stilbenes and Hyperlipidemias

Polydatin (PD) is a monocrystalline metabolite from the underground parts of Polygonum cuspidatum Sieb. et Zucc., a member of the Polygonaceae family, which has been traditionally used in Asian countries as both foodstuffs and medicine. PD, also reckoned as pieceid, 3,4',5-trihydroxystilbene-3-β-D-glucoside, (E)-piceid, (E)-polydatin, and trans-polydatin. It possesses potent biological activities i.e. analgesic, anti-inflammatory, antidiabetic, anticancer, and anti-atherosclerotic properties. The initial part of this report specifically explains distinct sequential mechanisms underlying the initiation and development of atherosclerotic plaques and later part deals with the pharmacological efficacy of PD in the management of major cardiac event i.e. atherosclerotic cardiovascular diseases (ASCVD) via modulation of a set of molecular mechanisms i.e. antioxidant potential, lipid and lipoprotein metabolism including total cholesterol (TC) and low density lipoprotein (LDL) levels, β-hydroxy-β-methyl-glutaryl-CoA reductase (HMG-R) expression and functionality, SIRT signalling, LDL-receptor (LDL-R), LDL oxidation status (Ox-LDL), effects on endothelial cells (ECs), smooth muscle cells (SMCs), macrophage, foam cell formation and plaque stabilization, inflammatory signalling pathways and hypertension. In contrast, one of the major insight into the potential cardioprotective molecular mechanism is the PD-mediated targeting of proprotein convertase subtilisin/kexin type-9 (PCSK-9) and LDL-R pathway, both at transcriptional and protein functional level, which makes it a better alternative therapeutic medicinal candidate to treat hypercholesterolemia, especially for the patients facing inadequate lipid lowering with classical HMG-R inhibitors (statins) and statin intolerance. Finally, to sum up the whole, we concluded that PD may be promoted from alternative to mainstream medicine in targeting risk factors mediated ASCVD.

Topics: Anticholesteremic Agents; Atherosclerosis; Cholesterol, LDL; Endothelial Cells; Fallopia japonica; Glucosides; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Lipoproteins, LDL; Plaque, Atherosclerotic; Receptors, LDL; Risk Factors; Stilbenes

Topics: Animals; Antineoplastic Agents; Apoptosis; Arachidonic Acid; Cell Degranulation; Chemical and Drug Induced Liver Injury; Glucosides; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipid Peroxidation; Neoplasm Metastasis; Neutrophils; Phytotherapy; Polygonum; Resveratrol; Stilbenes

Resveratrol is known to improve endothelial function in animals, but little is known about its effect on human subjects. Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors underlying endothelial dysfunction. We hypothesized that the modified resveratrol, Longevinex, improves endothelial function in patients with MetS. Thirty-four patients who had been treated for MetS and lifestyle-related disease were randomly assigned to group A, in which Longevinex was administered for 3 months and then discontinued for 3 months, whereas in the time-matched group B, Longevinex was administered between 3 and 6 months. These 2 groups of patients received similar drugs at baseline for diabetes mellitus, dyslipidemia, or hypertension. Flow-mediated dilatation significantly increased during the administration of Longevinex but decreased to baseline 3 months after the discontinuation of Longevinex in the group A patients. Conversely, in the group B patients, flow-mediated dilatation remained unchanged for the first 3 months without Longevinex but was significantly increased 3 months after the treatment with Longevinex. Longevinex did not significantly affect blood pressure, insulin resistance, the lipid profile or inflammatory markers during 6-month follow-up. These results demonstrate that Longevinex specifically improves endothelial function in subjects with MetS who were receiving standard therapy for lifestyle-related disease.

Topics: Aged; Diabetes Mellitus; Drug Compounding; Endothelium, Vascular; Female; Humans; Hyperlipidemias; Hypertension; Insulin Resistance; Life Style; Male; Metabolic Syndrome; Middle Aged; Resveratrol; Stilbenes; Vasodilation; Vasodilator Agents

The present study investigated the potential effects of pterostilbene (PT) on glycemic and lipid profiles, fat storage, cardiovascular indices, and hepatic parameters of rats fed with sucrose solution.. 24 male Wistar rats received either drinking water or a 40% sucrose solution over a period of 140 days. After this period, animals were randomly allocated into four groups (n = 6): Control (C), C + Pterostilbene (PT), Sucrose (S), and S + PT. Pterostilbene (40 mg/kg) was given orally for 45 consecutive days.. Pterostilbene did not influence morphometric and nutritional parameters. The insulin sensitivity index TyG was elevated in the C + PT group (p < 0.01) and reduced in S + PT group (p < 0.05). Basal glucose levels were lower in the S + PT group (p < 0.05), and the glycemic response was improved with PT treatment in glucose provocative tests. Conversely, rats from the C + PT group showed impaired glucose disposal during those tests. Lipid profile was partially improved by PT treatment. Hepatic oxidative stress in the S group was improved after PT treatment. In the C group, PT reduced SOD activity, glutathione levels, and increased catalase activity. Collagen content was reduced by PT treatment.. PT effects depends on the type of diet the animals were submitted. In rats fed with sucrose-solution, PT confirmed its positive effects, improving glucose and lipid profile, and acting as a potent antioxidant. The effects of PT on rats that consumed a normal diet were very discrete or even undesirable. We suggest caution with indiscriminate consume of natural compounds by healthy subjects.

Topics: Animals; Antioxidants; Blood Glucose; Dietary Sucrose; Hyperglycemia; Hyperlipidemias; Liver; Male; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Wistar; Stilbenes

ε-Viniferin (VNF), a naturally occurring oligostilbene (a resveratrol dimer), is mainly found in grapes and red wines. However, unlike resveratrol, the biological activity of VNF has not been widely studied. This study was conducted to investigate the beneficial effects of VNF on hyperglycemia and hyperlipidemia and further to reveal the underlying mechanism. The ameliorative effects of VNF in high-fat-diet and streptozotocin-induced type 2 diabetic rats were assessed physiologically, biochemically and histologically after oral administration of VNF (30 mg kg-1 and 60 mg kg-1) for 8 weeks. Western blotting and immunohistochemistry experiments were performed to determine the effects of VNF on the AMPK phosphorylation levels in the livers of diabetic rats. Molecular docking and molecular dynamics simulation were further performed to study the molecular-level interaction between VNF and AMPK. Meanwhile, the protective effects of VNF on the liver and kidney were also evaluated. The results showed that the VNF treatment caused a significant decrease in the concentrations of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein-cholesterol (LDL-C), and improved the glucose tolerance of diabetic rats. In addition, the liver and kidney damage indices such as alanine aminotransferase (ALT), aspartate aminotransaminase (AST), creatinine (CR), and blood urea nitrogen (BUN) were also lowered and improved. Moreover, VNF could increase the AMPK activation and attenuate histopathological changes in the liver of diabetic rats. The molecular docking and molecular dynamics simulation results revealed for the first time that VNF bound to the hinge region between the α- and β-units of AMPK and interacted with the active site of AMPK. In conclusion, VNF can effectively improve hyperglycemia and hyperlipidemia and exhibit protective effects on the liver and kidney functions. The underlying mechanism of VNF in hyperglycemia and hyperlipidemia may be related to the activation of AMPK in vivo. Our findings indicate that VNF is a potentially useful natural agent for the treatment of metabolic diseases, especially type 2 diabetes and hyperlipidemia.

Topics: AMP-Activated Protein Kinases; Animals; Benzofurans; Blood Glucose; Cholesterol, LDL; Diet, High-Fat; Humans; Hyperglycemia; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; Liver; Male; Rats; Rats, Sprague-Dawley; Stilbenes; Triglycerides

The aim of this study was to evaluate the potential effects of 2,3,4',5-tetrahydroxystilbene-2-O-β-d-glucoside (TSG) on the development of atherosclerotic plaque in ApoE

Topics: Animals; Apolipoproteins E; Atherosclerosis; Biological Transport; Cholesterol; Fatty Liver; Foam Cells; Glucosides; Hyperlipidemias; Inflammation; Lipid Metabolism; Macrophages; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; RAW 264.7 Cells; Stilbenes

The present study aimed to study lipid-lowering effect of seven traditional Chinese medicine monomers in zebrafish system. Zebrafish were fed with high fat diet to establish a hyperlipemia model, then fasted and bathed with seven traditional Chinese medicine monomers stigmasterol, triacontanol, chrysophanol, vanillic acid, shikimic acid, polydatin and oleanolic acid respectively. The oil red O staining was used to detect the blood lipids of zebrafish. Serum total cholesterol and triglyceride levels were detected to validate the lipid-lowering effect. The result showed that a zebrafish model of hyperlipemia could be established by feeding larvae zebrafish with high fat diet. Among the seven traditional Chinese medicine monomers, chrysophanol had lipid-lowering effect. Chrysophanol significantly reduced serum total cholesterol and triglyceride levels in adult zebrafish fed with high fat diet. Chrysophanol accelerated peristalsis frequency of zebrafish intestine and the excretion of high fat food. It is concluded that chrysophanol has lipid- lowering effect in zebrafish, and the mechanism of the effect may be due to the roles of chrysophanol in reducing lipid absorption from gastrointestinal tract and accelerating the excretion of food.

Topics: Animals; Anthraquinones; Diet, High-Fat; Fatty Alcohols; Glucosides; Hyperlipidemias; Hypolipidemic Agents; Larva; Lipids; Medicine, Chinese Traditional; Oleanolic Acid; Shikimic Acid; Stigmasterol; Stilbenes; Vanillic Acid; Zebrafish

Resveratrol is beneficial in obese and diabetic rodents. However, its low bioavailability raises questions about its therapeutic relevance for treating or preventing obesity complications. In this context, many related natural polyphenols are being tested for their putative antidiabetic and anti-obesity effects. This prompted us to study the influence of piceatannol, a polyhydroxylated stilbene, on the prevention of obesity complications in Zucker obese rats. A 6-week supplementation was followed by the determination of various markers in plasma, liver, adipose tissue and heart, together with a large-scale analysis of gut microbiota composition. When given in doses of 15 or 45 mg/kg body weight/day, piceatannol did not reduce either hyperphagia or fat accumulation. It did not modify the profusion of the most abundant phyla in gut, though slight changes were observed in the abundance of several Lactobacillus, Clostridium, and Bacteroides species belonging to Firmicutes and Bacteroidetes. This was accompanied by a tendency to reduce plasma lipopolysaccharides by 30 %, and by a decrease of circulating non-esterified fatty acids, LDL-cholesterol, and lactate. While piceatannol tended to improve lipid handling, it did not mitigate hyperinsulinemia and cardiac hypertrophy. However, it increased cardiac expression of ephrin-B1, a membrane protein that contributes to maintaining cardiomyocyte architecture. Lastly, ascorbyl radical plasma levels and hydrogen peroxide release by adipose tissue were similar in control and treated groups. Thus, piceatannol did not exhibit strong slimming capacities but did limit several obesity complications.

Topics: 3T3-L1 Cells; Adipose Tissue, White; Adiposity; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biomarkers; Dietary Supplements; Dysbiosis; Heart Diseases; Hydrogen Peroxide; Hyperlipidemias; Liver; Male; Mice; Myocardium; Obesity; Random Allocation; Rats, Zucker; Stilbenes

The excessive consumption of high cholesterol diet has been associated with an increased incidence oflipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim ofthese experiments was to investigate the protective effect of resveratrol co-administered with cholesterol diet inducedhyperlipidaemia in rabbits. Thirty rabbits divided into six groups of five animal (group= 5) each: group 1 = normal control,group 2 = cholesterol diet/high fat diet group only (HFD), group 3 = resveratrol 200 mg/kg (R200), group 4 = resveratrol400 mg/kg (R400), group 5 = HFD + R200 and group 6 = HFD + R400. The normal group was fed with standard animalfeeds only; while the HFD groups were fed with standard animal feeds + cholesterol diet (10% Groundnut oil, 20%Groundnut mill and 2% cholesterol). Resveratrol-treated rabbits received resveratrol suspended in 10 g/Lcarboxymethylcellulose (CMC) and the control group received the vehicle only, CMC. The preparations were administeredfor 8 weeks of experimental protocol. At the end of the study period, the animals were sacrificed. Blood and plasma sampleswere collected. Serum evaluation of lipid profile such as total cholesterol (TC), triacylglycerol (Tg), low density lipoproteincholesterol (LDP-c) and high density lipoprotein cholesterol (HDL-c) were also assessed. The results obtained showsignificant (P < 0.05) decrease in total cholesterol (TC), Low density lipoprotein cholesterol (LDP-c), total triacylglyceroland an increase in high density lipoprotein cholesterol (HDL-c) in resveratrol treated groups compared to HFD group only.In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrationsand might be beneficial in treatment of hyperlipidemia and atherosclerosis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cholesterol; Cholesterol, Dietary; Cholesterol, LDL; Hyperlipidemias; Male; Protective Agents; Rabbits; Resveratrol; Stilbenes; Triglycerides

Mulberroside A (MUL) was purified from an ethanol extract of Morus alba root, and oxyresveratrol (OXY) was produced by enzymatic conversion of MUL. Normal rats, Triton WR-1339-induced hyperlipidemic rats, and high-cholesterol diet (HCD)-induced hyperlipidemic rats were orally treated with MUL or OXY (1-5mg/kg/day). MUL and OXY were administered 1h prior to concomitant treatment with Triton WR-1339 for a further 24h, whereas the drugs were administered concurrently with HCD for 4weeks. Oral MUL and OXY pre-treatment vs. water pre-treatment of Triton WR-1339-induced hyperlipidemic rats significantly (p<0.05) reduced the levels of serum lipids in a dose-dependent manner, while high-density lipoprotein cholesterol (HDL-C, or "good" cholesterol) levels were increased. Oral MUL and OXY treatment of HCD-fed rats also showed a significant (p<0.05) dose-dependent decrease in serum lipids, coronary artery risk index (CRI), and atherogenic index (AI), but not HDL-C. Furthermore, MUL and OXY treatment of HCD-induced hyperlipidemic rats demonstrated a significant dose-dependent improvement in the histological features of hepatic fatty degeneration. Aspartate aminotransferase and alanine aminotransferase values in OXY-treated normal rats were not significantly different from those in water-treated control rats. These results indicate that MUL and OXY might be developed as novel antihyperlipidemic agents.

Topics: Animals; Body Weight; Cholesterol, Dietary; Disaccharides; Hyperlipidemias; Hypolipidemic Agents; Lipids; Male; Morus; Plant Extracts; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Stilbenes

The content of resveratrol is relatively high in Polygonum cuspidatum Sieb. et Zucc., and the resveratrol has the effect of blood vessel dilating, microcirculation improving, platelet aggregation inhibiting and anti-cancer. The objective of this paper was to study the effect of resveratrol on lipid metabolism in hyperlipidemia mice.. Through the establishment of an experimental mouse model of hyperlipidemia, the effect of resveratrol on change in total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) levels in mouse serum were determined.. Resveratrol group can apparently reduce TC, TG, LDL-c and AI of hyperlipidemic mice in a dose effect manner.. We concluded that resveratrol can effectively reduce blood lipid levels of hyperlipidemic mice.

Topics: Animals; Arteriosclerosis; Cholesterol; Dose-Response Relationship, Drug; Fallopia japonica; Hyperlipidemias; Lipid Metabolism; Male; Mice; Phytotherapy; Plant Extracts; Resveratrol; Stilbenes; Triglycerides

Effective and safe pharmacological interventions for hyperlipidemia remains badly needed. By incorporating the key pharmacophore of fibrates into the natural scaffold of resveratrol, a novel structural compound ZBH was constructed. In present study, we found ZBH reserved approximately one third of the sirtuin 1 (SIRT1) activation produced by resveratrol at in-vitro enzyme activity assay, directly bound to and activated all three peroxisome proliferator-activated receptor (PPAR) subtypes respectively in PPAR binding and transactivation assays. Moreover, ZBH (EC₅₀, 1.75 µM) activate PPARα 21 fold more efficiently than the well-known PPAR pan agonist bezafibrate (EC₅₀ 37.37 µM) in the cellular transactivation assays. In the high fat diet induced hyperlipidemic hamsters, 5-week treatment with ZBH significantly lowered serum triglyceride, total cholesterol, LDL-C, FFA, hyperinsulinemia, and improved insulin sensitivity more potently than bezafibrate. Meanwhile, serum transaminases, creatine phosphokinase and CREA levels were found not altered by ZBH intervention. Mechanism study indicated ZBH promoted the expression of PPARα target genes and SIRT1 mRNA. Hepatic lipogenesis was markedly decreased via down-regulation of lipogenic genes, and fatty acid uptake and oxidation was simultaneously increased in the liver and skeletal muscle via up-regulation of lipolysis genes. Glucose uptake and utilization was also significantly promoted in skeletal muscle. These results suggested that ZBH significantly lowered hyperlipidemia and ameliorated insulin resistance more efficiently than bezafibrate in the hyperlipidemic hamsters primarily by activating of PPARα, and SIRT1 promotion and activation. ZBH thus presents a potential new agent to combat hyperlipidemia.

Topics: Animals; Bezafibrate; Cricetinae; Diet, High-Fat; Drug Design; Gene Expression Regulation; Hyperinsulinism; Hyperlipidemias; Hypolipidemic Agents; Liver; Male; Muscle, Skeletal; Pentanoic Acids; PPAR alpha; Resveratrol; Sirtuin 1; Stilbenes; Triglycerides

Rhapontin was purified from a methanol extract from the roots of Rheum undulatum, and rhapontigenin was produced by an enzymatic transformation of rhapontin. Rats were fed a high-cholesterol diet to induce hyperlipidemia, followed by oral treatment with rhapontin or rhapontigenin (1-5 mg/kg/day). Rhapontin and rhapontigenin treatment resulted in a significant (p<0.05) dose-dependent decrease in the serum lipid level, while the high-density lipoprotein cholesterol level increased slightly compared with the experimental control. Furthermore, rhapontin and rhapontigenin treatment improved the pathological characteristics of the degenerating fatty liver in high-cholesterol diet-induced hyperlipidemic rats dose-dependently. Aspartate aminotransferase and alanine aminotransferase levels in rhapontin- and rhapontigenin-treated hyperlipidemic rats were not significantly different from those in the control. These results indicate that rhapontin and rhapontigenin can be used as potent antihyperlipidemic agents.

Topics: Animals; Cholesterol; Fatty Liver; Hyperlipidemias; Hypolipidemic Agents; Plant Extracts; Rats; Rats, Sprague-Dawley; Rheum; Stilbenes; Triglycerides

Novel phenoxyalkylcarboxylic acid derivatives based on the natural scaffolds, flavonoids, or resveratrol were designed, synthesized, and evaluated for hypolipidaemic activity. Among the compounds, 30b lowered the triglycerides by 48.5% (P < 0.05) and total cholesterol by 44.2% (P < 0.05), respectively, and was more effective than the reference drug fenofibric acid in a Triton WR-1339-induced hyperlipidaemic mice model orally (300 mg/kg body weight). 30b also showed 59.4% triglycerides lowering in an alloxan-induced diabetic mice model orally (150 mg/kg body weight). Receptor docking studies revealed that compound 30b could interact with the amino acid residues in the ligand-binding domain essential for the activation of the PPARα. The results indicate that resveratrol should be a better scaffold to derive a new class of hypolipidaemic agents in comparison with a flavonoid scaffold.

Topics: Animals; Carboxylic Acids; Cholesterol; Diabetes Mellitus, Experimental; Fenofibrate; Flavonoids; Hyperlipidemias; Hypolipidemic Agents; Magnetic Resonance Spectroscopy; Male; Mice; Models, Molecular; Molecular Structure; Polyethylene Glycols; Resveratrol; Stilbenes; Surface-Active Agents; Triglycerides

Consumption of a high-fat diet (HFD) enriched in saturated fat induces excessive weight gain due to adiposity, which can lead to metabolic complications, as well as increased risk of fatty liver disease and CVD. The present study investigated the underlying mechanism and dose-response effects of resveratrol (RV) on obesity, hepatic steatosis and dyslipidaemia in mice fed a HFD. Male C57BL/6J mice were fed a normal diet or a HFD (20 % fat, w/w) combined with 0·005 or 0·02 % (w/w) RV for 10 weeks. As expected, mice fed a HFD developed obesity, as shown by increased body weight gain, visceral fat, hepatic fat and plasma cholesterol. RV significantly reduced visceral fat and plasma NEFA. In the liver of HFD-fed mice, RV significantly reduced TAG and cholesterol, as well as lipid droplet number and size. A low dose of RV (0·005 %) appeared to be more effective than a higher dose of RV (0·02 %) for suppressing adiposity and hepatic steatosis development with a significant decrease in body weight gain, plasma TAG and total cholesterol levels. These changes were seemingly attributable to a suppression of the fatty acid (FA) synthase, glucose-6-phosphate dehydrogenase, and phosphatidate phosphohydrolase and/or an activation of FA oxidation in the liver and epididymal adipose tissue. In conclusion, daily consumption of a low dose of RV is effective for protecting against diet-induced obesity, hepatic steatosis and dyslipidaemia in HFD-fed mice.

Topics: Adiposity; Animals; Cholesterol; Diet; Diet, High-Fat; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fatty Acid Synthases; Fatty Liver; Glucosephosphate Dehydrogenase; Hyperlipidemias; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Phosphatidate Phosphatase; Resveratrol; Stilbenes; Triglycerides; Weight Gain

The contents of stilbene monomers, cis-resveratrol, trans-resveratrol, cis-piceid, trans-piceid, and tyrosol, were quantified in Vitis vinifera red wines, cvs. Cabernet Franc, Merlot, Sangiovese, and Syrah, 2006 and 2007 vintages, from the São Joaquim region, a new grape-growing region at southern Brazil. Moreover, the effect of chronic consumption of these wines on the antioxidant and hypolipidemic activities was monitored in C57BL6 LDL receptor knockout mice and treated with a hypercholesterolemic diet. Red wines from this region had substantial levels of resveratrols (the predominant forms were glycoside and trans) and tyrosol. Biomonitoring of antioxidant and hypolipidemic activities in vivo revealed that consumption of these wines increased the antioxidant capacity and reduced the hypercholesterolemia and hypertriglyceridemia promoted by the hypercholesterolemic diet. Significant correlations were found between the increase of antioxidant capacity markers, the decrease of lipid levels promoted by wine consumption, and the contents of stilbenes and tyrosol, supporting the important biological activity of these compounds.

Topics: Animals; Antioxidants; Brazil; Disease Models, Animal; Humans; Hyperlipidemias; Hypolipidemic Agents; Mice; Mice, Inbred C57BL; Mice, Knockout; Phenylethyl Alcohol; Stilbenes; Vitis; Wine

Accelerated atherosclerosis is a major diabetic complication initiated by the enhanced recruitment of monocytes into the vasculature. In this study, we examined the therapeutic potential of the phytonutrients ursolic acid (UA) and resveratrol (RES) in preventing monocyte recruitment and accelerated atherosclerosis.. Dietary supplementation with either RES or UA (0.2%) protected against accelerated atherosclerosis induced by streptozotocin in high-fat diet-fed LDL receptor-deficient mice. However, mice that received dietary UA for 11 weeks were significantly better protected and showed a 53% reduction in lesion formation while mice fed a RES-supplemented diet showed only a 31% reduction in lesion size. Importantly, UA was also significantly more effective in preventing the appearance of proinflammatory GR-1(high) monocytes induced by these diabetic conditions and reducing monocyte recruitment into MCP-1-loaded Matrigel plugs implanted into these diabetic mice. Oxidatively stressed THP-1 monocytes mimicked the behavior of blood monocytes in diabetic mice and showed enhanced responsiveness to monocyte chemoattractant protein-1 (MCP-1) without changing MCP-1 receptor (CCR2) surface expression. Pretreatment of THP-1 monocytes with RES or UA (0.3-10μM) for 15h resulted in the dose-dependent inhibition of H(2)O(2)-accelerated chemotaxis in response to MCP-1, but with an IC(50) of 0.4μM, UA was 2.7-fold more potent than RES.. Dietary UA is a potent inhibitor of monocyte dysfunction and accelerated atherosclerosis induced by diabetes. These studies identify ursolic acid as a potential therapeutic agent for the treatment of diabetic complications, including accelerated atherosclerosis, and provide a novel mechanism for the anti-atherogenic properties of ursolic acid.

Topics: Animals; Aortic Diseases; Atherosclerosis; Cardiovascular Agents; Cell Line; Chemokine CCL2; Chemotaxis, Leukocyte; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Dose-Response Relationship, Drug; Female; Humans; Hyperlipidemias; Kidney; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes; Oxidative Stress; Receptors, CCR2; Receptors, LDL; Resveratrol; Stilbenes; Time Factors; Triterpenes; Ursolic Acid

Hyperlipidemia is one of the vital coronary risk factors and is positively related to morbidity and mortality of coronary heart disease. There are numerous herbal medicines which are reported to exert good hypolipidemic actions with few side effects. In the present study, the hypolipidemic effects of polydatin, a compound from Polygonum cuspidatum Sieb. et Zucc, on hyperlipidemic rabbits were evaluated. Thirty-two male rabbits were fed a high fat/cholesterol diet for 6 weeks and another eight male rabbits fed a basic diet served as normal control. Three weeks after a high fat/cholesterol diet, the animals were orally administrated polydatin (25, 50, and 100 mg kg(-1) per day) by intubation for 3 weeks. The results showed that polydatin markedly decreased the serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic rabbits. The ratio of TC to high-density lipoprotein cholesterol (HDL-C) and the liver coefficient were also reduced. But both polydatin and high fat/cholesterol diet did not evidently affect body weight in hyperlipidemic rabbits. All these results suggest that polydatin from Polygonum cuspidatum has favorable potency to develop a hypolipemic and/or hepatoprotective agent in clinic. However the mechanism of hypolipemic action of polydatin is in need of further clarity.

Topics: Animals; Body Weight; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Fallopia japonica; Glucosides; Hyperlipidemias; Hypolipidemic Agents; Male; Phytotherapy; Plant Extracts; Plant Roots; Rabbits; Stilbenes; Triglycerides

Hyperlipidaemias are common in obese people, and they increase the risk of cardiovascular diseases such as coronary heart disease (CHD) and atherosclerosis (AS). Previous studies have shown that several drugs can depress serum cholesterol. However, they could cause serious side effects in various clinical settings. The objective of the present study was to evaluate the lipid-lowering effects of polydatin in high-fat/cholesterol (HFC)-fed hamsters. The levels of lipids in hamsters were measured enzymatically before and after the administration of polydatin. Significant differences between HFC and HFC+polydatin were detected for those concentrations. Decreased levels of serum TC, TG and LDL-C and the concentrations of hepatic TG were found. Experimental results also showed that polydatin elevated LDL-C/HDL-C and TC/HDL-C ratios. In concert with other effects, serum cholesterol-lowering effect in hamsters may contribute to the regulation properties attributed to polydatin.

Topics: Animals; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Cricetinae; Fallopia japonica; Glucosides; Hyperlipidemias; Hypolipidemic Agents; Male; Mesocricetus; Stilbenes; Triglycerides

It remains presently unknown whether vascular reactivity is impaired and whether maladaptive cardiac remodeling occurs before the onset of overt obesity and in the absence of hyperlipidemia. Normal female rats were fed a high-fat diet for 8 weeks and were associated with a modest nonsignificant increase of body weight (standard diet, 300 +/- 10, versus high-fat diet, 329 +/- 14 g) and a normal plasma lipid profile. In rats fed a high-fat diet, systolic (171 +/- 7 mm Hg) and diastolic blood pressures (109 +/- 3) were increased compared to a standard diet (systolic blood pressure, 134 +/- 8; diastolic blood pressure, 96 +/- 5 mm Hg), and acetylcholine-dependent relaxation of isolated aortic rings (high-fat diet, 22 +/- 5%, versus standard diet, 53 +/- 8%) was significantly reduced. Furthermore, perivascular fibrosis was detected in the heart of rats fed a high-fat diet. The exogenous addition of resveratrol (trans-3,5,4'-trihydroxystilbene) (0.1 microM) to aortic rings isolated from rats fed a high-fat diet restored acetylcholine-mediated relaxation (47 +/- 9%). The administration of resveratrol (20 mg/kg/day for 8 weeks) to rats fed a high-fat diet prevented the increase in blood pressure and preserved acetylcholine-dependent relaxation of isolated aortic rings. However, resveratrol therapy failed to attenuate the perivascular fibrotic response. These data have demonstrated that a high-fat diet fed to normal female rats can elicit a hypertensive response and induce perivascular fibrosis before the development of overt obesity and in the absence of hyperlipidemia. Resveratrol therapy can prevent the hypertensive response in female rats fed a high-fat diet but is without effect on the progression of perivascular fibrosis.

Topics: Acetylcholine; Animals; Antioxidants; Aorta; Blood Pressure; Dietary Fats; Female; Fibrosis; Hyperlipidemias; Myocardium; Nitroprusside; Obesity; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Vasodilation; Vasodilator Agents; Ventricular Dysfunction, Left

To study lipid-regulating action of 2, 3, 5, 4'-tetrahydroxy stilbene-2-O-beta-D-glucopyranoside (TSG) from Polygonum multiflorum on experimental model hyperlipidemic rats.. TSG 90 and 180 mg x kg(-10 x d(-1), atorvastatin mg kg(-1) x d(-1) and saline 2 mL x d(-1) were administered to hyperlipidemic rats. Groups of rats were determined and compared with those of saline group. The LDLR and HMGR mRNA expression were also detected.. TSG significantly reduced serum TC and LDL-C level and atherosclerosis index, increased the expression of LDLR in the liver cells.. TSG, which shows effects and mechanism in part like atorcastatin, is a major constituent with blood-lipid regulating effect of P. multiflorum and can be explored as a potent medication for hyperlipidemia. Effects on LDL-C and AI, as well as on gene expression of TSG were first reported.

Topics: Animals; Anticholesteremic Agents; Atorvastatin; Cholesterol, LDL; Glucosides; Hepatocytes; Heptanoic Acids; Hydroxymethylglutaryl CoA Reductases; Hyperlipidemias; Male; Plant Tubers; Plants, Medicinal; Polygonum; Pyrroles; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, LDL; RNA, Messenger; Stilbenes; Triglycerides

The effect of resveratrol, a polyphenolic compound present in grapes and other plants, on proteinuria, hypoalbuminemia and hyperlipidemia was studied in rats with glomerulonephritis. The nephritis was induced by an intravenous injection of anti-rat kidney glomerular basement membrane rabbit antiserum. Nephritic rats were given oral intubation of resveratrol (5 mg/day/100 g body weight) for 14 days, while control nephritic rats as well as normal ones were similarly given vehicle alone. By resveratrol treatment, enlargement in liver and kidney due to nephritis induction was significantly reduced, together with partial restoration of nephritis-induced reduction in body weight gain. Both proteinuria and hypoalbuminemia, characteristic symptoms to nephrotic syndrome, were significantly remedied, that is, urinary protein excretion was suppressed and serum albumin concentration was increased by resveratrol treatment. Resveratrol also suppressed significantly hyperlipidemia incident to nephritis, the hypotriglyceridemic action being more prominent than the hypocholesterolemic one. From these results, resveratrol is suggested to be a potent anti-glomerulonephritic food factor capable of suppressing proteinuria, hypoalbuminemia and hyperlipidemia at the same time.

Topics: Administration, Oral; Albumins; Animals; Anti-Inflammatory Agents, Non-Steroidal; Basement Membrane; Blood Urea Nitrogen; Body Weight; Cholesterol; Disease Models, Animal; Eating; Glomerulonephritis; Hyperlipidemias; Hypoproteinemia; Kidney; Kidney Glomerulus; Liver; Male; Organ Size; Proteinuria; Rabbits; Rats; Rats, Wistar; Resveratrol; Stilbenes; Triglycerides