mechanism. Diabetes was induced by daily 55 mg/kg intraperitoneal injections of streptozotocin (STZ) solution over five days. Diabetic mice were randomly divided into six groups and orally gavaged with SA (at three dosages) or glibenclamide (Glib), fenofibrate (Feno) or vehicle for 3 weeks. Our findings showed that STZ-induced diabetic mice had significantly increased fasting blood glucose, glycated hemoglobin (HbA1C), plasma Triglyceride (TG), and total cholesterol (TC) levels (p < 0.001, p < 0.001, p < 0.001, and p < 0.05, respectively) but decreased blood insulin, adiponectin, and leptin levels compared to those of the control group (p < 0.001, p < 0.001, and p < 0.001, respectively). Administration of SA to STZ-induced diabetic mice may lower blood glucose but it increased the insulin levels with restoration of the size of the islets of Langerhans cells, implying that SA protected against STZ-induced diabetic states within the pancreas. At the molecular level, SA treatment exerts an increase in skeletal muscle expression levels of membrane glucose transporter 4 (GLUT4) and phospho-Akt to increase the membrane glucose uptake, but the mRNA levels of PEPCK and G6Pase are decreased to inhibit hepatic glucose production, thus leading to its hypoglycemic effect. Moreover, SA may cause hypolipidemic effects not only by enhancing hepatic expression levels of peroxisome proliferator-activated receptor α (PPARα) with increased fatty acid oxidation but also by reducing lipogenic fatty acid synthase (FAS) as well as reducing mRNA levels of sterol regulatory element binding protein (SREBP)1C and SREBP2 to lower blood TG and TC levels. Our findings demonstrated that SA displayed a protective effect against type 1 diabetes and a hyperlipidemic state in STZ-induced diabetic mice.
Antrodia cinnamomea
Antrodia cinnamomea is a Taiwanese medicinal mushroom with multiple pharmacological activities. Antrodia cinnamomea solid-state cultivated mycelium (LAC) exerts health-related effects in animal and cell models, but clinical data is limited. This study aimed to determine the safety and effects of LAC on human physiological functions. In an open-label, single-arm study, 32 healthy men and women ingested LAC capsules for three months. The subjects were monitored during the study and one month after the study end-point. LAC consumption did not significantly change fasting blood glucose, blood pressure, and Triglyceride levels or liver and renal function indices. No adverse events occurred during the trial. Moreover, a significant change from baseline in total cholesterol levels was observed; men and women had decreases of 5.7% and 5.3%, respectively. Based on these, the ingestion of LAC-capsule has a considerable degree of safety and has the potential to reduce total cholesterol in healthy adults.
Antrodia cinnamomea (AC), a protogenic fungus that only grows on the heartwood of endemic Cinnamomum kanehirae Hayata in Taiwan, is used to treat a variety of illness including liver disease. However, little is known about the benefit of AC against obesity and the related hepatic disorder. Using high-fat-diet (HFD) feed mice, we aimed to investigate whether the extract of AC (ACE) could reduce excessive weight, body fat, and serum lipids and prevent the development of non-alcoholic fatty liver (NAFLD). C57BL/6 mice were divided into five groups fed with different diets: control, HFD, and HFD with 0.5%, 1%, or 2% of ACE, respectively. After 10 weeks the animals were sacrificed, with serum and liver collected. HFD-induced elevation of body weight gain, body fat deposition, and serum free fatty acid (FFA), triacylglycerol (TGs), total cholesterol, and ratio of LDL cholesterol (LDL-C)/HDL cholesterol (HDL-C), were significantly restored by ACE. ACE reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hepatic lipid deposits increased by HFD. ACE increased p-AMP activated protein kinase (pAMPK) but decreased Sterol regulatory element binding protein (SREBP), fatty acid synthase (FAS), 1-acylglycerol-3-phosphate acyltransferase (AGPAT), and 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase. The chemical analysis reveals ACE is full of triterpenes, the most abundant of which is Antcin K, followed by sulphurenic acid, eburicoic acid, antcin C, dehydrosulphurenic acid, antcin B, and propanoic acid. In conclusion, ACE should be used to prevent obesity and derived fatty liver. The applicability of ACE on NAFLD deserves further investigation.
Evaluation of Blood Lipid-Lowering Effects of Antrodia cinnamomea Mycelia Powder Complex
Objective: This study was conducted to assess the prenatal developmental blood lipid-lowering effects of an Antrodia cinnamomea mycelia powder complex according to the safety assessment guideline of Health Food announced by Ministry of Health and welfare, Executive Yuan of Taiwan. Methods: A total of 32 hyperlipidemia individuals with TC > 200 mg/dl were randomly divided in- to intervention group (n = 16) and placebo group (n = 16). Dietary intervention was provided for the intervention group for 2 months. Information on dietary intakes, physical examinations and blood samples was collected. Serum lipids were assayed at baseline and endpoint of the study pe- riod. Subjects take two capsules of A. cinnamomea mycelia powder complex or placebo twice a day. The study has 2 weeks run in period, 8 weeks intervention period, and 4 weeks follow-up period. All subjects measure body weight, body fat, blood pressure and biochemical parameters, including Triglycerides (TG), total cholesterol (TC), low density lipoprotein in cholesterol (LDL-C), high den- sity lipoprotein in cholesterol (HDL-C), blood sugar, kidney and liver function. Results: The results were found after 8 weeks intervention, the plasma total cholesterol and LDL-C were significantly decreased compared with the initial, and there was significantly difference (p < 0.05) compared with the placebo group. LDL-C/HDL-C and Triglyceride level has a decreasing trend. Conclusion: A. cinnamomea mycelia powder complex could decrease blood lipids.
The major pathologic hallmark of the alcoholic liver disease (ALD) is the representation of chronic alcohol-induced hepatocyte lipid accumulation. This study aims to investigate the hepatoprotective role of triterpenoids-enriched extracts from Antrodia cinnamomea mycelia (ACT) in chronic alcohol-induced liver injury mice, establishing in C57BL/6 mice through gradient alcohol feeding for 24 weeks. In long-term alcohol consumption mice, the significantly lost body weight, increased organ indexes, hepatic alanine aminotransferase and aspartate aminotransferase levels were all remissed after 6-week ACT orally administration, showing its hepatoprotective property. ACT suppressed the Triglyceride , total cholesterol and low-density lipoprotein levels, and enhanced high-density lipoprotein levels in serum or/and liver of chronic alcohol damaged mice. Combining with the pathological observations, ACT displayed an anti-steatosis effects to restrain the progress of ALD. Based on proteomic analysis and enzyme-linked immunosorbent assay, ACT had been confirmed to regulate the levels of lipid biogeneration-related factors and depressed the over-accumulation of hepatic reactive oxygen species. According to further data, ACT prevented alcoholic liver injury may be associated with mediating lipid metabolism-related to PGC-1α and NF-κB signaling. In summary, ACT protected the body against chronic alcohol ingest induced liver injury through its regulation lipid on metabolism.
HYPOLIPIDEMIC EFFECTS OF ANTRODIA CINNAMOMEA EXTRACTS IN HIGH-FAT DIET-FED HAMSTERS
Antrodia cinnamomea (AC) is a popular medicinal fungus used for treating hypertension, hepatotoxicity and tumors. This study aimed to examine the hypolipidemic properties of A. cinnamomea extracts (ACE) in high-fat diet-fed hamsters. Results showed that at concentrations 500, 1,000 and 1,500 mg/kg, ACE showed no significant effect on total cholesterol and high-density lipoprotein concentrations, but a trend of decrease in plasma Triglycerides and low-density lipoprotein (LDL) levels was noted, and a significant reduction in LDL was observed at 1,500 mg/kg ACE. ACE caused a significant decrease in liver Triglycerides and total cholesterol concentrations. ACE possessed the ability to enhance superoxide dismutase, catalase and glutathione peroxidase production, and reduced the thiobarbituric acid-reactive substances level in hyperlipidemic hamsters. These results conclude that ACE is able to lower the plasma Triglycerides and LDL, liver Triglycerides and total cholesterol concentrations, as well as enhancing the level of antioxidant enzymes.
apigenin 7-O-β-D glucoside
Oral administration of apigenin 7-O-β-D glucoside reverses hyperlipidemia and associated
vascular dysfunction in rats
Apigenin 7‑O‑β‑D‑glucoside is a flavonoid reported as smooth muscle relaxant, anti-
inflammatory, and anti-oxidant, suggesting its role in cardiovascular disease. The present study
aimed to investigate the effect of apigenin 7‑O‑β‑D‑glucoside on hyperlipidemia and associated
vascular dysfunction in rats. Oral administration of apigenin 7‑O‑β‑D‑glucoside to HFD and
tyloxopol-induced hyperlipidemic SD rats for 28 and 10 days that reduced significantly (p < 0.01),
total cholesterol, LDL, VLDL and Triglycerides , and increased HDL levels and also reduced the
total body weight and atherogenic index suggesting its antihyperlipidemic effect. This effect was
further confirmed when the compound also inhibited the key enzyme HMG-CoA reductase in the
biosynthesis of cholesterol.
Apigenin 7‑O‑β‑D‑glucoside is a flavonoid reported as smooth muscle relaxant, anti- inflammatory, and anti-oxidant, suggesting its role in cardiovascular disease. The present study aimed to investigate the effect of apigenin 7‑O‑β‑D‑glucoside on hyperlipidemia and associated vascular dysfunction in rats. Oral administration of apigenin 7‑O‑β‑D‑glucoside to HFD and tyloxopol-induced hyperlipidemic SD rats for 28 and 10 days that reduced significantly (p < 0.01), total cholesterol, LDL, VLDL and Triglycerides , and increased HDL levels and also reduced the total body weight and atherogenic index suggesting its antihyperlipidemic effect. This effect was further confirmed when the compound also inhibited the key enzyme HMG-CoA reductase in the biosynthesis of cholesterol. The devastating effects on vascular architecture such as change in the aortic intima, media, adventitia and also the endothelium damage, were reversed in apigenin 7‑O‑β‑D‑glucoside 5 mg/kg/day treated group. In the in vitro studies, the compound reversed the endothelial damage demonstrated by significant vasorelaxation in the aortic rings from hyperlipidemic rats treated with apigenin 7‑O‑β‑D‑glucoside 5 mg/kg/day, with EC50 value of 0.02 μg/mL (0.01-0.20) compared to hyperlipidemic HFD rats, similar to atorvastatin. These findings indicate that antihyperlipidemic effect of apigenin 7‑O‑β‑D‑glucoside is mediated through decrease in total cholesterol, LDL, VLDL, Triglyceride level and increase in level of HDL through inhibition of HMG-CoA inhibition and also improved the associated histopathological changes and endothelium dysfunction.
Aporosa lindleyana
cholesterol lowering effect OF Aporosa lindleyana IN MALE WISTAR RATS
Aporosa lindleyana is a green leafy vegetable of family Euphorbiaceae grown in tropical countries. In this study the effect of Aporosa lindleyana on the serum cholesterol level of hypercholestero-laemic rats and normocholesterolaemic Wistar rats fed on a cholesterol enriched diet was investigated. The results indicate that feeding of plant extract for two weeks reduces the total cholesterol in hypercholesterolaemic Wistar rats by 25.2% and normocholesterolaemic rats fed with cholesterol enriched diet by 37.7%. In addition the test group had significantly lower (p<0.05) total/HDL than the controls indicating that Aporosa lindleyana extract possesses hypochlosterolaemic activity.
Artemisia capillaris Thunb.extract
Antioxidant and lipid–lowering effects of Artemisia capillaris on a Rat Model of Hyperlipidemia
Objectives: This study was designed to evaluate lipid–lowering and antioxidant effects of Artemisia capillaris(A.
capillaris) using a model of hyperlipidemic rats induced by poloxamer-407.
Methods: Rats were previously treated by A. capillaris water extract, and intraperitoneally injected by poloxamer-407
to induce hyperlipidemia. Parameters of serum lipid and oxidative stress biomarkers were determined.
Results:
1. A. capillaris ameliorated the elevation of serum total cholesterol, Triglyceride , LDL–cholesterol and MDA level.
2. A. capillaris ameliorated the reduction of serum TAC and SOD activities.
3. A. capillaris ameliorated the reduction of serum GSH and GSH-reductase level.
Conclusions: According to these results, A. capillaris can be used to treat hyperlipidemia or as basis for making new
drugs for treating hyperlipidemia in the future.
Antioxidant and Lipid-lowering Effects of Artemisia capillaris on a Rat Model of Hyperlipidemia
Hyperlipidemia, also known as hyperlipoproteinemia, refers to the excess status of fatty substances including cholesterol, Triglycerides or lipoproteins in the bloodstream1,2). Hyperlipidemia is an important risk factor in developing heart disease and stroke which are leading causes of death in most developed countries, including Korea3,4). Accordingly, the appropriate control of lipid levels in the bloodstream is a standard strategy to prevent the development of vascular disease5). There are four classes of lipid lowering drugs: 3-hydroxy-3-methylglutaryl coenzyme A(HMG- CoA) reductase inhibitors commonly referred to as statins, bile acid sequestrants, nicotinic acid, and fibric acids6,7). These hypolipidemic agents lower lipid levels somewhat, but have a limitation due to lack of final clinical outcome in prevention of heart disease and stroke, and often adverse effects such as hepatotoxicity, myopathy or noncardiovascular death8,9)
Artemisinin (Artemisia annua L.)
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
Objectives: Artemisinin and its derivatives extracted from Artemisia annua, a Chinese herbal medicine, have variable biological effects due to structural differences. Up to date, the anti-obesity effect of dihydroartemisinin (DHA), a derivative of artemisinin, is unknown. The purpose of this study was to investigate the anti-adipogenic and lipolytic effects of DHA on 3T3-L1 preadipocytes.
Methods: Oil Red O staining and AdipoRed assay were used to measure lipid accumulation and Triglyceride (TG) content in 3T3-L1 cells, respectively. Cell count analysis was used to determine the cytotoxicity of 3T3-L1 cells. Western blot and real-time reverse transcription polymerase chain reaction analyses were used to analyze the expression of protein and mRNA in 3T3-L1 cells, respectively.
Results: DHA at 5 μM markedly inhibited lipid accumulation and reduced TG content in differentiating 3T3-L1 cells with no cytotoxicity. Furthermore, DHA at 5 μM inhibited the expression of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A as well as the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) in differentiating 3T3-L1 cells. Moreover, while DHA at 5 μM had no effect on the mRNA expression of adiponectin, it strongly suppressed that of leptin in differentiating 3T3-L1 cells. However, DHA at 5 μM had no lipolytic effect on differentiated 3T3-L1 cells, as assessed by no enhancement of glycerol release.
Conclusions: These results demonstrate that DHA at 5 μM has a strong anti-adipogenic effect on differentiating 3T3-L1 cells through the reduced expression and phosphorylation of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3.
Artemisia annua extract ameliorates high-fat diet-induced fatty liver by activating AMPK
Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. Recently, natural compounds that may be beneficial for improving NAFLD have received increasing attention. Artemisia annua L. is the source of antimalarial phytomolecule, artemisinin, which has been reported to prevent obesity. However, the effect of A. annua extract on hepatic lipid metabolism remains unclear. This study was performed to determine the protective effect of Artemisia annua extract (AAE) on high-fat diet (HFD)-induced hepatic lipid accumulation, and elucidate the molecular mechanisms behind its effects in vivo and in vitro. We found that HFD-fed mice with AAE administration (50 mg/kg/day) for 8 weeks dramatically reduced hepatic lipid accumulation compared to the control mice taken with HFD alone. The body and liver weights of AAE group were significantly lower than those of HFD group, and oral administration of AAE remarkably suppressed the serum levels of Triglyceride (TG), total cholesterol (TC), fasting glucose, alanine transaminase (ALT) and aspartate transaminase (AST) in HFD-fed mice. AAE significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in the liver of HFD-fed mice and HepG2 hepatocytes. Moreover, AAE downregulated the hepatic expression of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) in HFD-fed mice and high glucose-treated HepG2 cells. In addition, the inhibitory effects of AAE on the overexpression of SREBP-1c and FAS were attenuated by compound C, which is the specific AMPK inhibitor, in high glucose-treated HepG2 cells. These results indicated that AAE may represent a promising approach for the prevention and treatment of obesity-related NAFLD via the activation of AMPK and the regulation of AMPK-dependent lipogenic genes.
Artocarpus ovatus Blanco (Moraceae) ethanolic leaf extract
Artocarpus ovatus Blanco is a plant species of the Philippines belonging to the family Moraceae. This study evaluated the cholesterol–lowering activity of the A. ovatus ethanolic leaf extract in Sprague Dawley rats and its acute oral toxicity. It was found to be safe and non-toxic up to 2000 mg/kg BW of test animals based on the guidelines of OECD 425 main test. Post toxicity test gross necropsy results are unremarkable. In the cholesterollowering bioassay, the ethanolic extract treated rats at doses of 200, 400 and 600 mg/kg showed time dependent reduction of serum levels of total cholesterol, Triglycerides and low density lipoproteins with p-values less than 0.05. high density lipoproteins concentration improved, high catalase enzyme levels and unremarkable degree of lipid peroxidation were measured and observed after 14 days of oral administration of the extract.
In vivo cholesterol-lowering bioassay results Mean serum total cholesterol, Triglycerides , HDL and LDL values were significant to all the experimental groups (p values < 0.05). After the 14-day treatment period, groups III, IV, V and VI (200 to 600 mg/kg extract treated groups and positive control group) have decreased total cholesterol, Triglycerides and LDL levels. However post hoc analysis showed that groups IV and V (400 and 600 mg/kg extract treated groups) have no significant difference in reducing total cholesterol. The treatment groups (200 to 600 mg/kg extract treated groups) do not statistically differ in improving mean HDL serum levels with the positive control group (p values > 0.05). This demonstrates that the ethanolic extract exhibited cholesterol-lowering effect comparable to the positive control on animal rat models. Presence of excessive levels of cholesterol in the blood indicates a strong risk factor for cardiovascular diseases. Maintenance of low levels of cholesterol in the blood is clinically and importantly considered through the use of pharmaceutical agents such as the statin drugs (HMG-CoA reductase inhibitors) and the fibrates [11]. Medicinal plants can also be utilized as alternative sources of these established remedies but most of them must be clinically studied further. The results of this study suggest that the A. ovatus ethanolic leaf extract have a medicinal potential specifically in lowering cholesterol levels in rat animal models. Figures 1 to 4 present the mean total cholesterol, Triglycerides , HDL and LDL levels of the experimental groups.
Salix alba L. tree
Background: Low density lipoprotein oxidation is a major pathogenic pathway in Atherosclerosis. Previous studies suggested that aspirin, a commonly prescribed drug in patients with Atherosclerosis, when given in a dose of 300 mg/day may decrease LDL susceptibility to oxidative modification. However, the effect of the more common lower dose aspirin on LDL oxidation is not known.
Objectives: To examine the effect of aspirin administration (low dosage) on the susceptibility of LDL to oxidative modification in healthy volunteers.
Methods: Aspirin 75 mg was administered daily for 2 weeks to 10 healthy volunteers selected from the medical staff and students at the faculty of medicine. The main outcome measure was ex vivo oxidation of LDL by ultraviolet C irradiation or by peroxyl free radicals generated by AAPH (2,2′-azobis 2-amidinopropane hydrochloride). The extent of LDL oxidation was determined by measuring the formed amounts of thiobarbituric acid-reactive substances, lipid peroxides and conjugated dienes.
Results: Following exposure to UVc irradiation there was a significant (P 0.01) increase (10.8%) in TBARS concentrations and a significant (P < 0.05) increase (5.4%) in PD concentrations in LDL withdrawn after aspirin treatment as compared to LDL withdrawn before aspirin treatment. Following incubation with AAPH there was a significant (P < 0.05) increase (15%) in PD concentrations and a significant (P < 0.05) reduction (10%) of the LDL oxidation lag time in LDL withdrawn after aspirin intake as compared to LDL withdrawn before aspirin treatment.
Conclusions: Aspirin treatment given to healthy volunteers at a dose of 75 mg/day increased the susceptibility of their plasma LDL to oxidative modification ex vivo. Our study provides, for the first time, in vivo evidence of pro-oxidative properties of aspirin already suggested by previous in vitro trials.
A study was conducted to determine the effects of dietary hydroalcoholic willow bark extract powder (HWE) supplemented to broilers (14-42 days old) that were exposed to heat stress, on the performance, serum biochemical parameters, liver oxidative status and caecal microflora. The feeding trial was conducted on 120 Cobb 500 broilers (14 days old), assigned to three treatments (T0, T25, and T50), each treatment consisting of eight replicates (five chicks per replicate). The broilers were housed in an experimental hall at a 32 °C constant temperature and 23 hours light regimen. Unlike the dietary control treatment (T0), the experimental treatments were supplemented with 25 g HWE powder/100 kg diet (T25), and 50 g HWE powder 100 kg diet (T50), respectively. Dietary HWE powder did not affect the broilers’ performance significantly (14-42 days). A significantly lower amount of malondialdehyde was noticed in the liver of broilers from T25 and T50 treatments in comparison with broilers from T0. Also, the serum cholesterol, Triglycerides and alanine aminotransferase were significantly lower in broilers fed with T50, compared with those fed with T0. At 35 and at 42 days, the broilers from T25 and T50 recorded a significantly lower number of E. coli and staphylococci and a higher number of lactobacilli in the caecum than those of T0. It could be concluded that supplementation of dietary HWE powder reduced some of the adverse effects of heat stress, the most effective being the level of 50 g/100 kg diet.
Astragalus (Astragalus membranaceus)
Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protective effects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments and diet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of total cholesterol and LDL cholesterol (P < 0.05 to 0.01), increased HDL cholesterol levels (P < 0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P < 0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and this effect increased with higher TFA concentration. In in vivo experiments, TFA effectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve the Atherosclerosis profile.
Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protective effects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments and diet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of total cholesterol and LDL cholesterol ( to 0.01), increased HDL cholesterol levels ( ), and reduced the aortic fatty streak area by 43.6 to 63.6% ( ). We also found that TFA scavenged superoxide and hydroxyl radicals and this effect increased with higher TFA concentration. In in vivo experiments, TFA effectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve the atherosclerosis profile.
Astragalus membranaceus is a Traditional Chinese Medicine (TCM) belonging to the Leguminosae family. It has been used as antidiabetic, cardioprotective, and hepatoprotective in the TCM clinic. From the stems of A. membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, 14 oleanane type saponins (1–14) including eight new ones, astroolesaponins A (1), B (2), C1 (3), C2 (4), D (5), E1 (6), E2 (7), and F (8) were obtained, and their structures were elucidated by chemical and spectroscopic methods. Compounds 1–5, 7, 8, 11, and 13 showed decreased effects on Triglyceride levels in sodium oleate induced HepG2 cells.
Astragalus membranaceus is commonly used in traditional Chinese medicine for strengthening the host defense system. Astragalus membranaceus-polysaccharides is an effective component with various important bioactivities, such as immunomodulation, antioxidant, anti-diabetes, anti-inflammation and neuroprotection. In the present study, we determine the effects of Astragalus membranaceus-polysaccharides on metabolically stressed transgenic mice in order to develop this macromolecules for treatment of sporadic Alzheimer’s disease, a neurodegenerative disease with metabolic risk factors. Transgenic mice, at 10 weeks old prior to the appearance of senile plaques, were treated in combination of administrating high-fat diet and injecting low-dose streptozotocin to create the metabolically stressed mice model. Astragalus membranaceus-polysaccharides was administrated starting at 14 weeks for 7 weeks. We found that Astragalus membranaceus-polysaccharides reduced metabolic stress-induced increase of body weight, insulin and insulin and leptin level, insulin resistance, and hepatic Triglyceride . Astragalus membranaceus-polysaccharides also ameliorated metabolic stress-exacerbated oral glucose intolerance, although the fasting blood glucose was only temporally reduced. In brain, metabolic stress-elicited astrogliosis and microglia activation in the vicinity of plaques was also diminished by Astragalus membranaceus-polysaccharides administration. The plaque deposition, however, was not significantly affected by Astragalus membranaceus-polysaccharides administration. These findings suggest that Astragalus membranaceus-polysaccharides may be used to ameliorate metabolic stress-induced diabesity and the subsequent neuroinflammation, which improved the behavior performance in metabolically stressed transgenic mice.
Astragalus mongholicus
Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protective effects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments and diet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of total cholesterol and LDL cholesterol (P < 0.05 to 0.01), increased HDL cholesterol levels (P < 0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P < 0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and this effect increased with higher TFA concentration. In in vivo experiments, TFA effectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve the Atherosclerosis profile.
Astragalus mongholicus is a Chinese traditional medicine. In this study, we sought to explore potential benefits in cardiovascular disorders associated with excess cholesterol and hyperlipidemia. We have investigated the effects of A. mongholicus extract as a dietary supplement on hyperlipidemia and oxidative stress in rats maintained on a high- cholesterol diet. Diets were supplemented with A. mongholicus extract at 0.4 and 0.8% for five weeks, while control animals received no supplement. A. mongholicus extract administration to hyperlipidemic rats resulted in a significant decline in serum levels of total cholesterol, Triglycerides and low density lipoprotein-cholesterol, with an increase in serum high-density lipoprotein-cholesterol levels. Furthermore, A. mongholicus extract improved serum and heart antioxidant status as assessed by superoxide dismutase and glutathione peroxidase activities and reduced levels of lipid peroxidation. These results suggest that A. mongholicus extract consumption can improve lipid profiles, inhibit peroxidation, and increase the activity of antioxidant enzymes, and is thereby likely to reduce the risk of coronary heart disease associated with hyperlipidemia and oxidative stress.
Basella alba
Hypercholesterolemia is the major risk factor that leads to Atherosclerosis. Nowadays, alternative treatment using medicinal plants gained much attention since the usage of statins leads to adverse health effects, especially liver and muscle toxicity. This study was designed to investigate the hypocholesterolemic and Antiatherosclerotic effects of Basella alba (B. alba) using hypercholesterolemia-induced rabbits. Twenty New Zealand white rabbits were divided into 5 groups and fed with varying diets: normal diet, 2% high cholesterol diet (HCD), 2% HCD + 10 mg/kg simvastatin, 2% HCD + 100 mg/kg B. alba extract, and 2% HCD + 200 mg/kg B. alba extract, respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol, LDL, and Triglycerides and increased HDL and antioxidant enzymes (SOD and GPx) levels. The elevated levels of liver enzymes (AST and ALT) and creatine kinase were noted in hypercholesterolemic and statin treated groups indicating liver and muscle injuries. Treatment with B. alba extract also significantly suppressed the aortic plaque formation and reduced the intima: media ratio as observed in simvastatin-treated group. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and Atherosclerosis.
Twenty New Zealand white rabbits were divided into 5 groups and fed with normal diet (G1), 2% high cholesterol diet (HCD) (G2), 2% HCD + 10 mg/kg simvastatin
(G3), 2% HCD + 100 mg/kg B. alba extract (G4) and 2% HCD + 200 mg/kg B. alba extract (G5), respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol (TC), low density lipoptotein (LDL) and Triglyceride (TG). The significant increase in high density lipoprotein (HDL) and antioxidant enzymes; superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels observed in treatment with B. alba extract (G4 and G5) compared to the treatment with simvastatin (G3). The elevated levels of liver enzymes; alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and muscle enzyme; creatine kinase (CK) were noted in G2 and G3 indicate liver and muscle injuries. Treatment with simvastatin (G3) and B. alba extract (G4 and G5) significantly suppressed the aortic plaque formation. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and atherosclerosis.
The enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase is the key enzyme of the mevalonate pathway that produces cholesterol. Inhibition of HMG-CoA reductase reduces cholesterol biosynthesis in the liver. Synthetic drugs, statins, are commonly used for the treatment of hypercholesterolemia. Due to the side effects of statins, natural HMG-CoA reductase inhibitors of plant origin are needed. In this study, 25 medicinal plant methanol extracts were screened for anti-HMG-CoA reductase activity. Basella alba leaf extract showed the highest inhibitory effect at about 74%. Thus, B. alba was examined in order to investigate its phytochemical components. Gas chromatography with tandem mass spectrometry and reversed phase high-performance liquid chromatography analysis revealed the presence of phenol 2,6-bis(1,1-dimethylethyl), 1-heptatriacotanol, oleic acid, eicosyl ester, naringin, apigenin, luteolin, ascorbic acid, and α-tocopherol, which have been reported to possess antihypercholesterolemic effects. Further investigation of in vivo models should be performed in order to confirm its potential as an alternative treatment for hypercholesterolemia and related cardiovascular diseases.
Hypercholesterolemia is the major risk factor that leads to atherosclerosis. Nowadays, alternative treatment using medicinal plants gained much attention since the usage of statins leads to adverse health effects, especially liver and muscle toxicity. This study was designed to investigate the hypocholesterolemic and antiatherosclerotic effects of Basella alba (B. alba) using hypercholesterolemia-induced rabbits. Twenty New Zealand white rabbits were divided into 5 groups and fed with varying diets: normal diet, 2% high cholesterol diet (HCD), 2% HCD + 10 mg/kg simvastatin, 2% HCD + 100 mg/kg B. alba extract, and 2% HCD + 200 mg/kg B. alba extract, respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol, LDL, and Triglycerides and increased HDL and antioxidant enzymes (SOD and GPx) levels. The elevated levels of liver enzymes (AST and ALT) and creatine kinase were noted in hypercholesterolemic and statin treated groups indicating liver and muscle injuries. Treatment with B. alba extract also significantly suppressed the aortic plaque formation and reduced the intima: media ratio as observed in simvastatin-treated group. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and atherosclerosis.
Berberine
Regulation of PCSK9 by nutraceuticals
PCSK9, a critical Inhibitor of LDLR, is up-regulated by both HNF1α and SREBP-2 transcription factors. Besides
PCSK9, SREBP-2 up-regulates LDLR gene. Nutraceuticals, including curcumin and berberine, can decrease plasma
LDL-C levels through elevation of the hepatic LDLR via inhibiting HNF1α which is a specific transcription factor
for PCSK9 gene. Statins increase the expression of both PCSK9 and LDLR through the activation of SREBP-2,
resulting in PCSK9-mediated attenuation of their effects.
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL–cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an Inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
The aim of this study was to investigate the role of the mevalonate pathway in the cytostatic/cytotoxic effects of berberine, a natural plant alkaloid that reduces cholesterol concentration. Berberine as well as lovastatin, an Inhibitor of the mevalonate pathway, exerted dose-dependent cytostatic/cytotoxic effects against human breast cancer cells (MDA-MB231). Although the mevalonate pathway metabolites (mevalonic acid, farnesyl pyrophosphate, geranylgeranyl pyrophosphate) effectively reversed cytostatic/cytotoxic effects of lovastatin against MDA-MB231 cells, they were not effective in influencing the cytostatic/cytotoxic effects of berberine. The cytostatic/cytotoxic effects of berberine do not seem to result from inhibition of the mevalonate pathway.
Ethnopharmacological relevance
Rhizoma coptidis (Huanglian in Chinese) is commonly used in Chinese folk medicine to treat diarrhea, diabetes, hypertension, hyperlipidemia and tumors. This herb has increasingly gained attention because of its use as a hypolipidemic herb. Berberine (BBR) is the most important constituent of R. coptidis that contribute to the pharmacological efficacy of the herb.
Aim of the study
Pharmacokinetic studies have indicated that BBR has poor oral bioavailability. Interestingly, several reports show that absorbed BBR is extensively metabolized in rats and humans. We speculate that the BBR metabolites might be responsible for the pharmacological effects. The aim of this study is to examine BBR metabolites for their Triglyceride (TG)-lowering activities and the molecular mechanism to clarify BBR genuine effective forms in vivo.
Materials and methods
Four BBR metabolites were examined their TG-lowering effects with a commercial Triglyceride assay kit. Real-time PCR and Western blotting were used to confirm genes and proteins of interest, respectively.
Results
Among those BBR metabolites, M2 exhibited the more potential effects on TG-lowering and AMP-activated protein kinase (AMPK) activation in Hep G2 cells as compared with BBR. Moreover, BBR and M2 inhibited gene expressions of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), glycerol-3-phosphate acyltransferase (GPAT) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), but motivated gene expression of medium chain acyl-CoA dehydrogenase (mCAD) significantly.
Conclusions
The results suggested that the TG-lowering effects of BBR and M2 might be partially mediated by the up-regulation of lipolysis gene expressions and down-regulation of lipogenesis gene expressions through activation of the AMPK signaling pathway. BBR and its metabolites might be in vivo active forms of oral doses of BBR, and M2 might be a promising drug candidate against hyperlipidemia.
Lipid-lowering effect of berberine in human subjects and rats
Due to serious adverse effects and the limited effectiveness of currently available pharmacological therapies for obesity, many research efforts have focused on the development of drugs from natural products. Our previous studies demonstrated that berberine, an alkaloid originally isolated from traditional Chinese herbs, prevented fat accumulation in vitro and in vivo. In this pilot study, obese human subjects (Caucasian) were given 500 mg berberine orally three times a day for twelve weeks. The efficacy and safety of berberine treatment was determined by measurements of body weight, comprehensive metabolic panel, blood lipid and hormone levels, expression levels of inflammatory factors, complete blood count, and electrocardiograph. A Sprague-Dawley rat experiment was also performed to identify the anti-obesity effects of berberine treatment. The results demonstrate that berberine treatment produced a mild weight loss (average 5 lb/subject) in obese human subjects. But more interestingly, the treatment significantly reduced blood lipid levels (23% decrease of Triglyceride and 12.2% decrease of cholesterol levels) in human subjects. The lipid-lowering effect of berberine treatment has also been replicated in the rat experiment (34.7% decrease of Triglyceride and 9% decrease of cholesterol level). Cortisol, calcitriol, ACTH, TSH, FT4, and SHBG levels were not significantly changed following 12 weeks of berberine treatment. However, there was interestingly, an increase in calcitriol levels seen in all human subjects following berberine treatment (mean 59.5% increase, p = 0.11). Blood inflammatory factors (CRP, IL-6, TNFα, COX-2) and erythrocyte sedimentation rate (ESR) were not significantly affected by treatment with berberine. Tests of hematological, cardiovascular, liver, and kidney function following berberine treatment showed no detrimental side effects to this natural compound. Collectively, this study demonstrates that berberine is a potent lipid-lowering compound with a moderate weight loss effect, and may have a possible potential role in osteoporosis treatment/prevention.
Effects of berberine on lipid profile in subjects with low cardiovascular risk
Objective: To evaluate the efficacy as antihypercholesterolemic agent of berberine in patients with low cardiovascular risk.
Research design and methods: 144 Caucasian subjects were enrolled. After a 6-month run-in period following diet and practicing physical activity, patients were randomized to take placebo or berberine 500 mg twice a day, for 3 months, in a double-blind, placebo-controlled design. Berberine and placebo were then interrupted for 2 months (washout period), and all patients continued with only diet and physical activity. At the end of the washout period, patients restarted berberine or placebo twice a day for further 3 months. Anthropometric and metabolic parameters were assessed during the run-in period, at randomization, before and after the washout period.
Results: A decrease of body weight and BMI was observed after the run-in period. Berberine reduced total cholesterol, Triglycerides and LDL cholesterol and increased HDL cholesterol after 3 months from randomization and compared with placebo. After the washout period, lipid profile worsened; afterward, when berberine was reintroduced, lipid profile improved again both compared with the washout period, and with placebo.
Conclusions: Berberine is effective and safe to mildly improve lipid profile in subjects with low risk for cardiovascular disease.
Effect of Berberine Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion
Background: The aim of this study was to evaluate the effect of berberine administration on metabolic syndrome, insulin sensitivity, and insulin secretion.
Methods: A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients with a diagnosis of metabolic syndrome. Glucose and insulin levels after a dextrose load were measured. Triglycerides and high-density lipoprotein cholesterol concentrations at baseline were also measured. Twelve patients received berberine hydrochloride (500 mg) three times daily before meals for 3 months. The remaining 12 patients received placebo. Area under the curve (AUC) of glucose and insulin, total insulin secretion, first-phase of insulin secretion, and insulin sensitivity were assessed.
Results: After berberine administration, patients had a remission of 36% (P=0.037) in the presence of metabolic syndrome and a significant decrease in waist circumference in females (106±4 vs. 103±3 cm, P<0.05), systolic blood pressure (SBP) (123±7 vs. 115±9 mmHg, P<0.01), Triglycerides (2.4±0.7 vs. 1.4±0.5 mmol/L, P<0.01), area under the curve (AUC) of glucose (1182.1±253.6 vs. 1069.5±172.4 mmol/l, P<0.05), AUC of insulin (92,056±72,148 vs. 67,407±46,441 pmol/L, P<0.01), and insulinogenic index (0.78±0.69 vs. 0.62±0.46, P<0.05), as well as an increase in the Matsuda index (2.1±1.0 vs. 3.1±1.6, P<0.01).
Conclusions: Administration of berberine leads to remission of metabolic syndrome and decreases in waist circumference, SBP, Triglycerides , and total insulin secretion, with an increase in insulin sensitivity.
Efficacy of berberine in patients with type 2 diabetes mellitus
Berberine has been shown to regulate glucose and lipid metabolism in vitro and in vivo. This pilot study was to determine the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus patients. In study A, 36 adults with newly diagnosed type 2 diabetes mellitus were randomly assigned to treatment with berberine or metformin (0.5 g 3 times a day) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Significant decreases in hemoglobin A1c (from 9.5% ± 0.5% to 7.5% ± 0.4%, P < .01), fasting blood glucose (from 10.6 ± 0.9 mmol/L to 6.9 ± 0.5 mmol/L, P < .01), postprandial blood glucose (from 19.8 ± 1.7 to 11.1 ± 0.9 mmol/L, P < .01), and plasma Triglycerides (from 1.13 ± 0.13 to 0.89 ± 0.03 mmol/L, P < .05) were observed in the berberine group. In study B, 48 adults with poorly controlled type 2 diabetes mellitus were treated supplemented with berberine in a 3-month trial. Berberine acted by lowering fasting blood glucose and postprandial blood glucose from 1 week to the end of the trial. Hemoglobin A1c decreased from 8.1% ± 0.2% to 7.3% ± 0.3% (P < .001). Fasting plasma insulin and homeostasis model assessment of insulin resistance index were reduced by 28.1% and 44.7% (P < .001), respectively. Total cholesterol and low-density lipoprotein cholesterol were decreased significantly as well. During the trial, 20 (34.5%) patients experienced transient gastrointestinal adverse effects. Functional liver or kidney damages were not observed for all patients. In conclusion, this pilot study indicates that berberine is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism.
TRIB1 is a GWAS locus associated with plasma cholesterol and Triglycerides (TG) levels. In mice, liver-specific overexpression of TRIB1 lowers plasma lipid levels. Berberine (BBR) is a natural lipid lowering drug that reduces plasma LDL-cholesterol (LDL-C), total cholesterol (TC) and TG in hyperlipidemic patients and in mice by mechanisms involving upregulation of hepatic LDL receptor (LDLR). Here, we demonstrated that BBR treatment reduced plasma LDL-C, TC and TG in LDLR wildtype (WT) mice fed a high fat and high cholesterol diet and it only lowered TG in LDLR WT mice fed a normal chow diet. In hypercholesterolemic LDLR deficient mice (Ldlr−/−), BBR treatment reduced plasma TG levels by 51% compared to the vehicle control without affecting plasma cholesterol levels. Hepatic gene expression analysis revealed that Trib1 mRNA levels were significantly elevated by BBR treatment in all three mouse models and increases of Trib1 mRNA expression were associated with reduced expression of lipogenic genes including Cebpa, Acc1 and Scd1. In vitro studies further demonstrate that BBR induces TRIB1 mRNA expression by a transcriptional mechanism via ERK signaling pathway. These new findings warrant future in vivo studies to determine the causal role of Trib1 in BBR-mediated TG lowering independent of LDLR regulation.
Berberis lycium
Role of Berberis lycium in reducing serum cholesterol in Broilers
This study was planned to investigate the role of Berberis lycium in reducing serum cholesterol in broilers. Six experimental rations designated as A, B, C, D, E and F having 0, 0.5, 1.0, 1.5, 2.0 and 2.5% Berberis lycium were fed to 240 broiler chicks, randomly distributed into 24 replicates, so as to have 4 replicates per group and 10 chicks per replicate. The experiment lasted for 35 days. Average serum total cholesterol, Triglyceride , high density lipoprotein (HDL) and low density lipoprotein (LDL) were used as criteria of response. Average total serum cholesterol per chick was 129.33, 120.50, 116.50, 113.00, 101.67 and 114.00 mg/dl for group A, B, C, D, E and F respectively. Total serum cholesterol showed decreasing trend with the increasing level of Berberis lycium unto 2% (p<0.05). Mean serum Triglyceride level per chick was 60.00, 58.17, 58.00, 55.33, 50.17 and 48.50 mg/dl for group A, B, C, D, E and F respectively. Mean serum Triglyceride showed decreasing trend with the increasing level of Berberis lycium (p<0.05). serum Triglyceride was significantly lower in group F than other groups. Mean HDL per chick for the six experimental groups A, B, C, D, E and F was 52.08, 53.42, 60.42, 62.25, 62.92 and 54.50 mg/dl respectively. HDL showed increasing trend with the increase in the level of Berberis lycium unto 2%. The average serum LDL per chick was 65.25, 55.45, 44.48, 39.68, 28.72 and 49.80 mg/dl for group A, B, C, D, E and F respectively. LDL also showed decreasing trend with the increase in the level of Berberis lycium unto 2% (p<0.05). It was concluded that Berberis lycium added to feed at the rate of 2.0% can be used in broiler feed for reducing serum total cholesterol, Triglyceride and LDL and increasing HDL.
Role of Berberis lycium in reducing serum cholesterol in broilers
This study was planned to investigate the role of Berberis lycium in reducing serum cholesterol in broilers. Six experimental rations designated as A, B, C, D, E and F having 0, 0.5, 1.0, 1.5, 2.0 and 2.5% Berberis lycium were fed to 240 broiler chicks, randomly distributed into 24 replicates, so as to have 4 replicates per group and 10 chicks per replicate. The experiment lasted for 35 days. Average serum total cholesterol, Triglyceride , high density lipoprotein (HDL) and low density lipoprotein (LDL) were used as criteria of response. Average total serum cholesterol per chick was 129.33, 120.50, 116.50, 113.00, 101.67 and 114.00 mg/dl for group A, B, C, D, E and F respectively. Total serum cholesterol showed decreasing trend with the increasing level of Berberis lycium unto 2% (p<0.05). Mean serum Triglyceride level per chick was 60.00, 58.17, 58.00, 55.33, 50.17 and 48.50 mg/dl for group A, B, C, D, E and F respectively. Mean serum Triglyceride showed decreasing trend with the increasing level of Berberis lycium (p<0.05). Serum Triglyceride was significantly lower in group F than other groups. Mean HDL per chick for the six experimental groups A, B, C, D, E and F was 52.08, 53.42, 60.42, 62.25, 62.92 and 54.50 mg/dl respectively. HDL showed increasing trend with the increase in the level of Berberis lycium unto 2%. The average serum LDL per chick was 65.25, 55.45, 44.48, 39.68, 28.72 and 49.80 mg/dl for group A, B, C, D, E and F respectively. LDL also showed decreasing trend with the increase in the level of Berberis lycium unto 2% (p<0.05). It was concluded that Berberis lycium added to feed at the rate of 2.0% can be used in broiler feed for reducing serum total cholesterol, Triglyceride and LDL and increasing HDL.
Effect of Berberis lycium Royle on Lipid Profile in Alloxan Induced Diabetic Rabbits
Berberis lycium Royle (B.l.R) commonly known as Ishkeen (Kashmal and Darbald) is widely used in folk medicines for the treatment of Diabetes mellitus. Experimental diabetes use to alter the lipid profile. The aim of the present study was to evaluate the effects of Berberis lycium root bark on various lipid profiles in alloxan induced diabetic rabbits. Diabetes was induced by single intravenous injection of Alloxan (150 mg/kg).Oral administration of 250mg/kg and 500mg/kg crude powder of Berberis lycium root for four weeks resulted in significant reduction in total cholesterol, Triglyceride and low density lipids (LDLs) levels. Berberis lycium treatment increased the levels of high density lipids (HDLs). Furthermore same doses stabilized the weight of diabetic rabbits. Thus our investigation clearly shows that crude powder of Berberis lycium Royle has antihyperlipidemic effect.
Hyperlipidemia is a condition in which blood is overloaded with lipids. This condition is challenging for living beings. There are many ways to solve this problem but herbal medicines
take on paramount importance in this regard. The purpose of the current research was to inspect the effects of an aqueous extract of Berberis lycium Royle root bark on lipid profiles of Swiss albino mice in which diabetic phenotype was induced by alloxan. A single injection of Alloxan (150 mg/kg) was applied intravenously to induce diabetic phenotype. Alloxan induction raised the overall level of Triglycerides , low density- lipids (LDLs), and cholesterol and reduced the level of high density lipids (HDLs). Oral administration of 200 mg/kg aqueous extract of B. lycium Royle root bark for 28 days rescued all these changes. This study shows that the root bark extract of B. lycium Royle has antihyperlipidemic properties.
Berberine has been shown to have hypoglycaemic activity in several in vitro and in vivo models, although the mechanism of action is not fully known. Berberis lyceum Royle root produces high concentrations of berberine, and in traditional medicine, the whole extract of this plant is used widely to treat diabetes. The antidiabetic activity of the ethanol root extract of Berberis lyceum was compared with pure berberine in normal and alloxan-diabetic rats using similar doses of each. The concentration of berberine in the extract was determined to be 80% dry weight with only trace amounts of other alkaloids present. The purpose of the study was to investigate the effects of berberine and a whole extract of Berberis lyceum on blood glucose and other parameters associated with diabetes, to compare the effects of the crude extract with those of pure berberine and thus validate its use as a therapeutic agent, and finally to identify any contribution of the other components of the extract to these effects.
Oral administration of 50 mg/kg of Berberis extract and berberine to normal and experimental diabetic rats produced a significant (p < 0.05) reduction in blood glucose levels from days 3–7 days of treatment. Significant effects were also observed on the glucose tolerance, glycosylated haemoglobin, serum lipid profiles and body weight of experimental animals. Berberis extract and berberine demonstrated similar effects on all parameters measured, and although the extract was comparable in efficacy to berberine, it did not produce any effects additional to those shown by pure berberine. The results support the use of the extract in traditional medicine, and demonstrate that apart from being a highly cost-effective means of treating with berberine, the total extract does not appear to confer any additional benefits or disadvantages compared with the pure compound.
Chemistry and Biological Activities of Berberis lycium Royle
Berberis lycium Royle belonging to family Berberidaceae is a high-value medicinal plant with a known history of uses in folk medicine. It is used traditionally for curing a broad range of human illnesses and diseases in the Indian Himalayan region of Pakistan, India, and Bangladesh. Its ethnomedicinal uses include its use for treatment of jaundice, diabetes, eye infections, fractured bones, internal wounds, diarrhea, rheumatism, stomachache, and its use as a general body tonic. Although its every part has some medicinal properties, the most commonly used parts are roots and stem-bark. Its biologically active phytochemicals are alkaloids with berberine as the major one. An analysis of literature shows that its main biological activities are mainly attributed to berberine.Available literature shows that the plant has a wide range of biological activities including antihyperglycemic, antihyperlipidemic, anticancer and antitumor, wound and bone healing, antimicrobial, anticoccidial, antioxidant, hypotensive, immunity enhancing, antiurolithic, anthelmintic and hepatoprotective. Its wide use in folk medicine has prompted research in its phytochemical constituents and biological activities over the last four decades. Research in these lines is attesting its ethnomedicinal uses.This review paper is aimed to explore the chemistry and biological activities of this gifted medicinal plant.
Bergamot (Citrus bergamia)
The bergamot is a citrus fruit native to southern Italy with traditional uses that include improving immune response and cardiovascular function. There are a variety of phytochemicals that have been found in the bergamot including brutieridin and melitidin as well as other flavonoids, flavones O-glucosides and C-glucosides. Multiple clinical trials have provided evidence that different forms of orally administered bergamot can reduce total cholesterol and low-density lipoprotein cholesterol. In vitro mechanistic studies have provided evidence that polyphenols from the bergamot can alter the function of AMPK and pancreatic cholesterol ester hydrolase (pCEH). The use of bergamot in multiple clinical trials has consistently shown that it is well tolerated in studies ranging from 30 days to 12 weeks. This mini-review reports on the clinical studies performed with different forms of bergamot along with their effectiveness in reducing total cholesterol and LDL cholesterol in patients with hypercholesterolemia.
Backgrounds
Recent experiments suggest that Citrus bergamia extracts could benefit people with dyslipidemia and obesity but this needs to be further validated.
Methods
A total of 98 people age-matched older adults (65 years) with elevated blood lipids were enrolled to receive 12-week supplementation of a Citrus bergamia extracts-based formulation (CitriCholess)(n = 48) and placebo (n = 50).
Results
No group differences were found in baseline bodyweight, body mass index (BMI), blood cholesterol (TC), Triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and glucose levels. CitriCholess supplementation resulted in lower levels than placebo in TG (1.83 ± 0.92 vs. 1.95 ± 1.34 mmol/L, P = 0.612), TC (5.14 ± 0.98 vs. 5.44 ± 0.77 mmol/L, P = 0.097), and LDL-C (3.13 ± 0.74 vs. 3.43 ± 0.62 mmol/L, P = 0.032). Compared to placebo, CitriCholess also resulted in greater reductions in body weight (−0.604 ± 0.939 vs. 0.06 ± 0.74 kg, P < 0.01), waist circumferences (−0.60 ± 1.349 cm vs. -0.16 ± 1.503 cm, P < 0.01) and BMI (−0.207 ± 0.357 vs. 0.025 ± 0.274, P < 0.01). Additionally, females had a significantly higher level of HDL-C than males. TC was significantly correlated with LDL-C, and to a less degree, with TG. TG was inversely correlated with HDL-C. Body weight and waist circumference were negatively correlated with HDL-C and positively correlated with glucose.
Conclusion
12-week supplementation of CitriCholess could benefit lipid metabolism and weight management in old adults with dyslipidemia.
The aim of this research was to assess the impact of a well-characterized extract from Citrus bergamia juice on adipogenesis and/or lipolysis using mesenchymal stem cells from human adipose tissue as a cell model. To evaluate the effects on adipogenesis, some cell cultures were treated with adipogenic medium plus 10 or 100 μg/mL of extract. To determine the properties on lipolysis, additional mesenchymal stem cells were cultured with adipogenic medium for 14 days and after this time added with Citrus bergamia for further 14 days. To verify adipogenic differentiation, oil red O staining at 7, 14, 21, and 28 days was performed. Moreover, the expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), adipocytes fatty acid-binding protein (A-FABP), adipose Triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), monoglyceride lipase (MGL), 5′-adenosine monophosphate-activated protein kinase (AMPK)α1/2, and pAMPKα1/2 was evaluated by Western blot analysis and the release of glycerol by colorimetric assay. Citrus bergamia extract suppressed the accumulation of intracellular lipids in mesenchymal stem cells during adipogenic differentiation and promoted lipolysis by repressing the expression of adipogenic genes and activating lipolytic genes. Citrus bergamia extract could be a useful natural product for improving adipose mobilization in obesity-related disorders.
The results of five different clinical trials (Table 1) using bergamot in various forms suggest the polyphenol fraction can lower LDL-C and total cholesterol. Several studies suggested that bergamot polyphenols can reduce Triglycerides and increase HDL-C, however, the results were not consistent across all studies. One possible explanation for this variability (i.e. TG and HDL-C) is that bergamot preparation, extraction, and standardization varied in several studies. Consistently in all of the clinical trials bergamot appeared to be well tolerated with studies ranging from 30 days to 6 months. There are several weaknesses in the design of several of the clinical trials that used an open label design (Table 1). However, it should be noted that each patient can serve as their own control since cholesterol was quantified prior to bergamot and at the completion of the study. Three of the studies suggested an increase in HDL by up to 4 mg/dl (Table 1). This is significant because HDL is often difficult to increase apart from lifestyle changes. Regarding the mechanism of action there are several possible mechanisms that may be responsible for improving cholesterol lab values including activation of AMPK and inhibition of pancreatic cholesterol ester hydrolase (pCEH). As of now the suggestions that bergamot inhibits HMG-CoA reductase appear to be largely based on molecular modeling and will require further studies to confirm this proposed mechanism of action. Taken together, these early clinical trials along with the mechanistic studies that have been performed suggest that bergamot can reduce total cholesterol and LDL-C through mechanisms that are distinct from current pharmaceutical approaches.
BACKGROUND:
The role of lipid-lowering and hypoglycemic nutraceuticals in cardiovascular disease prevention is the focus in recent years. The most studied compounds and plants are sterols, soy, red fermented rice, policosanols, artichoke, berberine. Epidemiological and experimental evidences suggest that dietary polyphenols, especially flavonoids, might play a role in preventing atherosclerosis, owing to their pleiotropic metabolic, anti-inflammatory and antioxidant effects. Recent studies have shown that bergamot juice and albedo (Citrus Bergamia Risso et Poiteau), an endemic plant growing in a limited part of the Ionian coast of Calabria (Italy) has a unique content of flavonoids and glycosides, such as neoeriocytrine, neoesperidine, naringenine, routine, neodesmine, polyphenol and poncirine.
OBJECTIVE:
The aim of this study was to investigate the effects of a phytocomplex from bergamot fruit (EP3116520A1) as dietary supplement to a Mediterranean diet on body weight, body mass index (BMI), waist circumference, plasmatic lipid fractions, glucose and C – reactive protein (CRP) in subjects with the metabolic syndrome (MetS; according to NCEP-ATP III criteria) without pharmacological treatment, exept for basic treatment.
METHODS:
80 overweight adults (54% females, 46% males) with the diagnosis of Metabolic Syndrome (MetS), aged 45 ± 5 years, were enrolled and randomized to 2 groups: group A) followed a personalized low calorie Mediterranean diet (control group) and group B) enriched the same diet therapy with 1 tablet of a phytocomplex from bergamot fruit per day for 6 months (intervention group).
RESULTS:
After 6 months patients in the intervention group showed a significant reduction of total cholesterol (–15% ), LDL-Cholesterol (–22% ), Triglycerides (–23% ), blood glucose (–15% ), CRP (–40% ) and a significant increase in the HDL-Cholesterol (+ 14% ) levels compared to the control group (diet alone) where the changes were not significant, with not much significance in reduced body weight.
CONCLUSION:
Our findings suggest that bergamot supplementation improves significantly all aspects of metabolic profile in patients with MetS and is superior to diet alone.
Elevated serum cholesterol, Triglycerides and LDL levels are often associated with an increased incidence of atherosclerosis and coronary artery disease. The most effective therapeutic strategy against these diseases is based on statins administration, nevertheless some patients, especially those with metabolic syndrome fail to achieve their recommended LDL targets with statin therapy, moreover, it may induce many serious side effects. Several scientific studies have highlighted a strong correlation between diets rich in flavonoids and cardiovascular risk reduction. In particular, Citrus bergamia Risso, also known as bergamot, has shown a significant degree of hypocholesterolemic and antioxidant/radical scavenging activities. In addition, this fruit has attracted considerable attention due to its peculiar flavonoid composition, since it contains some flavanones that can act as natural statins. Hence, the study of bergamot flavonoids as metabolic regulators offers a great opportunity for screening and discovery of new therapeutic agents. Cholesterol metabolism, flavonoid composition and potential therapeutic use of C. bergamia Risso will be discussed in the following review.
black Cumin seeds (Nigella sativa L.)
Use of black cumin in layer diet as cholesterol lowering agents in egg yolk
This study was conducted to investigate the effects of different levels of black cumin seeds (Nigella
sativa L.) on egg production and cholesterol concentration in egg yolk of laying hens. A total of 60
commercial layer strain day old layer chicks were collected and divided into three groups treated with
1.0%, 1.5% and 2.0% black cumin inclusion. The concentrations of total lipids, total cholesterol,
phospholipids and triacylglycerols in serum and egg yolk were measured. Feeding of the diets with
1%, 1.5% and 2% black cumin seeds during the laying period found egg yolk cholesterol by 11.12,
9.88 and 9.83 mg/g respectively. The results found that feed efficiency ratio, egg production, body
weight, feed intake and egg weight were nonsignificant between the treatments. However, egg yolk
cholesterol concentration was found that 1.5% and 2.0% black cumin in diet were reduced cholesterol
concentration insignificance (P<0.05). So, dried black cumin supplementation in diets had no any
adverse effect on egg production and egg weight. Furthermore, egg yolk cholesterol concentrations
were decreased. Hence, it is concluded that black cumin (Nigella sativa L.) seeds and/or the active
principle are of interest as potential egg-yolk cholesterol–lowering agents.
The effects of Nigella sativa (NS) on plasma lipid concentrations are controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to obtain a conclusive result in humans. PubMed-Medline, SCOPUS, Web of Science, and Google Scholar databases were searched (up to August 2015) to identify RCTs investigating the impact of NS on total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and Triglycerides concentrations. A random-effects model and the generic inverse variance weighting method were used for quantitative data synthesis. Meta-regression, sensitivity analysis, and publication bias assessments were performed using standard methods. A total of 17 RCTs examining the effects of NS on plasma lipid concentrations were included. Meta-analysis suggested a significant association between NS supplementation and a reduction in total cholesterol (weighed-mean-difference [WMD]: -15.65mg/dL, 95% CI: -24.67, -6.63, p=0.001), LDL-C (WMD: -14.10mg/dL, 95% CI: -19.32, -8.88, p<0.001), and Triglyceride levels (WMD: -20.64mg/dL, 95% CI: -30.29, -11.00, p<0.001). No significant effect on HDL-C concentrations (WMD: 0.28mg/dL, 95% CI: -1.96, 2.53, p=0.804) was found. A greater effect of NS seed oil versus seed powder was observed on serum total cholesterol and LDL-C levels, and an increase in HDL-C levels was found only after NS seed powder supplementation. NS has a significant impact on plasma lipid concentrations, leading to lower total cholesterol, LDL-C, and TG levels while increased HDL-C is associated with NS powder only. Further RCTs are needed to explore the NS benefits on cardiovascular outcomes.
The aim of this systematic review and meta-analysis was to evaluate the effects of Nigella sativa (N. sativa) on glycemic control, lipid profiles, and biomarkers of inflammatory and oxidative stress. Two independent authors systematically examined online databases consisting of, EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until October 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of the studied trials. The heterogeneity among the included studies were assessed using the Cochrane’s Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. A total of 50 trials were included in this meta-analysis. We found a significant reduction in total cholesterol (WMD: −16.80; 95% CI: −21.04, −12.55), Triglycerides (WMD: −15.73; 95% CI: −20.77, −10.69), LDL-cholesterol (WMD: −18.45; 95% CI: −22.44, −14.94) and VLDL-cholesterol (WMD: −3.72; 95% CI: −7.27, −0.18) following supplementation with N. sativa. In addition, there was significant reductive effect observed with N. sativa on fasting glucose (WMD: −15.18; 95% CI: −19.82, −10.55) and HbA1C levels (WMD: −0.45; 95% CI: −0.66, −0.23). Effects of N. sativa on CRP (WMD: −3.61; 95% CI: −9.23, 2.01), TNF-α (WMD: −1.18; 95% CI: −3.23, 0.86), TAC (WMD: 0.31; 95% CI: 0.00, 0.63), and MDA levels (WMD: −0.95; 95% CI: −2.18, 0.27) were insignificant. This meta-analysis demonstrated the beneficial effects of N. sativa on fasting glucose, HbA1c, Triglycerides , total-, VLDL-, LDL-cholesterol levels.
Effect of Nigella Sativa on Lipid Profile in Albino Rats
Background: Coronary heart disease is a global health problem. Dyslipidemia is one of its major risk factors. The purpose of this study was to assess the effect of Nigella sativa seeds in the diet on lipid profile in albino rats.
Material and methods: Eighty-four albino rats were divided into six groups. Control groups I, III and V were given; low fat diet with 3% sunflower oil, high fat diet with 20% sunflower oil and high fat diet supplemented with 1% colic acid and 0.5% propylthiouracil as atherogenic elements respectively. The Experimental groups II, IV and VI were given above diets respectively supplemented with Nigella sativa seeds. Lipid profile was estimated at 0, 12 and 24 weeks.
Results: Albino rats fed on low fat diet containing 3% sunflower oil supplemented with Nigella sativa showed significant reduction in TC and LDL cholesterol and rise in HDL cholesterol. Those on high fat diet containing 20% sunflower oil with Nigella sativa seeds showed significant reduction in TG and LDL cholesterol and increase in HDL cholesterol. While in those given high fat diet with 20% sunflower oil, along with 1% cholic acid and 0.5% propylthiouracil with the addition of Nigella sativa, there was significant reduction in TC and LDL cholesterol and rise in HDL cholesterol.
Conclusion: Nigella sativa seeds in the diet has a favorable effect on lipid profile by lowering the Triglyceride , total cholesterol and LDL cholesterol and increasing the HDL cholesterol in albino rats.
Ameliorative effects of Nigella sativa on dyslipidemia
Introduction
Dyslipidemia is an established risk factor for ischemic heart disease. Nigella sativa (NS) is a medicinal plant that has been used for the treatment and prevention of a variety of diseases, in particular hyperlipidemia.
Methods
We reviewed the existing literature published until 2014 by using the following keywords: ‘‘Nigella sativa’’, ‘‘black cumin’’, ‘‘black seeds’’, ‘‘thymoquinone’’, and ‘‘lipid’’.
Results
In the conducted studies, different preparations of NS including seed powder (100 mg–20 g daily), seed oil (20–800 mg daily), thymoquinone (3.5–20 mg daily), and seed extract (methanolic extract especially), were shown to reduce plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and Triglycerides , but the effect on high-density lipoprotein cholesterol (HDL-C) was not significant. NS and thymoquinone have been reported to be safe and well tolerated with no severe adverse effect. In clinical trials, NS was found to be effective when added as adjunct to standard antihyperlipidemic and antidiabetic medications. Lipid-modifying effects of NS could be attributed to the inhibition of intestinal cholesterol absorption, decreased hepatic cholesterol synthesis, and up-regulation of LDL receptors.
Conclusions
Overall, the evidence from experimental and a clinical studies suggests that NS seeds are a promising natural therapy for dyslipidemic patients.
Nigella sativaprovides protection against metabolic syndrome
The seeds of Nigella sativa have been used in folk medicine all over the world. The plant has been of interest due to its low degree of toxicity and beneficial pharmacological properties like antihypertensive, hypoglycemic, antifungal, anti-inflammatory, antihistaminic, antioxidant, along with significant anti-neuplastic activities. The present clinical study was undertaken to ascertain the adjuvant effect of Nigella seeds on various clinical and biochemical parameters of metabolic syndrome. After final diagnosis and considering inclusion and exclusion criteria, one hundred and fifty nine patients were enrolled in this study. Patients were divided into two groups. In Group I (standard group), patients were advised to take simvastatin 10 mg once a day, metformin 500 mg twice a day, Enalapril 10 mg once a day, Atenolol 50 mg once a day and clopidagrel 75 mg once a day for a period of six weeks. In Group II (Nigella seeds group), patients were advised the above standard medication plus Nigella seeds 250 mg twice daily for a period of six weeks. Blood sugar both fasting and postprandial, fasting lipid profile and different parameters of obesity were recorded before therapy and after completion of therapy. It was found that the addition of Nigella seeds provide beneficial effects in all the clinical and biochemical parameters for the adult’s treatment panel-III of metabolic disorders especially in fasting blood sugar, low density lipoproteins and high density lipoproteins. No sign of toxicity of the plant appeared in the Group II. Improvement in all other parameters like blood pressure, circumference of waist and serum Triglyceride was also observed. Thus, Nigella seeds were found to be effective as an adjuvant therapy in patients of dyslipidemia and hyperglycemia.
The aim of the present study was to determine the effects of Nigella sativa (NS) oil on glucose metabolism and lipid concentrations in patients with type 2 diabetes (T2DM). In this double-blind randomized controlled clinical trial, 72 volunteer subjects at Endocrinology Clinics of Kermanshah were recruited. Participants were patients aged 30–60 years old with T2DM. They were randomly divided into intervention (n = 36) and placebo groups (n = 36) and received 3 g/day (one three times a day) NS oil or sunflower soft gel capsules for 12 weeks. At baseline and at the end of the trial, anthropometric indices, dietary intake and biochemical parameters were measured. Sixty-seven patients completed the trial (intervention n = 34, placebo n = 33). Since the data analysis was based on intention-to-treat approach, all 72 subjects (36 in each group) were included for data analysis. Two groups were similar in the baseline characteristics. After the intervention, weight and body mass index decreased in the intervention group compared to the baseline, but it was not significant between the two groups. Dietary intake in both groups changed compared to baseline. Comparison of the two groups indicated that fasting blood sugar, glycated hemoglobin, Triglyceride and low density lipoprotein–cholesterol changed significantly in intervention group compared to the placebo group (p < 0.05, adjusted for confounder factors). Insulin level and insulin resistance decreased and high density lipoprotein–cholesterol increased in the intervention group, but after adjusting for confounder factors, they were not significant. Supplementation with NS oil can improve glycemic status and lipid profile in patients with T2DM.
Blackcurrant (Ribes nigrum) Extract
Blackcurrant extract (BCE) ameliorates dyslipidemia in menopausal model animals and in elderly women at a risk of dyslipidemia. However, it is unknown whether the daily intake of BCE can prevent lipid abnormalities in healthy individuals. lipids are essential for the body, but they also cause arteriosclerosis. In this noncomparative pilot study, we examined the effects of BCE administered for 29 days on serum lipids in young healthy women. blood samples were collected before and on days 4 and 29 after BCE intake, and 20 lipoprotein fractions in the serum were separated using a gel-permeation high-performance liquid chromatography method to measure the triacylglycerol and cholesterol levels in lipoproteins. There were no effects on lipids on day 4 of BCE intake, but the total cholesterol level decreased on day 29. Furthermore, the levels of total very-low-density lipoprotein (VLDL) cholesterol, small VLDL cholesterol, and large low-density lipoprotein cholesterol were significantly decreased. These results suggest that the daily intake of BCE has a hypocholesterolemic effect in healthy women, and that it is effective in preventing Atherosclerosis.
Purposes: We previously showed that polyphenol-rich blackcurrant extract (BCE) showed a hypocholesterolemic effect in mice fed a high fat diet. As direct cholesterol removal from the body via the intestine has been recently appreciated, we investigated the effect of BCE on the modulation of genes involved in intestinal cholesterol transport using Caco-2 cells as an in vitro model.
Methods: Caco-2 cells were treated with BCE to determine its effects on mRNA and protein expression of genes important for intestinal cholesterol transport, low-density lipoprotein (LDL) uptake, cellular cholesterol content, and cholesterol transport from basolateral to apical membrane of Caco-2 cell monolayers. Cells were also treated with anthocyanin-rich or -poor fraction of BCE to determine the role of anthocyanin on BCE effects.
Results: BCE significantly increased protein levels of LDL receptor (LDLR) without altering its mRNA, which consequently increased LDL uptake into Caco-2 cells. This post-transcriptional induction of LDLR by BCE was markedly attenuated in the presence of rapamycin, an Inhibitor of mechanistic target of rapamycin complex 1 (mTORC1). In addition, BCE altered genes involved in cholesterol transport in the enterocytes, including apical and basolateral cholesterol transporters, in such a way that could enhance cholesterol flux from the basolateral to apical side of the enterocytes. Indeed, BCE significantly increased the flux of LDL-derived cholesterol from the basolateral to the apical chamber of Caco-2 monolayer. LDLR protein levels were markedly increased by anthocyanin-rich fraction, but not by anthocyanin-free fraction.
Conclusion: mTORC1-dependent post-transcriptional induction of LDLR by BCE anthocyanins drove the transport of LDL-derived cholesterol to the apical side of the enterocytes. This may represent a potential mechanism for the hypocholesterolemic effect of BCE.
Aim: Obesity is a chronic pathology of epidemic proportions. Mature adipocytes from a 3T3-L1 cell line were used as in vitro obesity model to test different bioactive compounds. We aim to evaluate cassis (Ribes nigrum) extract antioxidant activity and its antiadipogenic effect on mature adipocytes. Results: We produced an extract by using enzyme that combines cellulase and pectinase; we obtained high yield of the bioactive compound anthocyanin. Extract showed high antioxidant capacity. We conducted in vitro assays by adding the extract to adipocytes culture medium. Extract reduced intracellular levels of Triglyceride by 62% and cholesterol by 32%. Conclusion: Enzymatic extract’s high antioxidant activity was likely attributable to its high concentration of anthocyanin. This extract inhibits lipid accumulation in adipocytes.
Estrogen is involved in lipid metabolism. Menopausal women with low estrogen secretion usually gain weight and develop steatosis associated with abnormal lipid metabolism. A previous study showed that blackcurrant (Ribes nigrum L.) extract (BCE) had phytoestrogen activity. In this study, we examined whether BCE improved lipid metabolism abnormalities and reduced liver steatosis in ovariectomized rats, as a menopausal animal model. Twelve-week-old ovariectomized (OVX) rats were fed a regular diet (Ctrl) or a 3% BCE supplemented diet while sham rats were fed a regular diet for three months. Body weight, visceral fat weight, levels of serum Triglycerides , total cholesterol, and LDL cholesterol decreased in the BCE-treated OVX and sham rats, but not in OVX Ctrl rats. The results of hematoxylin and eosin staining revealed that BCE decreased the diameters of adipocytes and the nonalcoholic fatty liver disease activity score. Furthermore, quantitative RT-PCR indicated a decreased expression of hepatitis-related genes, such as tumor necrosis factor-α, IL-6, and IL-1β in OVX rats after BCE treatment. This is the first study that reported improvement of lipid metabolism abnormalities in OVX rats by BCE administration. These results suggest that the intake of BCE alleviated dyslipidemia and prevented nonalcoholic steatohepatitis during menopause in this animal model.
Bupleurum scorzonerifolium Willd.root extract
The aim of this study was to investigate the antiobesity and antihyperlipidemic effects of vinegar-baked Radix Bupleuri (VBRB) on high-fat diet– (HFD-) induced obese rats. After being fed HFD for two weeks, rats were dosed orally with VBRB or fenofibrate, once daily for further twelve weeks. VBRB (1.0 g kg−1 per day) produced effects similar to fenofibrate (100 mg kg−1) in reducing body weight (BW) gain, visceral fat-pad weights, plasma lipid levels, as well as hepatic Triglyceride and cholesterol content of HFD-fed rats. VBRB also lowered hepatic lipid droplet accumulation and the size of epididymal adipocytes in HFD-fed rats. VBRB and fenofibrate reversed the HFD-induced downregulation of hepatic peroxisome proliferator-activated receptor (PPAR)α. HFD-induced reductions in the hepatic levels of acyl-CoA oxidase (ACO) and cytochrome P450 isoform 4A1 (CYP4A1) proteins were reversed by VBRB and fenofibrate. The elevated expression of hepatic sterol regulatory element binding proteins (SREBPs) in HFD-fed rats was lowered by VBRB and fenofibrate. The results of this study show that VBRB suppresses BW gain and body fat accumulation by increasing fatty acid oxidation, an effect which is likely mediated via upregulation of PPARα and downregulation of SREBP expression in the liver of HFD-fed rats.
Abstract
Ethnopharmacological relevance
Hyperlipidemia is the systemic manifestation of abnormal lipid metabolism, characterized by elevated circulating levels of cholesterol and Triglyceride and a high risk of cardiovascular events. Radix Bupleuri (RB) is a traditional Chinese herbal product used to treat liver diseases. Our previous study demonstrated that Saikosaponins (SSs), the most potent bioactive ingredients in RB, ameliorate hepatic steatosis. However, whether SSs have anti-hyperlipidemia effects and plausible underlying mechanisms remain elusive.
Aim of the study
To comprehensively evaluate the lipid–lowering potential of SSs against hyperlipidemia in rats.
Materials and methods
RNA sequencing and untargeted metabolomics approaches were applied to analyze the changes in the liver transcriptome and serum lipid profile in long-term high-fat diet feeding-induced hyperlipidemia rats in response to SSs or positive drug simvastatin (SIM) intervention.
Results
Our data revealed that SSs significantly alleviated HFD-induced hyperTriglyceride mia and hypercholesterolemia. Combined with the analysis of gene ontology enrichment analysis and gene set enrichment analysis, we found that SSs remarkably repaired the unbalanced blood lipid metabolic spectrum in a dose-dependent manner by increasing the hepatic uptake of circulating fatty acids and facilitating mitochondrial respiration in fatty acid oxidation, comparable to SIM group. In addition, SSs markedly modulated cholesterol clearance by promoting intracellular cholesterol efflux, HDL remodeling, LDL particle clearance, and bile acid synthesis. SSs also efficiently protected the liver from lipid overload-related oxidative stress and lipid peroxidation, as well as substantially exaggerated inflammatory response.
Conclusion
Our research not only unraveled the intricate mechanisms underlying the lipid–lowering functions of SSs but also provided novel perspectives on developing an SSs-based therapeutic strategy for the treatment of hyperlipidemia.
C. pinnatifida Bge fruit Flavones
The effects of Crataegus pinnatifida (Chinese hawthorn) on metabolic syndrome: A review
Metabolic syndrome is described as a group of risk factors in which at least three unhealthy medical conditions, including obesity, high blood sugar, hypertension or dyslipidemia occur simultaneously in a patient. These conditions raise the risk for diabetes mellitus and cardiovascular diseases. Many recent studies have focused on herbal remedies and their pharmacological effects on metabolic syndrome. Crataegus pinnatifida or Chinese hawthorn has been widely used in the treatment of hyperlipidemia and cardiovascular diseases. Its leaves, fruits and seeds have various active substances such as, flavonoids, triterpenic acids and sesquiterpenes, which through different mechanisms can be beneficial in metabolic syndrome. Flavonoids found in the leaves of hawthorn can significantly reduce atherosclerotic lesion areas, the fruit extracts contain two triterpenic acids (oleanolic acid and ursolic acid), that have the ability to inhibit the acyl-coA-cholesterol acyltransferase (ACAT) enzyme and as a result reduce very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol levels. Another example regards a sesquiterpene found in the seeds of C. pinnatifida, which exhibits the ability to inhibit platelet aggregation, thus showing antithrombotic activity. Various studies have shown that C. pinnatifida can have beneficial effects on controlling and treating high blood sugar, dyslipidemia, obesity and Atherosclerosis. The aim of this review is to highlight the interesting effects of C. pinnatifida on metabolic syndrome.
Caesalpinia gilleisii Wall et Hook extract
Caesalpinia ferrea C. Mart. (Fabaceae) Phytochemistry, Ethnobotany, and Bioactivities: A Review
Caesalpinia ferrea C. Mart., popularly known as “Jucá” or “Pau-ferro”, belongs to the Fabaceae family, and is classified as a native and endemic species in Brazil. Numerous studies that portray its ethnobotany, chemical composition, and biological activities exist in the literature. The present study aimed to systematically review publications addressing the botanical aspects, uses in popular medicine, phytochemical composition, and bioactivities of C. ferrea. The searches focused on publications from 2015 to March 2020 using the Scopus, Periódicos Capes, PubMed, Google Scholar, and ScienceDirect databases. The leaves, fruits, seeds, and bark from C. ferrea are used in popular medicine to treat disorders affecting several systems, including the circulatory, immune, cardiovascular, digestive, respiratory, genitourinary, musculoskeletal, and conjunctive systems. The most commonly found chemical classes in phytochemical studies are flavonoids, polyphenols, terpenoids, tannins, saponins, steroids, and other phenolic compounds. The biological properties of the extracts and isolated compounds of C. ferrea most cited in the literature were antibacterial, antifungal, antioxidant, antiproliferative, anti-inflammatory, and healing potential. However, further studies are still needed to clarify a link between its traditional uses, the active compounds, and the reported pharmacological activities, as well as detailed research to determine the toxicological profile of C. ferrea.
Caparis decidua. fruit extract
Antiatherosclerotic effect of Caparis decidua. Fruit Extract in cholesterol-fed Rabbits
The fruit alcohol extract of the plant Capparis decidua (Frosk.).. Edgew was investigated for its Antiatherosclerotic activity. Hyperlipidemia was induced by atherodiet and cholesterol feeding to animals. Rabbits were fed Capparis decidua. (500 mg/kg body weight) or pitavastatin (0.2 mg/kg body weight) in distilled water along with standard laboratory diet and atherodiet for 60 days. C. decidua. fruit extract and pitavastatin were found to lower serum cholesterol, LDL–cholesterol, Triglyceride , phospholipid, and atherogenic index, but found to increase the HDL to total cholesterol ratio as compared with hyperlipidemic control group. Pitavastatin or C. decidua. fruit extract treated hyperlipidemic rabbits showed a decrease in the lipid profile of liver, heart, and aorta. The plant extract feeding brings about a definite regression of atheroma and hindered plaque formation in aorta as compared with the hyperlipidemic control group. Thus, this study demonstrates that C. decidua. fruit extract possesses hypolipidemic and Antiatherosclerotic effects.
Free fatty acids regulating action of Capparis decidua fruit on dyslipidemia in rats
Capparis decidua belongs to family Capparidaceae in wastelands of India. The study aim was to determine the role of C. decidua fruits on the free fatty acids (FFA) profile in fat-rich diet (FRD) dyslipidemic rats. The methanolic extract of edible fruit of C. decidua (CD) was given orally to obese dyslipidemic rats at the dose of 125 mg/kg and 250 mg/kg for consecutive 28 days. CD treatment in FRD rats significantly restricts the body weight gains. Blood lipid profile was altered dose dependently and significantly after 4-week treatment with CD to FRD. rats. It significantly (p<0.05) enhanced serum FFA especially, -linolinate, -linolinate, arachidonate, ecosapentaenoate, docosapentaenoate and docosahexaenoate. Moreover, 3-PUFA content was also enhanced (50.3% and 78.8%) in the serum of CD treated animals, whereas MUFA was lowered (31.1% and 40%). Therefore, Capparis decidua fruit has a promising role on dyslipidemia and obesity and has the capabilities to regulate beneficial free fatty acids. .
Caralluma fimbriata extract
Antiobesogenic and Antiatherosclerotic Properties of Caralluma fimbriata Extract
There is evidence that the principles present in the widely consumed Indian food plant C. fimbriata extract (CFE) suppress appetite, and provide antiobesogenic and metabolic benefits. The diet-Induced Obesity (DIO) rat model was used to investigate CFE’s anorexigenic effects. Rats were randomly divided into three groups: (i) untreated control (C), (ii) control for cafeteria diet (CA), and (iii) cafeteria diet fed + CFE treated. Rats in the test group received cafeteria diet and CFE from day one onwards. CFE was administered by gavage at three doses (25, 50, 100 mg/Kg BW per day) for 90 days. The antiobesogenic effects of CFE were evaluated by monitoring changes in feed intake, body weight, serum lipid and hormonal (leptin) profiles, fat pads, and liver weight. Antiatherosclerotic effects were measured by histology. CFE induced significant and dose-dependent inhibition of food intake, with dose-related prevention of gains in body weight, liver weight, and fat pad mass. Alterations in serum lipid profiles associated with weight gain were similarly inhibited, as were the typical increases in serum leptin levels. These data substantiate CFE’s reported anorexigenic effects. CFE treatment also conferred protection against atherogenesis. We conclude that CFE possesses antiobesogenic and Antiatherosclerotic properties.
The objective of the present study was to investigate the preventive effects of hydro-alcoholic extract of Caralluma fimbriata (CFE) and Metformin (Met) against high-fat diet (HF-diet) induced alterations in lipid metabolism in Wistar rats. The experimental animals were divided into five groups, two of which were fed with chow diet and the other three with HF- (60%) diet. CFE (200 mg/kg body weight/day) was administered through oral route to each group of chow-fed rats, HF-fed rats and Met (20 mg/kg body weight/day) to one of the HF-diet fed groups. At the end of 90 days of experimental period, hypercholestermia, hypertriglycerdemia, with decreased HDL-cholesterol and increased LDL, VLDL-cholesterol and atherogenic index and elevated levels of serum and hepatic transaminases and hepatic lipids (p < 0.05) and alterations in the activities of enzymes of lipid metabolism, and the liver showed mild to severe distortion of the normal architecture as well as prominence and widening of the liver sinusoids as observed in HF-fed rats, were prevented by CFE/Met treatment. The results showed that CFE/Met supplementation ameliorated significantly the disturbance in serum and hepatic transaminases, plasma and hepatic lipid profile and lipid metabolism under HF-fed conditions. It can be concluded from these results that CFE might be valuable in reducing the alterations related to lipid metabolism under high calorie diet consumption.
Antiobesogenic and Antiatherosclerotic Properties of Caralluma fimbriata Extract
There is evidence that the principles present in the widely consumed Indian food plant C. fimbriata extract (CFE) suppress appetite, and provide antiobesogenic and metabolic benefits. The Diet-Induced Obesity (DIO) rat model was used to investigate CFE’s anorexigenic effects. Rats were randomly divided into three groups: (i) untreated control (C), (ii) control for cafeteria diet (CA), and (iii) cafeteria diet fed + CFE treated. Rats in the test group received cafeteria diet and CFE from day one onwards. CFE was administered by gavage at three doses (25, 50, 100 mg/Kg BW per day) for 90 days. The antiobesogenic effects of CFE were evaluated by monitoring changes in feed intake, body weight, serum lipid and hormonal (leptin) profiles, fat pads, and liver weight. Antiatherosclerotic effects were measured by histology. CFE induced significant and dose-dependent inhibition of food intake, with dose-related prevention of gains in body weight, liver weight, and fat pad mass. Alterations in serum lipid profiles associated with weight gain were similarly inhibited, as were the typical increases in serum leptin levels. These data substantiate CFE’s reported anorexigenic effects. CFE treatment also conferred protection against atherogenesis. We conclude that CFE possesses antiobesogenic and antiatherosclerotic properties.
Carnosic Acid (Rosmarinus officinalis)
Rosemary (Rosmarinus officinalis L.) extracts (RE) are natural antioxidants that are used in food, food supplements and cosmetic applications; exert anti-inflammatory and anti-hyperglycaemic effects; and promote weight loss, which can be exploited to develop new preventive strategies against metabolic disorders. Therefore, the aim of the present study was to evaluate the preventive effects of rosemary leaf extract that was standardised to 20 % carnosic acid (RE) on weight gain, glucose levels and lipid homeostasis in mice that had begun a high-fat diet (HFD) as juveniles. The animals were given a low-fat diet, a HFD or a HFD that was supplemented with 500 mg RE/kg body weight per d (mpk). Physiological and biochemical parameters were monitored for 16 weeks. Body and epididymal fat weight in animals on the HFD that was supplemented with RE increased 69 and 79 % less than those in the HFD group. Treatment with RE was associated with increased faecal fat excretion but not with decreased food intake. The extract also reduced fasting glycaemia and plasma cholesterol levels. In addition, we evaluated the Inhibitory effects of RE in vitro on pancreatic lipase and PPAR-γ agonist activity; the in vitro findings correlated with our observations in the animal experiments. Thus, the present results suggest that RE that is rich in carnosic acid can be used as a preventive treatment against metabolic disorders, which merits further examination at physiological doses in randomised controlled trials.
Carnosic acid, a new class of lipid absorption inhibitor from sage
The methanolic extract from the leaves of Salvia officinalis L. (sage) showed significant inhibitory effect on serum Triglyceride elevation in olive oil-loaded mice (500 and 1000 mg/kg, p.o.) and inhibitory activity (IC(50): 94 microg/mL) against pancreatic lipase, which is participated in digestion of lipids. Through bioassay-guided separation using the inhibitory activity against pancreatic lipase activity, 4 abietan-type diterpenes (carnosic acid, carnosol, royleanonic acid, 7-methoxyrosmanol) and a triterpene (oleanolic acid) were isolated from the active fraction. Among these compounds, carnosic acid and carnosol substantially inhibited pancreatic lipase activity with IC(50) values of 12 microg/mL (36 microM) and 4.4 microg/mL (13 microM), respectively. Carnosic acid significantly inhibited Triglyceride elevation in olive oil-loaded mice at doses of 5-20 mg/kg (p.o.). However, other constituents (carnosol, royleanonic acid, oleanolic acid) did not show any effects at a dose of 200 mg/kg (p.o.). Furthermore, carnosic acid (20 mg/kg/day, p.o.) reduced the gain of body weight and the accumulation of epididymal fat weight in high fat diet-fed mice after 14 days.
Carnosic acid prevents obesity and hepatic steatosis in ob/ob mice
Aim: Carnosic acid (CA) inhibits adipogenesis in vitro. The present study evaluated the therapeutic effects of CA in ob/ob mice.
Methods: The experimental animals were given a standard chow diet with or without CA for 5 weeks. Bodyweight gain and food intake were measured during this period. Magnetic resonance imaging analysis, histological examination, serum chemistry analysis and intraperitoneal glucose tolerance test (IPGTT) were all performed.
Results: The mice fed CA experienced significant weight loss and reduced visceral adiposity, in addition to significantly reduced serum Triglyceride (TG) and cholesterol levels. Importantly, CA had a dramatic effect on the liver by reducing the hepatic TG content, thus decreasing serum alanine aminotransferase levels. In addition, IPGTT revealed that CA significantly improved glucose tolerance.
Conclusion: These data suggest that CA is a novel therapeutic agent for obesity-related non-alcoholic fatty liver disease.
Cashew leaves (Anacardium occidentale)
Cashew leaves (Anacardium occidentale) is a medicinal plant applied in the treatment of some non-scientific claims of common diseases in SouthWestern Nigeria such as hypertension. It contains phytochemicals such as Phenolic, flavonoids, steroids, triterpenes and 33.52% to 46.26% of dietary fiber. This work was therefore designed to determine the cholesterol lowering effect of Cashew leaf (Anacardium occidentale) extract on Egg Yolk Induced Hypercholesterolaemic Rabbits. Fifteen rabbits classified into control group A of five rabbits; experimental group B induced with hypercholesterolemia using 20% egg yolk(B1) and thereafter given cashew leaf ethanolic extract(B2) and group C of five rabbits induced with hypercholesterolemia using 20% egg yolk(C 1) thereafter treated with the aqueous extract of cashew leaf(C 2). Outcomes of biochemical evaluation of experimental rabbits were compared with the control rabbits. Plasma Total cholesterol(CHOL-T), Low Density Lipoprotein-cholesterol(LDL-C),Total Triglycerides (TG-T), high Density Lipoprotein-cholesterol (HDL-C) were evaluated in the rabbits by autoanalysis using ROCHE reagent on COBAS C111 autoChemistry analyzer. There was a significant increase in plasma total cholesterol, LDL-C, total Triglycerides and HDL-C when the rabbits were fed with normal meal containing 20% of powdered egg yolk of the total meal weight with water for seven days compared with control rabbits fed on normal diet and water for 7 days with p<0.05. A significant decrease was also obtained in plasma Total cholesterol and Total Triglycerides in the rabbits given 400mg/Kg of either ethanolic or aqueous extract of cashew leaves extract after they were being given 20% of powdered egg yolk of the total meal weight plus water for seven days which was more in ethanolic extract than the aqueous extract with p<0.05. There was also a significantly lower LDL-C in rabbits fed with normal meal containing 20% of powdered egg yolk of the total meal weight plus water for seven days followed by the administration of 400mg/Kg of ethanolic extract for another seven days. than when the rabbits were fed with normal meal containing 20% of powdered egg yolk of the total meal weight with water for seven days and also than in the rabbits induced with hypercholesterolemia using20% of powdered egg yolk of the total meal weight followed by aqueous cashew leaf extract (p<0.05). This work revealed the efficacy of 20% egg yolk at inducing hypercholesterolaemia while ethanonolic and aqueous extract have been found to decrease plasma levels of CHOL-T, TG-T and LDL-C and as such could be applied in the treatment of hypertecholesterolaemia which may result into hypertension.
Extract of the Anacardium occidentale leaves is used in the traditional treatment of diabetic diseases. The hypoglycemic effect of leaves aqueous extract was investigated using normoglycemic albino rats. The leaves aqueous extract was found to contain phytochemicals such as alkaloids, saponins, flavonoids and tannins. The aqueous extract significantly lowered the blood glucose concentration in the normal rats (p> 0.05). The extract produced about 33.7 % (305 ± 2.89 to 202 ± 4.04) mg/dl. The serum Triglyceride decreases by 48.28 % (435± 4.50 to 225 ± 1.50) mg/dl in the experimental rats. While serum total protein decreases by 18.41% (27.7 ± 2.54 to 22.6 ± 0.32) g/d and weight increase was 4.75 % (134.6 ± 5.02 to 128.5 ± 1.15) g. The result obtained indicated that the extract has a moderate hypoglycemic effect and may be used locally for the treatment of diabetes mellitus.
Celastrus Orbiculatus Thunb.
Previously, we found that Celastrus orbiculatus Thunb. (COT) decreases athero-susceptibility in lipoproteins and the aorta of guinea pigs fed a high-fat diet, and increases high-density lipoprotein (HDL). In the present study, we investigated the effect of COT in reducing lipid accumulation and promoting reverse cholesterol transport (RCT) in vivo and vitro. Healthy male mice were treated with high-fat diet alone, high-fat diet with COT (10.0 g/kg/d), or general fodder for 6 weeks. serum levels of total cholesterol (TC), Triglyceride (TG), HDL-C, non-HDL-C, and 3H-cholesterol in plasma, liver, bile, and feces were determined. Pathological changes and the levels of TC and Triglyceride in liver were examined. The expression of hepatic genes and protein associated with RCT were analyzed. COT administration reduced lipid accumulation in the liver, ameliorated the pathological changes, and lessened liver injury, the levels of TG, TC, and non-HDL-C in plasma were decreased significantly, and COT led to a significant increase in plasma HDL-C and apolipoprotein A (apoA1). 3H-cholesterol in plasma, liver, bile, and feces was also significantly increased in COT-treated mice compared to controls. Both mRNA and protein expression of SRB1, CYP7A1, LDLR, ATP-binding cassette transporters ABCA1, ABCG5, and LXRα were improved in COT-treated mice. An in vitro isotope tracing experiment showed that COT and its bioactive ingredients, such as celastrol, ursolic acid, oleanolic acid, and quercetin, significantly increased the efflux of 3H-cholesterol. They also increased the expression of SRB1, ABCA1, and ABCG1 significantly in macrophages. Our findings provided a positive role of COT in reducing lipid accumulation by promoting RCT. These effects may be achieved by activating the SRB1 and ABC transporter pathway and promoting cholesterol metabolism via the CYP7A1 pathway in vivo. The effective ingredients in vitro are celastrol, ursolic acid, oleanolic acid, and quercetin.
Celastrus orbiculatus Thunb. (COT) is a traditional Chinese herb. In this study, an experiment was designed to investigate the potential protective effect of COT on the development of non-alcoholic fatty liver disease (NAFLD) induced by high fat diet and to explore the underlying mechanisms. We established a guinea pig model of NAFLD and treated the animals with three doses of COT or 20 mg/kg/d simvastatin (a positive control drug) for 8 weeks. H&E staining of liver tissue sections indicated that COT remarkably improved histopathological change of liver induced by high fat diet. Serum biochemical assays revealed that COT significantly decreased ALT and AST activities in serum. Besides, COT also reduced body weight and liver weight of guinea pigs under high fat diet. Hepatic lipid analysis showed that COT remarkably decreased the contents of total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE) and Triglyceride (TG) in liver of guinea pigs fed high fat diet in a dose-dependent manner. The analysis of hepatic genes involved in cholesterol metabolism by quantitative real-time PCR revealed that COT upregulated the mRNA abundance of cholesterol 7alpha-hydroxylase A1 (CYP7A1) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Measurement of biochemical parameters in liver indicated that COT attenuated oxidative stress and lowered NO and iNOS levels in guinea pigs under high fat diet. These results reveal that administration of COT effectively ameliorates high-fat diet-induced NAFLD in guinea pigs through decreasing hepatic lipid levels, suppressing oxidative stress and lowering NO and iNOS levels in liver.
chalcone derivative, 1m-6
Background and Purpose
Atherosclerosis, resulting from lipid dysregulation and vascular inflammation, causes atherosclerotic cardiovascular disease (ASCVD), which contributes to morbidity and mortality worldwide. Chalcone and its derivatives possess beneficial properties, including anti-inflammatory, antioxidant and antitumour activity with unknown cardioprotective effects. We aimed to develop an effective chalcone derivative with antiatherogenic potential.
Experimental Approach
Human THP-1 cells and HUVECs were used as in vitro models. Western blots and real-time PCRs were performed to quantify protein, mRNA and miRNA expressions. The cholesterol efflux capacity was assayed by 3H labelling of cholesterol. LDL receptor knockout (LDLR−/−) mice fed a high-fat diet were used as an in vivo atherogenesis model. Haematoxylin and eosin and oil red O staining were used to analyse plaque formation.
Key Results
Using ATP-binding cassette transporter A1 (ABCA1) expression we identified the chalcone derivative, 1m-6, which enhances ABCA1 expression and promotes cholesterol efflux in THP-1 macrophages. Moreover, 1m-6 stabilizes ABCA1 mRNA and suppresses the expression of potential ABCA1-regulating miRNAs through nuclear factor erythroid 2-related factor 2 (Nrf2)/haem oxygenase-1 (HO-1) signalling. Additionally, 1m-6 significantly inhibits TNF-α-induced expression of adhesion molecules, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1), plus production of proinflammatory cytokines via inhibition of JAK/STAT3 activation and the modulation of Nrf2/HO-1 signalling in HUVECs. In Atherosclerosis-prone mice, 1m-6 significantly reduces lipid accumulation and atherosclerotic plaque formation.
Conclusion and Implications
Our study demonstrates that 1m-6 produces promising atheroprotective effects by enhancing cholesterol efflux and suppressing inflammation-induced endothelial dysfunction, which opens a new avenue for treating ASCVD.
Chenodeoxycholic acid (CDCA)
Background: The natural farnesoid X receptor (FXR) agonist chenodeoxycholic acid (CDCA) suppresses hepatic cholesterol and bile acid synthesis and reduces biliary cholesterol secretion and Triglyceride production. Animal studies have shown that bile acids downregulate hepatic LDL receptors (LDLRs); however, information on LDL metabolism in humans is limited.
Methods: Kinetics of autologous 125 I-LDL were determined in 12 male subjects at baseline and during treatment with CDCA (15 mg kg-1 day-1 ). In seven patients with gallstones treated with CDCA for 3 weeks before cholecystectomy, liver biopsies were collected and analysed for enzyme activities and for specific LDLR binding. serum samples obtained before treatment and at surgery were analysed for markers of lipid metabolism, lipoproteins and the LDLR modulator proprotein convertase subtilisin/kexin type 9 (PCSK9).
Results: Chenodeoxycholic acid treatment increased plasma LDL cholesterol by ~10% as a result of reduced clearance of plasma LDL–apolipoprotein (apo)B; LDL production was somewhat reduced. The reduction in LDL clearance occurred within 1 day after initiation of treatment. In CDCA-treated patients with gallstones, hepatic microsomal cholesterol 7α-hydroxylase and HMG-CoA reductase activities were reduced by 83% and 54%, respectively, and specific LDLR binding was reduced by 20%. During treatment, serum levels of fibroblast growth factor 19 and total and LDL cholesterol increased, whereas levels of 7α-hydroxy-4-cholesten-3-one, lathosterol, PCSK9, apoA-I, apoC-III, lipoprotein(a), Triglycerides and insulin were reduced.
Conclusions: Chenodeoxycholic acid has a broad influence on lipid metabolism, including reducing plasma clearance of LDL. The reduction in circulating PCSK9 may dampen its effect on hepatic LDLRs and plasma LDL cholesterol. Further studies of the effects of other FXR agonists on cholesterol metabolism in humans seem warranted, considering the renewed interest for such therapy in liver disease and diabetes.
dietary natural products as emerging lipoprotein(a)-lowering agents
Elevated plasma lipoprotein(a) (Lp(a)) levels are associated with an increased risk of cardiovascular disease (CVD). Hitherto, niacin has been the drug of choice to reduce elevated Lp(a) levels in hyperlipidemic patients but its efficacy in reducing CVD outcomes has been seriously questioned by recent clinical trials. Additional drugs may reduce to some extent plasma Lp(a) levels but the lack of a specific therapeutic indication for Lp(a)‐lowering limits profoundly reduce their use. An attractive therapeutic option is natural products. In several preclinical and clinical studies as well as meta‐analyses, natural products, including l‐carnitine, coenzyme Q 10, and xuezhikang were shown to significantly decrease Lp(a) levels in patients with Lp(a) hyperlipoproteinemia. Other natural products, such as pectin, Ginkgo biloba, flaxseed, red wine, resveratrol and curcuminoids can also reduce elevated Lp(a) concentrations but to a lesser degree. In conclusion, aforementioned natural products may represent promising therapeutic agents for Lp(a) lowering.
The effects on biliary lipids of 10 mg per kg per day of chenodeoxycholic acid (CDCA), 10 mg per kg per day of ursodeoxycholic acid (UDCA), and their equimolar combination (5 mg per kg per day of each), all administered for 45 to 60 days, were investigated in 18 patients with gallstones in a double-blind study with a balanced latin square design. The molar percentage of cholesterol in bile (initial value 9.7 ± 2.2) was significantly lower after UDCA (5.4 ± 1.3) and the combination (5.2 ± 1.2) than after CDCA (7.2 ± 1.7).
Nevertheless, when the ability to solubilize cholesterol was calculated, taking into account the percentage of biliary UDCA, then the differences in cholesterol saturation induced by UDCA alone and the combination also became considerable (saturation index: 0.94 ± 0.12 as compared to 0.81 ± 0.12).
The total bile acid pool increased significantly after treatment with CDCA and the combination, but not after UDCA. Lithocholic acid was increased significantly only by treatment with CDCA.
Diarrhea was observed in five patients with hypertransaminasemia and in four patients after CDCA, whereas both UDCA and the combination were well-tolerated.
We conclude that the administration of a combination of equimolar doses of CDCA and UDCA can be recommended for medical treatment of gallstones since it has greater effects on bile cholesterol saturation than either alone, is better tolerated than CDCA, and is less expensive than UDCA.
The effects of chenodeoxycholic acid (C.D.C.A.) therapy on plasma lipid and lipoprotein metabolism have been studied in eleven patients with hypertriglyceridæmia. Plasma-Triglycerides fell significantly by 79-986 mg. per 100 ml. (25-54%) in nine of the patients, the absolute fall being positively correlated with the pretreatment concentration. The Triglyceride -lowering effect of C.D.C.A. appeared to derive from a decreased secretion into plasma of the Triglyceride -rich very-low-density lipoprotein. Three patients also demonstrated relatively smaller falls (14-28%) in plasma-cholesterol. Treatment was well tolerated, although in nine patients the serum activities of aspartate and alanine amino-transferases rose slightly. Long-term clinical trials of C.D.C.A. in the treatment of hypertriglyceridæmia seem to be indicated.
Chenodeoxycholic acid therapy for hypertriglyceridaemia in men
Ten consecutive patients with hypertriglyceridaemia who adhered to a low carbohydrate diet without complete control of serum Triglycerides were started on chenodeoxycholic acid 750 mg daily and followed monthly for 6 months. Nine of these patients were then followed for a further month on placebo capsules and thereafter monthly for a further 6 months on clofibrate 2 g daily. 2 The mean serum Triglyceride level fell by 36% after dietary treatment alone (P less than 0.05) and by 47% from initial values on diet plus chenodeoxycholic acid (P less than 0.01). In the nine patients who proceeded to clofibrate therapy there was a rise in Triglyceride levels on placebo capsules to the level achieved by diet alone, and a further fall on diet plus clofibrate of 47% of initial values (P less than 0.05). 3 Chenodeoxycholic acid therapy is effective in the management of hypertriglyceridaemia not completely cured by dietary measures, and may be as efficacious as clofibrate.
Chitosan
This study presents a meta-analysis of studies that investigate the effectiveness of chitosan administration on lifestyle-related disease in murine models. A total of 34 published studies were used to evaluate the effect of chitosan supplementation. The effect sizes for various items after chitosan administration were evaluated using the standardized mean difference. Using Cochran’s Q test, the heterogeneity of effect sizes was assessed, after which a meta-ANOVA and -regression test was conducted to explain the heterogeneity of effect sizes using the mixed-effect model. Publication bias was performed using Egger’s linear regression test. Among the items evaluated, blood Triglyceride and HDL-cholesterol showed the highest heterogeneity, respectively. Other than blood HDL-cholesterol, total cholesterol, and Triglyceride in feces, most items evaluated showed a negative effect size with high significance in the fixed- and random-effect model (p < 0.0001). In the meta-ANOVA and -regression test, administering chitosan and resistant starch was revealed to be most effective in lowering body weight. In addition, chitosan supplementation proved to be an effective solution for serum TNF-α inhibition. In conclusion, chitosan has been shown to be somewhat useful in improving symptoms of lifestyle-related disease. Although there are some limitations in the results of this meta-analysis due to the limited number of animal experiments conducted, chitosan administration nevertheless shows promise in reducing the risk of cholesterol related metabolic disorder.
Properties of nanopowdered chitosan and its cholesterol lowering effect in rats
This study was carried out to compare the properties of nanopowdered chitosan (NPC) to commercially powdered chitosan (CPC) and examine the effect of NPC on serum and liver cholesterol lowering in rats. Twentyfour male rats of Sprague-Dawley strain were blocked into 3 groups and were raised for 8 weeks. high cholesterol diet, 2% CPC, or 2% NPC were given to 3 groups. NPC reduced total cholesterol by 46.6% and CPC reduced it by 18.6%. NPC also significantly reduced low density lipoprotein (LDL)-cholesterol by 55.7%, while CPC reduced by 36.8%. high density lipoprotein (HDL)-cholesterol content was increased more with NPC by 16.5% than with CPC by 9.6%. Triacylglycerol content was also decreased significantly by 42.8% with NPC, while reduced by 22.5% with CPC. The present study indicated that NPC feeding reduced total and LDL–cholesterol and triacylglycerol contents and increased HDL-cholesterol content.
Effects of Chitosan on Plasma Lipids and Lipoproteins: A 4-Month Prospective Pilot Study
Chitosan can favorably modulate plasma lipids, but the available data are not conclusive. We evaluated the effect of chitosan on plasma lipids and lipoproteins in 28 patients with plasma Triglyceride levels >150 mg/dL (mean age: 63 ± 12 years), not taking other lipid-lowering agents. All patients received a chitosan derived from fungal mycelium (Xantonet, Bromatech, Italy) at a fixed dose of 125 mg/d in addition to their current medications for 4 months. Polyacrylamide gel electrophoresis was used to measure low-density lipoprotein (LDL) subclasses. After treatment, total cholesterol reduced by 8%, LDL cholesterol by 2%, and Triglycerides by 19%, with a concomitant 14% increase in high-density lipoprotein cholesterol. We also found a beneficial effect of chitosan on LDL subclasses, with a significant increase in LDL-2 particles (from 37 ± 8% to 47 ± 8%, P = .0001) and a decrease (although not significant) in atherogenic small, dense LDL. Whether these findings may affect cardiovascular risk remains to be established in future studies.
Cholesterol-lowering properties and safety of chitosan
Chitosan (CAS 9012-76-4) is derived by alkaline deacetylation from chitin, an abundant polymeric product of natural biosynthesis especially in crustaceans. It is available in a primary, unorganised structure, but also in a microcrystalline form. As a dietary supplement, chitosan has been claimed to control obesity and to lower serum cholesterol. A variety of chitosan products have been freely available worldwide in health stores and pharmacies. This review summarises the current knowledge about cholesterol-lowering and safety properties of chitosan and focuses its possible application for the treatment of hypercholesterolaemia. Chitosan behaves as a polycationic(+) cellulose-like fibrillar biopolymer that forms films with negatively charged surfaces. It is not specifically hydrolysed by digestive enzymes in man, but limited digestion of chitosan due to bacterial flora and to the unspecific enzymes might occur. Negatively charged molecules in stomach attach strongly to the positive charged tertiary amino group (-NH3+) of chitosan. Therefore, chitosan reduces fat absorption from gastrointestinal tract by binding with anionic carboxyl groups of fatty and bile acids, and it interferes with emulsification of neutral lipids (i.e., cholesterol, other sterols) by binding them with hydrophobic bonds. In short-term animal studies the safety of chitosan has been good. There are only few studies with chitosan in humans. In man, dietary chitosan has been reported to reduce serum total cholesterol levels by 5.8-42.6% and low-density lipoprotein levels by 15.1-35.1%. In short-term trials up to 12 weeks, no clinically significant symptoms have been observed with chitosan compared to placebo. Mild and transitory nausea and constipation have been reported in 2.6-5.4% of subjects. Although chitosan has been clinically well tolerated, it cannot be recommended to people allergic to crustaceans.
This study presents a meta-analysis of studies that investigate the effectiveness of chitosan administration on lifestyle-related disease in murine models. A total of 34 published studies were used to evaluate the effect of chitosan supplementation. The effect sizes for various items after chitosan administration were evaluated using the standardized mean difference. Using Cochran’s Q test, the heterogeneity of effect sizes was assessed, after which a meta-ANOVA and -regression test was conducted to explain the heterogeneity of effect sizes using the mixed-effect model. Publication bias was performed using Egger’s linear regression test. Among the items evaluated, blood Triglyceride and HDL-cholesterol showed the highest heterogeneity, respectively. Other than blood HDL-cholesterol, total cholesterol, and Triglyceride in feces, most items evaluated showed a negative effect size with high significance in the fixed- and random-effect model (p < 0.0001). In the meta-ANOVA and -regression test, administering chitosan and resistant starch was revealed to be most effective in lowering body weight. In addition, chitosan supplementation proved to be an effective solution for serum TNF-α inhibition. In conclusion, chitosan has been shown to be somewhat useful in improving symptoms of lifestyle-related disease. Although there are some limitations in the results of this meta-analysis due to the limited number of animal experiments conducted, chitosan administration nevertheless shows promise in reducing the risk of cholesterol related metabolic disorder.
Cichorium intybus L. var. foliosum Hegi extract
Antioxidative effects of cichorium intybus root extract on LDL (low density lipoprotein) oxidation
The water extract of Cichorium intybus (WECI) showed a remarkable antioxidative effect on LDL, and Inhibitory effects on the production of thiobarbituric acid reactive substance and the Degradation of fatty acids in LDL. Vitamin E and unsaturated fatty acids in LDL were protected by adding WECI from the effects of metal catalyzed LDL oxidation. From the results obtained, we conclude that LDL oxidation is inhibited in vitro by the addition of WECI, and that LDL is protected by WECI from oxidative attack, as shown by agarose gel electrophoresis.
Cinnamomum Zeylanicum bark
Introduction
Atherosclerosis is one of the major causes of disability of blood vessels which can result in development of many cardiovascular disorders. There is a strong association between Atherosclerosis and insulin resistance and dyslipidemia.
Aim
To study the Anti-atherosclerotic potential of C. zeylanicum bark extract in insulin resistance associated Atherosclerosis and worsened Atherogenic Index (AI) associated with dyslipidemia, which are the predominant complications of steroid diabetes in Wistar rats.
Materials and Methods
A sum of 36 rats were categorized into five study groups and one plain control. In a 12 day study period, respective drug treatments were given every day throughout the study period whereas, dexamethasone dosage was started from day seven onwards. On day 12, fasting blood samples were collected and processed for lipid estimation and the determined values were also used to assess AI further. Animals were sacrificed under ether anaesthesia and the aorta was dissected away for its measurement and histopathological findings. One-way ANOVA was used to analyse the data and multiple comparison was done, interpreted based on Post-Hoc Scheffe test.
Results
high dose of dexamethasone (8 mg/kg/i.p) in Dexa Control (DC) group produced significant dyslipidemia, increased risk of atherogenicity (p<0.05) and caused severe thickening (78.5% compared to Plain Control (PC) of wall of aorta. Rosiglitazone (ROSI) (8 mg/kg and 16 mg/kg) and C. zelanicum (CZE) extract treatments (500 mg/kg and 250 mg/kg) significantly prevented dyslipidemia, well maintained AI compared to dexa control (p<0.05). However, both the CZE treatments protected the aorta from Atherosclerosis (40.3% and 30.2% compared to DC) and significantly prevented the dyslipidemia and reduced the risk of atherogenicity compared to ROSI treatment (p<0.05). Although, the CZE did not show difference in significance in maintaining very low density lipoprotein when compared to ROSI (p>0.05). The atherosclerotic changes were completely absent in both the CZE treatments whereas, ROSI treatments did not prevented the Atherosclerosis of aorta completely as they showed moderate and mild atherosclerotic changes in the aorta.
Conclusion
The aqueous extract of C. zelanicum bark exhibited marked protection against dexamethasone induced Atherosclerosis and also minimized the atherogenic risk in Wistar rats.
Purpose
According to the World Health Organization (WHO), approximately 150 million people worldwide have type 2 diabetes. It is a growing health concern. Common and cassia cinnamon have been reported to have anti-diabetic and lipid–lowering effects. The objective was to determine if the combination of common and cassia cinnamon (Cinnamomum verum and C. aromaticum) reduces fasting blood glucose, insulin, glycosylated hemoglobin (HA1C), Triglyceride , total cholesterol, HDL cholesterol and LDL cholesterol levels in people with type 2 diabetes.
Methods
Fifty (50) type 2 diabetic participants were randomized to receive either 140 mg of Cinnamonforce twice daily or placebo over 13 weeks. Physical and laboratory measurements were taken at baseline, 2 weeks, 4 weeks, 8 weeks and at the end of the trial, 13 weeks.
Results
There were no significant improvements in fasting glucose, insulin and lipid parameters between treatment and placebo groups. At endpoint, subjects in the treatment group were found to have a marginally non-significant higher fasting blood glucose level than subjects taking the placebo (p=0.085). There was a non-significant decrease in HA1c in the treatment group versus the placebo group (p=0.172). In secondary outcomes, significant differences in weight (p= 0.008), BMI (p= 0.001) and waist-to-hip ratio (p=0.020) were detected in the treatment versus placebo groups.
Conclusion
The combination of common and cassia cinnamon do not impact fasting glucose, insulin and lipid measurements. Through power calculations, there may be an effect on HA1c, however, the sample size in this study was not sufficient to detect a trend, if any. Although secondary outcomes in this study, common and cassia cinnamon should be further investigated for weight loss.
Clerodendrum minahassae
Leilem, which is known with the botanical name Clerodendrum minahassae, is a plant species commonly used as a component of almost all meat- and fish-based cuisine. In addition to enhancing the flavor and taste suited to the local people, leaves of leilem is also believed to possess high level of natural antioxidant. The leaves of this plant has also been used as traditional medicine to treat stomachache and lung diseases. Our previous study revealed that ethanol extract of leilem has beneficial antihyperlipidemic and Antiatherosclerotic effects on the aorta of Wistar rats fed with high lipid and cholesterol levels. The present study was aimed at investigating the phytochemical contents and antioxidant activity of ethanol extract of leilem leaves. Phytochemical screening was carried out using standard methods of precipitation and coloration reactions. In addition, the total phenolics and flavonoids were determined by using spectrophotometric methods. Finally, the leaf extract of leilem was assayed to evaluate its in vitro antioxidant properties using 1,1-Diphenyl picryl hydrazyl (DPPH) radical assay and ferric reducing antioxidant potential (FRAP) assay. The phytochemical screening of leilem leaves revealed the presence of alkaloids, saponins, flavonoids, steroids, and phenols, while terpenes and tannins were not detected. The extract of leilem leaves showed estimated phenolics and flavonoid content of 139.88 mg/g and 34.46 mg/g respectively. Concentration of leilem leave extract required for 50% inhibition of DPPH radical scavenging effect (IC50) was recorded as 565.45 μg/mL. At 1 mg/mL concentration, the aqueous extract of leilem leaves showed ferric reducing power of 123.62 μmoles/mg in FRAP assay. These findings suggest that the ethanol extract of leilem has potential in vitro antioxidant activities. Overall, results obtained from this study support our previous finding that the extract of leilem leaves has beneficial antihyperlipidemic and Antiatherosclerotic effects and can be used as an alternative to synthetic antioxidants.
Codonopsis pilosula (Franch.)Nannf.root extract
The study explored the nature and structure of ultrasonically extracted Codonopsis pilosulae crude polysaccharides (CPCPs) and the effects of CPCPs on hypoglycemic effects and gut flora in a high glucose and high-fat feeding and STZ-induced T2DM mice model. The results showed that the CPCPs consisted mainly of polysaccharides, uronic acids, proteins and SO42−. CPCPs consisted of β-type pyranose and exhibited porous, irregular fibrillation and aggregation, and inhibited the activity of α-amylase and α-glucosidase. 1 g/kg CPCPs reduced diabetic symptoms, including modulation of body weight and blood biochemistry levels, reduced blood sugar and lipids, liver, kidney, pancreas indices, oxidative damage and inflammatory factor levels in T2DM mice. For diabetic mice gut microbes, 1 g/kg CPCPs reduced the ratio of Firmicutes and Bacteroidetes; at the genus level and reduced Enterobacter abundance and increased Bacteroides abundance. These results suggested that CPCPs may be effective supplements for preventing or treating of T2DM.
Coenzyme Q10
Context: Previous meta-analyses have suggested that the effects of coenzyme Q10 (CoQ10) on lipid profiles remain debatable. Additionally, no meta-analysis has explored the optimal intake of CoQ10 for attenuating lipid profiles in adults.
Objective: This study conducted a meta-analysis to determine the effects of CoQ10 on lipid profiles and assess their dose-response relationships in adults.
Methods: Databases (Web of Science, PubMed/Medline, Embase, and the Cochrane Library) were systematically searched until August 10, 2022. The random effects model was used to calculate the mean differences (MDs) and 95% CI for changes in circulating lipid profiles. The novel single-stage restricted cubic spline regression model was applied to explore nonlinear dose-response relationships.
Results: Fifty randomized controlled trials with a total of 2794 participants were included in the qualitative synthesis. The pooled analysis revealed that CoQ10 supplementation significantly reduced total cholesterol (TC) (MD -5.53 mg/dL; 95% CI -8.40, -2.66; I2 = 70%), low-density lipoprotein cholesterol (LDL-C) (MD -3.03 mg/dL; 95% CI -5.25, -0.81; I2 = 54%), and Triglycerides (TGs) (MD -9.06 mg/dL; 95% CI -14.04, -4.08; I2 = 65%) and increased high-density lipoprotein cholesterol (HDL-C) (MD 0.83 mg/dL; 95% CI 0.01, 1.65; I2 = 82%). The dose-response analysis showed an inverse J-shaped nonlinear pattern between CoQ10 supplementation and TC in which 400-500 mg/day CoQ10 largely reduced TC (χ2 = 48.54, P < .01).
Conclusion: CoQ10 supplementation decreased the TC, LDL-C, and Triglyceride levels, and increased HDL-C levels in adults, and the dosage of 400 to 500 mg/day achieved the greatest effect on TC.
The Redox Status of Coenzyme Q10 in Total LDL as an Indicator of In Vivo Oxidative Modification
Familial combined hyperlipidemia (FCH) is characterized by a familial occurrence of a multiple-type hyperlipidemia, associated with coronary risk. The latter may be related to increased levels of small, dense LDL particles that have been found to be more prone to oxidative modification. We isolated total LDL as fresh as possible from 12 normolipidemic relatives with a buoyant LDL subfraction profile (group 1), 7 normolipidemic subjects with a dense LDL subfraction profile (group 2), and 16 hyperlipidemic FCH subjects with a dense LDL subfraction profile (group 3). In these nonobese and normotensive men, we studied the resistance of total LDL against Cu2+-oxidation in vitro. In addition, we analyzed the α-tocopherol and the coenzyme Q10 contents of LDL and determined their relation to LDL oxidizability. LDL isolated from group 3 subjects was more susceptible to oxidative modification than LDL from group 1 subjects (lag time: 60.4±8.1 versus 70.4±11.4 minutes; P<.05). For the combined groups, the ratio of ubiquinol-10 to polyunsaturated fatty acids in LDL, together with the basal amount of dienes in LDL, were good predictors of the rate of LDL oxidation (R2=.73, P=.0001). In groups 2 and 3, the redox status of coenzyme Q10 (ubiquinol-10/ubiquinone-10) and the ratio of ubiquinol-10 to α-tocopherol in LDL were reduced compared with group 1 (P<.05). The K-value, a measure of the LDL density, correlated with the the redox status (r=.37, P<.05). We conclude that in subjects with FCH total LDL is more prone to oxidation, due to the predominance of dense LDL particles. In addition, the decreased redox status of coenzyme Q10 in LDL from subjects with a dense LDL subfraction profile suggests that the LDL in the circulation has already undergone some oxidation.
dietary natural products as emerging lipoprotein(a)-lowering agents
Elevated plasma lipoprotein(a) (Lp(a)) levels are associated with an increased risk of cardiovascular disease (CVD). Hitherto, niacin has been the drug of choice to reduce elevated Lp(a) levels in hyperlipidemic patients but its efficacy in reducing CVD outcomes has been seriously questioned by recent clinical trials. Additional drugs may reduce to some extent plasma Lp(a) levels but the lack of a specific therapeutic indication for Lp(a)‐lowering limits profoundly reduce their use. An attractive therapeutic option is natural products. In several preclinical and clinical studies as well as meta‐analyses, natural products, including l‐carnitine, coenzyme Q 10, and xuezhikang were shown to significantly decrease Lp(a) levels in patients with Lp(a) hyperlipoproteinemia. Other natural products, such as pectin, Ginkgo biloba, flaxseed, red wine, resveratrol and curcuminoids can also reduce elevated Lp(a) concentrations but to a lesser degree. In conclusion, aforementioned natural products may represent promising therapeutic agents for Lp(a) lowering.
Coptis chinensis Franch.root extract
Hypoglycemic and hypocholesterolemic effects of Coptis chinensis franch inflorescence
Hypocholesterolemic and hypoglycemic activities of Coptis chinensis franch inflorescence (Coptis inflorescence) were studied using animal models. serum total and LDL cholesterol of rats fed a diet containing 1% cholesterol and 0.5% cholic acid increased, as compared with those of rats fed a normal diet. The level of total and LDL cholesterol were reduced markedly in a dose dependent manner, in rats given Coptis inflorescence extract orally at doses of 0.25, 0.5 g/kg.day for 4 weeks. In diabetic rats induced by alloxan, Coptis inflorescence extract showed a significant (p < 0.05) blood sugar lowering activity at all experimented doses (0.125, 0.25 and 0.5 g/kg.day). The highest reduction of blood sugar was about 58% when the rats were given Coptis inflorescence extract orally at a dose of 0.5 g/kg.day for 3 weeks. The 100 g dried water extract of Coptis inflorescence contained 8.11 g total alkaloid, 3.34 g berberin, 1.08 g palmatine and 0.66 g jatrorrhizine, which had long been identified as active compounds in Coptis chinensis franch root (Coptis root). Thus, the results suggest that Coptis inflorescence would be effective in the prevention and management of coronary artery disease by lowering serum cholesterol and blood sugar.
Costus spicatus (Jacq.) Sw.
Atheroprotective Properties of Costus spicatus (Jacq.) Sw. in Female Rats
Background: Costus spicatus (Jacq.) Sw. is a medicinal species frequently prescribed for the treatment of cardiovascular diseases. This study aims to evaluate the effects of this species against the development of Atherosclerosis. Methods: First, an anatomical study of the C. spicatus leaves was performed. Then, the extract (ESCS) was obtained and submitted to phytochemical analysis. Female rats were treated with a single dose of ESCS (2000 mg/kg) to assess acute toxicity. Other groups of female rats received an atherogenic diet for 60 days. After 30 days, the animals were treated orally with ESCS (30 and 300 mg/kg), rosuvastatin (5 mg/kg), or vehicle once daily for 30 days. serum lipids oxidized low-density lipoprotein, soluble adhesion molecules, interleukins 1β and 6, and markers of renal and liver function were measured. Renal function, blood pressure, electrocardiography, and vascular reactivity were also evaluated. Arteries, heart, liver, and kidney were also collected to evaluate the tissue redox state and histopathological analysis. Results: Prolonged treatment with ESCS induces significant hypolipidemic and antioxidant effects, that prevent endothelial dysfunction and modulated the local inflammatory process, reducing the evolution of the atherosclerotic disease. Conclusions: This study provides a scientific basis for the popular use of C. spicatus for the treatment of Atherosclerosis.
Crataegus pinnatifida Bge. var majorN.E.Br. fruit extract
The effects of Crataegus pinnatifida (Chinese hawthorn) on metabolic syndrome: A review
Metabolic syndrome is described as a group of risk factors in which at least three unhealthy medical conditions, including obesity, high blood sugar, hypertension or dyslipidemia occur simultaneously in a patient. These conditions raise the risk for diabetes mellitus and cardiovascular diseases. Many recent studies have focused on herbal remedies and their pharmacological effects on metabolic syndrome. Crataegus pinnatifida or Chinese hawthorn has been widely used in the treatment of hyperlipidemia and cardiovascular diseases. Its leaves, fruits and seeds have various active substances such as, flavonoids, triterpenic acids and sesquiterpenes, which through different mechanisms can be beneficial in metabolic syndrome. Flavonoids found in the leaves of hawthorn can significantly reduce atherosclerotic lesion areas, the fruit extracts contain two triterpenic acids (oleanolic acid and ursolic acid), that have the ability to inhibit the acyl-coA-cholesterol acyltransferase (ACAT) enzyme and as a result reduce very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol levels. Another example regards a sesquiterpene found in the seeds of C. pinnatifida, which exhibits the ability to inhibit platelet aggregation, thus showing antithrombotic activity. Various studies have shown that C. pinnatifida can have beneficial effects on controlling and treating high blood sugar, dyslipidemia, obesity and Atherosclerosis. The aim of this review is to highlight the interesting effects of C. pinnatifida on metabolic syndrome.
Consumption of functional foods for managing plasma cholesterol level has gained acceptance globally. The hypocholesterolaemic and vascular protective effects of the dried fruit of Crataegus pinnatifida, hawthorn (Shan Zha), were investigated in rats fed with normal diet, high cholesterol diet (HCD) or HCD plus Shan Zha 80% ethanolic extract treatment (30 or 100 mg/kg/day, p.o.) for 4 weeks. Shan Zha extract markedly reversed the increased plasma total cholesterol and high density lipoprotein cholesterol induced by HCD with a dose-dependent improvement on the atherogenic index. It also demonstrated good hepatoprotective function by reducing lipid content in the liver. The blunted endothelium-mediated aortic relaxation in HCD-fed rats was restored by high dosage of Shan Zha extract treatment. The current results showed that Shan Zha extract could provide its cholesterol lowering effect by up-regulating hepatic CYP7A1 mRNA expression which leads to enhanced bile acid biosynthesis. It is postulated that the hypocholesterolaemic effect is the primary beneficial effect given by Shan Zha extract; it then leads to other secondary beneficial effects such as vascular protective and hepatoprotective functions. Thus, Shan Zha extract could provide an overall improvement on the hepatic and vascular systems that may be important in relieving hypercholesterolaemia-related complications.
Crocetin
Objective:
Inhibition of lipid metabolism in breast cancer has been suggested as an effective approach for cancer therapy. Saffron-derived crocetin (Crt) and crocin (Cro) with the known anticancer activity, have shown hypolipidemic effect in diabetes and Atherosclerosis. Here, we investigated the effect of Crt/Cro on lipid content in breast cancer.
Materials and Methods:
A multi-model approach involving in vivo, in vitro and in silico studies was applied. The 4T1-induced breast cancer in mice was used to investigate the effect of Crt/Cro on cholesterol (Chl) and Triglyceride (TG) levels in serum and tumor tissues. The Chl/Triglyceride levels were also assessed in the cytosol of MDA-MB-231 and MCF-7 breast cancer cell lines 6, 12 and 24 hr after Crt/Cro treatment. The interaction between Crt/Cro and hydroxymethylglutaryl coenzyme A reductase (HMGCR) was also computed by docking analysis.
Results:
Crt reduced both serum (p=0.003) and tumor (p=0.011) Chl and Triglyceride (p=0.001) levels in mice. Cro reduced Triglyceride levels in tumor (p=0.014) and serum (p=0.002) and Chl level in tumor (p=0.013) tissues. Crt reduced both Chl and Triglyceride in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Cro reduced both Chl and Triglyceride in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Crt binds to the active site of HMGCR with higher affinity (ΔG0=-6.6 kcal/mol) than simvastatin (ΔG0 =-6.0 kcal/mol).
Conclusion:
Crt and Cro effectively decreased Chl/Triglyceride content in the sera of tumor bearing mice, in breast tumors and breast cancer cell lines. Crt showed a higher hypolipidemic potential than Cro. In silico analysis indicated Crt binding in the HMGCR active site.
Crocin
effect of crocin on glycated human low-density lipoprotein: A protective and mechanistic approach
Human low-density lipoprotein (LDL) is known to have a role in coronary artery diseases when it undergoes modification due to hyperglycaemic conditions. Plant products like crocin play an essential role in protecting against oxidative stress and in the production of advanced glycation end-products (A.G.E.s). In this study, the anti-glycating effect of crocin was analyzed using various biochemical, spectroscopic, and in silico approaches. Glycation-mediated oxidative stress was confirmed by nitroblue tetrazolium, carbonyl content, and lipid peroxidation assays, and it was efficiently protected by crocin in a concentration-dependent manner. A.N.S. fluorescence, thioflavin T (ThT) assay, and electron microscopy confirmed that the structural changes in LDL during glycation lead to the formation of fibrillar aggregates, which can be minimized by crocin treatment. Moreover, secondary structural perturbations in LDL were observed using circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR), where crocin was found to prevent the loss of secondary structure in glycated LDL. Spectroscopic studies like U.V. absorbance, fluorescence spectroscopy, CD, FTIR, and fluorescence resonance energy transfer (FRET) provided insights into the interaction mechanism between LDL and crocin. Molecular docking supports these results with a highly negative binding energy of −10.3 kcal/mol, suggesting the formation of a stable LDL-crocin complex. Our study indicates that crocin may be a potent protective agent against coronary artery diseases by limiting the glycation of LDL in people with such disorders.
The pancreatic lipase Inhibitors were isolated from the fructus of Gardenia jasminoides ELLIS, and their antihyperlipidemic activities were measured. Gardeniae fructus (GF) water extract inhibited pancreatic lipase activity. Crocetin and crocin were isolated from GF water extract as Inhibitors of pancreatic lipase with an IC50 value of 2.1 and 2.6 mg/ml (triolein as a substrate). Crocin and crocetin significantly inhibited the increase of serum Triglyceride level in corn oil feeding-induced Triglyceride mic mice, as well as that of serum Triglyceride and total and LDL cholesterol levels in Triton WR-1339-induced hyperlipidemic mice. These compounds also showed hypolipidemic activity in hyperlipidemic mice induced by high cholesterol, high fat or high carbohydrate diets for 5 weeks. The results suggest that the hypolipidemic activity of GF and its component crocin may be due to the inhibition of pancreatic lipase and crocin, and its metabolite, crocetin, can improve hyperlipidemia.
Cuphea carthagenensis
Abstract
Ethnopharmacological relevance
Although Cuphea carthagenensis (Jacq.) J. F. Macbr. is used in Brazilian folk medicine in the treatment of Atherosclerosis and circulatory disorders, no study evaluating these effects has been conducted. The aim of this study was to evaluate the possible hypolipemiant and antiatherogenic activity of the ethanol soluble fraction obtained from C. carthagenensis (ES-CC) in an experimental Atherosclerosis model using New Zealand (NZ) rabbits undergoing cholesterol-rich diet (CRD).
Material and methods
Dyslipidemia and atherogenesis were induced by administration of standard commercial diet increased of 1% cholesterol (CRD) for 8 weeks. ES-CC was orally administered at doses of 10, 30 and 100 mg/kg, once daily for four weeks, starting from the 4th week of CRD diet. Body weight measurements were weekly carried out from the beginning of experiments for 8 weeks. serum levels of Triglyceride (TG), total cholesterol (TC) and their fractions (LDL-C, VLDL-C and HDL-C) were measured at the beginning of experiments and at weeks four and eight. After euthanasia of rabbits, aorta segments (aortic arc, thoracic, abdominal and iliac segments) were macroscopically and microscopically evaluated and the intima and media layers of the arteries were measured. Additionally, the antioxidant activity of ES-CC and its influence on the functioning of hepatic antioxidant enzymes were also determined.
Results
CRD induced dyslipidemia and major structural changes in the aortic wall. In addition, an increase in lipid peroxidation and a reduction of hepatic glutathione and serum nitrite levels were observed. Treatment with ES-CC was able to prevent the increase in TC, LDL-C, VLDL-C levels and Triglycerides and promoted an increase in HDL-C levels in NZ rabbits. These effects were accompanied by a significant reduction in oxidative stress and modulation of the catalase and superoxide dismutase function. Moreover, the intima and media layers of the arterial segments were significantly reduced by ES-CC treatment.
Conclusions
This study demonstrated that ES-CC reduces serum lipids and hepatic oxidative stress when orally administered to NZ rabbits. In addition, it was able to prevent the development of CRD-induced Atherosclerosis.
Curcuma longa L. extract
It is generally accepted that free-radical induced blood lipid peroxidation and especially peroxidized LDL play a central role in the pathogenesis of Atherosclerosis and related cardiovascular disease. Moreover, recent research highlights the key contribution of apolipoprotein B (apo B) to atherogenesis as the main inductor of one of its earlier steps, i.e. macrophage prolipheration. This has led us to investigate the apo B response to a very effective phenolic lipid-antioxidant, namely an hydroalcoholic extract of Curcuma longa, which according to our previous work does not show any toxic effects and decreases the levels of blood lipid peroxides, oxidized lipoproteins and fibrinogen. The present study shows that a daily oral administration of the extract decreases significantly the LDL and apo B and increases the HDL and apo A of healthy subjects. This and recent data on the increased anti-atherogenic action of the physiological antioxidant tocopherol in the presence of phenolic co-antioxidants (which eliminate the tocopheroxyl radical), justifies planned clinical research to test the usefulness of the curcuma extract as a co-antioxidant complement to standard treatments to prevent or retard Atherosclerosis.
Curcumin
Atherosclerosis is a major cause of cardiovascular disease caused by high cholesterol. Reduced intestinal cholesterol absorption has been shown to exert strong cholesterol–lowering and antiatherogenic effects. Previously, we reported that curcumin reduced cholesterol absorption in high-fat diet–fed hamster by downregulating the intestinal expression of Niemann-Pick C1-like 1. Here, we tested the hypothesis that supplementation with curcumin can also reduce intestinal cholesterol absorption in high-fat diet–fed apolipoprotein E knockout (ApoE−/−) mice and prevent Atherosclerosis development. ApoE−/− mice were fed a high-fat diet supplemented with or without curcumin (0.1% w/w) for 16 weeks. Aortic sinus sections revealed that curcumin supplementation reduced the extent of atherosclerotic lesions by 45%. Curcumin treatment also reduced cholesterol accumulation in the aortas by 56% and lowered plasma total cholesterol and low-density lipoprotein cholesterol levels. Moreover, the antiatherogenic and cholesterol–lowering effects of curcumin coincided with a significant decrease in intestinal cholesterol absorption. It was reduced by nearly 51%, and the decreased cholesterol absorption was modulated by inhibiting the intestinal expression of Niemann-Pick C1-like 1, predominantly in the duodenal and jejunal segments of the small intestine. These findings support the hypothesis that curcumin supplementation reduces intestinal cholesterol absorption and prevents Atherosclerosis in high-fat diet–fed ApoE−/− mice. Curcumin affords a potent antiatherogenic action by inhibiting intestinal cholesterol absorption in the mouse.
Regulation of PCSK9 by nutraceuticals
PCSK9, a critical Inhibitor of LDLR, is up-regulated by both HNF1α and SREBP-2 transcription factors. Besides
PCSK9, SREBP-2 up-regulates LDLR gene. Nutraceuticals, including curcumin and berberine, can decrease plasma
LDL-C levels through elevation of the hepatic LDLR via inhibiting HNF1α which is a specific transcription factor
for PCSK9 gene. Statins increase the expression of both PCSK9 and LDLR through the activation of SREBP-2,
resulting in PCSK9-mediated attenuation of their effects
Background
dietary phytosterols (PS) are well-known hypocholesterolaemic agents. Curcumin elicits hypolipidaemic and anti-inflammatory effects in preclinical studies, however, consistent findings in humans are lacking.
Objective
Concurrent PS and curcumin supplementation may exhibit enhanced hypocholesterolaemic and anti-inflammatory effects to optimise cardio-protection. The objective of this trial was to investigate the effects of dietary intervention with PS with or without curcumin on blood lipids (primary outcome) in hypercholesterolaemic individuals.
Methods
A double-blinded, randomised, placebo-controlled, 2 × 2 factorial trial was conducted in hypercholesterolaemic individuals. Participants received either placebo (PL, no phytosterols or curcumin), phytosterols (PS, 2 g/d), curcumin (CC, 200 mg/d) or a combination of PS and curcumin (PS-CC, 2 g/d–200 mg/d respectively) for four weeks. Primary outcomes included fasting total cholesterol (TC), LDL–cholesterol, HDL-cholesterol, Triglycerides (TG), TC-to-HDL-C ratio (TC:HDL-C). Secondary outcomes included anthropometrics and fasting blood glucose concentrations.
Results
Seventy participants with a mean (±SEM) fasting TC concentration of 6.57 ± 0.13 mmol/L completed the study (PL, n = 18; PS, n = 17; CC, n = 18; PS-CC, n = 17). PS and PS-CC supplementation significantly lowered TC, LDL–cholesterol and TC:HDL-C post-intervention (p < 0.05). Reductions from baseline in the PS group were 4.8% and 8.1% for TC and LDL–cholesterol respectively (p < 0.05). CC exhibited non-significant reduction (2.3% and 2.6%) in TC and LDL-C respectively, however, the PS-CC resulted in a greater reduction in TC (11.0%) and LDL–cholesterol (14.4%) than either of the treatments alone (p < 0.0001). The reduction in the PS-CC treatment was significantly greater compared to those for CC (p < 0.05) or PL (p < 0.01) alone. Plasma HDL-cholesterol and Triglyceride concentrations remained unchanged across all groups. No adverse side effects were reported.
Conclusions
The addition of curcumin to phytosterol therapy provides a complementary cholesterol–lowering effect that is larger than phytosterol therapy alone. Implications of these findings include the development of a single functional food containing both the active ingredients for enhanced lipid–lowering and compliance in hypercholesterolaemic individuals.
Cyclocarya paliurus
Cymodocea nodosa
This study aims to evaluate for the first time the effects of Cymodocea nodosa sulphated polysaccharide (CNSP) on lipase activity in vitro and in vivo to high fat diet (HFD)-rats on body weight, lipid profile and liver-kidney functions. The administration of CNSP decreases the body weight and inhibits lipase activity of obese rats in serum and intestine as compared with untreated HDF-rats. This decrease in lipase activity leads to lipid regulation shown by the decrease of total cholesterol (T-Ch), Triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) and an increase in high density lipoprotein cholesterol (HDL-C) levels in HFD-rats. Additionally, CNSP administration to HFD-rats induces anti-oxidant activity observed by the increase of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities and the decrease in Thiobarbituric acid reactive substances (TBARS) levels and protects liver-kidney functions proven by a decrease in the levels of toxicity parameters in blood.
Cynara scolymus L.leaves extract
hypolipidemic and antiatherogenic effects of Cynara scolymus in cholesterol-fed rats
Cynara scolymus L., Asteraceae, are traditionally used to treat dyspepsia. This study evaluated the hypolipidemic and antiatherogenic effects of an aqueous extract prepared from the leaves of C. scolymus in rat’s model. Hypercholesterolemic rats (1% cholesterol and 0.5% cholic acid for 15 days) were treated (0.5 ml/200 g) with extract of C. scolymus (150, 300, or 600 mg/kg p.o.; n = 6) or simvastatin (4 mg/kg p.o.; n = 6) once per day for 30 days along with hypercaloric diet. A control group (C) was given water (0.5 ml/200 g; n = 6). A high–cholesterol diet was maintained throughout the treatment period. Rats treated with extract of C. scolymus (150, 300, or 600 mg/kg) and simvastatin showed significant decreases in serum levels of total cholesterol (−46.9%, −51.9%, −44%, and −41.9%, respectively) and low-density lipoprotein-cholesterol (LDL-C; −52.1%, −54.8%, −51.9%, and −46.7%, respectively), compared with group C (p < 0.005). Biochemical analyses revealed significant decrease in the concentration of IL-1, IL-6, TNF-α, IFN-γ, C-reactive protein, oxidized–LDL, and antioxidized–LDL in rats treated with extract of C. scolymus (150, 300, or 600 mg/kg). There were no differences in serum ALT enzyme activity between the groups. Our results suggest that hypolipidemic and antiatherogenic effects could be related with the presence of polar substances present in aqueous extract of C. scolymus.
Cynodon dactylon extract
Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study, Anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normal diet, sham group received a high cholesterol diet (HCD; 1.50% cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg-1), moderate (200 mg kg-1) and maximum (400 mg kg-1) doses via gavages. The last group received atorvastatin (10 mg kg-1) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including total cholesterol (TC), Triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed in the blood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon-treated groups. Treatment of HCD animals with C. dactylon positively changed lipid profile by lowering of TC, Triglyceride and LDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall.
d-Allulose
d-Allulose, a C-3 epimer of d-fructose, is a rare sugar reported to be a non-caloric sweetener having several health beneficial effects including anti-hyperglycemia and anti-obesity. However, the impact of dietary d-allulose on cholesterol metabolism remains unclear. Therefore, we studied the effects of d-allulose on the cholesterol metabolism of Golden Syrian hamsters, an animal model with a lipid metabolism similar to that of humans. Hamsters received either normal diet (ND) or high-fat diet (HFD) with or without 3% d-allulose for 4 or 8 weeks. While there were no significant differences in total serum cholesterol levels between the groups, d-allulose significantly increased HDL-cholesterol levels in ND-fed hamsters and decreased LDL–cholesterol levels in HFD-fed hamsters, causing an overall decrease in the LDL/HDL ratio. Furthermore, dietary d-allulose decreased serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels in both diets. In conclusion, d-allulose may favorably modulate cholesterol metabolism by reducing PCSK9 in hamsters.
d-Glucaric acid
The beneficial properties of different vitamins, minerals, and other micronutrients have been studied for quite some time. But only recently has the potential usefulness of d-glucaric acid and its derivatives in disease prevention been demonstrated. d-Glucaric acid is an end product of the d-glucuronic acid pathway in mammals. Its dietary sources include different fruits and vegetables. In the present study, d-glucaric acid content in various fruits and vegetables was found to range from about 0.1 g/kg in grapes and lettuce to about 3.5 g/kg in apples and broccoli. It was also shown that purified diets containing calcium d-glucarate or potassium hydrogen d-glucarate markedly lowered serum levels of cholesterol in female Sprague-Dawley rats. The d-glucarates reduced total serum cholesterol in rats by up to 14% (P<0.05) and lowered LDL–cholesterol by up to 35% (P<0.05), but had no effect on HDL cholesterol. These results provide a starting point for further studies of the mechanism by which d-glucaric acid salts lower serum cholesterol.
Dendropanax morbifera
Obesity is the most common metabolic disease in developed countries and has become a global epidemic in recent years. Obesity is associated with various metabolic abnormalities, including glucose intolerance, insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Leaves from the plant Dendropanax morbiferus are beneficial to health as they contain high levels of vitamin C and tannin. There have been seminal studies on the anticancer, antimicrobial, antidiabetes, and antihyperglycemic effects of treatments with D. morbiferus trees. Herein, we investigated the toxicity of D. morbiferus water (DLW) extracts in vitro, and demonstrated no toxicity at 5–500 μg/mL in 24–72-h experiments with 3T3-L1 cells. The DLW increased cell viability at 48 h and inhibited adipogenesis in 3T3-L1 cells by reducing intracellular Triglyceride levels and glucose uptake. In addition, mRNA and protein expression levels of adipogenesis-related genes were lowered by DLW, suggesting antiobesity effects in mouse 3T3-L1 cells. Because few studies have demonstrated cholesterol–lowering effects of D. morbiferus, we investigated the activities of adipogenic transcriptional factors following treatments of 3T3-L1 cells with D. morbiferus and observed increased CEBPα, CEBPβ, PPARγ, and SREBP1 activities in the cells, indicating that DLW extracts inhibit adipogenesis.
Dioscorea zingiberensis
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL–cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an Inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Dioscoreaceae (Dioscorea nipponica Makino)
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL–cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an Inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Diospyros kaki Thunb. extracts
cholesterol–lowering effect of astringent persimmon fruits (Diospyros kaki Thunb.) extracts
This study aimed to investigate the effects of ethanol extract of astringent persimmon on antioxidant activity, cholesterol, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity, and mRNA expression of cholesterol metabolism-related genes in human hepatoma cell line (HepG2 cells). In the results, DPPH and ABTS radical scavenging activity showed that the different types cultivars of astringent persimmon was similar to Vitamin C as positive control. However, there are not significant differences among samples. In addition, our results showed that cholesterol amounts and HMG-CoA reductase activity were inhibited by astringent persimmon in HepG2 cells. Further, treatment with astringent persimmon upregulated the expression of LDL receptor and SREBP-2, and also increased the level of HDL-associated ABCA1. Taken together, our results indicate that astringent persimmon regulate cholesterol accumulation by inhibiting the oxidative stress and controlling the levels of LDL & HDLassociated gene.
Elaeocarpus Ganitrus
ANTIOXIDANT AND lipid lowering effectS OF ELAEOCARPUS GANITRUS IN cholesterol FED RABBITS
Elaeocarpus ganitrus Roxb. is reported to exhibit multifarious pharmacological activities. However no scientific study has been conducted to evaluate Antiatherosclerotic /lipid lowering activity of E. ganitrus Roxb. The present study was designed to investigate the antihyperlipidaemic and antioxidant activity of 70% ethanolic extract of E. ganitrus seed (EGEE) in cholesterol fed hyperlipidaemic rabbits. The EGEE was administered at a dose level of 250 and 500 mg/kg/day (p.o.) for 60 days to hyperlipidaemic rabbits. lipid profile in serum and antioxidant parameters in tissues (Liver, Heart and Aorta) were determined. The statistical analysis was carried out using one way ANOVA followed by Tukey’s multiple comparison tests. EGEE showed a decrease in the levels of serum total cholesterol, Triglycerides , phospholipids, LDL, VLDL (P ≤ 0.01, ≤ 0.001) in a dose dependant manner in treated animals. HDL ratio improved profoundly as well as marked decline was noticed in atherogenic index after administration with EGEE. A considerable decrease in lipid per oxidation and a significant elevation in Glutathione, Catalase and SOD levels (P ≤ 0.01, ≤ 0.001) were observed in EGEE treated rabbits. The overall experimental results suggests that the biologically active phytoconstituents such as phytosterols, fats, alkaloids, flavonoids, carbohydrates, proteins and tannins present in the EGEE may be responsible for the significant hypolipidaemic as well as antioxidant activity, signifying the potential protective role in coronary heart disease.
Emodin
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL–cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an Inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Epigallocatechin gallate (EGCG)
effect of EGCG on lipid absorption and plasma lipid levels in rats
Catechins, compounds derived from green tea, have been shown to reduce plasma cholesterol levels and the rate of cholesterol absorption. We investigated the dose response and the mechanism of action of epigallocatechin gallate (EGCG) on these parameters in rats. Wistar rats were fed a diet high in cholesterol and fat containing either none, 0.25% (0.2 g/day/kg BW), 0.5% (0.4 g/day/kg/BW) or 1.0% (0.7 g/day/kg BW) of EGCG. After 4 weeks of treatment, total cholesterol and low density lipoprotein plasma levels were significantly reduced in the group fed 1% EGCG when compared to the no treatment group. Plasma Triglycerides and high-density lipoprotein levels did not change significantly. Following a single oral application of a liquid test-meal, intestinal cholesterol absorption in Wistar rats was 79.3% in the control group. In the group treated with 0.1 g/kg BW EGCG intestinal cholesterol absorption decreased to 73.7% and in the group treated with 0.5 g/kg BW of EGCG intestinal cholesterol absorption fell significantly to 62.7% (P = 0.005). Total fat absorption was very efficient in the control group (99.5% of the applied dose) and decreased significantly but moderately in the group treated with the highest doses of EGCG (0.75, 1 g/kg BW). In an in-vitro biliary micelle model, the addition of 55 microM to 1300 microM EGCG not only decreased cholesterol solubility dose-dependently in these micelles but also altered the size of the mixed lecithin/taurocholate/cholesterol micelles as demonstrated by light scattering. This study provides evidence suggesting that the cholesterol–lowering effect of green tea is mainly elicited by EGCG, one of the most abundant catechins contained in green tea. It is suggested that one of the underlying mechanisms by which EGCG affects lipid metabolism is by interfering with the micellar solubilization of cholesterol in the digestive tract, which then in turn decreased cholesterol absorption.
Eritadenine (Lentinus edodes)
Cardiovascular diseases are among the main causes of death in our society and there is a strong correlation between enhanced blood cholesterol levels and the development of such diseases. The popular edible fungus, shiitake mushroom (Lentinus edodes), has been shown to produce a blood cholesterol lowering compound designated eritadenine, and the hypocholesterolemic action of this compound has been quite extensively examined in rats. Eritadenine is suggested to accelerate the removal of blood cholesterol either by stimulating tissue uptake or by inhibiting tissue release; there are no indications of this compound inhibiting the biosynthesis of cholesterol. If shiitake mushrooms are to be used as a source for a potential cholesterol reducing product, it is of great importance to determine the content of eritadenine in the mushrooms as accurately as possible. Hence, in paper I methanol extraction was used to recover as much as possible of the hypocholesterolemic agent from the fungal cells. In order to analyse the target compound, a reliable and reproducible HPLC method for separation, identification and quantification of eritadenine was developed. The amounts of eritadenine in fruit bodies of four commercially cultivated shiitake mushrooms were determined, and the mushrooms under investigation exhibited up to ten times higher levels of eritadenine (3.17-6.33 mg/g dry mushrooms) than previously reported. Not only the fruit bodies of shiitake, but also its mycelia contain eritadenine. Growing fruit bodies of shiitake is a fairly demanding and time consuming process. Hence, in search for a source of eritadenine, submerged (liquid) cultivation of shiitake mycelia could be an alternative.
Eucommia ulmoides Oliver extract Chlorogenic acid
Biological Values of Acupuncture and Chinese Herbal Medicine: Impact on the Life Science
Intracellular glucose and lipid metabolic homeostasis is vital for maintaining basic life activities of a cell or an organism. glucose and lipid metabolic disorders are closely related with the occurrence and progression of diabetes, obesity, hepatic steatosis, cardiovascular disease, and cancer. Chlorogenic acid (CGA), one of the most abundant polyphenol compounds in the human diet, is a group of phenolic secondary metabolites produced by certain plant species and is an important component of coffee. Accumulating evidence has demonstrated that CGA exerts many biological properties, including antibacterial, antioxidant, and anticarcinogenic activities. Recently, the roles and applications of CGA, particularly in relation to glucose and lipid metabolism, have been highlighted. This review addresses current studies investigating the roles of CGA in glucose and lipid metabolism.
Hypercholesterolemia is a major risk factor for the development of cardiovascular disease and nonalcoholic fatty liver disease. Natural compounds have been proved to be useful in lowering serum cholesterol to slow down the progression of cardiovascular disease and nonalcoholic fatty liver disease. In the present study, the hypocholesterolemic and hepatoprotective effects of the dietary consumption of chlorogenic acid were investigated by monitoring plasma lipid profile (total cholesterol, Triglycerides , high-density lipoprotein and low-density lipoprotein) in Sprague-Dawley rats fed with a normal diet, a high–cholesterol diet or a high–cholesterol diet supplemented with chlorogenic acid (1 or 10 mg/kg/day p.o.) for 28 days. Chlorogenic acid markedly altered the increased plasma total cholesterol and low-density lipoprotein but decreased high-density lipoprotein induced by a hypercholesterolemic diet with a dose-dependent improvement on both atherogenic index and cardiac risk factor. lipid depositions in liver were attenuated significantly in hypercholesterolemic animals supplemented with chlorogenic acid. It is postulated that hypocholesterolemic effect is the primary beneficial effect given by chlorogenic acid, which leads to other secondary beneficial effects such as atheroscleroprotective, cardioprotective and hepatoprotective functions. The hypocholesterolemic functions of chlorogenic acid are probably due to the increase in fatty acids unitization in liver via the up-regulation of peroxisome proliferation-activated receptor α mRNA.
Chlorogenic acid as a natural hydroxycinnamic acid has protective effect for liver. Endotoxin induced metabolic disorder, such as lipid dysregulation and hyperlipidemia. In this study, we investigated the effect of chlorogenic acid in rats with chronic endotoxin infusion. The Sprague-Dawley rats with lipid metabolic disorder (LD group) were intraperitoneally injected endotoxin. And the rats of chlorogenic acid-LD group were daily received chlorogenic acid by intragastric administration. In chlorogenic acid-LD group, the area of visceral adipocyte was decreased and liver injury was ameliorated, as compared to LD group. In chlorogenic acid-LD group, serum Triglycerides , free fatty acids, hepatic Triglycerides and cholesterol were decreased, the proportion of C20:1, C24:1 and C18:3n-6, Δ9-18 and Δ6-desaturase activity index in the liver were decreased, and the proportion of C18:3n-3 acid was increased, compared to the LD group. Moreover, levels of phosphorylated AMP-activated protein kinase, carnitine palmitoyltransferase-I, and fatty acid β-oxidation were increased in chlorogenic acid-LD group compared to LD rats, whereas levels of fatty acid synthase and acetyl-CoA carboxylase were decreased. These findings demonstrate that chlorogenic acid effectively improves hepatic lipid dysregulation in rats by regulating fatty acid metabolism enzymes, stimulating AMP-activated protein kinase activation, and modulating levels of hepatic fatty acids.
Eugenia jambolana
The aim of the present study was to investigate the Antiatherosclerotic effect of active principle (FIIc) isolated from aqueous fruit pulp extract of Eugenia jambolana. Crude aqueous extract of E. jambolana was subjected to purification using chromatographic techniques which yielded purified active compound (FIIc). Purity of FIIc was tested by HPLC. Phytochemical investigation of FIIc by NMR, IR, and UV spectra showed that the purified compound is -hydroxy succinamic acid. The streptozotocin- (STZ-) induced diabetic rats were fed atherosclerotic (Ath) diet containing 1.5 mL olive oil containing 8 mg (3, 20,000 IU) vitamin and 40 mg cholesterol for 5 consecutive days. The STZ-induced diabetic rats receiving Ath diet were orally administered FIIc at doses of 10, 15, and 20 mg/kg, and results were compared with reference drug, that is, glibenclamide (600 g/mg) and healthy control. 30-day treatment with FIIc resulted in significant ( ) improvement in blood glucose, serum lipid profile, apolipoproteins (Apo and apo ), and endothelial dysfunction parameters. Histomorphological studies also confirmed biochemical findings. Our results showed that FIIc has protective effect on hyperglycemia-induced Atherosclerosis.
Eugenol (Syzygium aromaticum)
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL–cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an Inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Euphorbia prostrate
A Database of Anti-Diabetic and Anti-Cancer Plant Species from the Family Euphorbiaceae
In alloxan-induced (150mg/Kg) serum biochemical parameters were were investigated in whole plant (methanolic extract) of Euphorbia prostrata (EP) (250 and 500 mg/Kg/day per oral for 14 days). The typical anti-diabetic medicine was glibenclamide (5 mg/kg/day per oral for 14 days). When compared to the control group alloxan-induced diabetics had higher fasting blood glucose, cholesterol and Triglyceride levels. Euphorbia prostrate extract (at dosages of 250 and 500 mg/kg) had an anti-diabetic levels significantly. In comparison to the 250 mg/Kg dose of Euphorbia prostrate, the 500 mg/Kg dose yielded more significant (P< 0.05) outcomes. At the end of the effect, lowering fasting blood glucose research, the levels of serum cholesterol and and Triglycerides were also reduced [22].
extruded Amaranth (Amaranthus caudatus L.)
Hypercholesterolemic rabbits, obtained by a special diet, were divided in three groups, and each group was fed a different diet for 21 days. The diets were: extruded amaranth diet (EAD), diet with amaranth oil (AOD) and a control diet. Growth rates of rabbits were similar in all groups. After being fed the experimental diets, total cholesterol and LDL-C concentrations were lower in rabbits fed the EAD than in those fed the AOD or the control diet. Triglycerides and VLDL-C concentrations were approximately 50% lower in rabbits fed the EAD and the AOD than in rabbits fed the control diet. No significant differences were found among HDL-C concentrations of the three groups. These results demonstrate that the consumption of extruded amaranth reduces LDL and total cholesterol levels and may be another option to prevent coronary heart diseases.
Fargesin
Background and aims
Fargesin mainly functions in the improvement of lipid metabolism and the inhibition of inflammation, but the role of fargesin in atherogenesis and the molecular mechanisms have not been defined. We aimed to explore if and how fargesin affects Atherosclerosis by regulating lipid metabolism and inflammatory response.
Methods and results
ApoE−/− mice were fed a high-fat diet to form atherosclerotic plaques and then administrated with fargesin or saline via gavage. Oil Red O, HE and Masson staining were performed to assess atherosclerostic plaques in apoE−/− mice. [3H] labeled cholesterol was used to detect cholesterol efflux and reverse cholesterol transport (RCT) efficiency. Enzymatic methods were performed to analyze plasma lipid profile in apoE−/− mice. Immunohistochemistry was used to analyze macrophage infiltration. THP-1-derived macrophages were incubated with fargesin or not. Both Western blot and qRT-PCR were applied to detect target gene expression. Oil Red O staining was applied to examine lipid accumulation in THP-1-derived macrophages. ELISA and qRT-PCR were used to examine the levels of inflammatory mediotors. We found that fargesin reduced atherosclerotic lesions by elevating efficiency of RCT and decreasing inflammatory response via upregulation of ABCA1 and ABCG1 expression in apoE−/− mice. Further, fargesin reduced lipid accumulation in THP-1-derived macrophages. Besides, fargesin increased phosphorylation of CEBPα in Ser21 and then upregulated LXRα, ABCA1 and ABCG1 expression in THP-1-derived macrophages. In addition, fargesin could reduce ox-LDL-induced inflammatory response by inactivation of the TLR4/NF-κB pathway.
Conclusion
These results suggest that fargesin inhibits Atherosclerosis by promoting RCT process and reducing inflammatory response via CEBPαS21/LXRα and TLR4/NF-κB pathways, respectively.
Ficus microcarpa (L.) extract
Hypolipidaemic and antioxidant activities of Ficus microcarpa (L.) in hypercholesterolemic rats
Saponifiable and unsaponifiable fractions of Ficus microcarpa leaves hexane extract have been phytochemically studied and evaluated for its hypolipidaemic and antioxidant effects in hypercholesterolemic rats. The effect of the extract on the lipid profile was assessed by measuring the levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), Triglycerides , phospho and total lipids. lipid peroxides, glutathione and superoxide dismutase were measured as antioxidants. The work was extended to evaluate liver function indices as well as the histopathological picture of the liver after treatment. Treatment with leaves extract (500 mg kg⁻¹ body weight) 5 times/week for 9 weeks at the same time of cholesterol administration (30 mg/0.3 mL 0.7% tween/animal) recorded an improvement of lipid profile, antioxidants, liver function enzymes and the liver histopathological picture. The lipoidal matters of the unsaponifiable fraction of the hexane extract by GC/MS led to the identification of 22 compounds, while saponifiable fraction by (MS/MS) technique led to identification of 13 unsaturated and saturated fatty acid methyl ester derivatives. It can be concluded that the hexane extract of F. microcarpa L has been proved to have hypolipidaemic and antioxidant effects in hypercholesterolemic rats through its role in counteracting LDL oxidation, enhancement of HDL synthesis and inhibition of lipid peroxidation.
Ganoderma lucidum extract (Ganoderma lucidum Polysaccharide)
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
cholesterol–lowering properties of Ganoderma lucidum in vitro, ex vivo, and in hamsters and minipigs
Results
Organic fractions containing oxygenated lanosterol derivatives inhibited cholesterol synthesis in T9A4 hepatocytes. In hamsters, 5% Gl did not effect LDL; but decreased total cholesterol (TC) 9.8%, and HDL 11.2%. Gl (2.5 and 5%) had effects on several fecal neutral sterols and bile acids. Both Gl doses reduced hepatic microsomal ex-vivo HMG-CoA reductase activity. In minipigs, 2.5 Gl decreased TC, LDL– and HDL cholesterol 20, 27, and 18%, respectively (P < 0.05); increased fecal cholestanol and coprostanol; and decreased cholate.
Conclusions
Overall, Gl has potential to reduce LDL cholesterol in vivo through various mechanisms. Next steps are to: fully characterize bioactive components in lipid soluble/insoluble fractions; evaluate bioactivity of isolated fractions; and examine human cholesterol lowering properties. Innovative new cholesterol–lowering foods and medicines containing Gl are envisioned.
Garcinia daedalanthera
cholesterol–lowering effects of Extract from Garcinia daedalanthera in Hyperlipidemic rats
Background: A native plant from Indonesia, Garcinia daedalanthera has been scientifically proven have antidiabetic effects and antioxidant activity. We hypothesized that Garcinia daedalanthera can modulate the lipid profiles of hyperlipidemic rats. Objective: This study aimed to evaluate the antihyperlipidemic potential of Garcinia daedalanthera extract. Materials and Methods: Garcinia daedalanthera leaves extract (GDE) were orally administrated to high fat diet-induced rats for 15 days. After the end of experimental period (43 days) the lipid profiles were estimated along with histopathological liver examination of animals. Results: The results showed that Garcinia daedalanthera extract significantly reduced the level of serum total cholesterol, total Triglycerides and low-density lipoprotein as compared to control group with an increasing level of serum high-density lipoprotein. Furthermore, the extract has a favorable effect on histopathological study. Conclusion: This study proved antilipidemic property by lowering altered levels of lipid profile in male wistar rats and suggest lipid lowering effects of Garcinia daedalanthera extract which serves as a new potential natural product for preventing hyperlipidemia.
Garcinia gummi-gutta (Malabar tamarind)
In our society cholesterol related diseases are increasing day by day. The major reason for this is our eating habit or food habit. Eating foods containing trans fats, which are often found in fast food and commercially baked breads, cookies, and snack foods. It was observed that while peoples taking the fruits of Garcinia gummi-gutta in their food preparations have low cholesterol level. Some peoples are eating boiled fruits and drinking water in which the fruits peels are boiled in order to reduce the cholesterol level. This study was carried out to explore the phytochemical constituents of the solvent extracts of Garcinia gummi-gutta fruit and in vitro analysis of its cholesterol lowering effect. The cholesterol lowering effect was carried out in vitro using common fatty food materials like ghee, fats of pork and chicken, hen egg and cod liver oil. Each food materials were treated with extract and incubated for a number of days and each day the cholesterol level was estimated by Zak’s method. From the data, pork and chicken fat, egg yolk and ghee shows significant reduction in the cholesterol level. From the present study it can be concluded that the constituents present in the extracts may be responsible for the cholesterol lowering activity.
Garcinia Mangostana L. Rind extract
Hypercholesterolemia contributes to the incidence of coronary heart disease which is the leading cause of death in the world 1. diet modification and hypolipidemic drugs, including herba, one of which is Garcinia mangostana L. will effectively reduce total cholesterol 3.
A research a posttest control group design 20, type of research was a laboratory experimental research 15. The population was male white mice aged 3 – 4 weeks weighing 100-200 grams 12. Hypercholesterolemia in male white rats was with MDLT induction ( high – fat diet food ) 7. Data collection of total cholesterol levels measurement used enzymatic spectrophotometer method, data analysis used Variant Analysis statistical test ( ANOVA ) with significance level ? < 0.05 15.
The effect of Garcinia mangostana L. rind extract on total cholesterol reduction in white rats was grouped into a negative control group, positive control group and four dose treatment groups 4. Identification of hypercholesterolaemia in white rats was examined for total cholesterol on day 8 16. The effect of Garcinia Mangostana L rind extract on reducing total cholesterol was examined on day 22 3,16 .
The results of the examination showed the administration of Garcinia mangostana L. rind extract in all dosage groups effectively reduced total cholesterol levels with a significance level of p < 0.05.
Gardenia jasminoides J. Ellis extract GJ-4
Background
GJ-4 is extracted from Gardenia jasminoides J. Ellis (Fructus Gardenia) with crocin composition and has been demonstrated to improve memory deficits in several dementia models in our previous studies.
Objective
This study aimed to evaluate the effects of GJ-4 on hyperlipidemic vascular dementia (VD) and explore the underlying mechanisms.
Design
In the current study, we employed a chronic hyperlipidemic VD rat model by permanent bilateral common carotid arteries occlusion (2-VO) based on high-fat diet (HFD), which is an ideal model to mimic the clinical pathogenesis of human VD.
Results
Our results showed that GJ-4 could significantly reduce serum lipids level and improve cerebral blood flow in hyperlipidemic VD rats. Additionally, treatment with GJ-4 remarkedly ameliorated memory impairment and alleviated neuronal injury. Mechanistic investigation revealed that the neuroprotective effects of GJ-4 might be attributed to the inhibition of microglia-mediated neuro-inflammation via regulating the M1/M2 polarization. Our data further illustrated that GJ-4 could regulate the phenotype of microglia through activating the peroxisome proliferator-activated receptor-γ (PPAR-γ) and subsequently inhibited nuclear factor-κB (NF-κB) nuclear translocation and increased CCAAT/enhancer-binding protein β (C/EBPβ) expression.
Conclusion
Our results implied that GJ-4 might be a promising drug to improve VD through the regulation of microglial M1/M2 polarization and the subsequent inhibition of neuro-inflammation.
Genistein
diets containing the soya-derived phytoestrogens, genistein and daidzein, decrease plasma cholesterol in humans and experimental animals. The mechanisms responsible for the hypocholesterolaemic effects of these isoflavones are unknown. The present study was conducted to determine if genistein and daidzein regulate hepatocyte cholesterol metabolism and apolipoprotein (apo) B secretion in cultured human hepatoma (HepG2) cells. ApoB secretion was decreased dose-dependently by up to 63% and 71% by genistein and daidzein (100 microM; P<0.0001) respectively. In contrast, no effect on apoAI secretion was observed. Cellular cholesterol synthesis was inhibited 41% by genistein (100 microM; P<0.005) and 18% by daidzein (100 microM; P<0.05), which was associated with significant increases in 3-hydroxy-3-methylglutaryl-CoA reductase mRNA. Cellular cholesterol esterification was decreased 56% by genistein (100 microM; P<0.04) and 29% by daidzein (100 microM; P<0.04); however, mRNA levels for acyl-CoA:cholesterol acyltransferase (ACAT) 1 and ACAT2 were unaffected. At 100 microM, both isoflavones equally inhibited the activities of both forms of ACAT in cells transfected with either ACAT1 or ACAT2. Genistein (100 microM) and daidzein (100 microM) significantly decreased the activity of microsomal triacylglycerol transfer protein (MTP) by 30% and 24% respectively, and significantly decreased MTP mRNA levels by 35% and 55%. Both isoflavones increased low-density lipoprotein (LDL)-receptor mRNA levels by 3- to 6-fold (100 microM; P<0.03) and significantly increased the binding, uptake and degradation of (125)I-labelled LDL, suggesting that enhanced reuptake of newly secreted apoB-containing lipoproteins contributed to the net decrease in apoB secretion. These results indicate that genistein and daidzein inhibit hepatocyte apoB secretion through several mechanisms, including inhibition of cholesterol synthesis and esterification, inhibition of MTP activity and expression and increased expression of the LDL-receptor.
Ginger
BACKGROUND
Although the antioxidant properties of ginger have been revealed, there is little available information on the effectiveness of ginger on inflammatory disorders such as Atherosclerosis. This study was carried out to examine the effect of ginger on improving the complication of Atherosclerosis.
METHODS
This study was a double-blind, placebo-controlled, randomized clinical trial conducted on patients with Atherosclerosis. Participants in the ginger and control groups received 1600 mg of powdered ginger or placebo (wheat flour) in capsules daily for 8 weeks. Weight, body mass index (BMI), fasting blood sugar (FBS), cholesterol, Triglyceride (TG), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), high-density lipoprotein (HDL), lipoprotein (a) [Lp(a)], high-sensitivity C-reactive protein (hs-CRP), and total anti-oxidant capacity (TAC) were assessed before and after the intervention.
RESULTS
Ginger consumption in the intervention group significantly reduced serum Lp(a) level (27.25 ± 1.30 ng/ml vs. 23.57 ± 0.97 ng/ml) (P = 0.040) and also the level of hs-CRP in the intervention group was 1.90 ± 0.33 µg/ml and 1.24 ± 0.15 µg/ml (P = 0.010) before and after intervention, respectively, but the levels of Lp(a) and hs-CRP were not decreased significantly in the placebo group. The level of TAC in the ginger group was 0.71 ± 0.05 mM and after the trial was 0.57 ± 0.04 mM (P = 0.050); no significant differences were seen in TAC when ginger was administered at 1600 mg/daily for 60 days. Also the level of Lp(a) and hs-CRP but not TAC reduced significantly in ginger group compared to placebo group after intervention.
CONCLUSION
This study showed that ginger had anti-Atherosclerosis and anti-glycemic properties associated through a significant decreased Lp(a) and FBS in patients with Atherosclerosis supplemented with ginger.
Diabetes mellitus is the most common endocrine disorder, causes many complications such as micro- and macro-vascular diseases. Anti-diabetic, hypolipidemic and anti-oxidative properties of ginger have been noticed in several researches. The present study was conducted to investigate the effects of ginger on fasting blood sugar, Hemoglobin A1c, apolipoprotein B, apolipoprotein A-I, and malondialdehyde in type 2 diabetic patients. In a randomized, double-blind, placebo-controlled, clinical trial, a total of 41 type 2 diabetic patients randomly were assigned to ginger or placebo groups (22 in ginger group and 19 in control group), received 2 g/day of ginger powder supplement or lactose as placebo for 12 weeks. The serum concentrations of fasting blood sugar, Hemoglobin A1c, apolipoprotein B, apolipoprotein A-I and malondialdehyde were analyzed before and after the intervention. Ginger supplementation significantly reduced the levels of fasting blood sugar, hemoglobin A1c, apolipoprotein B, apolipoprotein B/apolipoprotein A-I and malondialdehyde in ginger group in comparison to baseline, as well as control group, while it increased the level of apolipoprotein A-I (p<0.05). It seems that oral administration of ginger powder supplement can improves fasting blood sugar, hemoglobin A1c, apolipoprotein B, apolipoprotein A-I, apolipoprotein B/apolipoprotein A-I and malondialdehyde in type 2 diabetic patients. So it may have a role in alleviating the risk of some chronic complications of diabetes.
BACKGROUND
Although the antioxidant properties of ginger have been revealed, there is little available information on the effectiveness of ginger on inflammatory disorders such as Atherosclerosis. This study was carried out to examine the effect of ginger on improving the complication of Atherosclerosis.
METHODS
This study was a double-blind, placebo-controlled, randomized clinical trial conducted on patients with Atherosclerosis. Participants in the ginger and control groups received 1600 mg of powdered ginger or placebo (wheat flour) in capsules daily for 8 weeks. Weight, body mass index (BMI), fasting blood sugar (FBS), cholesterol, Triglyceride (TG), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), high-density lipoprotein (HDL), lipoprotein (a) [Lp(a)], high-sensitivity C-reactive protein (hs-CRP), and total anti-oxidant capacity (TAC) were assessed before and after the intervention.
RESULTS
Ginger consumption in the intervention group significantly reduced serum Lp(a) level (27.25 ± 1.30 ng/ml vs. 23.57 ± 0.97 ng/ml) (P = 0.040) and also the level of hs-CRP in the intervention group was 1.90 ± 0.33 µg/ml and 1.24 ± 0.15 µg/ml (P = 0.010) before and after intervention, respectively, but the levels of Lp(a) and hs-CRP were not decreased significantly in the placebo group. The level of TAC in the ginger group was 0.71 ± 0.05 mM and after the trial was 0.57 ± 0.04 mM (P = 0.050); no significant differences were seen in TAC when ginger was administered at 1600 mg/daily for 60 days. Also the level of Lp(a) and hs-CRP but not TAC reduced significantly in ginger group compared to placebo group after intervention.
CONCLUSION
This study showed that ginger had anti-Atherosclerosis and anti-glycemic properties associated through a significant decreased Lp(a) and FBS in patients with Atherosclerosis supplemented with ginger.
Ginkgo biloba L leaves extract
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
Globularia alypum L
The beneficial health effects of plant polyphenols were frequently attributed to their powerful hypolipemiant and antioxidant effects. We hypothesized that administration of Globularia alypum (Ga) lyophilized methanolic extract would ameliorate glycemia, lipid parameters, reverse cholesterol transport, as well as lipoproteins peroxidation, in diabetic rats. Diabetes was induced in male Wistar rats, weighing 250±10 g by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg body weight). Diabetic rats (n=20) were divided into two groups, and fed during 4 weeks diets containing 20% casein (D) or a casein diet supplemented with a Ga extract (1 g/kg BW) (DGa). At d28, in DGa vs D group, glycemia was lowered by 81%, while insulinemia was markedly increased by 72%. Liver and serum lipid values were significantly decreased (P< 0.05). Lecithin:cholesterol acyltransferase (LCAT) activity was improved (+48%). Indeed, HDL3-PL (enzyme substrate) and HDL3-UC (acyl group acceptor) concentrations were respectively reduced by 50 and 52%, whereas HDL2-CE values (product of LCAT reaction) were increased (+35%). Atherogenicity ratios VLDL–LDL-C/HDL-C, TC/HDL-C and apoB/apoA were lowered respectively by 50%, 25% and 71%. Moreover, VLDL–LDL and HDL3peroxidation was decreased by 47 and 75%, respectively.In STZ-induced diabetic rat, Globularia alypum extract reduces glycemia, liver and serum lipids values, VLDL–LDL and HDL3 lipid peroxidation and ameliorates the reverse cholesterol transport. Therefore, Ga extract may be useful for preventing diabetes and lipid disorders.
Glycyrrhiza glabra L.
Atheroprotective effects of Glycyrrhiza glabra L.
Cardiovascular diseases associated with Atherosclerosis are the major cause of death in developed countries. Early prevention and treatment of Atherosclerosis are considered to be an important aspect of the therapy of cardiovascular disease. Preparations based on natural products affect the main pathogenetic steps of atherogenesis, and so represent a perspective for the long-term prevention of Atherosclerosis development. Numerous experimental and clinical studies have demonstrated the multiple beneficial effects of licorice and its bioactive compounds—anti-inflammatory, anti-cytokine, antioxidant, anti-atherogenic, and anti-platelet action—which allow us to consider licorice as a promising atheroprotective agent. In this review, we summarized the current knowledge on the licorice Anti-atherosclerotic mechanisms of action based on the results of experimental studies, including the results of the in vitro study demonstrating licorice effect on the ability of blood serum to reduce intracellular cholesterol accumulation in cultured macrophages, and presented the results of clinical studies confirming the ameliorating activity of licorice in regard to traditional cardiovascular risk factors as well as the direct Anti-atherosclerotic effect of licorice.
Green tea extract Tea polyphenol
cholesterol–lowering effect of a Theaflavin-Enriched Green Tea Extract
Background Tea consumption has been associated with decreased cardiovascular risk, but potential mechanisms of benefit are ill-defined. While epidemiologic studies suggest that drinking multiple cups of tea per day lowers low-density lipoprotein cholesterol (LDL-C), previous trials of tea drinking and administration of green tea extract have failed to show any impact on lipids and lipoproteins in humans. Our objective was to study the impact of a theaflavin-enriched green tea extract on the lipids and lipoproteins of subjects with mild to moderate hypercholesterolemia.
Methods Double-blind, randomized, placebo-controlled, parallel-group trial set in outpatient clinics in 6 urban hospitals in China. A total of 240 men and women 18 years or older on a low-fat diet with mild to moderate hypercholesterolemia were randomly assigned to receive a daily capsule containing theaflavin-enriched green tea extract (375 mg) or placebo for 12 weeks. Main outcome measures were mean percentage changes in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and Triglyceride levels compared with baseline.
Results After 12 weeks, the mean ± SEM changes from baseline in total cholesterol, LDL-C, HDL-C, and Triglyceride levels were −11.3% ± 0.9% (P = .01), −16.4% ± 1.1% (P = .01), 2.3% ± 2.1% (P = .27), and 2.6% ± 3.5% (P = .47), respectively, in the tea extract group. The mean levels of total cholesterol, LDL-C, HDL-C, and Triglycerides did not change significantly in the placebo group. No significant adverse events were observed.
Conclusion The theaflavin-enriched green tea extract we studied is an effective adjunct to a low-saturated-fat diet to reduce LDL-C in hypercholesterolemic adults and is well tolerated.
Gymnema sylvestre R. Br. leaf extract
Gymnema sylvestre R. Br. leaf extract (25–100 mg/kg) when orally administered to experimentally induced hyperlipidaemic rats for 2 weeks, reduced the elevated serum Triglyceride (TG), total cholesterol (TC), very low-density lipoprotein (VLDL)-and low-density lipoprotein (LDL)-cholesterol in a dose-dependent manner. The decreased serum high-density lipoprotein (HDL)-cholesterol and antiatherogenic index (AAI) in hyperlipidaemia were also reversed towards normalization. The ability of this extract (at 100 mg/kg) to lower Triglyceride and TC in serum and its Antiatherosclerotic potential were almost similar to that of a standard lipid lowering agent—clofibrate.
Gynostemma pentaphyllum (Thunb.) Makino extract Gypenosides
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
This study characterized chemical structures of tetraploid jiaogulan saponins, and investigated their cholesterol–lowering effects and mechanisms in hamsters fed a high-fat diet (HFD). Nine saponins, including five reported for the first time, were obtained from total jiaogulan saponins (TJS) and elucidated for their chemical structures according to 2D NMR and HR-MS data. Administration of TJS effectively decreased plasma total cholesterol by 17.4% and 32.6%, triacylglycerols by 22.8% and 47.7% and LDL-C by 22.0% and 40.2%, respectively. Moreover, supplementation with TJS significantly increased faecal excretion of total cholesterol and bile acids by 43.8% and 64.4%, respectively. TJS significantly up-regulated intestinal mRNA levels of ABCG5/8, LXRα, hepatic mRNA CYP7A1 and ABCG5 in hamsters on HFD. In addition, TJS decreased cholesterol micelle solubility and suppressed cholesterol uptake in cultured Caco-2 cells. Taking together, TJS may reduce plasma cholesterol by increasing faecal cholesterol excretion and through modulation of genes involved in cholesterol absorption and metabolism.
Hawthorn (Crataegus oxyacantha)
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
Herniaria hirsuta L.
Etnopharmacological relevance
Infusions of Herniaria hirsuta L., Herniaria glabra L. and Herniaria fontanesii J.Gay are well known in Moroccon folk medicine for the treatment of biliary dyskinesia, (uro)lithiasis or as a diuretic. Herniariae Herba which can contain H. glabra and H. hirsuta is known in Europe as an urological drug.
Aim of the study
To investigate the efficacy of a standardized infusion of Herniaria hirsuta against choleltihiasis, and evaluation of its genotoxicity.
Methods and materials
An analytical HPLC-UV method to quantify flavonoids and saponins present in the extract of H. hirsuta was developed and validated. An in vivo experiment to evaluate the cholesterol lowering effect of a infusion of H. hirsuta in the gall bladder of dogs was carried out. Dogs were divided into 3 groups i.e. control dogs (CG), dogs treated with ursodeoxycholic acid (UDCA) (2×7.35 mg/kg body weight/day) and dogs treated with the standardized infusion (HG) (2×48.5 mg/kg body weight/day). Dogs were fed a fatty diet during 120 days after which a diet without additional fat was introduced till day 180. Treatment started 30 days after introduction of the fatty diet and lasted till the end of the experiment. A bile and blood sample of each dog was collected every 30 days, after which the concentration of cholesterol was determined. An Ames test was performed according to the OECD-guidelines.
Results
The validated HPLC-UV method showed a linear calibration model and an acceptable precision for the total flavonoid content (total content 4.51%) as well as the total saponin content (12.74%). The in vivo experiments already showed a minor difference for bile cholesterol between CG and HG after 30 days of treatment with the infusion, and the difference was more pronounced after 90 days of treatment. Even 30 days after discontinuation of the cholesterol-rich diet a significant difference remained between CG and HG. There was no statistically significant difference in blood cholesterol. The Ames test showed that the infusion of H. hirsuta could be considered as being free from genotoxic risks.
Conclusion
A method for the standardization of a infusion of Herniaria hirsuta was developed and validated. Prolonged use of this standardized H. hirsuta extract resulted in a cholesterol–lowering effect in the bile of dogs. Since this pharmacological effect prevents the formation of gallstones and can contribute to solving existing gallstones, a standardized infusion of H. hirsuta may have a positive effect in the treatment of gallstones in human patients.
cholesterol lowering effect in the gall bladder of dogs by Herniaria hirsuta
Infusions of Herniaria hirsuta L., H. glabra L. and H. fontanesii J. Gay (Caryophyllaceae) are well known in Moroccon folk medicine for the treatment of biliary dyskinesia, (uro)lithiasis or as a diuretic, and in Europe as an urological drug [1, 2]. An in vivo experiment to evaluate the cholesterol lowering effect of a decoction of H. hirsuta in the gall bladder of dogs was carried out. Three groups of dogs i.e. control dogs (CG), dogs treated with ursodeoxycholic acid (UDCA) (2 × 7.35 mg/kg body weight/day) and dogs treated with the standardized decoction (HG) (2 × 48.5 mg/kg body weight/day) were fed a fatty diet during 120 days after which a diet without additional fat was introduced till day 180 [3]. Treatment started 30 days after the start of the fatty diet and lasted until the end of the experiment. A bile and blood sample of each dog was collected every 30 days, after which the cholesterol level was determined. The in vivo experiments already showed a minor difference for bile cholesterol between CG and HG after 30 days of treatment with the decoction, and a more pronounced difference after 90 days of treatment. Even 30 days after discontinuation of the cholesterol-rich diet a significant difference remained between CG and HG. There was no significant difference in blood cholesterol between the groups. Prolonged use of this standardized H. hirsuta extract resulted in a cholesterol–lowering effect in the bile of dogs. Since this pharmacological effect prevents the formation of gallstones and can contribute to solving existing gallstones, a standardized decoction of H. hirsuta may have a positive effect in the treatment of gallstones in human patients.
Hesperetin
Evaluation of hesperetin 7-O-lauryl ether as lipid–lowering agent in high–cholesterol-fed rats
The lipid–lowering efficacy of hesperetin was revealed in preliminary studies on experimental animals. As such, the current study compared the effect of hesperetin 7-O-lauryl ether, with that of hesperetin and lovastatin on the lipid profile and cholesterol-regulating mechanism in high–cholesterol-fed rats. Male rats were fed a high–cholesterol diet (1%, wt/wt) or high–cholesterol diet supplemented with lovastatin (1, 0.02%, wt/wt), hesperetin (2, 0.02%, wt/wt), or hesperetin 7-O-lauryl ether (3, 0.031%, wt/wt) for six weeks. The supplemental amount of 3 was 0.066 mmol/100 g diet as an equivalent to the supplemental amount of 2. The plasma total cholesterol and Triglyceride levels were significantly lowered by the 2 and 3 supplements compared with the control or 1-supplemented group. The hepatic HMG-CoA reductase activities were also significantly lower in all the supplemented groups compared with the control group, and the hepatic ACAT activity was significantly lower in the 2- and 3-supplemented groups. The supplementation of 3 resulted in a higher excretion of total neutral sterol and total fecal sterol compared with the control or 1-supplemented group. Accordingly, overall, compound 3, exhibited a more potent plasma lipid–lowering effect than compound 1 based on inhibiting cholesterol biosynthesis and esterification, while also increasing the fecal sterol excretion.
This study examined the lipid–lowering effect of hesperetin 7-O-lauryl ether in high–cholesterol-fed rats. The supplementation of this compound was effective in altering lipid metabolism and lowering plasma cholesterol level.
Hordeum vulgare L.extract
Pharmacological and therapeutic potential of Hordeum vulgare
Introduction
One of the first grains to be cultivated was Hordeum vulgare, which was grown in the Fertile Crescent, a region of Western Asia near the Nile River in North-East Africa and many other regions like russia, china. It has a lot of soluble fiber, especially beta-glucans, which help control blood sugar and lower cholesterol. It is a grain of the Poaceae family and is one of the earliest plants with the greatest significance in Chinese medicine. Traditional Chinese Medicine (TCM) practitioners have used it for treating hyperprolactinemia, obesity etc. Hordeum vulgare is used in the preparation called “Smilax” which is used for weight loss in china. Hordeum vulgare has been used as a poultice to treat burns and wounds because it is thought to be anti-inflammatory, anti-fatigue, diuretic, antioxidant, aphrodisiac, antiviral, antiprotozoal, astringent, demulcent, digestive, expectorant, febrifuge, antimutagenic, and emollient.
Methodology
The online databases including scopus, web of science, Google Scholar, and PubMed, were searched using different keywords: Hordeum vulgare, antinflammatory activity, traditional uses, and antimutagenic activity, Chinese herb, hordeum vulgare. The purpose of this review was therefore to summarize the previously reported phytopharmacological status of the chosen plant species.
Results
The results of our analysis revealed that Hordeum vulgare Linn. contains dietary fiber, vitamins, minerals, and phytochemicals including, flavonoids, saponins, etc. In addition, previous research has demonstrated that plant extracts and isolated principles of Hordeum vulgare also possess significant pharmacological activity including antiviral, anti-inflammatory, febrifuge, anti-mutagenic and others.
Discussion
Hordeum vulgare has a good potential for generating therapeutics for the treatment of inflammation, obesity, cancer and also worked as dietary supplements for minerals and vitamin deficiency, according to the below-mentioned human and animal studies. Also, clinical research has shown that Hordeum vulgare is a safe and efficient herb for human intake and thus should be included in dietary intakes and as active constituents in pharmaceutical formulations.
Conclusion
This review will talk about how the plant chemicals in Hordeum vulgare can be used to treat and prevent diseases. This review also helps the researchers to work on the Hordeum vulgare with the focus on bioactivity and toxicity.
Ipomoea batatas (L.) leaves
Objectives
Cardiovascular diseases, especially Atherosclerosis, are the leading cause of human mortality in Indonesia. Ipomoea batatas (L.) is a food plant used in Indonesian traditional medicine to treat cardiovascular diseases and related conditions. We assessed the Anti-atherosclerotic activity of the aqueous extract of I. batatas leaves in a rat model of high-fat diet-induced Atherosclerosis and its mechanism.
Methods
The presence of amino acid content in the I. batatas L. purple variant was determined by liquid chromatography high-resolution mass spectrometry (LC-HRMS). Thirty male Wistar rats were divided into five groups (n=6/group), i.e., standard diet group (SD), high-fat diet group (HF), and HF plus I. batatas L. extracts orally (625; 1,250; or 2,500 mg/kg) groups. The numbers of macrophages and aortic wall thickness were analyzed histologically. Immunohistochemical analyses were performed to assess foam cells-oxidized low-density lipoprotein (oxLDL), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF) expression in the aorta.
Results
LC-HRMS analysis showed nine amino acid content were identified from I. batatas L. In vivo study revealed that oral administration of I. batatas L. leaf extract alleviated foam cells-oxLDL formation and aortic wall thickness caused by high-fat diet Atherosclerosis rats. Further, I. batatas L. leaf extract promoted the number of macrophages and modulated VEGF and eNOS expression in the aorta.
Conclusions
I. batatas L. leaf extract shows a positive anti-Atherosclerosis effect. Furthermore, the mechanism may promote the macrophages, eNOS, VEGF expressions, and inhibition of foam cells-oxLDL formation and aortic wall thickness with the best dosage at 2,500 mg/kg. This could represent a novel approach to prevent cardiovascular diseases.
Jackbean (Canavalia ensiformis) seed protein
cholesterol lowering effect of jackbean (Canavalia ensiformis) seed protein.
1. Feeding jackbean (Canavalia ensiformis) protein to hypercholesterolemic rats considerably lowered cholesterol levels in the experimental animals than when the animals were fed casein (control) diets. 2. The cholesterol levels in various components of test animals fed the Canavalia diet ranged from 53.3 +/- 1.7 to 74.8 +/- 3.4 mg/g (plasma); from 11.1 +/- 7.4 to 23.3 +/- 5.4 mg/g (liver); from 7.1 +/- 0.7 to 9.3 +/- 1.7 mg/g (kidney) and 1.9 +/- 0.3 to 3.2 +/- 0.6 mg/g (heart). 3. Total lipid levels estimated for the animals on the test diets ranged from 80.0 +/- 2.4 to 130.1 +/- 9.1 mg/g (plasma); from 19.1 +/- 3.4 to 28.5 +/- 1.1 mg/g (liver); from 17.0 +/- 4.1 to 23.0 +/- 6.0 mg/g (kidney) and from 13.2 +/- 4.0 to 18.0 +/- 2.5 mg/g (heart). 4. Total protein levels in plasma of experimental animals were not significantly different (P less than 0.05) after feeding the control or test diets.
Kenaf (Hibiscus cannabinus L., Malvaceae)
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL–cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an Inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Kepuh (Sterculia foetida) Leaves
Cardiovascular disease causes the highest mortality rate in the world. Atherosclerotic plaque is the most common etiology of cardiovascular disease. high levels of cholesterol in circulation is the pathophysiology of Atherosclerosis formation. Atherosclerosis risk can be lowered to 20-40% with statins. Statins are effective in lowering total and LDL cholesterol, but these drugs have been reported to cause side effects. Therefore, it needed an alternative medicine to prevent the process of Atherosclerosis using kepuh leaves (Sterculia foetida). Flavonoids contained in Kepuh leaves improve lipid profiles. The aims of this study is to prove the effectiveness of Sterculia foetida in lowering cholesterol, Triglyceride and reduce the amount of foam cells on high-fat-diet induced rats. The research design is quasi-experimental with post test only design. Animals are grouped into normal group, negative control group and three treatment groups that were given kepuh leaves extract at the dose of 200 mg/kgBB, 400 mg/kgBB, and 800 mg/ kgBB. Rats were given high-fat diet of initial intravenous adrenaline injection 0.006 mg/200 gBB and duck egg yolks 5 g/kgBB for 21 days. cholesterol and Triglycerides were measured by enzymatic methods and aortic tissue stained with HE. ESf reduce cholesterol significantly and reduce the amount of foam cells on aorta.
L‐carnitine
l-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes
Background
Patients with type 2 diabetes are under high oxidative stress, and levels of hyperglycemia correlate strongly with levels of LDL oxidation. Carnitine favorably modulates oxidative stress.
Objective
This objective of this study was to evaluate the efficacy of l-carnitine on the reduction of oxidized LDL cholesterol in patients with type 2 diabetes.
Design
Eighty-one patients with diabetes were randomly assigned to 1 of 2 treatment groups for 3 mo. The 2 groups received either 2 g l-carnitine once daily (n = 41) or placebo (n = 40). The following variables were assessed at baseline, after washout, and at 1, 2, and 3 mo of treatment: body mass index, fasting plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, HDL cholesterol, Triglycerides , apolipoprotein A1, apolipoprotein B-100, oxidized LDL cholesterol, thiobarbituric acid–reactive substances, and conjugated dienes.
Results
At the end of the study period, the l-carnitine-treated patients showed significant improvements compared with the placebo group in the following markers: oxidized LDL levels decreased by 15.1 compared with 3.0 U/L (P < 0.001); LDL cholesterol decreased by 0.45 compared with 0.16 mmol/L (P < 0.05); Triglycerides decreased by 1.02 compared with 0.09 mmol/L (P < 0.001); apolipoprotein A1 concentrations decreased by 0.12 compared with 0.03 mg/dL (P < 0.05); apolipoprotein B-100 concentrations decreased by 0.13 compared with 0.04 mg/dL (P < 0.05); thiobarbituric acid–reactive substance concentrations decreased by 1.92 compared with 0.05 (P < 0.001), and conjugated diene concentrations decreased by 0.72 compared with 0.11 in the placebo group (P < 0.001).
Conclusion
Our study indicates that oral administration of l-carnitine reduces oxidized LDL cholesterol levels in patients with type 2 diabetes.
effects of L-carnitine supplementation on lipid profiles in patients with coronary artery disease
Background
L-carnitine (LC) plays an important physiologic role in lipid metabolism. To date, no clinical study has been performed to examine the effect of LC supplementation on the lipid status of coronary artery disease (CAD) patients. The aim of this study was to investigate the lipid lowering effects of LC supplementation (1000 mg/d) in CAD patients.
Methods
CAD patients were identified by cardiac catheterization as having at least 50 % stenosis of one major coronary artery. Forty-seven subjects were recruited and randomly assigned to the placebo (n = 24) and to the LC (n = 23) groups. The intervention was administered for 12 weeks. The levels of LC, lipid profiles, and antioxidant enzyme activity (superoxide dismutase, SOD) were measured.
Results
The subjects in the LC group had significantly higher SOD activity (20.7 ± 4.2 versus 13.1 ± 2.9 U/mg of protein, P < 0.01), high density lipoprotein-cholesterol (1.34 ± 0.42 vs. 1.16 ± 0.24 mmol/L, HDL-C, P = 0.03), and apolipoprotein-A1 (Apo-A1, 1.24 ± 0.18 vs. 1.12 ± 0.13 g/L, P = 0.02) than those in the placebo group at week 12. Triglyceride (TG) level was slightly significantly reduced (1.40 ± 0.74 vs. 1.35 ± 0.62 mmol/L, P = 0.06) and the level of LC was negatively correlated with Triglyceride and apolipoprotein-B (Apo-B), and positively correlated with HDL-C and Apo-A1 after LC supplementation. Additionally, SOD activity was significantly negatively correlated with lipid profiles (total cholesterol, TG, and Apo-B) after supplementation.
Conclusion
LC supplementation at a dose of 1000 mg/d showed significantly increased in HDL-C and Apo-A1 levels and a slight decrease in Triglyceride levels but no other changes in other lipids in CAD patients, and this lipid–lowering effect may be related to its antioxidant ability. Further studies should be conducted to define an optimal dose of LC for lipid–lowering in patients with CAD.
dietary natural products as emerging lipoprotein(a)-lowering agents
Elevated plasma lipoprotein(a) (Lp(a)) levels are associated with an increased risk of cardiovascular disease (CVD). Hitherto, niacin has been the drug of choice to reduce elevated Lp(a) levels in hyperlipidemic patients but its efficacy in reducing CVD outcomes has been seriously questioned by recent clinical trials. Additional drugs may reduce to some extent plasma Lp(a) levels but the lack of a specific therapeutic indication for Lp(a)‐lowering limits profoundly reduce their use. An attractive therapeutic option is natural products. In several preclinical and clinical studies as well as meta‐analyses, natural products, including l‐carnitine, coenzyme Q 10, and xuezhikang were shown to significantly decrease Lp(a) levels in patients with Lp(a) hyperlipoproteinemia. Other natural products, such as pectin, Ginkgo biloba, flaxseed, red wine, resveratrol and curcuminoids can also reduce elevated Lp(a) concentrations but to a lesser degree. In conclusion, aforementioned natural products may represent promising therapeutic agents for Lp(a) lowering.
Lablab purpureus (Linn.) Sweet extract
Lablab purpureus (L) bean is an undervalued or underutilized orphan crop in many tropical countries, where different forms of malnutrition are associated with stunting growth and cognitive deficiencies. We previously reported that L. purpureus contains ω-3 α-linolenic acid (ALA, C18:3, ω-3), which can act as the precursor of ω-3 docosahexaenoic acid (DHA, C22:6, ω-3). Inadequate level of DHA impairs growth, development, and cognitive performance. Therefore, we evaluated if supplementation of L. purpureus seed flour (LPS) affects the nutritional status, in terms of body weight gain, plasma proteins, and DHA levels of malnourished model rats. Three groups of rats, namely, controls, malnourished alone (MN), and 15% LPS-supplemented malnourished (MN + LPS) rats were fed with LPS for 12 weeks. Afterward, body weight, liver weight, brain weight, plasma proteins, micronutrients, lipid profile, and fatty acid profile of plasma, liver, and brains were determined by standard methods. The levels of liver lipid peroxide (LPO) and proinflammatory TNFα were also measured. The body weight, liver weight, serum total proteins and micronutrients (iron/potassium), and the levels of docosahexaenoic acid significantly increased in the plasma, liver, and brain of MN + LPS rats. Moreover, LPO and TNFα levels reduced significantly in MN + LPS rats. in vitro analysis revealed a significant free radical scavenging and antioxidative potential of L. purpureus seed extract. Thus, L. purpureus not only replenishes protein-energy malnutrition, but also increases the levels of DHA, an indispensable polyunsaturated fatty acid for brain cognition. Finally, our results suggest that L. purpureus might benefit human malnutrition and related cognitive deficits.
Dolichos lablab Protects Against Nonalcoholic Fatty Liver Disease in Mice Fed high-Fat diets
Hyacinth bean, Dolichos lablab or Lablab purpureus, has been used for centuries in India and China as an edible pod and animal forage, as well as to treat diarrhea and other gastrointestinal disease in traditional Korean medicine. Recently, we have demonstrated that D. lablab extract (DLL-Ex) prevented free fatty acid-induced lipid accumulation in an in vitro cellular nonalcoholic fatty liver disease (NAFLD) model. In this study, we, thus, aimed at clarifying the hepatoprotective effects of DLL-Ex in a high-fat diet-induced in vivo animal NAFLD model, as well as at elucidating underlying mechanisms of identified effects. Sixty, 6-week-old, male C57BL/6J mice were randomly divided into six groups: a control group fed a low-fat diet, four high-fat diet (HFD) groups, three receiving daily oral supplementation of DLL-Ex (25, 50, and 100 mg/kg/day), and one HFD group receiving daily oral supplementation of MILK (100 mg/kg/day). effects of DLL-Ex supplementation were evaluated by histopathological and histochemical assessments. DLL-Ex supplementation inhibited HFD-induced increases in body weight and body fat mass and ameliorated increases in body weight, manifested as decreased liver function tests, lower serum Triglycerides and cholesterol levels, and increased serum adiponectin levels. The expression of hepatic genes involved in lipid droplet accumulation and in fatty acid uptake was also decreased. We provide evidence of a protective effect of DLL-Ex against HFD-induced fatty liver disease in an animal model.
Leonurine Herba Leonuri (Leonurus artemisia)
Background/aims: Previous studies have demonstrated that leonurine, a unique alkaloid compound of Herba leonuri, can exert anti-oxidative and anti-inflammatory effects on the development of Atherosclerosis (AS). This study was designed to investigate the effects of leonurine on cholesterol efflux from THP-1 macrophage-derived foam cells and development of atherosclerotic lesions in apoE-/- mice, and further determine the potential mechanisms.
Methods: Human THP-1 cells were fully differentiated into foam cells by the pre-treatment with phorbol-12-myristate-13-acetate (PMA) and oxidized density lipoproteins (ox-LDL). After cells were incubated with various concentrations of leonurine, Oil Red O staining and high-performance liquid chromatography (HPLC) assays were utilized to detect cellular lipid accumulation and cholesterol content, respectively. Cellular cholesterol efflux was determined by liquid scintillation counting. The mRNA and protein levels of ATP-binding cassette transporter A1/G1 (ABCA1/G1), peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor α (LXRα) in foam cells were assessed using real-time quantitative PCR (RT-qPCR) and western blot analyses, respectively. Plasma Triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) levels in apoE-/- mice were evaluated using enzymatic methods. The atherosclerotic lesion sizes and collagen contents in aortic roots were determined by Oil Red O and Masson’s trichrome staining, respectively.
Results: Oil Red O staining and liquid scintillation counting assays showed that leonurine significantly inhibited lipid accumulation and promoted 3H-cholesterol efflux in human THP-1 macrophage-derived foam cells in a concentration-dependent manner. Besides, both the mRNA and protein levels of ABCA1/G1, PPARγ and LXRα were enhanced by leonurine, which were attenuated by LXRα siRNA or PPARγ siRNA transfection. Finally, leonurine improved plasma lipid profile, decreased atherosclerotic lesion sizes, increased collagen contents and amplified PPARγ, LXRα and ABCA1/G1 expressions in aortic roots of apoE-/- mice.
Conclusions: Leonurine can promote cholesterol efflux and alleviate cellular lipid accumulation by magnifying the expression of ABCA1/G1 in a PPARγ/LXRα signaling pathway-dependent manner in human THP-1 macrophage-derived foam cells and abate atherogenesis in apoE-/- mice, which may offer a promising therapeutic intervention of leonurine in protecting against AS.
Leonurus japonicus Houtt extract
Background: Artemisia princeps Pamp (APP), Leonurus japonicas Houtt (LJH), and Gardenia jasminoides Ellis fruit (GJE) have been traditionally used in East Asia to treat women’s diseases related to reproductive system. They may attenuate the deterioration of energy, lipid, glucose and bone metabolism by estrogen deficiency. The present study explored the combination of APP, LJH, and GJE to overcome the symptoms of estrogen deficiency and the mechanism was explored.
Methods: Ovariectomized (OVX) rats were divided into five groups and fed high-fat diets supplemented with 2 % dextrin (control), 2 % APP, 2 % APP + LJH (15:5), APP + LJH + GJE (10:5:5) or 17β-estradiol (30 μg/kg bw/day) for 8 weeks. After 8 weeks of their consumption, energy, lipid, glucose and bone metabolisms were investigated and hepatic insulin signaling and fatty acid metabolism were determined.
Results: APP + LJH + GJE, but not APP itself, improved energy metabolism and attenuated a decrease in energy expenditure by the same amount as estrogen. Moreover, APP + LJH + GJE reduced visceral fat and intramuscular fat and increased lean body mass measured by DEXA by as much as the positive-control. APP itself suppressed increased LDL cholesterol and Triglyceride levels in OVX rats and APP + LJH + GJE alleviated dyslipidemia in OVX rats. Overnight-fasted serum insulin levels and HOMA-IR were reduced in the descending order of APP, APP + LJH, APP + LJH + GJE, positive-control in OVX rats. APP and APP + LJH elevated insulin secretion in the 1st part of OGTT to decrease serum glucose levels while APP + LJH + GJE reduced serum glucose levels without increasing serum insulin levels during OGTT. APP + LJH + GJE decreased insulin resistance during ITT in OVX rats more than the positive-control. The APP + LJH + GJE group exhibited increased hepatic peroxisomal proliferator-activated receptor-γ coactivator-1α expression, which increased the number of genes involved in fatty acid oxidation and decreased fatty acid synthesis. Hepatic insulin signaling (pAkt and pGSK-1β) was also potentiated to reduce phosphoenolpyruvate carboxykinase proteins.
Conclusion: The combination of APP + LJH + GJE attenuated various menopausal symptoms in OVX rats. Thus, it may have potential as a therapeutic agent for the treatment of postmenopausal symptoms.
Leptadenia pyrotechnica extract
The aim of the present study was to evaluate the hypolipidemic and Antiatherosclerotic efficacy of methanolic extract of the aerial part of L. pyrotechnica in cholesterol fed rabbits. Male rabbits were randomly assigned to three groups: Groups I normal control; Group II cholesterol (500 mg / kg b. wt. / day) with coconut oil (5 ml/rabbit / day) and Group III , cholesterol + L. pyrotechnica extract (250 mg / kg b. wt./ day) orally. The whole study lasted for 60 days.
Licorice extract
OBJECTIVE: We previously demonstrated the beneficial effects of dietary flavonoids derived from the ethanolic extract of licorice root against atherosclerotic lesion development in association with inhibition of low-density lipoprotein (LDL) oxidation in atherosclerotic mice. Administration of licorice extract to normolipidemic subjects also inhibited LDL oxidation. In the present study, we extended our investigation to analyze the antiatherogenic effects of licorice-root extract consumption in moderately hypercholesterolemic patients.
METHODS: Supplementation of licorice root extract (0.1 g/d) to patients for 1 mo was followed by an additional 1 mo of placebo consumption.
RESULTS: Licorice consumption 1) reduced patients’ plasma susceptibility to oxidation (by 19%); 2) increased resistance of plasma LDL against three major atherogenic modifications: oxidation (by 55%), aggregation (by 28%), and retention, estimated as chondroitin sulfate binding ability (by 25%); 3) reduced plasma cholesterol levels (by 5%), which was due to a 9% reduction in plasma LDL cholesterol levels; and 4) reduced (by 14%) plasma triacylglycerol levels. After the 1 mo of placebo consumption, these parameters reversed toward baseline levels. Licorice extract supplementation also reduced systolic blood pressure by 10%, which was sustained during the placebo consumption.
CONCLUSIONS: dietary consumption of licorice-root extract by hypercholesterolemic patients may act as a moderate hypocholesterolemic nutrient and a potent antioxidant agent and, hence against cardiovascular disease.
Linum usitatissmum L.seed extract
Being rich in polyunsaturated fatty acids, flaxseed (Linum usitatissimum L.) is thought to be able to decrease lipid levels and dampen inflammation. In this pilot study, we aimed to determine whether flaxseed supplementation could improve the profiles of lipids and inflammatory mediators in patients with severe hyperlipidemia resistant to conventional lipid–lowering pharmacotherapy and requiring lipoprotein apheresis. To this end, six patients received, blindly—in addition to their normal lipoprotein apheresis regimen—a 10-week dietary supplementation with flaxseed (28 g/d) administered in biscuits. This was followed by a 10-week washed out-period and a 10-week supplementation phase with whole wheat placebo. blood samples were collected at the end of each phase, before the lipoprotein apheresis session. The primary endpoint was the lipid profile and the secondary endpoints were the concentrations of inflammatory mediators and tolerability. Flaxseed supplementation was well-tolerated and resulted in a consistent and significant decrease in total cholesterol and low-density lipoprotein (LDL) levels. The median (and range) percentage decrease was 11.5% (0–18.8) and 7.3% (4.4–26.6), for cholesterol (p = 0.015) and LDL-C (p = 0.003), respectively. On the other hand, there was no significant effect of flaxseed on lipoprotein(a) (Lp(a)), C-reactive protein (CRP), and interleukin 6 (IL-6) concentrations. These observations indicate that flaxseed can produce a cholesterol– and LDL–lowering effect in patients treated with lipoprotein apheresis. Thus, flaxseed supplementation may help to control cholesterol in this patient population. The flaxseed supplementation protocol applied may be of use for further adequately-powered studies to validate and extend our findings.
Lonicera japonica Thunb.extract
This study investigated the effects of honeysuckle extract (Lonicera japonica, HE) on the growth performance and lipid metabolism of juvenile grass carp (Ctenopharyngodon idella). HE at doses of 10 g kg-1 (LHE), 20 g kg-1 (MHE), and 40 g kg-1 (HHE) were individually mixed with the basal diet and fed to grass carp for 10 weeks, and ginseng extract (20 g kg-1, GSE) was used as a positive control. The results showed that HE administration exerted no effect on growth performance, but the hepatosomatic index (HSI) and muscle and liver lipid contents were significantly decreased in the LHE and MHE groups. The serum levels of LDL-c, total Triglyceride (TG) and total cholesterol (TC) also declined in the HE-treated groups. Moreover, the disordered vacuolization and nucleus migration in the liver were alleviated in the MHE and HHE groups, and mRNA expressions of lipogenesis-related genes, such as acc1, fas, srebp1, and pparγ decreased. Similarly, the expression of genes related to lipolysis, such as cpt1, atgl, lpl, and pparα, was found to be significantly increased in the MHE and HHE groups compared with the control. Taken together, HE can effectively improve the lipid metabolism and ameliorate the lipid deposition of grass carp and thus may be a promising feed additive in aquaculture.
lupin protein isolate (Lupinus albus)
cholesterol–lowering effect of whole lupin (Lupinus albus) seed and its protein isolate
This study describes the hypocholesterolaemic effect of whole lupin and its protein in hamsters. The diets were: casein (control group HC), lupin protein isolate (group HPI) and whole lupin seed (group HWS). diets from HPI and HWS promoted a significant reduction of total cholesterol and non-HDL cholesterol in the hamsters’ plasma as compared with HC. The true digestibility of HPI and HC groups were similar and differed significantly from the HWS one, which in turn showed a significant difference in total sterol excretion as compared to the former groups. Histological analysis of the liver revealed that animals fed on HPI and HWS diets presented a low level of steatosis (level 1) as compared to the ones fed on HC diet (level 4). Our findings demonstrate that protein isolate from Lupinus albus from Brazil has a metabolic effect on endogenous cholesterol metabolism and a protector effect on development of hepatic steatosis.
cholesterol–lowering effects of dietary Lupin (Lupinus albus var Multolupa) in Chicken diets
The present study was undertaken to investigate the effect of different concentrations of lupin seeds (0, 200, and 400 g/kg), with and without cholesterol added (10 g/kg), in chicken diets on performance, relative liver weight, liver fat, intestinal pH and viscosity, and different blood serum parameters (glucose, cholesterol, Triglycerides , total biliary salts, amylase, total protein and albumin, and globulin fractions). Increasing the lupin content in the diet reduced weight gain and feed consumption and increased feed-to-gain ratio. A decrease in liver fat, cecal pH, serum glucose, cholesterol, total biliary salts, and total protein and an increase in jejunum viscosity were observed with increasing concentration of lupins. serum albumin, β-globulin, γ-globulin, and albumin:globulin ratio were reduced by the addition of lupin in the diet. cholesterol supplementation of diets had no effect on the performance, cecal pH, and serum Triglycerides . Relative liver weight, liver fat, jejunum viscosity, serum cholesterol, total biliary salts, and total protein were increased, and serum glucose was reduced by addition of cholesterol. cholesterol increased serum albumin, α-1 globulin, α-2 globulin, and β-globulin and reduced albumin:globulin ratio and amylase. These results indicate that inclusion of lupin seed in chicken diets causes a growth depression and a reduction of serum cholesterol and glucose and modifies other physiological parameters.
Lupinus angustifolius L.
The present study was undertaken to investigate the effect of cholesterol-enriched casein (CAS) and blue lupin seed (BL) diets on the cholesterol metabolism of intact (INT) and ileorectal anastomosed (IRA) pigs. For 3 weeks, four groups of six pigs were allocated to the treatments (CAS-INT, CAS-IRA, BL-INT, and BL-IRA). diet-induced hypercholesterolemia was inhibited by the BL through a substantial decrease in plasma LDL–cholesterol. The BL also reduced liver esterified and total cholesterol, increased hepatic LDL receptor synthesis and HMG-CoA reductase activity, and stimulated intestinal bile acid reabsorption. The neutral sterol output was higher in BL- than in CAS-fed pigs. The bile acid output was lower in IRA than in INT pigs. Surgery also prevented steroid microbial transformation, but it did not influence plasma cholesterol levels.
These results suggest that the hypocholesterolemic effect of the BL, compared with the CAS, is attributable to impaired intestinal cholesterol absorption, probably involving increased bile acid reabsorption and higher contents of dietary phytosterols, both factors that reduce the micellar solubilization of cholesterol. Furthermore, according to our data, the contribution of the large intestine to cholesterol metabolism is very weak.
lutein
We developed a nano-emulsion of lutein disolved in medium chain Triglyceride (MCT) oil with d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) as the surfactant. The average particle size was 223.6 nm, with a polidispersity index (PDI) of 0.5 and a zeta (ζ) potential of −17 mV. Then the efficacy of this nano emulsion was compared to regular lutein in preventing cholesterol induced liver injury in guinea pigs. Twenty-four animals fed a hypercholesterolemic diet (0.025% cholesterol) were randomly assigned to either one of three groups: control, lutein (3mg/day of regular lutein) or nano (3mg/day lutein as nano-emulsion). After 6 weeks the guinea pigs were sacrificed and their tissues were collected for analyses. As we hypothesized there was significantly more lutein in the tissues and plasma of the animals receiving the nano-emulsion when compared to the other treatments (liver p< 0.001, plasma p< 0.001, adipose (P< 0.001) and eyes (p< 0.001) indicating a greater bioavailability of this carotenoid when a nano-delivery system is used. In terms of liver health, the nano group showed reduced hepatic steatosis scores (P<0.05) and reduced hepatic total and esterified cholesterol accumulation (P<0.05). Alanine amino transferase (ALT), a marker for liver damage was also reduced in the nano group (P<0.05). oxidized LDL in plasma, a marker of oxidative stress and Atherosclerosis risk, was lower in the nano group (2.8±1.0) when compared to the control group (7.9±2.1) (P<0.05) and hepatic OxLDL was lower in both lutein and nano groups when compared to controls: 9.2 ± 4.3 ng/mL, 12.3 ± 4.3 ng/mL and 21.7 ± 14.4 ng/mL, respectively (P<0.05). Results indicate that giving lutein as a nano-formulation increases this compound’s bioavailability and this higher lutein concentration provides greater protection against cholesterol-induced hepatic steatosis and oxidative stress than regular lutein.
Lycium chinense extract Polysaccharides
Anti-obesity and hypolipidemic effects of Lycium chinense leaf powder in obese rats
This study aimed to elucidate the obesity control, hypolipidemic, and antioxidant effects of Lycium chinense leaf powder intake by obese rats. Obesity was induced in rats through 13 weeks of high-fat diet. The obese rats were then divided into four different groups, which were fed for 8 weeks with general diet (G), high-fat diet (F), 5% L. chinense leaf powder with a high-fat diet (FLP5), or 10% L. chinense leaf powder with a high-fat diet (FLP10). The body weight gain of the FLP5 group was significantly lower than that of the F group. Also, the obesity index of the FLP5 and FLP10 group was significantly lower than that of the F group. serum Triglyceride and low-density lipoprotein (LDL)-cholesterol levels in the FLP5 group were significantly lower than those of the F group. The intake of L. chinense leaf powder did not seem to significantly affect the levels of serum homocysteine, leptin, and ghrelin compared to the control group without L. chinense leaf powder intake. The glutathione content in the liver was significantly higher in the FLP5 group than in the G group, but the glutathione S-transferase activity was significantly lower than in the F group. The thiobarbituric acid-reactive substances levels in the liver and kidney were relatively lower in the FLP5 and FLP10 groups than in the G group. In summary, intake of L. chinense leaf powder in obese rats coincided with a lowering of body weight and levels of serum Triglyceride and LDL–cholesterol. It also displayed antioxidant effects.
Lycopene
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL–cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an Inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Background
Cardiovascular disease is associated with oxidative stress, inflammatory processes, and vascular dysfunction. Lycopene, a carotenoid found in tomatoes, is an antioxidant with a protective effect on lipid peroxidation and Anti-atherosclerotic capacity. This review summarises current evidence on the effect of lycopene on serum lipid concentrations and blood pressure.
Methods
We searched the PubMed and Cochrane databases for intervention studies between 1955 and September 2010 investigating the effect of lycopene on blood lipids or blood pressure for a minimum duration of 2 weeks. We conducted meta-analyses using a random effect model of all studies fitting the inclusion criteria. Additionally, we conducted subgroup meta-analysis of serum lipid concentrations by lycopene dosage and subgroup meta-analysis by baseline blood pressure.
Results
Twelve studies (13 trial arms) meeting the inclusion criteria investigated the effect of lycopene on serum lipids, and four studies examined its effect on blood pressure. Meta-analysis on serum lipids revealed a significant cholesterol–lowering effect of lycopene for total serum cholesterol (mean change ± SE: −7.55 ± 6.15 mg/dl; p = 0.02) and low-density-lipoprotein (LDL) cholesterol (mean change ± SE: −10.35 ± 5.64 mg/dl, p = 0.0003) in the subgroup of trials using lycopene dosages of ≥25 mg daily, whereas subgroup meta-analysis of trials using lower lycopene dosages was not significant. Meta-analysis of the effect of lycopene on systolic blood pressure of all trials suggested a significant blood pressure reducing effect (mean systolic blood pressure change ± SE: −5.60 ± 5.26 mm Hg, p = 0.04).
Conclusions
Our meta-analysis suggests that lycopene taken in doses ≥25 mg daily is effective in reducing LDL cholesterol by about 10% which is comparable to the effect of low doses of statins in patient with slightly elevated cholesterol levels. More research is needed to confirm suggested beneficial effects on total serum cholesterol and systolic blood pressure.
Madhuca longifolia bark extract
Background: Madhuca longifolia (mahua) is a tropically growing tree found in various parts of India mostly on plain lands. The tree is considered a boon by the tribals who are forest dwellers because of its manifold medicinal properties. Studies show that in animals, alcoholic extracts of this tree produce beneficial effects on diabetic and lipid profile. It is the purpose of this study to know whether these beneficial effects are observed in Santhals many of whom are regular consumers of Madhuca longifolia drinks.
Methods: Diabetic and lipid profile of blood along with standard anthropometric parameters were measured in a population of Santhal tribe (only males were chosen) many of whom, but not all, are regular consumers of mahua drinks. These findings were statistically analysed and compared using student’s t-test and inference drawn.
Results: Results show that anthropometric parameters do not differ much, but FBS. HbA1c, cholesterol and LDL these parameters are lower in mahua consumers compared to those in non-consumers. HDL is raised in mahua consumers compared to the other group. No significant effect was observed in case of VLDL and Triglycerides .
Conclusions: Study shows that regular mahua drinks among Santhal tribe do improve diabetic and lipid profile, except Triglycerides and VLDL. Further and more elaborate studies are needed to have proper insight and practical gains in this regard.
Mangifera indica
Introduction:
cholesterol lowering activity of Mangifera indica L. has been determined by earlier researchers and kernel, leaf and bark have shown significant activity. However, the specific cholesterol lowering activity of leaf methanol extract has not been determined.
Materials and Methods:
The present study involved evaluation of cholesterol lowering potential of methanol extract of M. indica leaves using high cholesterol diet model in albino Wistar rats. The acute oral toxicity at a dose of 5000 mg/ kg body weight was also determined in female albino Wistar rats. Phytoconstituents Iriflophenone 3-C-β-D-glucoside and mangiferin were quantified in methanol extracts of different varieties of mango leaves using high performance liquid chromatography.
Results and Discussion:
Significant cholesterol lowering activity was observed with methanol extract of M. indica leaves, at dose of 90 mg/kg body weight in rats and it was also found to be safe at dose of 5000 mg/kg rat body. Iriflophenone 3-C-β-D-glucoside and mangiferin were found to be in the range of 1.2 to 2.8% w/w and 3.9 to 4.6% w/w, respectively which along with 3 β taraxerol and other sterols could be contributing to the cholesterol lowering activity of mango leaves extract.
Conclusions:
The phytosterols rich extract of Mangifera indica leaves is a good source of nutraceutical ingredient that have the potential to lower serum cholesterol levels.
Mango ginger (Curcuma amada Roxb.)
Mango ginger (Curcuma amada Roxb.) is a spice commonly consumed in Asian countries. Health beneficial hypoTriglyceride mic property of mango ginger has been reported earlier. In this investigation, the anti-hypercholesterolemic influence of dietary mango ginger was evaluated in experimental rats. dietary mango ginger powder (10%) or its equivalent of 10 mg% curcumin-containing portion was fed along with 1% cholesterol supplemented diet in Wistar rats for 5 weeks. The treatment countered the liver and serum total and LDL + VLDL associated cholesterols and increased the HDL associated cholesterol while it had no influence on cholesterol levels in animals, maintained on normal diet. dietary C. amada and its curcumin-free portion were effective in lowering liver cholesterol in animals, maintained on basal diet, while the curcumin-containing component of C. amada was ineffective. The biliary secretion of total lipids and bile acids was increased by dietary C. amada and both of its components. While biliary cholesterol was increased in animals fed with whole mango ginger, no such increases were noticed in groups fed with either components of mango ginger. cholesterol absorption in ligated rat intestinal loops was not affected by mango ginger or either of its components. Thus, the present study has evidenced that the spice mango ginger possesses beneficial anti-hypercholesterolemic activity in hypercholesterolemic situation. This information is complementary to the earlier report on the health beneficial hypoTriglyceride mic influence of this spice.
Medicago sativa L.extract
Increased serum cholesterol and LDL cholesterol were reduced by 38 – 41.7% and 48 – 53.3% respectively when fed with alfalfa seed extract from the beginning or in established hyperlipidaemic model. LDL–cholesterol lowering was maximum (64.4%) in a model fed with alfalfa meals without cholesterol. An increase in HDL- cholesterol total cholesterol is suggestive of beneficial role since it is associated with low incidence of Atherosclerosis. Possible mechanism of lipid lowering activity of Medicago sativa seed extract is worked out.
Alfalfa was reported to be hypocholesterolemic and Antiatherosclerotic. Saponin glycosides were suggested to be responsible for this activity by neutralizing cholesterol in the stomach, enabling it to be excreted from the body. This makes alfalfa superior to the current anti-cholesterol medications which act by blocking cholesterol synthesizing apparatus. This study was undertaken in an attempt to prepare an alfalfa extract with high saponin content and free or low content of other toxic constituents found in alfalfa (canavanine and coumestrol), which causes serious side effects. A patent process was used to render alfalfa toxin free and to produce a drug present in the international market. Our study is based on monitoring the Egyptian crop at two different localities for its saponin, canavanine and coumestrol contents at different growth stages. The study showed that the tested extract of the chosen stage to be biologically studied (hypocholesterolemic and Antiatherosclerotic effects) on the basis of the highest saponin content was just before fruiting stage of the locality A. This stage was free from both coumestrol and canavanine. The study proved that the Egyptian crop of alfalfa was found to safely reduce natural cholesterol and to possess a strong Antiatherosclerotic activity. This extract (I) produced the most significant decrease in total cholesterol and LDL–cholesterol by 85.1 and 88%, respectively, of the corresponding levels in hypercholesterolemic rabbits. This decrease is more significant than that produced by gemfibrozil (73 and 74%) upon concomitant administration with a cho-lesterol enriched diet using the same animal model at the tested dose level. Also, it was obvious that all alfalfa preparations produced
significant antioxidant properties. All alfalfa extracts possessed Antiatherosclerotic activity as observed by the almost normalization of the aortic sections upon concomitant use of alfalfa extracts with cholesterol-enriched diet.
Melinjo (Gnetum gnemon) seeds
HMG-CoA Reductase Inhibitory Activity of Gnetum gnemon Seed Extract and Identification of Potential Inhibitors for lowering cholesterol Level
Objectives: Melinjo (Gnetum gnemon) seeds have been known to have some biological properties. One of them is ant hypercholesterolemia. The present study investigated in vitro and in silico methods to predict potential antihypercholesterolemic of the Melinjo seed extracts of through HMG-CoA reductase Inhibitory activity. Methods: Melinjo seed powders were successively extracted by reflux method using five solvents with gradient polarity including: n-hexane, dichloromethane, ethyl acetate and methanol. All extracts were evaluated in vitro using HMG-CoA Reductase assay kit, to analyze the Inhibitory activity. Molecular docking of the phytochemical content of the seeds were carried out using Auto Dock Vina, and also Ligand Scout to analyses interaction between ligand and receptor. Results: Dichloromethane extract demonstrated the highest Inhibitory activity against HMG-CoA reductase with IC50 value is 0.40 μg/mL, followed by that of ethyl acetate extract. UPLC-MS analyses showed that dichloromethane extract contained trans-resveratrol, piceid, gnetin C, gnetol, isorhapontigenin, ɛ-viniferin, gnemonol L, and gnemonol M. Molecular docking studies demonstrated that dimer of resveratrol such as gnemonol L, gnemosida, and ɛ-viniferin have better free binding energy than that of monomer. piceid, gnetin C, gnemonol L, and gnemonol M could be considered as HMG-CoA reductase Inhibitor. Conclusion: Gnetum gnemon seed extract showed strong HMG-CoA reductase activity. Resveratrol dimer promises as a potential lead compound to design/synthesize anti-cholesterol.
Melissa officinalis
Background
The purpose of this study was to investigate the safety and effects of Melissa officinalis, a good source of bioactive components, on apolipoprotein (Apo)B, Apo A-I, and their ratio, lipids ratios and intercellular adhesion molecule-1(ICAM-1) in patients with type 2 diabetes.
Methods
For the present randomized, double-blinded, placebo-controlled clinical trial, 70 type 2 diabetic patients aged 20–65 years old were randomly assigned to receive hydroalcoholic extract of M. officinalis (HEMO) (700 mg/d) or placebo twice-daily for 12 weeks.
Results
There were significant differences in serum Apo A-I, TC/ HDL-c and LDL-c/ HDL-c between the two groups at the end of the study (p < 0.05), but we did not show significant differences in the values for Apo B, Apo B/Apo A-I, TG/HDL-c, ICAM-1 and liver enzymes include AST, ALT, and ALP between the study groups. Although both groups showed a significant reduction in ICAM-1, AST and, ALP (p < 0.05), no significant differences in ICAM-1, AST and, ALP were observed. At end, in M. officinalis group, there was a significant increase in Apo A-I (p = 0.003) and significant reduction in TG/HDL-c (p = 0.05) compared with initial values, as well as in placebo group, there was a significant rising in Apo B/Apo A-I (p = 0.02) and significant reduction in Apo A-I (p = 0.001) compared with baseline values.
Conclusions
M. officinalis is safe and effective in improvement of Apo A-I, Apo B/Apo A-I, and lipids ratios as key factors promoting cardiovascular disease (CVD) in type II diabetic patients.
Miracle fruit (Synsepalum dulcificum)
The cholesterol–lowering activity of miracle fruit (Synsepalum dulcificum)
Miracle fruit (Synsepalum dulcificum) is famous for its uniqueness of modifying sour taste to sweetness. However, its cholesterol–lowering activity has not been reported. This study investigated the effect of S. dulcificum on the compositional changes of plasma lipids in hamsters fed a high–cholesterol control diet. Six groups of hamsters were fed either a control diet or one of the five experimental diets containing 2% ethanol extract of leaves, 2% water extract of leaves, 2% ethanolic extract of seeds (ES), 2% water extract of seeds, or 2% dry pulp. Results showed that ES decreased the plasma total cholesterol (TC). Two triterpenoids (lupeol acetate and β-amyrin acetate) were isolated from the ES and they added to a diet could decrease TC by 15%–20% in hamsters. It was concluded that ES showed potent TC-lowering activity and triterpenoid was one of the active components of ES.
Practical applications
In recent years, people are more interested in phytochemicals from functional foods treated for hyperlipidemia because they possessed fewer side effects than the synthetic drugs. The triterpenoids isolated from the miracle fruit may be promising candidates for the development of cholesterol–lowering agent, especially for patients whose blood cholesterol level and body weight are high. Meanwhile, the miracle fruit have a good potential as cholesterol–lowering functional food or a natural source of cholesterol–lowering agent.
Monacolin k
Hypercholesterolemia and elevated homocysteine concentrations are associated with cardiovascular risk. Previous studies have demonstrated a cholesterol–lowering effect of red yeast rice (RYR) supplements which contained 5 to 10 mg of monacolin K. We hypothesized that the intake of a low monacolin K dose may likewise reduce low-density lipoprotein-cholesterol (LDL-C) and other plasma lipids. In secondary analyses, we tested the homocysteine lowering effect of folic acid, which was also included in the study preparation. Therefore, we conducted a randomized, double-blind, and placebo-controlled intervention study. One hundred forty-two nonstatin-treated participants with hypercholesterolemia (LDL-C ≥ 4.14 ≤ 5.69 mmol/L) were randomized to the supplement group with RYR or the placebo group. Participants of the supplement group consumed 3 mg monacolin K and 200 μg folic acid per day. A significant (P < .001) reduction of LDL-C (-14.8%), total cholesterol (-11.2%), and homocysteine (-12.5%) was determined in the supplement group after 12 weeks. A total of 51% of the participants treated with RYR achieved the limit of LDL-C <4.14 mmol/L advised and 26% reached the threshold level of homocysteine <10 μmol/L. No significant changes were exhibited within the placebo group. Other parameters remained unchanged and no intolerances or serious adverse events were observed. In conclusion, we demonstrated that a low dose of daily 3 mg monacolin K from RYR reduces the concentration of LDL-C; a risk factor for cardiovascular diseases.
The yeast Monascus purpureus, as a result of fermentation on rice, produces metabolically active components known as monacolin, the most representative one is the monacolin k, equipped with high affinity towards the enzyme HMG-CoA reductase. Meanwhile in literature it is widely reported as treatment with policosanol allows a reduction in blood of cholesterol (LDL/tot), Triglycerides and, on the other hand, an increased level of HDL. Given these circumstances and considering the fact that the action of fermented rice by Monascus purpureus is given by a set of factors not strictly related to monacolin k itself, the objective of the MONAPOL clinical trial is to verify the profiles of effectiveness and tolerability of a galenic comparable to a dietary supplement containing a dry extract of fermented red rice by Monascus purpureus associated with another one titrated in policosanol. The study is aimed, in a period of 3 months, for a representative cohort of 210 subjects presenting mild to moderate hypercholesterolemia uncomplicated unfamiliar (PCs currently outside indication comparing to the start of treatment with Inhibitors of HMG-CoA reductase). At the Faculty of Pharmacy of University of Turin, the study of the formulation, the verification of stability of molecules present in the galenic and the preparation thereof, were conducted. Galenics present advantages such as the ability to use specific ingredients in order, firstly not to incur in dietary intolerances, secondly the possibility to select the source of supply that best ensures the high quality of raw materials. The analytical HPLC method necessary for the pharmacokinetic study, already on going for enrolled patients, was set up. The benefit derived from treatment is considered as both absolute and percentage reduction compared to levels resulting in hematic withdrawal before the start of the study, of lipid metabolic disorder pathologies indexes; blood analysis of subjects were performed both by venipuncture and self-diagnostics device. Considering the new regulations on “Services Pharmacy” it seems appropriate and relevant to assess the reliability of self-diagnostics tools comparing the results obtained with those ones resulting from analyses carried out in authorized laboratories.
Mori Folium leaves extract
Context: Folium Mori, the leaf of Morus alba L. (Moraceae), has been used in traditional Chinese medicine (TCM) for treating diabetes. However, it is unclear which components in the mulberry leaf are effective for the treatment of type 2 diabetes mellitus (T2DM).
Objective: To investigate the flavonoids and polyphenols in mulberry leaves and their antihyperglycemic and antihyperlipidemic effects in T2DM rats.
Materials and methods: Male Sprague-Dawley rats were divided into five groups: normal control (NC), diabetic control (DBC), diabetic group with 0.3 mg/kg b.w./day rosiglitazone (RSG), diabetic group with 7 g/kg b.w./day TCM formula and diabetic group with 2 g/kg b.w./day Folium Mori extract (FME). After 4 weeks, the rats were sacrificed; biochemical parameters, gene and protein expression were measured.
Results: The FBG level was significantly lower in the FME group than in the DBC group (p < 0.05). In oral glucose tolerance test, the AUC was significantly lower in the FME group (p < 0.05). The HOMA-IR level was significantly decreased in the FME group (p < 0.05). FME decreased the total cholesterol (TC), Triglyceride (TG) and low density lipoprotein (LDL) levels (p < 0.05). FME increased the mRNA and protein expression of IRS-1, PI3K p85α and Glut-4 increased significantly (p < 0.05). Histological analysis revealed amelioration of lipid accumulation following FME treatment. Additionally, immunohistochemical analysis displayed stronger staining of Glut-4 in the FME group compared to the DBC group.
Discussion and conclusion: FME could decrease the body weight, blood glucose, TG, TC and LDL levels, and improve insulin resistance. FME possessed significant antihyperglycemic and antihyperlipidemic activities via the IRS-1/PI3K/Glut-4 signalling pathway.
Moringa oleifera Lam.leaves extract
Rabbits were fed Moringa oleifera (200mg/kg/day, p.o.) or lovastatin (6mg/kg/day, p.o.) in banana pulp along with standard laboratory diet and hypercholesterolaemic diet for 120 days. Moringa oleifera and lovastatin were found to lower the serum cholesterol, phospholipid, Triglyceride , VLDL, LDL, cholesterol to phospholipid ratio and atherogenic index, but were found to increase the HDL ratio (HDL/HDL-total cholesterol) as compared to the corresponding control groups. Treatment with M. oleifera or lovastatin in normal rabbits decreased the HDL levels. However, HDL levels were significantly increased or decreased in M. oleifera- or lovastatin-treated hypercholesterolaemic rabbits, respectively. Lovastatin- or M. oleifera-treated hypercholesterolaemic rabbits showed decrease in lipid profile of liver, heart and aorta while similar treatment of normal animals did not produce significant reduction in heart. Moringa oleifera was found to increase the excretion of faecal cholesterol. Thus, the study demonstrates that M. oleifera possesses a hypolipidaemic effect.
Moringa oleifera is used in Thai traditional medicine as cardiotonic. Recent studies demonstrated its hypocholesterolaemic effect. However, to be clinically useful, more scientific data are needed. Aim of the Study: We investigated the antioxidant, hypolipidaemic and Antiatherosclerotic activities of Moringa oleifera leaf extract. Materials and Methods: Scavenging activity of the extract on 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), and the Inhibitory effect on Cu2+-induced low-density lipoprotein (LDL) oxidation were determined in in vitro experiment. The effects of the extract on cholesterol levels, conjugated diene (CD) and thiobarbituric acid reactive substances (TBARS) and plaque formations in cholesterol-fed rabbits were investigated.
Results: We found that in scavenging DPPH radicals the extract and Trolox® had IC50 of 78.15 ± 0.92 and 2.14 ± 0.12 μg/ml, respectively. The extract significantly (P < 0.05) prolonged the lag-time of CD formation and inhibited TBARS formation in both in vitro and ex vivo experiments in a dose-dependent manner. In hypercholesterol-fed rabbits, at 12 weeks of treatment, it significantly (P < 0.05) lowered the cholesterol levels and reduced the atherosclerotic plaque formation to about 50 and 86%, respectively. These effects were at degrees comparable to those of simvastatin.
Conclusions: The results indicate that this plant possesses antioxidant, hypolipidaemic and Antiatherosclerotic activities and has therapeutic potential for the prevention of cardiovascular diseases.
ABSTRACT Objective: Moringa oleifera Lam. (Moringaceae), a small rapid growing, evergreen, deciduous tree is an important medicinal plant. Leaves and fruits of this plant are used for various ailments, as a nutritional supplement and also as vegetables. The current study involves in the determination of best combination of the cholesterol–lowering potential of a blend of methanol extracts of M. oleifera leaf and fruits, developed based on in vitro FIC index studies and evaluate the combination of this extracts in hypercholesterolemic animal models. Methods: Leaf and fruit methanol extracts and their combinations were tested in in vitro lipase inhibition assay to determine the best combination using fractional Inhibitory concentration (FIC) index. Hypercholesterolemia was induced with Triton WR-1339 (a non-ionic detergent) and with high cholesterol diet for acute and chronic model respectively and the cholesterol–lowering effect of 1:1 blend of M. oleifera leaf and fruits methanol extracts was evaluated. Results: The FIC index values indicated that M. oleifera leaf and fruit extracts blended in 1:1 proportion was the best combination in in vitro lipase inhibition assay. This blend, when evaluated in vivo, showed a significant decrease in serum total cholesterol level from 24 h through 48 h in triton model. In high cholesterol diet model, the extract blend showed a significant reduction in serum Triglycerides levels at 3 and 6 w of treatment. Conclusion: The results indicate that the blend of M. oleifera at the tested dose could be lowering cholesterol and Triglyceride levels by inhibiting the absorption of cholesterol and can be developed as a standardized blend for dietary supplement market. Keywords: Moringa oleifera, cholesterol, Lipase, FIC, Triton, high-fat diet, Niazirin
Morus alba
The free and bound phenolic extracts of leaves from three mulberry species, Morus alba Linn., M. multicaulis Perr., and M. laevigata Wall. from Yunnan (China), were evaluated for the first time to examine their phenolic composition, antioxidant, and cholesterol–lowering capacity in HepG2 cells. The result showed that the total phenolic content of six extracts were ranged from 0.54 to 17.63 mg GAE/g DW, and the total flavonoids content varied from 0.52 to 35.62 mg RE/g DW. Chlorogenic acid, Rutin, and Catechin were the main compounds in the selected mulberries. The antioxidant properties in a positive correlation with the phenolic contents of mulberries were exhibited. The free phenolic extract of M. multicaulis Perr. significantly decrease the intracellular cholesterol content in HepG2 cells. In a word, the free phenolic extracts of M. multicaulis Perr. could be used as for further nutritional studies for cholesterol–lowering in the food and medicine industries.
Morus laevigata
The free and bound phenolic extracts of leaves from three mulberry species, Morus alba Linn., M. multicaulis Perr., and M. laevigata Wall. from Yunnan (China), were evaluated for the first time to examine their phenolic composition, antioxidant, and cholesterol–lowering capacity in HepG2 cells. The result showed that the total phenolic content of six extracts were ranged from 0.54 to 17.63 mg GAE/g DW, and the total flavonoids content varied from 0.52 to 35.62 mg RE/g DW. Chlorogenic acid, Rutin, and Catechin were the main compounds in the selected mulberries. The antioxidant properties in a positive correlation with the phenolic contents of mulberries were exhibited. The free phenolic extract of M. multicaulis Perr. significantly decrease the intracellular cholesterol content in HepG2 cells. In a word, the free phenolic extracts of M. multicaulis Perr. could be used as for further nutritional studies for cholesterol–lowering in the food and medicine industries.
Morus multicaulis
The free and bound phenolic extracts of leaves from three mulberry species, Morus alba Linn., M. multicaulis Perr., and M. laevigata Wall. from Yunnan (China), were evaluated for the first time to examine their phenolic composition, antioxidant, and cholesterol–lowering capacity in HepG2 cells. The result showed that the total phenolic content of six extracts were ranged from 0.54 to 17.63 mg GAE/g DW, and the total flavonoids content varied from 0.52 to 35.62 mg RE/g DW. Chlorogenic acid, Rutin, and Catechin were the main compounds in the selected mulberries. The antioxidant properties in a positive correlation with the phenolic contents of mulberries were exhibited. The free phenolic extract of M. multicaulis Perr. significantly decrease the intracellular cholesterol content in HepG2 cells. In a word, the free phenolic extracts of M. multicaulis Perr. could be used as for further nutritional studies for cholesterol–lowering in the food and medicine industries.
Morus rubra
Protective effect of Morus rubra L. leaf extract on diet-induced Atherosclerosis in diabetic rats
The Antiatherosclerotic effect of aqueous leaves extract of Morus rubra was studied in streptozotocin-induced diabetic rats fed with atherosclerotic (Ath) diet [1.5 ml olive oil containing 8 mg (3, 20,000 IU) vitamin D2 and 40 mg cholesterol] for 5 consecutive days. A short-term toxicity assessment was also conducted in healthy rats to examine toxic effects of the extract. Oral administration of extract to diabetic rats (100, 200 and 400 mg/kg body weight per day for a period of 30 days) produced significant (p<0.001) fall in fasting blood glucose (FBG) in a dose-dependent manner. Treatment with the extract (400 mg/kg) showed significant (p<0.001) improvement in body weight and serum lipid profile i.e., total cholesterol, Triglyceride , HDL-cholesterol, LDL–cholesterol and VLDL–cholesterol, when compared with diabetic control. Endothelial dysfunction parameters (sVCAM-1, Fibrinogen, total NO levels and oxidized LDL), apolipoprotein A and apolipoprotein B were significantly (p<0.001) reversed to near normal, following treatment with the extract. Thus, our study shows that aqueous leaf extract of Morus rubra (400 mg/kg) significantly improves the homeostasis of glucose and fat and possesses significant Anti-atherosclerotic activity.
Musa sapientum L. extract
Diabetes mellitus affects lipid levels resulting in diabetic dyslipidemia as well as electrolyte loss from the body. Musa sapientum has been reported to possess antidiabetic properties. This study assessed the lipid profile and electrolyte composition in alloxan-induced diabetic rats treated with methanol leaf extract of M. sapientum (cMEMSL). Diabetes was induced with alloxan (120 mg/kg i.p.). Seventy-five male albino rats were divided into 5 groups of 15 rats each. Group 1 was control; groups 2-5 were made diabetic and treated with 0.2 ml 0.9% NaCl, cMEMSL (250 mg/kg and 500 mg/kg), and glibenclamide (5 mg/kg), respectively, for 14 days. blood samples were obtained from the retro orbital sinus after light anesthesia from 5 animals in each group on days 2, 7, and 14 for lipids and electrolyte analysis. lipid profile of diabetic treated (cMEMSL and glibenclamide) animals showed significant reduction (p < .05) in total cholesterol, Triglyceride , and low density lipoprotein (LDL) levels. The high density lipoprotein (HDL) level in the treatment groups increased significantly (p < .05) compared with diabetic untreated. Sodium, potassium, and phosphate ions significantly increased in all diabetic treatment groups while chloride ion significantly decreased compared with diabetic untreated. There was no significant difference in calcium and bicarbonate ion concentration in all the groups. This study has showed additional properties of Musa sapientum to include its ability to restore electrolyte balance, reduce cholesterol, Triglyceride , LDL, and increase the HDL levels in diabetic animals.
Myrmecodia Platytyrae
Myrmecodia plant or ant-nest plant is from Rubiaceae family. Rubiaceae are mainly tropical woody plants, consist mostly of trees and shrubs and can be found in temperate regions. Myrmecodia platytyrea (MyP) are believed to have medicinal value. This study was designed in order to investigate the effect of MyP extract as anti hypercholesterolemic agent. The results showed that treatment of MyP can significantly reduce (p<0.05) low density lipoprotein (LDL) compared to negative control group. The extract was significantly increase (p<0.05) high density lipoprotein (HDL) concentration compared to negative control group. Besides that, MyP increased fecal cholesterol and fecal bile compared to normal control group. It was also found that lipid profile was significantly decreased (p<0.05) in MyP treatment group. All biochemistry data showed that MyP water extract was not toxic at all.
Naringin
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL–cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an Inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Naringin enhances reverse cholesterol transport in high fat/low streptozocin induced diabetic rats
Naringin, a citrus-derived flavonoid with antihyperglycemic, antihyperlipidemic, and antioxidant properties, is reported to be a useful nutraceutical in the management of diabetes and its complications. This study investigated the mechanism of antiatherogenic properties of naringin in type 2 diabetes (T2DM) using high fat-low streptozocin rat model of T2DM. Rats were treated daily with 50, 100 and 200 mg/kg naringin orally for 21days. Levels of biomarkers of T2DM, lipid profile and activity of paraoxonase (PON) were assayed spectrophotometrically. The levels of expression of hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase (Hmgcr), scavenger receptor class B member 1 (Scarb1), aryl hydrocarbon receptor (Ahr), hepatic Lipase (Lipc), and lecithin-cholesterol acyltransferase (Lcat) were assessed using relative reverse transcriptase polymerase chain reaction technique. Naringin treatment resulted in a dose-dependent significant (p < 0.05) decrease in the levels of plasma cholesterol and Triglyceride from 84.84 ± 1.62 to 55.59 ± 1.50 mg/dL and 123.03 ± 15.11 to 55.00 ± 0.86 mg/dL, respectively, at 200 mg/kg naringin. In the liver, Scarb1 and Ahr were significantly (p < 0.05) upregulated at 200 mg/kg naringin while Lipc and Lcat were significantly (p < 0.05) upregulated by 50 mg/kg naringin. T2DM-induced decrease in PON activities in the plasma, liver and HDL was significantly (p < 0.05) reversed by 200 mg/kg naringin treatment. These genes play critical roles in reverse cholesterol transport and hence our results showed that the antiatherogenic property of naringin in T2DM involves enhancement of reverse cholesterol transport and PON activity.
Negroamaro polyphenolic extract
Purpose
The aim of the study was to evaluate the vascular anti-inflammatory effects of polyphenolic extracts from two typical South Italy red wines, the specific contribution of individual polyphenols and the underlying mechanisms of action.
Methods
Human endothelial cells were incubated with increasing concentrations (1–50 μg/mL) of Primitivo and Negroamaro polyphenolic extracts (PWPE and NWPE, respectively) or pure polyphenols (1–25 μmol/L), including hydroxycinnamic acids (p-coumaric, caffeic and caftaric acids), flavonols (kaempferol, quercetin, myricetin) or stilbenes (trans-resveratrol, trans-piceid) before stimulation with lipopolysaccharide. Through multiple assays, we analyzed the endothelial–monocyte adhesion, the endothelial expression of adhesion molecules (ICAM-1, VCAM-1 and E-Selectin), monocyte chemoattractant protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF), as well as ROS intracellular levels and the activation of NF-κB and AP-1.
Results
Both PWPE and NWPE, already at 1 μg/mL, inhibited monocyte adhesion to stimulated endothelial cells, a key event in triggering vascular inflammation. They down-regulated the expression of adhesion molecules, ICAM-1, VCAM-1, E-Selectin, as well as MCP-1 and M-CSF, at mRNA and protein levels. All polyphenols reduced intracellular ROS, and everything, except caftaric acid, inhibited the endothelial expression of adhesion molecules and MCP-1, although with different potency. Flavonols and resveratrol significantly reduced also the endothelial expression and release of M-CSF. The decrease in endothelial inflammatory gene expression was related to the inhibition of NF-κB and AP-1 activation but not to intracellular oxidative stress.
Conclusions
This study showed multiple anti-inflammatory and Anti-atherosclerotic properties of red wine polyphenolic extracts and indentified specific bioactive polyphenols which could counteract inflammatory diseases including Atherosclerosis.
Nelumbinis folium
hyperTriglyceride mia is a condition characterized by high Triglyceride levels and is a major risk factor for the development of cardiovascular diseases. The present study was designed to investigate the Inhibitory effect of roasted Nelumbinis folium (RN), which is a medicinal substance produced by heating lotus leaves, on lipid metabolism in high fat/cholesterol (HFC) diet-induced hyperTriglyceride mia. Except for those in the control group, Sprague–Dawley rats were fed an HFC diet for four weeks to induce hyperTriglyceride mia. During the next nine weeks, the control, regular diet; HFC, HFC diet, FLU, fluvastatin (3 mg/kg/day); RNL, RN (100 mg/kg/day); RNH, RN (200 mg/kg/day) were orally administered together with the diet, and the experiments were conducted for a total of 13 weeks. The weight of the epididymal adipose tissue, liver, and heart of rats in the HFC diet group significantly increased compared to those in the control group but improved in the RN-treated group. It was also confirmed that vascular function, which is damaged by an HFC diet, was improved after RN treatment. The levels of insulin, glucose, Triglycerides , total cholesterol, and low-density lipoprotein increased in the HFC diet group compared to those in the control group, while the administration of RN attenuated these parameters. In addition, the administration of RN significantly reduced the gene expression of both LXR and SREBP-1, which indicated the Inhibitory effect of the biosynthesis of Triglycerides caused by RN. The results indicated that RN administration resulted in an improvement in the overall lipid metabolism and a decrease in the concentration of Triglycerides in the HFC diet-induced rat model of hyperTriglyceride mia. Therefore, our findings suggest that the RN can be a candidate material to provide a new direction for treating hyperTriglyceride mia.
Nelumbo nucifera
Browning of fresh-cut plants is mainly attributed to the enzymatic browning of phenolic compounds induced by polyphenol oxidase (PPO), producing browning products such as anthraquinones, flavanol oxides, and glycosides, which are usually considered to be non-toxic. Could browning bring any benefits on behalf of their bioactivity? Our previous study found that browned lotus root extracts (BLREs) could reduce the cholesterol level in obese mice as fresh lotus root extracts (FLREs) did. This study aimed to compare the mechanisms of FLRE and BLRE on cholesterol metabolism and verify whether the main component’s monomer regulates cholesterol metabolism like the extracts do through in vitro experiments. Extracts and monomeric compounds are applied to HepG2 cells induced by free fatty acids (FFA). Extracellular total cholesterol (TC) and Triglyceride (TG) levels were also detected. In addition, RT-PCR and Western blot were used to observe cholesterol metabolism-related gene and protein expression. The in vitro results showed that BLRE and FLRE could reduce TC and Triglyceride levels in HepG2 cells. In addition, BLRE suppressed the synthesis of cholesterol. Meanwhile, FLRE promoted the synthesis of bile acid (BA) as well as the clearance and efflux of cholesterol. Furthermore, the main monomers of BLRE also decreased cholesterol synthesis, which is the same as BLRE. In addition, the main monomers of FLRE promoted the synthesis of BAs, similar to FLRE. BLRE and FLRE promote cholesterol metabolism by different pathways.
Ethnopharmacological relevance: Nelumbo nucifera Gaertn. leaves have been used as medicinal herbs in the past 1300 years, specifically utilized to cure hyperlipidemia, hyperglycemia, and obesity. It has been recorded in the most famous medicinal book in China for more than 400 years. The present study aims to identify the potential therapeutic activities of the flavonoids isolated from Nelumbo nucifera leaves.
Materials and methods: Nelumbo nucifera leaf flavonoids (NLF) were tested for the inhibition of lipase, α-glucosidase, and α-amylase activities in vitro. A single dose of NLF was administered by oral gavage in mice for acute toxicity. Wistar rats with high-fat diet-induced hyperlipidemia and two other animal models were used to evaluate the hypolipidemic effects of NLF.
Results: Our in vitro biochemistry tests revealed that the NLF showed high Inhibitory activity against porcine pancreatic lipase, α-amylase, and α-glucosidase with IC50 values of 0.38 ± 0.022, 2.20 ± 0.18, and 1.86 ± 0.018 mg/mL, respectively. Furthermore, the NLF significantly lowered the lipid components, such as the total cholesterol, Triglycerides , low-density lipoprotein cholesterol, and malondialdehyde, in various established in vivo systems and raised the high-density lipoprotein cholesterol. Moreover, the NLF alleviated high-fat diet-induced lipid accumulation in the liver.
Conclusions: The results demonstrate that NLFs can effectively ameliorate hyperlipidemia and inhibit the key enzymes related to type 2 diabetes mellitus. Our findings may provide new pharmacological basis for the treatment of hyperlipidemia, hyperglycemia, and obesity using NLFs.
Niacin
Objectives: This study sought to assess the efficacy of niacin for reducing cardiovascular disease (CVD) events, as indicated by the aggregate body of clinical trial evidence including data from the recently published AIM-high (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/high Triglycerides : Impact on Global Health Outcomes) trial.
Background: Previously available randomized clinical trial data assessing the clinical efficacy of niacin has been challenged by results from AIM-high, which failed to demonstrate a reduction in CVD event incidence in patients with established CVD treated with niacin as an adjunct to intensive simvastatin therapy.
Methods: Clinical trials of niacin, alone or combined with other lipid-altering therapy, were identified via MEDLINE. Odds ratios (ORs) for CVD endpoints were calculated with a random-effects meta-analyses. Meta-regression modeled the relationship of differences in on-treatment high-density lipoprotein cholesterol with the magnitude of effect of niacin on CVD events.
Results: Eleven eligible trials including 9,959 subjects were identified. Niacin use was associated with a significant reduction in the composite endpoints of any CVD event (OR: 0.66; 95% confidence interval [CI]: 0.49 to 0.89; p = 0.007) and major coronary heart disease event (OR: 0.75; 95% CI: 0.59 to 0.96; p = 0.02). No significant association was observed between niacin therapy and stroke incidence (OR: 0.88; 95% CI: 0.5 to 1.54; p = 0.65). The magnitude of on-treatment high-density lipoprotein cholesterol difference between treatment arms was not significantly associated with the magnitude of the effect of niacin on outcomes.
Conclusions: The consensus perspective derived from available clinical data supports that niacin reduces CVD events and, further, that this may occur through a mechanism not reflected by changes in high-density lipoprotein cholesterol concentration.
Niacin is considered to be a powerful drug for the treatment of lipid and lipoprotein abnormalities connected with “residual cardiovascular risk”, which persist in high-risk patients even when the target goals of LDL-C are achieved with statin therapy. Recent large randomized clinical studies – AIM-high (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/high Triglycerides ) and HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) – delivered some disappointing results, leading to the conclusion that no further benefit (decreased parameters of cardiovascular risk) is achieved by adding niacin to existing statin therapy in patients with high cardiovascular risk. Moreover, in these studies, several adverse effects of the treatment were observed; therefore, niacin treatment for hypolipidemias is not recommended. In this paper, we analyze the mechanisms underlying the hypolipidemic and antiatherogenic effects of niacin as well as some limitations of the designs of the AIM high and HP2-THRIVE studies. We also provide the possibilities of rational usage of niacin for specific types of dyslipidemias.
Niacin Therapy, HDL cholesterol, and Cardiovascular Disease: Is the HDL Hypothesis Defunct?
high-density lipoprotein cholesterol (HDL-C) has been shown in epidemiologic studies to be associated with cardiovascular (CV) risk and thus significant efforts have been focused on HDL-C modulation. Multiple pharmaceutical agents have been developed with the goal of increasing HDL-C. Niacin, the most widely used medication to raise HDL-C, increases HDL-C by up to 25 % and was shown in multiple surrogate end point studies to reduce CV risk. However, two large randomized controlled trials of niacin, AIM-high and HPS2-THRIVE, have shown that despite its effects on HDL-C, niacin does not decrease the incidence of CV events and may have significant adverse effects. Studies of other classes of agents such as cholesteryl ester transfer protein (CETP) Inhibitors have also shown that even dramatic increases in HDL-C do not necessarily translate to reduction in clinical events. While these findings have cast doubt upon the importance of HDL-C modulation on CV risk, it is becoming increasingly clear that HDL function-related measures may be better targets for CV risk reduction. Increasing ApoA-I, the primary apolipoprotein associated with HDL, correlates with reduced risk of events, and HDL particle concentration (HDL-P) inversely associates with incident CV events adjusted for HDL-C and LDL particle measures. cholesterol efflux, the mechanism by which macrophages in vessel walls secrete cholesterol outside cells, correlates with both surrogate end points and clinical events. The effects of niacin on these alternate measures of HDL have been conflicting. Further studies should determine if modulation of these HDL function markers translates to clinical benefits. Although the HDL cholesterol hypothesis may be defunct, the HDL function hypothesis is now poised to be rigorously tested.
Nicotinic acid
Objective: To determine the efficacy of nicotinic acid on the lipid profile of diabetic and non diabetic rats.
Methods: This was an experimental study done at the Institute of Molecular Biology and Biotechnology, The University of Lahore, Pakistan between May 2010 to July 2010. Nicotinic acid was administered to a hypercholesterolemic group and a hypercholesterolemic + diabetic Group of Albino rats for 42 days and response to therapy was recorded on day 21 and day 42 of the experiment. Comparison among these two groups as well as three control groups was determined by Analysis of Variance (ANOVA) and differences were considered significant at (P<0.05). A total of 50 rats were included in the study.
Results: lipid profile of the hypercholesterolemic group as well as hypercholesterolemic + diabetic group as compared with the control groups showed highly significant improvement on the day 21 and day 42 of the experiment. The values of serum total cholesterol (TC), Triglycerides (TG), low density lipoprotein (LDL) cholesterol and total lipids (TL) showed highly significant decrease whereas serum high density lipoprotein (HDL) cholesterol showed highly significant increase.
Conclusion: Nicotinic acid is the most effective agent available in increasing HDL cholesterol and lowering serum TC, Triglycerides (TG), LDL cholesterol and TL in hypercholesterolemic Diabetic and hypercholesterolemic non-diabetic Albino rats.
Nuciferine
The purpose of this study was to investigate whether dietary nuciferine affects lipid metabolism in broiler chickens. Four treatment groups were made from 120 1-day-old broiler chickens including the base diet group (normal control [NC], supplemented with 0 mg/kg of nuciferine) and groups treated with 25 mg/kg, 100 mg/kg, and 400 mg/kg of dietary nuciferine, which was supplemented for 42 d. The results showed that body weight, average daily weight gain, and absolute and relative fat and liver weight were significantly decreased with nuciferine supplementation. The plasma concentration of triiodothyronine, free triiodothyronine, thyroxine, and free thyroxine was significantly decreased in the nuciferine-supplemented group, but the plasma glucagon concentration was significantly increased. The plasma and hepatic Triglyceride (TG) and total cholesterol (TC) concentrations were significantly decreased in the nuciferine group, but plasma and hepatic nonesterified fatty acid concentration, hepatic lipase activity, and hepatic glycogen content were significantly increased. Hepatic histological examination showed that fat cell volume and size in the 100 and 400 mg/kg group were smaller than those in the NC group. The fatty degeneration in the liver was decreased with nuciferine supplementation. The fat cell volume and size were shrunk in the nuciferine group. dietary nuciferine supplementation significantly decreased the gene expression level of HMGCR, SREBP2, ACC, and SPEBP-1C, but significantly increased the gene expression level of LXR-α, CYP7A1, and CPT-I. The results indicated that nuciferine exhibited strong reduced fat deposition activities and reflected not only by decrease of the concentration of Triglyceride and TC but also by reduction in the key gene expression level of HMGCR, SREBP2, ACC, and SPEBP-1c and elevation of the key gene expression level of LXR-α, CYP7A1, and CPT-I. Taken together, our results suggested that the ability of nuciferine on reducing fat deposition in broiler chickens by regulating lipid metabolism was associated with the balance of Triglyceride and TC concentration.
Nuciferine Prevents Hepatic Steatosis by Regulating lipid metabolismin Diabetic Rat Model
Objective
This study investigatesthe nuciferine capacity to regulate the liver’s lipid metabolism regarding steatosis and injury in STZ-induced diabetic rats.
Materials and Methods
The rats were randomly divided into groups control, diabetic and nuciferine 200 mg/kg/ day treatment. After 4 days of STZ injection, the nuciferine group was treated and administered via oral gavages for 4 weeks. At the end of experiment, blood, liver, myocardial and muscular samples were collected.
Results
Nuciferine-treated significantly increased the body weight from 339.4g to 367.8g, but significantly decreased the food and water intake compared with diabetic rats. Also, the nuciferine-treated rats had significantly decreased TC, TG, and FFAs in the liver compared with the diabetic group, especially the serum markers of blood glucose. These were associated with the gene expression related to lipogenesis which was significantly down-regulated; the gene expression involved in lipolysis and fatty acid β-oxidation was significantly up-regulated. Discussion and
Conclusion
The data provide evidence that nuciferine supplementation could protect the liver by regulating lipid metabolism gene expression resulting in decreasing the steatosis and injury in diabetic rat. Thus, nuciferine could be developed as a diabetic adjuvant food additive in future.
Ocimum sanctum L.extract
Administration of fresh leaves of Ocimum sanctum (Tulsi) mixed as 1 g and 2 g in 100 gms of diet given for four weeks, brought about significant changes in the lipid profile of normal albino rabbits. This resulted in significant lowering in serum total cholesterol, Triglyceride , phospholipid and LDL–cholesterol levels and significant increase in the HDL-cholesterol and total faecal sterol contents.
It has been reported that Ocimum sanctum L. (OS) leaves decrease serum lipid profile in normal and diabetic animals. No experimental evidences support the anti-hyperlipidemic and antioxidative actions against hypercholesterolemia. Moreover the identity of the specific chemical ingredients in OS leaves responsible for these pharmacological effects are unknown. Since OS leaves are rich in essential oil (EO). Therefore the present study was conducted to investigate the anti-hyperlipidemic and antioxidative activities of EO extracted from OS leaves in rats fed with high cholesterol (HC) diet. EO was extracted by the hydrodistillation method and the chemical constituents were then identified by Gas Chromatography-Mass Spectrometry. The experiment was performed in Male Wistar rats fed with 2.5 g%(w/w) of cholesterol diet for seven weeks. During the last 3 weeks, rats were daily fed with EO. The results showed that phenyl propanoid compounds including eugenol and methyl eugenol were the major constituents of EO. EO suppressed the high serum lipid profile and atherogenic index as well as serum lactate dehydrogenase and creatine kinase MB subunit without significant effect on high serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in rats fed with HC diet. In addition, EO was found to decrease the high levels of thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPx) and superoxide dismutase (SOD) without impacting catalase (CAT) in the cardiac tissue while in the liver, it decreased high level of TBARS without significantly effecting GPx, SOD and CAT. Histopathological results confirmed that EO preserved the myocardial tissue. It can be concluded that EO extracted from OS leaves has lipid–lowering and antioxidative effects that protect the heart against hypercholesterolemia. Eugenol that is contained in EO likely contribute to these pharmacological effects.
Oenothera villosa Thunb extract
Background
Studies have shown that evening primrose oil (EPO) supplementation might be effective in improving lipid profile, however, the results are inconsistent. This study was performed to determine the direction and magnitude of the EPO effect on the lipid profile.
Methods
PubMed, Scopus, Cochrane Library, Embase and Web of Science databases and Google Scholar were searched up to September-2019. Meta-analysis was performed using the random-effects model. lipid profile including high-density lipoprotein (HDL), total cholesterol (TC), Triglyceride (TG), and low-density lipoprotein (LDL) was considered as the primary outcome.
Results
A total of 926 articles were identified through database searching, of which, six RCTs were included in the meta-analysis. There were six studies on HDL, TC, and Triglyceride and four studies on LDL. EPO supplementation had no significant effect on TC, TG, LDL, and HDL. However, in subgroup analysis, a significant reduction in Triglyceride at a dose of ≤4 g/day (weighted mean difference [WMD] = −37.28 mg/dl; 95% CI: −73.53 to −1.03, p = .044) and a significant increase in HDL in hyperlipidemic subjects (WMD = 5.468 mg/dl; 95% CI: 1.323 to 9.614, p = .010) was found.
Conclusion
Oral intake of EPO at a dose of ≤4 g/day significantly reduces serum Triglyceride levels and significantly increases HDL levels in hyperlipidemic subjects.
Olea europaea seeds
Our previous work demonstrated the presence of compounds with hypocholesterolemic capacity in olive seeds. These compounds were extracted using CO2-expanded ethyl acetate and identified as tyrosol, hydroxytyrosol, and β-sitosterol using GC–MS. This work describes the extraction of these compounds from different olive seeds using pressurized ethyl acetate. Their solubility in ethyl acetate at temperatures ranging from 40–200 °C was theoretically predicted by Hansen solubility parameters. The content of these compounds was estimated by GC–MS, as well as, the reduction of the micellar cholesterol solubility (RMCS) capacity of extracts enabling to establish the optimum extraction temperature at 100 °C. A GC–MS method was developed and validated in terms of its analytical characteristics for a sensitive determination and quantification of tyrosol, hydroxytyrosol, and β-sitosterol in different olive seeds. Within varieties, Manzanilla seeds presented the highest concentration of tyrosol, hydroxytyrosol, and the lowest concentration of β-sitosterol, as well as the highest RMCS capacity.
Olive leaf extract
Background
The anti-atherogenic effect of olive leaf extract is supposed to be related to its activities of anti-oxidation and anti-inflammation.
Aim of the study
To prove the effect of anti-Atherosclerosis by olive leaf extract (OLE) and to elucidate the mechanism behind.
Methods
Twenty-four rabbits were assigned to the control, high lipid diet (HLD) and OLE group that were fed with standard diet, HLD and HLD supplemented with OLE, respectively. serum levels of Atherosclerosis related markers, Triglyceride (TG), total cholesterol (T-CHO), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and malondialdehyde (MDA) were detected at the ends of week 2, 4 and 6. Surface lesions and thickness of intimas were measured at the end of week6. The protein and/or mRNA expressions of inflammation factors, monocyte chemoattractant protein (MCP)-1, vascular cell adhesion molecule (VCAM)-1, nuclear factor-kappa B (NF-κB) and tumor necrosis factor α (TNF-α) were investigated by immunohistochemistry and RT-PCR.
Results
Atherosclerotic lesions were found in the HLD and OLE groups but not in the control group. In comparison with that in the HLD group, reduced size and thickness of intima (0.31 ± 0.26 in the HLD group versus 0.10 ± 0.03 mm in the OLE group) were found in the OLE group. The MDA level, an indicator of antioxidant status, was 35.27 ± 15.37 in the HLD group and 20.63 ± 11.52 nmol/ml in the OLE group. The level of CHO, Triglyceride and LDL-C were 104.46 ± 30.34, 2.48 ± 1.11, 82.83 ± 28.44 mmol/l in the HLD group versus 83.03 ± 27.23, 1.84 ± 0.44, 59.51 ± 23.72 mmol/l in the OLE group. Down-regulated expressions of MCP-1, VCAM-1, NF-κB and TNF-α at both protein and mRNA level (P < 0.05) were also found with the administration of OLE.
Conclusion
This study proved the effect of OLE on inhibition of Atherosclerosis, which is related to the suppressed inflammatory response.
Pactimibe Sulfate
The objective of the present study was to determine whether a novel acyl-CoA:cholesterol acyltransferase (ACAT) Inhibitor, pactimibe sulfate (CS-505), could reduce atherosclerotic lesions beyond and independent of the reduction achieved by cholesterol lowering alone from two different types of lesions. (1) Early lesion model. Twelve-week-old apolipoprotein E (apoE)−/− mice were treated with 0.03 or 0.1% (w/w) CS-505, 0.1 or 0.3% avasimibe (CI-1011), or 3% cholestyramine for 12 weeks. Each treatment significantly reduced plasma cholesterol by a similar degree (43–48%). The Antiatherosclerotic activity of 0.1% CS-505, however, was more efficacious than the effects of the other treatments (90% versus 40–50%). (2) Advanced lesion model. Twenty-four-week-old apoE−/− mice were treated with 0.03 or 0.1% CS-505 or 0.1% CI-1011 for 12 weeks. CS-505 at 0.1% revealed enhanced lesion reduction compared with 0.1% CI-1011 (77% versus 54%), whereas the plasma cholesterol–lowering effect of 0.1% CS-505 was almost the same as that of 0.1% CI-1011. Furthermore, immunohistochemical analysis demonstrated that CS-505 significantly reduced the number of macrophages and expression of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13. These data indicate that CS-505 can reduce and stabilize atherosclerotic lesions. This Antiatherosclerotic activity is exerted via both cholesterol lowering and direct ACAT inhibition in plaque macrophages.
Paeonia lactiflora Pall
Ethnopharmacological relevance: Total glucosides of paeony (TGP), compounds extracted from the roots of Paeonia lactiflora Pall, have been used as an anti-inflammatory drug for the treatment of rheumatoid arthritis (RA) in China. Inflammation plays a critical role in the development of atherosclerotic vascular disease. Risk of cardiovascular diseases is significantly higher in patients with RA than in normal population. It has a great significance to study the effects of TGP on Atherosclerosis.
Aim of the study: To investigate the effects of TGP on Atherosclerosis induced by excessive administration of vitamin D and cholesterol in rats and study the mechanisms involved.
Materials and methods: Atherosclerosis was induced by excessive administration of vitamin D and cholesterol in rats. TGP was intragastrically administered for 15 weeks. The serum concentrations of total cholesterol (TC), Triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) were measured by automatic biochemistry analyzer. apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) were determined by immunoturbidimetry method, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay (ELISA) method. The morphological changes of aorta were observed with optical microscopy.
Results: Compared to controls, TGP significantly lowered the serum level of TC, TG, LDL-C, ApoB, TNF-alpha, IL-6 and CRP, increased the ratios of HDL-C/LDL-C and ApoA1/ApoB, decreased the intima-media thickness (IMT) of abdominal aortal wall and improved the morphological change of the aorta.
Conclusions: TGP may attenuate the development of atherosclerotic disease. The beneficial effects are associated with its lowering blood lipids and inhibiting the expression of inflammatory cytokines.
Paeonia Suffruticosa peel extract
With improvement in living standards and average life expectancy, atherosclerotic cardiovascular disease incidences and mortality have been increasing annually. Paeonia suffruticosa, a natural herb, has been used for the treatment of atherosclerotic cardiovascular disease for thousands of years in Eastern countries. Paeonol is an active ingredient extracted from Paeonia suffruticosa. Previous studies have extensively explored the clinical benefits of paeonol. However, comprehensive reviews on the cardiovascular protective effects of paeonol have not been conducted. The current review summarizes studies reporting on the protective effects of paeonol on the cardiovascular system. This study includes studies published in the last 10 years. The biological characteristics of Paeonia suffruticosa, pharmacological mechanisms of paeonol, and its toxicological and pharmacokinetic characteristics were explored. The findings of this study show that paeonol confers protection against atherosclerotic cardiovascular disease through various mechanisms, including inflammation, platelet aggregation, lipid metabolism, mitochondria damage, endoplasmic reticulum stress, autophagy, and non-coding RNA. Further studies should be conducted to elucidate the cardiovascular benefits of paeonol.
Panax ginseng C.A.Mey.extract
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
Passiflora edulis Sims. seed extract
effects of Passiflora edulis on the metabolic profile of diabetic Wistar rat offspring
Dry extract of the genus Passiflora has been shown to help control glycemia and lipid levels. The objective of this study was to evaluate the effects of passion fruit (P. edulis) on the biochemical profile of offspring from diabetic rats. Diabetes was induced by streptozotocin. The diabetes group consisted of 10 rats with glucose levels greater than 200 mg/dL; the nondiabetic (control) group consisted of 10 rats with glucose levels less than 120 mg/dL. After the diagnosis of diabetes, the mating phase was started. By day 21 of pregnancy, the offspring were born; the dams were kept in individual cages with their offspring until the weaning period. The offspring were then divided into 4 groups (n=15 each): G1 were offspring from control dams, G2 were offspring from treated nondiabetic dams, G3 were offspring from diabetic dams, and G4 were offspring from treated diabetic dams. For 30 consecutive days, G1 and G3 offspring were treated with vehicle (oral gavage) and G2 and G4 offspring were treated with passion fruit juice (oral gavage). After 30-day treatment, the animals were anesthetized and killed, and blood was drawn immediately for analysis of the biochemical profile (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, Triglycerides , and glucose). The G2 and G4 rats showed significantly reduced total cholesterol, Triglyceride , and low-density lipoprotein cholesterol levels and an increased high-density lipoprotein cholesterol level. The use of passion fruit juice improved lipid profiles, suggesting that this plant may have beneficial effects in the prevention and treatment of dyslipidemias and hyperglycemia.
Persea americana Mill
cholesterol–lowering Activity of Persea americana Mill
Several plant extracts were screened for their 3-hydroxy-3-methylglutaryl coenzyme A reduc-
tase Inhibitory activity. Persea americana Mill. was one of the most active extracts. The bioactive compo-
nent was identified using bioassay-guided scheme through the use of various chromatographic techniques.
Quercitrin and afzelin were identified using LC-MS techniques.
Persimmon tannin
The purpose of this study was to investigate whether persimmon tannin is associated with cholesterol efflux and macrophage-reverse cholesterol transport (RCT). In J774A.1 macrophage cells, persimmon tannin could inhibit cellular cholesterol accumulation and promote 22-NBD-cholesterol efflux through inhibiting the phosphorylation of ERK1/2 and up-regulating the protein levels of PPARγ. Macrophage RCT in vivo was evaluated by injecting 22-NBD-cholesterol-loaded J774A.1 macrophages intraperitoneally into C57BL/6J mice. Administration of persimmon tannin significantly (P < 0.05) decreased the cholesterol concentration in both serum and liver, and increased faecal cholesterol excretion compared with the high–cholesterol group. In transcriptional levels, persimmon tannin enhanced the expression of cholesterol transport-related genes (ABCA1, LCAT, ABCG5/G8, NPC1L1 and CYP7A1) and their upstream nuclear receptors (PPARγ, PPARα and LXRα). Moreover, the regulation of persimmon tannin on RCT-related genes might be mediated by its inhibition on ERK1/2 in mice. Therefore, persimmon tannin promoted macrophage reverse cholesterol transport through the regulation on ERK1/2-PPARγ signaling pathway both in vitro and in vivo.
Phaseolus vulgaris Linn extract
The cholesterol–lowering property of beans has been shown in several studies. The propose of the present work was to investigate the effect of black beans (Phaseolus vulgaris, L.) without hulls on blood cholesterol of hypercholesterolemic rats. Four groups of 8 male rats, Wistar strain, initial body weight of 200 g were kept at +/- 25 degrees C in a light-dark cycle of 12 h, for 28 days. The group Standard received a basal casein diet. Group Control received the basal diet added of 1% cholesterol plus 0.1% cholic acid. The group BB received a diet similar to the Control, substituted by 30% black beans, on dry-weight. The group SBB received black beans without hulls, equivalent to 30% of whole beans. The addition of cholesterol and cholic acid raised blood cholesterol levels of rats on Control diet by 58%, in relation to the Standard. BB diet reduced blood cholesterol by 15% (non-significant-NS) and SBB diet reduced (p < 0.05) by 35%, in relation to the Control diet. The levels of HDL-cholesterol were reduced (p < 0.05) by both bean diets. SBB diet promoted a higher excretion of fecal cholesterol, compared to the Control. This suggests that beans without hulls promote a higher cholesterol output and that the whole beans, although had lowered blood cholesterol (NS), kept it in the enterohepatic circulation. The hypocholesterolemic compounds of beans seem to be located in the inner part of the grain. Further studies are necessary to identify these compounds and to elucidate their mechanisms of action.
Pinellia ternata(Thunb) Breit.)extract
Context: Clinically, Pinellia ternata (Thunb.) Breit. (Araceae) (PT) has been widely used in the treatment of Atherosclerosis and hyperlipidaemia, but the underlying mechanisms are still not clearly understood.
Objective: This research was conducted to confirm the mechanism by which PT affects carotid artery intimal hyperplasia.
Materials and methods: An intestinal hyperplasia Sprague-Dawley rat model was established by carotid artery injury. The rats were randomly divided into five groups (n = 8): sham, model, PT (with daily intragastric administration of 10 g/mL/kg PT tubers water extract), PT+LY294002 (with intraperitoneal injection of 50 mg/kg LY294002 + 10 g/mL/kg PT) and endothelial progenitor cells (EPCs) (with injection of 5 × 105/cells), and treated for 4 or 8 weeks.
Results: HE staining showed that PT attenuated intimal hyperplasia. RT-PCR, Western blotting and immunohistochemistry showed that PT increased the expression of vascular endothelial growth factor (VEGF) and eNOS in the atherosclerotic carotid artery. PT increased the Dil-acLDL+/FITC-UEA-1+ population (from 0.41 ± 0.085% to 0.60 ± 0.092%) in the blood, decreased TCHO, TG, LDL-C, IL-6 and TNF-α levels, and increased HDL-C and IL-10 levels in the blood. However, these changes were reversed by the PI3K/Akt pathway Inhibitor LY294002.
Discussion and conclusions: PT can be developed as an Atherosclerosis and carotid intimal hyperplasia treatment drug. Therefore, further study will focus on the effects of PT on intimal hyperplasia in wire-injured Atherosclerosis patients and explore in depth some other relevant molecular mechanisms.
Platycodon grandiflorus (Jacq.)A.DC. extract
The root of Platycodon grandiflorum (PG) has long been used as a traditional herbal medicine in Asian country. Platycondin D (PD), triterpenoid saponin that is a main constituent of PG, exhibits various biological activities such as anti-inflammatory, anti-oxidant, anti-diabetic, and anti-cancer effects. A previous study showed that PD had cholesterol–lowering effects in mice that develop hypercholesterolemia, but the underlying molecular mechanisms have not been elucidated during the last decade. Here, we demonstrated that both PG and PD markedly increased levels of cell surface low-density lipoprotein receptor (LDLR) by down-regulation of the E3 ubiquitin ligase named inducible degrader of the LDLR (IDOL) mRNA, leading to the enhanced uptake of LDL-derived cholesterol (LDL-C) in hepatic cells. Furthermore, cycloheximide chase analysis and in vivo ubiquitination assay revealed that PD increased the half-life of LDLR protein by reducing IDOL-mediated LDLR ubiquitination. Finally, we demonstrated that treatment of HepG2 cells with simvastatin in combination with PG and PD had synergistic effects on the improvement of LDLR expression and LDL-C uptake. Together, these results provide the first molecular evidence for anti-hypercholesterolemic activity of PD and suggest that PD alone or together with statin could be a potential therapeutic option in the treatment of atherosclerotic cardiovascular disease.
The root of Platycodon grandiflorus (PG), with hepatoprotective and anti-oxidation effects, has a long history of being used as food and herbal medicine in Asia. However, the mechanism of PG against non-alcoholic fatty liver disease (NAFLD) is still not clear. The aim of this study was to investigate the mechanism of PG suppressing the development of NAFLD induced by a high-fat diet (HFD) in mice. Male C57BL/6J mice were fed with either a standard chow diet or a HFD, either supplemented with or without PG, for 16 weeks. serum lipids, liver steatosis, oxidative stress and insulin sensitivity were determined. Expressions or activities of hepatic enzymes in the related pathways were analyzed to investigate the mechanisms. PG significantly reduced HFD-induced hepatic injury and hyperlipidemia, as well as hepatic steatosis via regulating phosphorylation of acetyl-CoA carboxylase (p-ACC) and expression of fatty acid synthase (FAS). In addition, PG ameliorated oxidative stress by restoring glutathione (GSH) content and antioxidant activities, and improved insulin sensitivity by regulating the PI3K/Akt/GSK3β signaling pathway. Our data showed that dietary PG have profound effects on hepatic insulin sensitivity and oxidative stress, two key factors in the pathogenesis of NAFLD, demonstrating the potential of PG as a therapeutic strategy for NAFLD.
cholesterol–lowering effect of platycodin D in hypercholesterolemic ICR mice
This study investigates the in vivo hypocholesterolemic action of platycodin D and its in vitro evidence for the cholesterol–lowering properties. In order to examine the effects of platycodin D on hypercholesterolemia in male ICR mice, platycodin D with doses of 15, 30 or 50 mg/kg was orally administered for 8 weeks. Changes in body weight and daily food intake were measured regularly during the experimental period. Final contents of Triglyceride and different types of cholesterol in the serum, livers and feces were determined. The effects of platycodin D on cholesterol metabolism were further investigated with several in vitro assays, including antioxidant effect on low density lipoprotein oxidation, inhibition of human acyl-coenzyme A:cholesterol acyltransferase (hACAT) and serum lipoprotein associated-phospholipase A2 (Lp-PLA2), as well as the regulation of farnesoid X receptor. The formation of insoluble complex between platycodin D and cholesterol was also investigated. Following an eight week experimental period, the body weights of platycodin D-fed mice were less than those of control mice on a high cholesterol diet by 11.2 ± 5% (P < 0.01) with 15 mg/kg platycodin D, 11.7 ± 5% (P < 0.01) with 30 mg/kg platycodin D, and 23.4 ± 7.9% (P < 0.0001) with 50 mg/kg platycodin D, respectively. A decrease in daily food consumption was also noted in most of the treated animals. Triglyceride and cholesterol concentrations were decreased in serums and livers, but increased in feces. Some of the in vitro observations revealed that the hypocholesterolemic effect of platycodin D is partly associated with inhibition to hACAT activity and antagonism to the farnesoid X receptor as well as the formation of insoluble complex with between platycodin D and cholesterol. Both in vivo and in vitro results demonstrate a potential value of platycodin D as a novel cholesterol–lowering and anti-atherogenic candidate.
Pleurotus ostreatus extract
lipid lowering effects of oyster mushroom (Pleurotus ostreatus) in humans
Elevated cholesterol and triacylglycerol levels are known risk factors for cardiovascular diseases. A number of animal studies have indicated that the consumption of oyster mushrooms (Pleurotus ostreatus) can positively influence the lipid profile. The present intervention study for the first time investigated the cholesterol lowering properties of an oyster mushroom diet in humans. A total of 20 subjects (9 male, 11 female; 20–34 years) were randomized to take either one portion of soup containing 30 g dried oyster mushrooms or a tomato soup as a placebo on a daily basis for 21 days. Standardized blood concentrations of lipid parameters and oxidized low density lipoprotein were measured at the baseline (t0) and after 21 days (t21). Treatment with oyster mushroom soup decreased triacylglycerol concentrations (−0.44 mmol/L; p = 0.015) and oxidized low density lipoprotein levels (−7.2 U/mL; p = 0.013) significantly, and showed a significant tendency in lowering total cholesterol values (−0.47 mmol/L; p = 0.059). No effects on low density lipoprotein and high density lipoprotein levels were found. The beneficial effects of oyster mushroom on blood serum parameters may be attributed to the presence of linoleic acid, ergosterol and ergosta-derivatives which showed notable activity in oxygen radical absorbance capacity and cyclooxygenase inhibition assays in vitro.
hypolipidemic Activities of dietary Pleurotus ostreatus in Hypercholesterolemic Rats
This work was conducted to investigate dietary supplementation of oyster mushroom fruiting bodies on biochemical and histological changes in hyper and normocholesterolemic rats. Six-week old female Sprague-Dawley albino rats were divided into three groups of 10 rats each. Feeding a diet containing a 5% powder of Pleurotus ostreatus fruiting bodies to hypercholesterolemic rats reduced plasma total cholesterol, Triglyceride , low-density lipoprotein (LDL), total lipid, phospholipids, and LDL/high-density lipoprotein ratio by 30.18, 52.75, 59.62, 34.15, 23.89, and 50%, respectively. Feeding oyster mushrooms also significantly reduced body weight in hypercholesterolemic rats. However, it had no adverse effects on plasma albumin, total bilirubin, direct bilirubin, creatinin, blood urea nitrogen, uric acid, glucose, total protein, calcium, sodium, potassium, chloride, inorganic phosphate, magnesium, or enzyme profiles. Feeding mushroom increased total lipid and cholesterol excretion in feces. The plasma lipoprotein fraction, separated by agarose gel electrophoresis, indicated that P. ostreatus significantly reduced plasma β and pre-β-lipoprotein but increased α-lipoprotein. A histological study of hepatic cells by conventional hematoxylin-eosin and oil red O staining revealed normal findings for mushroom-fed hypercholesterolemic rats. These results suggest that a 5% P. ostreatus diet supplement provided health benefits by acting on the atherogenic lipid profile in hypercholesterolemic rats.
We studied the effect of the edible mushroom Pleurotus ostreatus (4% in diet containing 1 % of cholesterol) on serum and liver lipids in female rats with hereditary enhanced sensitivity to alimentary cholesterol. We found that the consumption of the mushroom-containing diet prevented serum cholesterol increase which was manifested at the end of the 4th week of the experiment. At the end of the 7th week of the experiment the choles-terolemia was lowered by almost 40% as compared with control animals kept on the same diet but without the mushroom. The decrease in serum cholesterol levels is a consequence of the decreased cholesterol concentrations of very-low-density lipoproteins and of low-density lipoproteins.
Policosanol
cholesterol–lowering effects of policosanol in rabbits.
Policosanol is a natural mixture of higher primary aliphatic alcohols isolated and purified from sugar cane (Saccharum officinarum, L.) wax, whose main component is octacosanol. Policosanol (5-200 mg/kg) orally administered for 4 weeks to normocholesterolemic New Zealand rabbits significantly reduced total cholesterol and low density lipoprotein cholesterol (LDL-C) serum levels in a dose dependent manner. serum Triglyceride levels of treated and control animals were significantly different, but the reduction observed was not dose-dependent. high density lipoprotein cholesterol (HDL-C) levels remained unchanged. Results indicate that the reduction in total cholesterol values induced by policosanol is mainly mediated through a decrease in LDL-C levels.
The effect of policosanol, a mixture of high-molecular-weight aliphatic alcohols isolated from sugar-cane wax, on casein-induced hypercholesterolaemia in rabbits was studied. When policosanol was administered by the oral route once daily for 30 d (50mg/kg) the increases in plasma total cholesterol and LDL–cholesterol (LDC-C) were significantly reduced when compared with the control group. The incorporation of 3H2O into sterols in the liver was significantly depressed, suggesting inhibition of hepatic cholesterol biosynthesis. The oral administration of policosanol raised the rate of removal of 125l-labelled LDL from serum. Kinetic parameters calculated following injection of [125I]LDL showed than in casein-fed rabbits, the terminal half-life (t½) was significantly decreased after policosanol treatment. The hepatic LDL-binding activity was increased after policosanol administration which suggested that the enhanced clearance was due, at least in part, to increased receptor-mediated uptake of LDL by the liver. Considered together, these results suggest that policosanol can significantly reduce the increase of plasma LDL-C in rabbits fed on a wheat starch-casein diet by reducing cholesterol biosynthesis in the liver. Such an effect could account for the enhancement of LDL catabolism through the receptor-mediated pathway.
Antiatherosclerotic Efficacy of Policosanol, Red Yeast Rice Extract and Astaxanthin in the Rabbit
The effects of policosanol (P), of extract of red yeast rice (rice fermented with Monascus purpureus) (RYE) and of astax-anthin (A) (constituents of Armolipid®) were investigated in a model of experimental Atherosclerosis provoked in the rabbit by atherogenic cholesterol-enriched feed (ACEF). P and RYE and their combination were able to lower the increase of serum total cholesterol and of LDL cholesterol elicited by 3-month feeding with ACEF. They also were able to reduce the increase of blood malondial-dehyde (MDA), a tracer of lipid peroxidation by the free radicals released by ACEF. When combined, the substances developed either additive or potentiated effects, supporting the rationale of their combination. Remarkable was the protective effect on lipid infiltration in the aortic wall provoked by ACEF, which was reduced by P and by RYE and almost completely prevented by the addition of A to the P-RYE combination.
Polygonum cuspidatum
Resveratrol (Res) was previously reported to be capable of lowering plasma TC and LDL-C. The mechanism behind Res is not clearly understood, although it is presumed to have an effect on bile acid metabolism in the liver: a significant way in eliminating cholesterol from the body. As one of the major metabolites of Res in the liver, resveratrol glucuronides (Gres) is suspected to also contribute to the overall cholestrol-lowering activity of Res, which needs to be studied. In this research, when HepG2 steatosis hepatic cells were treated with Res and Gres at different concentration levels, Res and Gres showed similar activity in lowering cellular TC content. The presence of Res and Gres caused a significant increase in hepatic CYP7A1 and BSEP, indicating the increase in the synthesis and efflux of bile acids, respectively. The reduction of HMG-CoAR tied to a decrease in de novo synthesis of cholesterol and the increase of ABCG5 suggested the increase of direct efflux of cholesterol. All above variations reduced the hepatic cholesterol level, which triggered the significant enhancement of LDLR, illustrating the improvement of clearance of LDL-C from the plasma and prevention of Atherosclerosis. Overall, this study demonstrated both Res and Gres might have capabilities in lowering hepatic cholesterol through increasing in the synthesis and efflux of bile acids, and decreasing in synthesis and increasing in the efflux of cholesterol. Gres would have preferred potential than Res because of its lower cytotoxicity, which indicated that the action of the metabolites should also be considered in the future studies.
Polygonum cuspidatum (PC) has been reported to exert a potent antihyperlipidemic effect. However, its mechanisms of action and active ingredients remain elusive and require further research. In this study, we first conducted in vivo experiments to validate that Polygonum cuspidatum extract (PCE) could ameliorate the blood lipid level in hyperlipidemia model rats. Then, ultrahigh performance liquid chromatography coupled with Q-Exactive MS/MS (UPLC-QE-MS/MS) was applied to verify its 12 main active ingredients. The pharmacophore matching model was employed to predict the target point of the active ingredient, and 27 overlapping genes were identified via database and literature mining. String online database and Cytoscape software were utilized to construct a Protein-Protein Interaction (PPI) network, followed by function annotation analysis and pathway enrichment analysis. The results showed that the PI3K/AKT signaling pathway and its downstream FOXO3/ERα factors were significantly enriched. Furthermore, in vitro experiments were performed to determine the lipid content and oxidative stress (OS) indicators in OA-induced HepG2 cells, and immunofluorescence and western blotting analysis were carried out to analyze the effects of PCE on related proteins. Our experimental results show that the mechanism of antihyperlipidemic action of PCE is related to the activation of the PI3K/AKT signaling pathway and its downstream FOXO3/ERα factors, and polydatin and resveratrol are the main active ingredients in PCE that exert antihyperlipidemic effects.
Polygonum multi forum Thunb.root extract
Review of clinical studies of Polygonum multiflorum Thunb. and its isolated bioactive compounds
Polygonum multiflorum Thunb. (PMT), officially listed in the Chinese Pharmacopoeia, is one of the most popular perennial Chinese traditional medicines known as He shou wu in China and East Asia, and as Fo-ti in North America. Mounting pharmacological studies have stressed out its key benefice for the treatment of various diseases and medical conditions such as liver injury, cancer, diabetes, alopecia, Atherosclerosis, and neurodegenerative diseases as well. International databases such as PubMed/Medline, Science citation Index and Google Scholar were searched for clinical studies recently published on P. multiflorum. Various clinical studies published articles were retrieved, providing information relevant to pharmacokinetics-pharmacodynamics analysis, sleep disorders, dyslipidemia treatment, and neurodegenerative diseases. This review is an effort to update the clinical picture of investigations ever carried on PMT and/or its isolated bio-compounds and to enlighten its therapeutic assessment.
Polymnia Sonchifolia Poepp.
This study was carried out to investigate the effect of Yacon (Polymnia sonchifolia Poepp. & Endl.) powder on cholesterol–lowering and anti-obesity effects in rats fed a high fat-high cholesterol diet for 4 weeks to induce hyperlipidemic and obese rat model. Weight-matched male Sprague-Dawley rats were assigned to four groups according to dietary fat, cholesterol levels and Yacon powder levels. Experimental groups were normal diet group (N), high fat-high cholesterol diet group (HFC), high fat-high cholesterol diet with 5% Yacon powder group (HFC-PSL) and high fat-high cholesterol diet with 10% Yacon powder group (HFC-PSH). The body weight gain and FER were increased by a high fat-high cholesterol diet, but gradually decreased in the Yacon powder fed groups compared with the HFC group. Food intake was lower in HFC groups compared with N group. The liver and adipose tissue weights of HFC group were heavier than those of N group, whereas those of groups administered Yacon powder were gradually decreased. The serum ALT, AST, ALP and LDH activities elevated by a high fat-high cholesterol diet were significantly decreased by Yacon powder administration. Levels of serum total cholesterol, LDL–cholesterol, atherogenic index and cardiac risk factor showed a decreasing tendency in the Yacon powder fed groups compared with HFC group. The serum HDL-cholesterol level decreased in the HFC group and markedly increased in the Yacon powder fed groups. Levels of total cholesterol and Triglyceride in liver and adipose tissues were lower in Yacon powder administered groups than those in HFC group. These results suggest that Yacon powder may improve lipid metabolism of serum, liver, and adipose tissue and potentially reduce lipid storage.
Pomegranate (Punica granatum L.)
Pomegranate (Punica granatum L.) will be examined by looking at the ability between pomegranate extracts or fractions, which are more effective in lowering total blood cholesterol and Triglyceride levels in mice. This study aims to determine the active pomegranate fraction that can reduce the total cholesterol levels and Triglyceride in mice. The research method used was an experimental method with a Completely Randomized Design (CRD) which was divided into 6 treatment groups, and test animals divided into 6 treatment groups namely negative control given aquades, positive control fed a high-fat diet, given simvastatin, given 25 mg/grBB of pomegranate methanol fraction, given 50 mg/grBB of pomegranate methanol fraction, given 100 mg/grBB of pomegranate methanol fraction, each treatment group will be divided into 4 male mice.Based on the results of this study that the active fraction that has an effect in reducing blood cholesterol levels and mice Triglycerides is the treatment given 100mg/grBB of pomegranate water methanol fraction.
Primitivo polyphenolic extract
Purpose
The aim of the study was to evaluate the vascular anti-inflammatory effects of polyphenolic extracts from two typical South Italy red wines, the specific contribution of individual polyphenols and the underlying mechanisms of action.
Methods
Human endothelial cells were incubated with increasing concentrations (1–50 μg/mL) of Primitivo and Negroamaro polyphenolic extracts (PWPE and NWPE, respectively) or pure polyphenols (1–25 μmol/L), including hydroxycinnamic acids (p-coumaric, caffeic and caftaric acids), flavonols (kaempferol, quercetin, myricetin) or stilbenes (trans-resveratrol, trans-piceid) before stimulation with lipopolysaccharide. Through multiple assays, we analyzed the endothelial–monocyte adhesion, the endothelial expression of adhesion molecules (ICAM-1, VCAM-1 and E-Selectin), monocyte chemoattractant protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF), as well as ROS intracellular levels and the activation of NF-κB and AP-1.
Results
Both PWPE and NWPE, already at 1 μg/mL, inhibited monocyte adhesion to stimulated endothelial cells, a key event in triggering vascular inflammation. They down-regulated the expression of adhesion molecules, ICAM-1, VCAM-1, E-Selectin, as well as MCP-1 and M-CSF, at mRNA and protein levels. All polyphenols reduced intracellular ROS, and everything, except caftaric acid, inhibited the endothelial expression of adhesion molecules and MCP-1, although with different potency. Flavonols and resveratrol significantly reduced also the endothelial expression and release of M-CSF. The decrease in endothelial inflammatory gene expression was related to the inhibition of NF-κB and AP-1 activation but not to intracellular oxidative stress.
Conclusions
This study showed multiple anti-inflammatory and Anti-atherosclerotic properties of red wine polyphenolic extracts and indentified specific bioactive polyphenols which could counteract inflammatory diseases including Atherosclerosis.
Propolis extract
The ethanolic extract of propolis (EEP) is beneficial in increasing high density lipoprotein (HDL) cholesterol (HDL-C) and diminishing risks of Atherosclerosis. In this study, we examined the effects of EEP on reverse cholesterol transport in mice. 3H –cholesterol laden macrophage was injected intraperitoneally into mice fed by gastric gavage with EEP. Plasma lipid level was determined and 3H-cholesterol was traced in plasma, liver and feces. The effects of EEP on ATP-binding cassette transporter A1 and G1 (ABCA1 and ABCG1) and scavenger receptor BI (SR-BI) in mice liver and in cultured cells were also investigated. EEP administration led to a significant increase in HDL-C and peritoneal macrophage-original 3H-cholesterol in plasma, liver and feces. Liver protein expressions of ABCA1 and ABCG1 were increased but SR-B1 was not. In vitro experiments with HepG2 and Raw264.7 cell lines confirmed the above results. The finding of these studies shows that EEP-enhanced reverse cholesterol transport may have resulted from EEP stimulated plasma HDL level and hepatic ABCA1 and ABCG1 expression.
Prosopis cineraria bark
dietary antioxidants and flavonoids like phytochemicals occurred in several herbs have potential to improve cardiovascular health. Prosopis cineraria (Fabaceae) is also widely uses on above basis for traditional therapeutic purposes. It is the Thar Desert prominent tree. This study evaluated the hypolipidemic and Antiatherosclerotic effects of Prosopis cineraria bark extract in hyperlipidemic rabbits. The rabbits were made to induce exogenously hyperlipidemic through orally administration of high fat diet and cholesterol powder (500mg/Kg body weight per day in 5 ml of coconut oil orally for 15 days). The induced hyperlipidemic rabbits were treated comparatively by bark extract of Prosopis cineraria and standard drug. The administration of Prosopis cineraria bark extract (70% ethanol) significantly (P ≤ 0.001) reduced serum total cholesterol (88%), LDL-C (95%), Triglyceride (59%), VLDL-C (60%) and also ischemic indices (Total cholesterol/LDL-C and LDL-C/HDL-C). The Prosopis cineraria bark extract also significantly (P ≤ 0.001) prevented the atherogenic changes in aorta. Toxicity profile parameters were also examined and remained under normal ranges. Results indicated that Prosopis cineraria bark has hypolipidemic and Antiatherosclerotic efficacy along with non-toxic nature.
Pueraria lobata (Willd.) Ohwi root extract
Context
Atherosclerosis (AS) is the main cause of cardiovascular and cerebrovascular diseases. Pueraria lobata (Willd.) Ohwi (Fabaceae) has a positive effect on improving these diseases.
Objective
The P. lobata effect on the proliferation and inflammation of vascular smooth muscle in AS and the potential mechanism were investigated.
Materials and methods
By feeding a high-fat diet to 8-week-old apolipoprotein E knockout mice, an Atherosclerosis model was created. H&E and IHC staining were used to analyse the histopathology of mice. CCK-8, TUNEL, and scratch tests were used to detect cell proliferation, apoptosis, and migration after 24 h treatment, respectively. ELISA was performed to evaluate the level of IL-6 and IL-8. The target miRNA and its downstream target gene were screened by the bioinformatics method; RT-qPCR has conducted to analyse the expression of these genes.
Results
In the aortic tissue and serum of AS mice, puerarin can lower the expression of α-SMA and the inflammatory proteins IL-6 and IL-8. Puerarin (200 M) decreased hVSMC proliferation, migration, and IL-6 and IL-8 secretion by more than half. The Inhibitory impact of puerarin on hVSMC was decreased by overexpression of miR-29b-3p. IGF1 was miR-29b-3p’s downstream target gene. IGF1 expression increased almost 3-fold in AS mice and hVSMC, but miR-29b-3p mimic inhibited it. The effect of miR-29b-3p on hVSMC was reversed when IGF1 was overexpressed.
Discussion and conclusions
Puerarin inhibits the proliferation and inflammation of vascular smooth muscle in AS through the miR-29b-3p/IGF1 pathway. Puerarin may have a beneficial effect in the treatment of Atherosclerosis and offer a novel therapy option.
Puerarin
Roles and mechanisms of puerarin on cardiovascular disease：A review
Cardiovascular diseases (CVDs) are now the leading cause of mortality and morbidity worldwide，resulting in a large global economic burden. Recently, complementary and alternative medicine, such as traditional Chinese medicine (TCM) have received great attention. Puerarin (Pue) is an isoflavone isolated from the roots of Pueraria lobata (Willd.) Ohwi (also named “Ge gen” in China), and is a versatile TCM herb used for the treatment of fever, diarrhea, diabetes mellitus CVDs and cerebrovascular diseases. Numerous lines ofin vitro studies, as well as in vivo animal experiments have established that Pue offers beneficial roles against the progression of Atherosclerosis, ischemic heart diseases, heart failure hypertension and arrhythmia by inhibiting pathological processes, such as the mitigation of endothelium injury, protection against inflammation, the disturbance of lipid metabolism, protection against ischemic reperfusion injury, anti-myocardial remodeling and other effects. Here, we provide a systematic overview of the pharmacological actions and molecular targets of Pue in cardiovascular disease prevention and treatment, to provide insights into the therapeutic potential of Pue in treating cardiovascular diseases.
Quercetin
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL–cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an Inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Background
Quercetin, one of the most widely distributed flavonoids in plants, has been demonstrated to reduce hyperlipidaemia and atherosclerotic lesion formation. reverse cholesterol transport (RCT) plays a crucial role in exporting cholesterol from peripheral cells, which is one mechanism utilized in the prevention and treatment of Atherosclerosis. The aim of this study is to investigate whether quercetin reduces lipid accumulation by improving RCT in vivo.
Methods
apolipoprotein E-deficient mice fed a high-fat diet were used to investigate the effect of quercetin on RCT by an isotope tracing method, and the underlying mechanisms were clarified by molecular techniques.
Results
These novel results demonstrated that quercetin significantly improved [3H]-cholesterol transfer from [3H]-cholesterol-loaded macrophages to the plasma (approximately 34% increase), liver (30% increase), and bile (50% increase) and finally to the feces (approximately 40% increase) for excretion in apolipoprotein E-deficient mice fed a high-fat diet. Furthermore, quercetin markedly increased the cholesterol accepting ability of plasma and high-density lipoprotein (HDL) and dramatically decreased the content of malondialdehyde in plasma and oxidized phosphocholine carried by HDL. Therefore, the underlying mechanisms of quercetin in improving RCT may be partially due to the elevated cholesterol accepting ability of HDL, the increased expression levels of proteins related to RCT, such as ATP-binding cassettes (ABC) A1 and G1, and the improved antioxidant activity of HDL.
Conclusion
Quercetin accelerates RCT in an Atherosclerosis model, which is helpful in clarifying the lipid–lowering effect of quercetin.
A ruthenium derivative of quercetin with enhanced cholesterol–lowering activity
A ruthenium(II) p-cymene derivative of quercetin was synthesized and functionally tested for cholesterol–lowering ability via direct 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) inhibition. Ruthenium complexation dramatically increased the inhibition potency of the parent quercetin toward HMGR, with a consequent enhancement of the cholesterol–lowering effect in hepatic cells.
Quillaja saponaria extract
Quillaja saponin extracts are known to reduce plasma cholesterol levels in humans. Here we study the mechanism of this effect with Quillaja Dry saponin extract (QD). In vitro model of Triglyceride lipolysis is used to quantify the effect of QD on the solubilization of cholesterol and of the lipolysis products (fatty acids and monoglycerides) in the dietary mixed micelles (DMM). We found that QD extract decreases significantly both the cholesterol (from 80% to 20%) and saturated fatty acids (SFA, from 70% to 10%) solubilised in DMM. Series of dedicated experiments prove that QD may act by two mechanisms: (1) direct precipitation of cholesterol and (2) displacement of cholesterol from the DMM. Both mechanisms lead to increased cholesterol precipitation and, thus, render cholesterol bio-inaccessible. We prove also that the saponin molecules are not the active component of QD, because highly purified Quillaja extract with very similar saponin composition does not exhibit cholesterol–lowering or SFA-lowering effect. The effect of QD extract on cholesterol solubilisation is most probably caused by the high-molecular weight polyphenol molecules, present in this extract. The reduced SFA solubilisation is caused by Ca2+ ions of relatively high concentration (1.25 wt%), also present in QD extract, which precipitate the fatty acids into calcium soaps.
Quinine (Cinchona bark)
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
Radix Paeoniae Rubra extract
Radix Paeoniae Alba (Baishao, RPA) has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensive effect or not is seldom studied. This study was to evaluate the protective effect of RPA on hypertensive rats. Alcohol in conjunction with a high fat diet– (ACHFD-) induced hypertensive rats and spontaneously hypertensive rats (SHR) was constantly received either RPA extract (25 or 75 mg/kg) or captopril (15 mg/kg) all along the experiments. As a result, RPA extract (75 mg/kg) could significantly reduce systolic blood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including Triglyceride , total cholesterol, LDL–cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT) and aspartate transaminase (AST) in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO) and endothelin (ET) levels.
Radix Salviae Miltiorrhizae extract
Danshen was able to reduce the risk of the patients with coronary heart disease (CHD), but the mechanism is still widely unknown. Biochemical indices (lipid profile, markers of renal and liver function, and homocysteine (Hcy)) are closely associated with CHD risk. We aimed to investigate whether the medicine reduces CHD risk by improving these biochemical indices. The patients received 10 Danshen pills (27 mg/pill) in Dashen group, while the control patients received placebo pills, three times daily. The duration of follow-up was three months. The serum biochemical indices were measured, including lipid profiles (LDL cholesterol (LDL-C), HDL-C, total cholesterol (TC), Triglycerides (TG), apolipoprotein (Apo) A, ApoB, ApoE, and lipoprotein (a) (Lp(a))); markers of liver function (gamma-glutamyl transpeptidase (GGT), total bilirubin (TBil), indirect bilirubin (IBil), and direct bilirubin (DBil)); marker of renal function (uric acid (UA)) and Hcy. After three-month follow-up, Danshen treatment reduced the levels of TG, TC, LDL-C, Lp(a), GGT, DBil, UA, and Hcy (P < 0.05). In contrast, the treatment increased the levels of HDL-C, ApoA, ApoB, ApoE, TBil, and IBil (P < 0.05). Conclusion. Danshen can reduce the CHD risk by improving the biochemical indices of CHD patients.
Mouse peritoneal macrophages were incubated in DMEM with pox-LDL and Rradix Salviae Miltiorrhizae (RSM) to investigate the effects of RSM on the internalization of peroxidized low density lipoprotein (pox-LDL) by using lipid analysis and electron microscopy. lipid peroxide (LPO) concentrations were increased slightly in the medium after incubation of macrophages with normal LDL (n-LDL), while decreased significantly in the media after incubation of macrophages with pox-LDL. In the three groups with pox-LDL, it could be found that there was a dose-dependent decrease of concentrations of LPO and total cholesterol (TCH) in the two RSM groups, and the decrease in the two RSM groups was much greater than in the group without RSM. RSM accelerated a more decrease of LPO than cholesterol contents in the media containing pox-LDL. The ultrastructural studies also showed that RSM induced the accumulation of lipid droplets in the cytoplasm of mouse peritoneal macrophages. The results suggested that RSM could accelerate the phagocytosis and degradation of pox-LDL by macrophages.
Radix Scutellariae
Traditional herbal formulas made from Scutellariae Radix (SR), the root of Scutellaria baicalensis, have previously been used in the treatment of inflammatory diseases, such as Atherosclerosis. The aim of the present study was to investigate the effects of SR on low-density lipoprotein (LDL) oxidation and inflammation in macrophages, which are early events in the development of Atherosclerosis. high-performance liquid chromatography photo-diode array analysis was used to obtain a three-dimensional chromatogram of SR. The antioxidative effects of SR were evaluated by determining its scavenging activities against ABTS and DPPH radicals. The Inhibitory effect of SR on LDL oxidation was examined using a thiobarbituric acid-reactive substance assay and a relative electrophoretic mobility assay. In addition, the anti-inflammatory effects of SR were evaluated in lipopolysaccharide (LPS)-induced RAW264.7 murine macrophage cells. The results showed that SR exhibited radical-scavenging activities in a dose-dependent manner; in addition, SR attenuated the Cu2+-induced oxidation of LDL as well as significantly inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) expression in LPS-induced RAW264.7 cells. Furthermore, SR induced the protein expression of heme oxygenase-1 (HO-1) in RAW264.7 cells. In conclusion, the results of the present study demonstrated that SR decreased the oxidation of LDL and suppressed inflammatory responses in macrophages, which occurred at least in part via the induction of HO‑1. These results therefore suggested that SR may be a potential therapeutic agent for the treatment of Atherosclerosis.
Resveratrol
effect of red wine consumption on lipoprotein (a) and other risk factors for Atherosclerosis
Epidemiological studies have pointed to the role of alcohol, and red wine in particular, in reducing the incidence of coronary heart disease. This study attempted to distinguish, in vivo, the effects of com- ponents specific to red wine and those of alcohol on lipoproteins, antioxidant status and membrane fluidity. Volunteers ( n = 2 0 ) were given 200 ml of red wine per day for 10 days. Following a 6-week washout, this was repeated with white wine. Changes within treatment groups were analysed by
paired t tests and repeated measures analysis of variance was used to distinguish effects of red wine components and alcohol. LDL was prepared by ultracentrifugation and all other assays were by conventional laboratory techniques. No effect with either treatment was detected on total cholesterol, Triglycerides , HDL or measures of antioxidant status, including the susceptibility of LDL to oxidation. Red wine reduced LDL cholesterol ( p < 0 . 0 1 ) , and both treatments reduced LDL apo B ( p < 0 . 0 1 ) and increased LDL chohapo B ratio ( p < 0 . 0 1 ) , implying an increase in LDL size. Potential anti-atherogenic changes specific to red wine were reduction in lipoprotein (a) ( p < 0.001) and increased membrane fluidity ( p < 0 . 0 1 ) . These results are not in keeping with the proposed role of red wine components in free-radical protection, but the reduction in lipoprotein (a) merits further investigation.
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL–cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an Inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
dietary natural products as emerging lipoprotein(a)-lowering agents
Elevated plasma lipoprotein(a) (Lp(a)) levels are associated with an increased risk of cardiovascular disease (CVD). Hitherto, niacin has been the drug of choice to reduce elevated Lp(a) levels in hyperlipidemic patients but its efficacy in reducing CVD outcomes has been seriously questioned by recent clinical trials. Additional drugs may reduce to some extent plasma Lp(a) levels but the lack of a specific therapeutic indication for Lp(a)‐lowering limits profoundly reduce their use. An attractive therapeutic option is natural products. In several preclinical and clinical studies as well as meta‐analyses, natural products, including l‐carnitine, coenzyme Q 10, and xuezhikang were shown to significantly decrease Lp(a) levels in patients with Lp(a) hyperlipoproteinemia. Other natural products, such as pectin, Ginkgo biloba, flaxseed, red wine, resveratrol and curcuminoids can also reduce elevated Lp(a) concentrations but to a lesser degree. In conclusion, aforementioned natural products may represent promising therapeutic agents for Lp(a) lowering.
Rhein
Rheum palmatum has been used most frequently in the weight-reducing formulae in traditional Chinese medicine. However, the components of Rheum palmatum that play the antiobesity role are still uncertain. Here, we tested the weight-reducing effect of two major Rheum palmatum compounds on db/db mouse. We found that rhein (100 mg kg−1 day−1), but not emodin, reduced the fat weight in db/db mouse. Using diet-induced obese (DIO) C57BL/6 mice, we identified that rhein blocked high-fat diet-induced obesity, decreased fat mass and the size of white and brown adipocytes, and lowered serum cholesterol, LDL cholesterol, and fasting blood glucose levels in the mice. To elucidate the underlying mechanisms, we used reporter assay and gene expression analysis and found that rhein inhibited peroxisome proliferator-activated receptor γ (PPARγ) transactivity and the expression of its target genes, suggesting that rhein may act as a PPARγ antagonist. Our data indicate that rhein may be a promising choice for antiobesity therapy.
Rhizoma Atractylodis Macrocephalae extract
The invention discloses a kind of Rhizoma Atractylodis Macrocephalae extract and purposes with effect for reducing blood fat, the Rhizoma Atractylodis Macrocephalae extract is prepared by the following method to obtain：Method one, take bighead atractylodes rhizome root medicinal material to pulverize and sieve, be put into extractor and first extract, then separate, Rhizoma Atractylodis Macrocephalae extract is obtained after separation；Separating and keeping CO in extraction process2Flow：55~70L/h；Method two, bighead atractylodes rhizome root medicinal material is taken, crushed, add 3~8 times of amount petroleum ethers, 0.5~3 h of ultrasound, refluxing extraction 1~4 time, every time 0.5~8.0 h；Merging filtrate is concentrated under reduced pressure into organic solvent-free residual.The Rhizoma Atractylodis Macrocephalae extract has regulating blood lipid action.It can be widely applied to the medicine or health food with effect for reducing blood fat.
Rhizoma Coptidis extract
It is hypothesized that Rhizoma Coptidis (RC) alkaloids exert their hypolipidemic effects primarily by targeting the gastrointestinal tract and liver. Thus, this study was conducted to evaluate the antihyperlipidemic mechanisms of RC alkaloids (at a daily dose of 140 mg/kg for 35 days) in high-fat and high–cholesterol induced hyperlipidemic B6 mice. After treatment, serum lipid parameters were determined, the expression of lipid metabolism related genes and pathways such as the sterol regulatory element binding proteins (SREBPs) and bile acid signaling in mice were also investigated. Meanwhile, Illumina sequencing was used to investigate the differences in gut microbiota of B6 mice. The results indicated that RC alkaloids reduced the body weight gain and serum total cholesterol (TC), Triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total bile acids (TBA) and lipopolysaccharide of B6 mice. Liver fat deposition and epididymal adipose cell size were also deceased in therapy group. RC alkaloids feeding significantly promoted the abundance of Sporobacter termitidis, Alcaligenes faecalis, Akkermansia muciniphila in the gut of mice, whereas, the abundance of Escherichia coli, Desulfovibrio C21_c20, Parabacteroides distasonis was suppressed. The observed antihyperlipidemic effects of RC alkaloids can also be attributed to their action as agonists of FXR and TGR5, activators for SREBP2, LDLR, UCP2 and CYP7A1, Inhibitors of HMGCR, TXNIP, TLR4 and JNK. Therefore, this study expands current knowledge on hypolipidemic mechanisms of RC alkaloids and presents new evidence supporting a key role for RC alkaloids as regulators of lipid homeostasis by modulation gut microbiota and hepatic lipid metabolism.
Rhizoma Polygonati extract
Polygonatum odoratum (Mill.) Druce belongs to the genus Polygonatum family of plants. In traditional Chinese medicine, the root of Polygonatum odoratum, Rhizoma Polygonati Odorati, is used both for food and medicine to prevent and treat metabolic disorders such as hyperlipidemia, hyperglycemia, obesity and cardiovascular disease. However, there is no solid experimental evidence to support these applications, and the underlying mechanism is also needed to be elucidated. Here, we examined the effect of the extract of Rhizoma Polygonati Odorati (ER) on metabolic disorders in diet-induced C57BL/6 obese mice. In the preventive experiment, the ER blocked body weight gain, and lowered serum total cholesterol (TC), Triglyceride (TG) and fasting blood glucose, improved glucose tolerance test (GTT) and insulin tolerance test (ITT), reduced the levels of serum insulin and leptin, and increased serum adiponectin levels in mice fed with a high-fat diet significantly. In the therapeutic study, we induced obesity in the mice and treated the obese mice with ER for two weeks. We found that ER treatments reduced serum Triglyceride and fasting blood glucose, and improved glucose tolerance in the mice. Gene expression analysis showed that ER increased the mRNA levels of peroxisome proliferator-activated receptors (PPAR) γ and α and their downstream target genes in mice livers, adipose tissues and HepG2 cells. Our data suggest that ER ameliorates metabolic disorders and enhances the mRNA expression of PPARs in obese C57BL/6 mice induced by high-fat diet.
Roselle (Hibiscus sabdariffa)
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
Rosemary (Rosmarinus officinalis)
Investigation of the effect of oral administration of rosemary (Rosmarinus officinalis) as powder on lipid profiles and blood glucose in healthy and type-2 diabetic human patients was done. Forty-five type-2 diabetic patients and 15 non-diabetic persons of age 40 years or older participated in the study. Patients selected in this study had fasting blood glucose in the range 160-300 mg/dl, and high lipid profiles levels. In addition, patients were allowed to take their routine diet and usual diabetic medicine but not any other health medication. All participants were told to take 3 g of rosemary per day for 4 weeks. Plasma lipid profiles and blood glucose were measured before and after rosemary administration. Significant effect of rosemary is obviously noticed in diabetic patients. lipid profiles (low density lipoprotein LDL, Triglycerides and cholesterol) decreased by 31-35%, and blood glucose decreased by 21%. In addition, high density lipoprotein (HDL) in both diabetic and non diabetic persons increased by 22%. Rosemary showed favorable changes in lipid profiles and blood glucose levels in type-2 diabetic patients. Key words: Type-2 diabetes, rosemary, dyslipidemia, blood glucose.
Saffower Yellower
hypolipidemic effect of safflower yellow and primary mechanism analysis
We examined the hypolipidemic effect of safflower yellow (SY) on hyperlipidemic mice and its influence on the biological synthesis of cholesterol in cells. Over 4 weeks, the levels of total cholesterol, Triglyceride , low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in serum were detected using a kit; mouse liver samples were acquired for paraffin sections, and mouse liver cells were observed under light microscope. Chinese hamster ovary cells were cultured in vitro, and an amphotericin B-cell model was adopted to observe the Inhibitory effect of SY on the biological synthesis of intracellular cholesterol. An enzyme-linked immunosorbent assay was used to detect the survival rate of Chinese hamster ovary cells. The middle and high doses of SY significantly reduced the levels of total cholesterol, Triglycerides , and low-density lipoprotein cholesterol in the serum of hyperlipidemic mice and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (P < 0.05), and the fatty liver of hyperlipidemic mice was significantly alleviated. SY had a protective effect on Chinese hamster ovary cells following amphotericin B injury (P < 0.01). SY exerts significant hypolipidemic effects and prevents fatty liver in a mechanism associated with inhibition of the biosynthesis of intracellular cholesterol.
Saffron (Crocus sativus)
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
Saikosaponins isolated from Bupleurum falcatum L. II.
Several metabolic actions of saikosaponins isolated from the root of Bupleurum falcatum L. were examined using albino rats. Hepatic protein synthesis from leucine-14C(U) was enhanced. Glycogen content in the liver was increased, but oxidation of glucose-14C(U) in the liver was not changed. Elevation of plasma levels of cholesterol, Triglycerides and p-ospholipids by cholesterol feeding was reduced. Although hepatic lipogenesis and cholesterogenesis from acetate-1-14C of glucose-14C(U) were stimulated, the elimination of i.p. injected cholesterol-4-14C from plasma was acclerated. Fecal excretion of i.p. injected cholesterol-4-14C, expressed as total-14C including bile acids-14C and neutral sterols-14C, was increased. Among the saikosaponins isolated from Bupleurum falcatum L., saikosaponins a and d, but not c, had metabolic actions as well as anti-inflammatory action. These metabolic actions and anti-inflammatory action of saikosaponins may confirm the clinical application of Bupleurum falcatum L, which has been widely used in the prescriptions of the oriental medicine, and may suggest possible mechanisms for the actions of its active principles.
Sambiloto (Andrographis paniculata)
cholesterol is one of the causes of coronary heart disease. The research objective is Assessing dosege of Sambiloto extract in reducing blood cholesterol levels rats (Rattus norvegicus) hypercholesterolemia. The research method is experimental, using Completely Randomized Design (CRD) 3 replications, 6 treatments are: 1) D0 = normal control; 2) D1 = positive control of cholesterol; 3) D2 = comparator simvastatin 2mg/200 g body weight; 4) D3 = dose of 100 mg sambiloto/200 g body weight; 5) D4 = dose 200 mg sambiloto / 200 g body weight; 6) D5 = dose of 400 mg sambiloto/200 g body weight. Rats that have been tested are white male Wistar rats aged 2 months, weight ± 200 g. Analysis using Anova, and further test using DMRT, α 5%. The results of the experiment showed that sambiloto extract of 100 mg/200 g body weight, 200 mg/200 g body weight; 400 mg/200 g body weight and a simvastatin comparator 2 mg/200 g body weight all of that can reduce the total cholesterol level of rats blood that be made hypercholesterolemia. Interestingly, the dose of 400 mg/200 g body weight has the same ability as simvastatin dose of 2 mg/200 g body weight in reducing total blood cholesterol levels of rats by 51%, considering the risk of hypocholesterolemia.
Seabuckthorn
cholesterol lowering POTENTIAL OF SEABUCKTHORN
The present study was designed to investigate the effect of Seabuckthorn on lipid profile, its antioxidant potency and its effect on hemodynamic changes and baroreceptor mediated blood pressure regulatory mechanisms in hypercholesterolemic rats. For induction of hypercholesterolemia rats were fed with fructose in drinking water and in vivo experiment had done to investigate the hemodynamic as well as the biochemical profile of seabuckthorn. It is a natural product and investigations carried out so far do not report any apparent toxic effect. Based on the results of the present study, it is recommended that seabuckthorn pulp oil may be supplemented with normal diet for providing protection against hypercholesterolemia. The fall in blood pressure of animals having a normal lipid profile suggests that it may have a hypotensive effect. Hence, its use as a lipid–lowering agent needs to be carefully monitored especially in people with cardiac problems. Conclusive evidence shows that baroreceptor modulation of heart rate is impaired in animals and patients with Atherosclerosis. It has been suggested that oxygen free radicals produced in Atherosclerosis may contribute to baroreceptor dysfunction. Seabuckthorn prevented the development of hypertension and reduced insulin resistance in chronically fructose-fed rats and reduced vascular superoxide anion production through lowering the NAD (P) H oxidase activity in hypertensive rats.
Silymarin
effect of silymarin and its polyphenolic fraction on cholesterol absorption in rats
This study evaluated the influence of silymarin (SM) and polyphenolic fraction (PF) of silymarin on cholesterol absorption in rats fed on high cholesterol diet (HCD). HCD induced a remarkable increase in hepatic, plasma, VLDL and LDL cholesterol, a decrease in HDL cholesterol and an elevation in triacylglycerol (TAG) levels in plasma, VLDL and in the liver. SM and PF were administered as dietary supplements (1.0%) in HCD for 18 days. Intestinal cholesterol absorption was measured by dual-isotope plasma ratio method, which calculates percent of cholesterol absorption from the ratio of two labelled cholesterol doses, one given intragastrically (14C) and one intravenously (3H). Silymarin and PF significantly reduced cholesterol absorption in rats fed on HCD and caused significant decreases in plasma and VLDL cholesterol and content of cholesterol and TAG in the liver. The level of HDL cholesterol was significantly increased after silymarin, but not after administration of PF. The levels of TAG in plasma and VLDL were not affected by either silymarin or PF. These results suggest that the inhibition of cholesterol absorption caused by silymarin and its polyphenolic fraction could be a mechanism contributing to the positive changes in plasma cholesterol lipoprotein profile and in lipid content in liver.
effect of Silybin on lipid Profile in Hypercholesterolaemic Rats
Introduction
Hyperlipidemia is a major cause of Atherosclerosis and Atherosclerosis associated conditions, such as Coronary Heart Disease (CHD), ischaemic cerebrovascular disease and peripheral vascular disease. Though there are hypolipidemic drugs available, the search for a more efficacious hypo lipidemic agent was always going on.
Aim
To study the effect of Silybin on lipid profile in Hypercholesterolaemic rats.
Materials and Methods
After grant of permission from animal ethics committee, the animals were divided into four groups of eight each (normal control, Experimental control with high cholesterol diet, high cholesterol diet + Silybin 300mg, high cholesterol diet + Silybin 600mg). At the end of 60 days the animals in all the groups were subjected to overnight fasting followed by plasma and liver biochemical analyses.
Statistical Analysis
The data were analysed by ANNOVA followed by Duncan’s multi range test and the value of p≤0.05 was used as the criterion for statistical significance.
Results
The rats fed on high cholesterol diet showed significant increase in serum total cholesterol, Triglycerides , LDL-C and VLDL-C. Treatment with Silybin significantly decreased serum total cholesterol (24%), Triglycerides (21%), LDL-C (24%) in a dose dependent manner. Rats treated with Silybin (300 and 600 mg/kg) showed significant increase in hepatic HDL –C and decrease in other lipid profiles.
Conclusion
Treatment with Silybin significantly decreased both serum and hepatic total cholesterol, Triglycerides , VLDL-C, LDL-C and increased HDL-C at both doses.
Sophora japonica L.flower
effect of Sophora japonica Extract on lipid Content in high Fat diet Fed Rats
The effect of hot water extract of Sophora japonica Linne (Koehwa) flower on lipid content were studied in terms of hematological variables in rats fed with high fat diet. Experimental rats were divided into basal diet only (BDG), high fat diet control (FDC), high fat diet and 6% Sophora japonica extract powder (FD6S), and high fat diet and 12% Sophora japonica extract powder (FD12S) groups. The levels of hematological variables were not significantly different among the four groups, whereas transferrin concentration and glutamic oxaloacetate transaminase (GOT) activity in serum metabolic variables were significantly different. Transferrin concentration was higher in the FD6S and FD12S groups than in BDG and FDC groups. FD6S and FD12S groups showed significantly lower level of GOT activity. Total cholesterol levels of FD6S and FD12S groups were 220.38 and 205.02 mg/dL in the serum, respectively. Total cholesterol levels of FD6S and FD12S groups were lower than that of FDC group (341.38 mg/dL) and the same level as that of FDG group (216.18 mg/dL). HDL- and LDL–cholesterol levels of FDC group were 26.84 and 62.91 mg/dL, whereas those of FD12S group were 38.02 and 44.16 mg/dL. Supplementation of 12% Koehwa extract powder remarkably increased HDL-cholesterol level and greatly decreased LDL–cholesterol level. Atherogenic indices in FD6S and FD12S groups were significantly lower than those of yje FDG group. The FD12S group supplemented with Koehwa extract showed lower Triglyceride concentration than that of the FDC group. These results suggested that dietary supplementation of Koehwa extracts did not have any adversary effect on the hematological variables, but improved the lipid content and reduced hepatic damage of the high fat fed rats.
Soy bean extract isoflavone
Background:Clinical trials have reported the cholesterol–lowering effects of soy protein intake, but the components responsible are not known.
Objective:This meta-analysis was primarily conducted to evaluate the precise effects of soy isoflavones on lipid profiles. The effects of soy protein that contains enriched and depleted isoflavones were also examined.
Design:PUBMED was searched for English-language reports of randomized controlled trials published from 1990 to 2006 that described the effects of soy protein intake in humans. Eleven studies were selected for the meta-analysis.
Results:Soy isoflavones significantly decreased serum total cholesterol by 0.10 mmol/L (3.9 mg/dL or 1.77%; P= 0.02) and LDL cholesterol by 0.13 mmol/L (5.0 mg/dL or 3.58%; P< 0.0001); no significant changes in HDL cholesterol and triacylglycerol were found. Isoflavone-depleted soy protein significantly decreased LDL cholesterol by 0.10 mmol/L (3.9 mg/dL or 2.77%; P= 0.03). Soy protein that contained enriched isoflavones significantly decreased LDL cholesterol by 0.18 mmol/L (7.0 mg/dL or 4.98%; P< 0.0001) and significantly increased HDL cholesterol by 0.04 mmol/L (1.6 mg/dL or 3.00%; P= 0.05). The reductions in LDL cholesterol were larger in the hypercholesterolemic subcategory than in the normocholesterolemic subcategory, but no significant linear correlations were observed between reductions and the starting values. No significant linear correlations were found between reductions in LDL cholesterol and soy protein ingestion or isoflavone intakes.
Conclusions:Soy isoflavones significantly reduced serum total and LDL cholesterol but did not change HDL cholesterol and triacylglycerol. Soy protein that contained enriched or depleted isoflavones also significantly improved lipid profiles. Reductions in LDL cholesterol were larger in hypercholesterolemic than in normocholesterolemic subjects.
Soy leaf extract
Soy-leaf extracts exert their cardioprotective effects by inducing endothelium-dependent vasodilation in the arteries, and they favorably modulate the serum lipid profile. In this study, we investigated the atheroprotective effects of an ethanol extract of soy leaf (ESL) in human umbilical vein endothelial cells (HUVECs) and high–cholesterol diet (HCD)-fed low-density lipoprotein receptor deficient (LDLR−/−) mice. ESL induced the expression of Krüppel-like factor 2 (KLF2), an endothelial transcription factor, and endothelial nitric oxide synthase (eNOS), and suppressed the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) through moderate inflammatory signal activation, not only in tumor necrosis factor-α (TNF-α)-stimulated HUVECs but also in 7-ketocholesterol (7-KC)-stimulated HUVECs. ESL supplementation reduced aortic lesion formation in Western diet-fed LDLR−/− mice by 46% (p < 0.01) compared to the HCD group. ESL also markedly decreased the aortic expression levels of VCAM-1, ICAM-1, monocyte chemotactic protein-1 (MCP-1), TNF-α, IL-6, IL-1β, matrix metallopeptidase 9 (MMP-9), and fractalkine, while the expression of KLF2 was significantly increased. These results suggest that ESL supplementation has potential for preventing HCD-induced Atherosclerosis effectively.
Spergularia purpurea
The purpose of this study was to examine the effect of single and repeated oral administration of the aqueous extract of Spergularia purpurea (SP) at a dose of 10 mg/kg in normal and streptozotocin-induced diabetic rats. In normal rats, the aqueous extract of SP induced a significant decrease of the plasma cholesterol concentrations 6 h after a single oral administration (P<0.05) and 2 weeks after repeated oral administration (P<0.05). The plasma Triglycerides levels increased significantly 6 h after a single oral administration (P<0.05) and decreased 2 weeks after repeated oral administration (P<0.05).
In diabetic rats, SP treatment caused a significant decrease of plasma cholesterol levels after a single (P<0.01) and repeated (P<0.01) oral administration. A significant increase of Triglycerides levels was observed 6 h after a single oral administration of the SP aqueous extract (P<0.01). One week after repeated oral administration of SP aqueous extract, the plasma Triglycerides levels were significantly decreased (P<0.005) and still dropped after 2 weeks (P<0.01).
On the other hand, the repeated oral administration of SP aqueous extract caused a significant decrease of body weight after 2 weeks of treatment in both normal (P<0.001) and diabetic (P<0.01) rats.
We conclude that the aqueous extract of SP exhibits a cholesterol and body weight-lowering activities in both normal and severe hyperglycaemic rats.
Stigmasterol
In this study, incorporation of gallic acid into typical phytosterols (β-sitosterol and stigmasterol) through Steglich esterification was optimized employing the protection and deprotection strategy. A novel mechanism leading to side esterification was discovered. Complication of the phenolic hydroxyl groups and side reactions were successfully reduced under the optimized conditions. The structural identity and purity of galloyl stigmasterol and galloyl β-sitosterol were confirmed by NMR, FT-IR, and HPLC-MS. Evaluation of galloyl β-sitosterol and galloyl stigmasterol revealed their excellent antioxidant and cholesterol–reducing activities. Significant enhancement of cholesterol–reducing activity by galloylation was unveiled especially for β-sitosterol. Galloyl β-sitosterol had slightly better antioxidant activity at ambient temperature and better cholesterol–reducing activity. Molecular modeling suggested that a subtle difference of galloyl β-sitosterol and galloyl stigmasterol in activities could be attributed to variation of molecular rigidity and conformation. The excellent properties of galloyl β-sitosterol and galloyl stigmasterol suggested their great potential application in the food industry.
Suji leaf (Dracaena angustifolia Roxb.)
Activity Test of Suji Leaf Extract (Dracaena angustifolia Roxb.) on in vitro cholesterol lowering
cholesterol is a natural substance with physical characteristic similar to fat but has a steroidal group. The body requires cholesterol in normal amount; however, it will harm the body in excess amount. high cholesterol levels in the blood are dangerous because of the precipitation of cholesterol and other fatty substances resulting in Atherosclerosis. Suji leaf (Dracaena angustifolia Roxb.) used as a natural dye has a high flavonoid content that is inferred to have cholesterol–lowering activity. This study aims to test the in vitro activity of suji leaf (Dracaena angustifolia Roxb.) extract in decreasing cholesterol level with various concentrations and to find the effective concentration (EC50). The method of extraction used was remaceration method with 70% ethanol solvent. Analysis of cholesterol–lowering activity was done by Lieberman-Burchard method by making variation of ethanol extract 400 ppm, 500 ppm, 600 ppm, 700 ppm, and 800 ppm. The results showed the percentage of cholesterol–lowering activity by 33.62%, 36.15%, 46.61%, 56.39% and 64.05% respectively. Value of EC50 activity of suji leaf extract is 632.50 ppm.
taioba (Xanthosoma sagittifolium) leaf
The consumption of vegetables has been correlated with reduced risk of chronic non-communicable diseases due to the high fiber content and bioactive compounds found in vegetables. The arrowleaf elephant ear (Xanthosoma sagittifolium), which is known in Brazil as taioba, is a common plant in tropical America. Although its leafy portion possesses a high nutritional value, it is not widely consumed and has not been well studied. This study assessed the effect of lyophilised taioba leaf (LTL) as a hypolipidemic and prebiotic agent. Thirty-two Wistar rats were assigned to four groups: group 1 was fed a high-fat diet containing 3.67% (w/w) cellulose (low cellulose — LCEL); group 2 received a high-fat diet supplemented with 10% (w/w) cellulose (CEL); group 3 received a high-fat diet supplemented with 10% (w/w) inulin (INU); and group 4 was fed a high-fat diet supplemented with 28.4% LTL (TAI) to provide 10% (w/w) taioba fiber. The groups were fed their respective diets for 4 weeks. The addition of LTL to the diet resulted in reduced weight gain, reduced liver fat, and increased fecal mass and lipid, in addition to higher fecal short chain fatty acid and bile salt concentrations, compared to the LCEL group. Additionally, only the TAI group exhibited a lower serum cholesterol concentration and a higher body ash content (p < 0.05) than the LCEL group. Both the high bile salt binding capacity and high fermentability of LTL suggest that this plant may have a protective effect against cardiovascular diseases and bowel cancer.
Tangeretin
One of the pathways to reduce cholesterol production in the liver is through the inhibition of HMG-Coa reductase (HMGCR) by current drugs, statins. However, these have side effects if consumed in prolonged periods. Tangeretin and trans-ethyl caffeate as alternative drugs in reducing hypercholesterolemia and preventing Atherosclerosis have never been reported. Their effects on inhibiting HMGCR activity were investigated through enzymatic method (in vitro and in vivo). The toxicity property was analyzed on the serum Glutamate Oxalate Transaminase (SGOT)/serum Glutamate Piruvate Transaminase (SGPT) levels and rat liver histology. The results showed that both compounds inhibited HMGCR activity significantly compare to the control simvastatin (p < 0.05). Tangeretin which showed very good activity in inhibiting HMGCR (83.8 of % inhibition, equal to simvastatin) was selected and used for anti-hypercholesterolemia in vivo assessment. Furthermore, tangeretin was shown to effectively reduced Total cholesterol (TC) and Low Density Lipoprotein (LDL), and increased high Density Lipoprotein (HDL) levels significantly compared to the simvastatin group (p < 0.05). Tangeretin group was also proven to inhibit HMGCR rat liver activity significantly compare to the control simvastatin (p < 0.05). The toxicity study on the SGOT/SGPT levels and liver histology revealed that there were no side effects after administration by tangeretin. Results found that both tangeretin and trans-ethyl caffeate are potent candidates as anti-hypercholesterolemia agent in vitro. In addition, tangeretin was also shown to be safe and suitable as an alternative treatment for controlling hypercholesterolemia in vivo as well as have potency for preventing Atherosclerosis.
Taxillus sutchuenensis (Lecomte) Danser extract
Bushenkangshuai tablet (BSKS) is a Chinese herbal compound which has been used for the treatment of cardiovascular and cerebrovascular diseases in China for decades. This study intends to explore the molecular mechanism of BSKS against Atherosclerosis in ApoE−/− mice. ApoE−/− mice were fed with western-type diet for 6 weeks and then were given BSKS for 6 weeks. The results showed that BSKS attenuated the size of the atherosclerotic lesion, reduced visceral adipose content, and decreased blood lipids. We also found that BSKS promoted the expression of adiponectin and its receptors, inhibited the expression of Toll-like receptor 4 and nuclear factor-kappa B, decreased the levels of interleukin-1 beta, monocyte chemotactic protein-1, and vascular cell adhesion molecule-1, and increased the levels of interleukin-10 and adiponectin. Our data provided evidence that BSKS exerted an Antiatherosclerotic effect by lowering blood lipids and inhibiting inflammatory response via TLR4 and NF-κB signaling pathway.
Teucrium polium L.
Background
Cardiovascular diseases are among the most common causes of mortality worldwide. Therefore, it is necessary to control the risk factors of these patients. Since the level of inflammatory markers and lipid profiles has increased in cardiovascular diseases and due to the increasing role of plants in the treatment of diseases, the current study aimed to investigate the effect of hydroalcoholic extract of Teucrium polium on inflammatory markers and lipid profile in hypercholesterolemic rats.
Materials and methods
A total of 24 adult male Wistar rats were randomly divided into four groups of six each and treated with oral administration for 8 weeks. The control group received normal diet, the sham group received high–cholesterol diet and experimental groups 1 and 2 received high–cholesterol diet in the 8 weeks and doses of 85 and 170 mg/kg, respectively, of the T. polium hydroalcoholic extract (TPHAE) in the second 4 weeks. At the beginning and the end of the study, rats were examined for biochemical parameters. The mean level of variables for each group was presented as mean ± standard error of mean.
Results
The results of this study showed that, after administration of TPHAE, there was a significant decrease in the mean of inflammatory markers in all groups compared to sham group (P<0.001). Also, administration of the extract significantly reduced the serum levels of Triglyceride , cholesterol and LDL–cholesterol and significantly increased the serum HDL-cholesterol levels. In addition, the 170 mg/kg dose of TPHAE was the most effective in reducing serum levels of inflammatory and lipid markers.
Conclusion
Treatment with TPHAE caused dose-dependent decrease in serum levels of inflammatory markers and lipid profile in hypercholesterolemic rats. Therefore, it can be applied as a natural product for the management of cardiovascular diseases.
Thearubigins (from Black Tea)
Rats were fed a high fat diet containing 0.2% black tea polyphenols, theaflavins, theasinensin A or thearubigins for 4 weeks. The hepatic cholesterol concentration was significantly lower in rats fed the theaflavins, theasinensin A or thearubigins diet than in those fed the control diet without black tea polyphenols. Theasinensin A and thearubigins significantly accelerated fecal neutral and acidic steroid excretion, respectively. These results suggest that theasinensin A and thearubigins might induce the hepatic cholesterol–lowering activity through the promotion of fecal steroid excretion.
Theasinensin A (from Black Tea)
Rats were fed a high fat diet containing 0.2% black tea polyphenols, theaflavins, theasinensin A or thearubigins for 4 weeks. The hepatic cholesterol concentration was significantly lower in rats fed the theaflavins, theasinensin A or thearubigins diet than in those fed the control diet without black tea polyphenols. Theasinensin A and thearubigins significantly accelerated fecal neutral and acidic steroid excretion, respectively. These results suggest that theasinensin A and thearubigins might induce the hepatic cholesterol–lowering activity through the promotion of fecal steroid excretion.
Trigonella foenum-graecum L seed extract
Background.
Trigonella foenum graecum L. (Fenugreek, FG) is used in many countries as a medicinal plant. Evidence has suggested the hypolipidemic effect of Fenugreek; however, its actual mechanism has not been determined yet.
Objectives.
The purpose of our research was to investigate the effect of Fenugreek on lipid profile, liver histology and LDL receptor gene expression in male hamsters fed with high cholesterol diet.
Methods.
These animals were given normal diet (ND), high cholesterol diet (HCD: 2% cholesterol and 0.5% cholic acid added to ND), HCD supplemented with 2g and 8g fenugreek per 100g ND (HCD+FG2 and HCD+FG8) respectively for four weeks. At the end of treatment, serum lipids, lipoproteins and liver enzymes were measured. Finally, LDL receptor (LDLR) gene expression was determined in the liver of the studied animals using Real Time-PCR method and liver histological changes were evaluated by H&E staining method.
Results.
A significant reduction was observed in serum Triglyceride (p<0.01), total cholesterol, low and very low density cholesterol, aspartate and alanine transaminases in HCD+FG8 group (p<0.05) compared with HCD group, while serum level of HDL-c (p<0.01) increased. In addition, LDLR gene expression in HCD+FG8 group increased 7.8 folds. The results confirm the protection effect of liver tissue in HCD+FG8 group against pathological changes. There was no significant change in LDLR gene expression in HCD+FG2 group. In conclusion, fenugreek ameliorated dyslipidemia by up-regulation of LDLR gene expression and can be used as a protective agent against hypercholesterolemia.
Typha angustifolia L.extract
Typha angustifolia extract reduces diet-induced hyperlipidemia in rats
Objective
To observe the lipid–lowering effect of Typha angustifolia extract (TAE) in Sprague Dawley rats.
Methods
The rats were randomly divided into six groups, including the hypercholesterolemic diet (HYD) group. Ad libitum food was given to the animals for 60 d to establish dyslipidemia models. The rats were received an ig administration of 1 mL medicine daily. After 120 d the animals were sacrificed by cervical dislocation; blood was collected to measure total cholesterol (TC), Triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), nitric oxide (NO), and endothelin (ET) plasma concentration; Livers were collected to measure ApoE mRNA and protein expression; Morphologic changes of aorta ventralis tissue were also observed.
Results
Compared with HYD group, TAE had the ability of reducing TC, TG, LDL-C, NO, and ET (P < 0.01), thereby increasing ApoE mRNA and protein expression of the liver (P < 0.01).
Conclusion
These results suggested that TAE was capable of effectively decreasing the circulating lipids levels and enhancing the protective effects of artery.
Urolithin B
Scope
HDL cholesterol is inversely related to the incidence of Atherosclerosis. Polyphenols including ellagitannins have been shown to exert antiatherogenic properties. Urolithin B is formed from ellagitannins by components of the gut microbiota, and urolithins might be involved in beneficial effects against cardiovascular diseases in vitro. In this study, the influence of urolithin B on several parameters involved in the lipid plaque deposition and the reverse cholesterol transport is investigated.
Methods and results
In apoE−/− mice and two different macrophage cell lines, the influence of urolithin B and its phase II conjugated metabolite on lipid plaque deposition, cholesterol uptake, and expression of ABCA1 and SR-BI is tested. It is shown that urolithin B decreases lipid plaque deposition, both urolithin B and urolithin B sulfate modulate expression of SR-BI and ABCA1, and cholesterol efflux increases from cholesterol laden macrophages to HDL particles as well as to reverse lipid uptake by stimulated THP-1 macrophages.
Conclusions
Urolithin B can decrease lipid plaque deposition, and urolithin B and urolithin B sulfate are able to induce reverse cholesterol transport by influencing expression of key proteins of this pathway. Urolithin B may represent the basis for development of new drugs for prevention and treatment of Atherosclerosis in humans.
Ursodeoxycholic acid
Administration of ursodeoxycholic acid (UDCA) has been shown to decrease serum total and low density lipoprotein (LDL) cholesterol in hypercholesterolemic patients with primary biliary cirrhosis. Results of previous studies prompted us to postulate that the cholesterol–lowering effect of UDCA may be due, at least in part, to a direct increment in hepatic LDL receptor binding [Bouscarel et al., Biochem J, 1991;280:589; Bouscarel et al., lipids 1995;30:607]. The aim of the present investigation was to determine the ability of UDCA to enhance hepatocellular LDL receptor recruitment, as determined by its effect in vivo on LDL uptake, and its effect in vitro on LDL binding, under conditions of moderately elevated serum cholesterol. Study groups consisted of male golden Syrian hamsters fed either a standard chow diet (control), a 0.15% cholesterol-containing diet, or a 0.15% cholesterol-containing diet supplemented with either 0.1% UDCA, or 0.1% chenodeoxycholic acid (CDCA). cholesterol feeding increased (P<0.01) total serum cholesterol by 44%, and was associated with a 10-fold accumulation of cholesteryl esters in the liver (P<0.01). In vivo, hepatic uptake of [U-(14)C]sucrose-labeled hamster LDL was increased (P<0.05) to a level of 454+/-101 microl in animals fed a cholesterol-containing diet supplemented with UDCA, compared to that either without UDCA (337+/-56 microl), or with CDCA (240+/-49 microl). The hepatic uptake of [U-(14)C]sucrose-labeled methylated human LDL, a marker of LDL receptor-independent LDL uptake, was unaffected by bile acid feeding. In vitro, specific binding of [125I]hamster LDL to isolated hepatocytes was determined at 4 degrees C, in presence and absence of 700 micromol/l UDCA. The K(D) ranged from 25 to 31 microg/ml, and was not affected by either cholesterol feeding or UDCA. In the presence of UDCA, the B(max) was increased by 19% (P<0.05) in cells isolated from control animals and by 29% (P<0.01) in cells isolated from hamsters fed a cholesterol-supplemented diet. In conclusion, in dietary hypercholesterolemic hamsters, both chronic in-vivo and acute in-vitro treatments with UDCA resulted in restoration of hepatic LDL binding and uptake to levels observed in control hamsters.
cholesterol–lowering effect of ursodeoxycholic acid in patients with primary biliary cirrhosis
We have previously shown in a 2-yr controlled trial that hypercholesterolemia, frequent in primary biliary cirrhosis, is lowered by ursodeoxycholic acid (13 to 15 mg daily). To further investigate this effect, we analyzed the influence of long-term ursodeoxycholic acid administration on serum lipids, lipoproteins and bile acids. The study involved a subgroup of 33 noncirrhotic patients (17 received ursodeoxycholic acid and 16 received a placebo) analyzed at inclusion and after 2 yr. The total serum cholesterol concentration was markedly reduced in the ursodeoxycholic acid–treated patients in comparison with the controls (mean ± S.E.M. = 7.49 ± 0.42 mmol/L and 7.07 ± 0.23 mmol/L at entry and 4.44 ± 0.40 mmol/L and 6.89 ± 0.27 mmol/L at 2 yr in the ursodeoxycholic acid and placebo groups, respectively; p < 0.02). Quantitatively, this decrease was mainly caused by a fall in low-density–lipoprotein cholesterol, but very low density–lipoprotein cholesterol levels also fell significantly. high-density–lipoprotein cholesterol levels remained stable in both groups, but the high-density–lipoprotein2/high-density–lipoprotein3 cholesterol ratio fell significantly during ursodeoxycholic acid treatment. No significant change occurred in total Triglyceride or total phospholipid levels. In the treated group, the proportion of ursodeoxycholic acid increased (up to 60% of total circulating bile acids), whereas that of cholic and chenodeoxycholic acids fell significantly. In conclusion, the cholesterol–lowering effect of ursodeoxycholic acid could be related to an improvement of cholestasis, modifications in cholesterol metabolism or both. Changes in endogenous bile acid composition induced by ursodeoxycholic acid might be the common denominator of these two mechanisms.
Vernonia amygdalina leave extract
We investigated the lipid–lowering effects of methanolic extract of Vernonia amygdalina (VA) leaves in rats fed an high cholesterol diet, and compared with a standard hypolipidemic drug, Questran (Qu). The effects of VA on the lipid profile were assessed by measuring the levels of total cholesterol, Triglyceride , low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, lipid peroxidation (LPO), phospholipid, and glutathione (GSH) in the plasma and liver of the rats. Administration of cholesterol at a dose of 30 mg/0.3 ml, five times in a week for nine consecutive weeks resulted in a significant increase (p < 0.05) in plasma and post mitochondrial fraction (PMF) cholesterol levels by 33% and 55%, respectively. However, treatment with extract of VA at doses of 100 and 200 mg/kg caused a dose dependent reduction in the plasma and PMF cholesterol by 20%, 23% and 23%, 29%, respectively. Similar reduction in cholesterol levels was obtained in Qu-treated rats. Furthermore, VA at 200 mg/kg decreased the plasma and PMF LDL–cholesterol levels by 23% and 49%, and also decreased plasma and PMF Triglyceride levels by 29% and 28%, respectively. Also, VA at 100 and 200 mg/kg caused a dose-dependent increase in plasma HDL-cholesterol levels by 41% and 59%, respectively. However, there were no significant differences (p > 0.05) in the PMF HDL-cholesterol and phospholipid levels of the treated rats when compared to hypercholesterolemic rats. There were significant decreases (p < 0.05) in the LPO levels of extract-treated rats. Precisely, VA at 100 and 200 mg/kg decreased the levels of plasma and PMF LPO by 38%, 42% and 35%, 45%, respectively. In addition, VA augmented the cholesterol-induced decrease in PMF glutathione levels of the rats. Taken together, these results suggest the lipid–lowering effects of VA and, probably serve as a new potential natural product for the treatment of hyperlipidemia.
Welsh onion (Allium fistulosum L., Amaryllidaceae)
Background
Allium fistulosum (Welsh onion) is a traditional medicinal plant used for the treatment of colds, influenza, abdominal pain, headache, and heart disease. This study evaluated the effects of A. fistulosum ethanolic extract (AFE) and aqueous extract (AFW) on body weight and other obesity-related parameters.
Methods
Male 8-week-old C57BL/6 J mice were fed either a standard chow diet (normal control) or a high-fat diet (HFD) either alone (HFD-control) or in combination with G. cambogia extract containing hydroxycitric acid (HCA, an herbal weight-loss supplement), conjugated linoleic acid (CLA, a weight-loss supplement), orlistat (a clinically available anti-obesity drug), AFW, or AFE (n = 6 mice per group) for 6 weeks. At the end of 6 weeks, several body weight and obesity-related parameters were examined, including: liver and adipose weight, adipocyte size, serum lipid profiles, liver expression of adenosine monophosphate-activated protein kinase (AMPK), and adipose tissue expression of uncoupling protein 2 (UCP2).
Results
high-performance liquid chromatography showed that both AFE and AFW contain ferulic acid and quercetin. Oral administration of AFW and AFE to HFD-fed mice decreased body weight as well as liver and adipose tissue weight and adipocyte size. serum lipid profiles and adiponectin levels were improved in HFD-fed mice treated with AFE but not AFW. However, both AFW and AFE significantly attenuated HFD-induced changes in serum leptin and insulin-like growth factor 1 levels, liver expression of AMPK, and adipose tissue expression of UCP2.
Conclusions
The findings from this study suggest that A. fistulosum extracts have potential as functional food materials for weight control in obesity.
Xanthohumol
Xanthohumol, a hop-derived prenylated flavonoid, promotes macrophage reverse cholesterol transport
Xanthohumol, a prominent prenyl flavonoid from the hop plant (Humulus lupulus L.), is suggested to be antiatherogenic since it reportedly increases high-density lipoprotein (HDL) cholesterol levels. It is not clear whether xanthohumol promotes reverse cholesterol transport (RCT), the most important antiatherogenic property of HDL; therefore, we investigated the effects of xanthohumol on macrophage-to-feces RCT using a hamster model as a CETP-expressing species. In vivo RCT experiments showed that xanthohumol significantly increased fecal appearance of the tracer derived from intraperitoneally injected [3H]-cholesterol-labeled macrophages. Ex vivo experiments were then employed to investigate the detailed mechanism by which xanthohumol enhanced RCT. cholesterol efflux capacity from macrophages was 1.5-fold higher in xanthohumol-fed hamsters compared with the control group. In addition, protein expression and lecithin-cholesterol acyltransferase activity in the HDL fraction were significantly higher in xanthohumol-fed hamsters compared with the control, suggesting that xanthohumol promoted HDL maturation. Hepatic transcript analysis revealed that xanthohumol increased mRNA expression of abcg8 and cyp7a1. In addition, protein expressions of liver X receptor α and bile pump export protein were increased in the liver by xanthohumol administration when compared with the control, implying that it stimulated bile acid synthesis and cholesterol excretion to feces. In conclusion, our data demonstrate that xanthohumol improves RCT in vivo through cholesterol efflux from macrophages and excretion to feces, leading to antiAtherosclerosis effects. It remains to be elucidated whether enhancement of RCT by xanthohumol could prove valuable in humans.
Xuezhikang
Background: Xuezhikang (XZK) is an extract of fermented red yeast rice that has lipid–lowering properties.
Objective: To evaluate the effects of XZK on lipids in subjects with dyslipidemia but no coronary heart disease.
Methods: A total of 116 adults with baseline non-high-density lipoprotein cholesterol (non-HDL-C) levels of approximately 208 mg/dL and low-density lipoprotein cholesterol (LDL-C) levels of approximately 175 mg/dL were randomized to either placebo or XZK 1200 or 2400 mg daily and treated for 12 weeks.
Results: A majority of the patients were white (53.4%) or Asian (37.1%). Daily XZK 1200 mg and 2400 mg for 4 to 12 weeks resulted in statistically significant (P < .001) and clinically meaningful decreases in non-HDL-C (∼24% reduction) and LDL-C (∼27% reduction) compared with placebo. XZK treatment at either dose enabled approximately 50% of subjects to reduce their LDL-C levels by ≥ 30%. Doubling the XZK daily dose from 1200 to 2400 mg at treatment week 8 caused an additional 4.6% reduction in LDL-C. Significant benefits were also observed across secondary efficacy variables, including total cholesterol (TC), apolipoprotein B (Apo B), Triglycerides , HDL-C, the TC/HDL-C ratio, and the Apo B/Apo A-I ratio, at treatment week 8 or 12. XZK was safe and well tolerated. Safety and tolerability profiles were similar across treatment groups. Most adverse events were gastrointestinal. No subject experienced myopathy or markedly elevated liver transaminases or creatine kinase.
Conclusion: Xuezhikang significantly reduced non-HDL-C and LDL-C, and was well tolerated. Further, longer-term studies in more diverse patient populations are needed to corroborate these findings.
Yucca schidigera extact
Anti-inflammatory and anti-arthritic effects of yucca schidigera: A review
Yucca schidigera is a medicinal plant native to Mexico. According to folk medicine, yucca extracts have anti-arthritic and anti-inflammatory effects. The plant contains several physiologically active phytochemicals. It is a rich source of steroidal saponins, and is used commercially as a saponin source. Saponins have diverse biological effects, including anti-protozoal activity. It has been postulated that saponins may have anti-arthritic properties by suppressing intestinal protozoa which may have a role in joint inflammation. Yucca is also a rich source of polyphenolics, including resveratrol and a number of other stilbenes (yuccaols A, B, C, D and E). These phenolics have anti-inflammatory activity. They are Inhibitors of the nuclear transcription factor NFkappaB. NFkB stimulates synthesis of inducible nitric oxide synthase (iNOS), which causes formation of the inflammatory agent nitric oxide. Yucca phenolics are also anti-oxidants and free-radical scavengers, which may aid in suppressing reactive oxygen species that stimulate inflammatory responses. Based on these findings, further studies on the anti-arthritic effects of Yucca schidigera are warranted.
Zingiber officinale Roscoe extract
Background & aims
Hypertension, dyslipidaemia, and chronic inflammation contribute to the development of cardiovascular disease (CVD). Zingiber officinale has been suggested to reduce these CVD risk factors; however, the clinical evidence remains unclear. This systematic review aims to analyse the effect of Z. officinale as a sole intervention on these risk factors.
Methods
In this PRISMA-based systematic review, we included randomised clinical trials from PubMed, Scopus and Cochrane Database of Systematic Reviews (July 2020) analysing Triglycerides , low- and high-density lipoprotein (LDL, HDL), total cholesterol, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin 1, 6, 10, systolic and/or diastolic blood pressure as outcomes. Quality of studies was evaluated by JADAD and the Cochrane risk-of-bias tools.
Results
A total of 24 studies were included, mostly (79.2%) showing low risk of bias. These were based on obesity and cardio-metabolic derangements (33.3%), type 2 diabetes mellitus (37.5%), and miscellaneous conditions (29.2%). While total cholesterol and Triglycerides levels mostly improved after Z. officinale, results were inconsistent for other blood lipids markers. Inflammatory markers (CRP, TNF-α) were more consistently reduced by Z. officinale, while only 3 studies reported a non-significant reduction of blood pressure.
Conclusions
Although there remains a paucity of studies, Z. officinale may be beneficial for improving dyslipidaemia and inflammation.
α-Lipoic Acid
To investigate the cholesterol–lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (−55%) than either the PS (−24%) or the αLA (−25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (−47%) or in combination with PS (−54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21–22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (+52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLR protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone.
lipid lowering effect of Antioxidant Alpha-Lipoic Acid in Experimental Atherosclerosis
Accumulating data demonstrated that hypercholesterolemia and oxidative stress play an important role in the development of Atherosclerosis. In the present study, a protective activity of alpha-lipoic acid; a metabolic antioxidant in hypercholesterolemic-induced animals was investigated. Eighteen adult male New Zealand White (NZW) rabbit were segregated into three groups labelled as group N, HCD and ALA (n = 6). Group N (normal control) was fed with normal chow, the rest (HCD and ALA) were fed with 100 g/head/day of 1% cholesterol rich diet to induce hypercholesterolemia. Four point two mg/body weight of alpha lipoic acid was concomintantly supplemented to the ALA group. Drinking water was given ad-libitum. The study was designed for 10 weeks. blood sampling was taken from the ear lobe vein at the beginning, week 5 and week 10. Plasma was prepared for lipid profile estimation and microsomal lipid peroxidation index indicated with malondialdehyde (MDA) formation. At the end of the experiment, the animals were sacrificed and the aorta were excised for intimal lesion analysis. The plasma total cholesterol (TC) and low density lipoprotein (LDL) levels were found to be significantly low in ALA group compared to that of the HCD group (p<0.05). Similarly, low level of MDA (p<0.05) in ALA group was observed compared to that of the HCD group showing a significant reduction of lipid peroxidation activity. Histomorphometric intimal lesion analysis of the aorta showing less of atheromatous plaque formation in alpha lipoic acid supplemented group (p<0.05) compared to HCD group. These findings suggested that alpha lipoic acid posses a dual lipid lowering and Anti-atherosclerotic properties indicated with low plasma TC and LDL levels and reduction of athero-lesion formation in hypercholesterolemic-induced rabbits.
