isoquercitrin and Hyperlipidemias

Lifestyle and genetic factors contribute to the initiation of oxidative stress and inflammation in diabetes mellitus (DM). Oxidative stress and lipid peroxidation worked in an orchestrated manner and reported to be strongly associated with the formation of the hyperlipidemic condition in DM patients. Isoquercetin, a bioactive constituent isolated from guava leaves has attracted considerable attention because of its antidiabetic activity. The antidiabetic activity of guava leaves may be due to the presence of isoquercetin at a significant level. However, how isoquercetin regulates different pathways in DM is insufficiently studied. We have selected versatile regulators of oxidative stress and inflammatory pathways to fully analyze if isoquercetin effectively modulated the genes of these pathways. At the end of our experimental duration, rats were dissected and analyzed for the oxidative stress, lipid peroxidation, inflammatory and lipid markers. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is believed to be the key regulator of expression of various antioxidant enzyme genes and it is directly or indirectly related to nuclear factor Kappa- B (NF-kB) and AMP-activated protein kinase (AMPK) pathways. Therefore, we tend to study the effects of STZ on Nrf2, NF-kB and AMPK pathway and how the isoquercetin treatment performs at a molecular level to overcome the burden of DM. The results of our study provided convincing evidence of significant pharmacological properties of isoquercetin in context of its ability to inhibit the oxidative stress elicited by the STZ through generation of the free radicals and regulation of the expression of Nrf2 pathway-associated proteins and genes and it also reduced the burden of hyperlipidemia and inflammation. By taking the above results into consideration isoquercetin can be studied further to elucidate its antidiabetic effects at various levels.

Topics: AMP-Activated Protein Kinases; Animals; Cytokines; Diabetes Mellitus, Experimental; Gene Expression Regulation; Hyperlipidemias; Inflammation; NF-E2-Related Factor 2; Oxidative Stress; Quercetin; Rats; Streptozocin

Hepatic LDL receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) regulate the clearance of plasma LDL-cholesterol (LDL-C): LDLR promotes it, and PCSK9 opposes it. These proteins also express in pancreatic β cells. Using cultured hepatocytes, we previously showed that the plant flavonoid quercetin-3-glucoside (Q3G) inhibits PCSK9 secretion, stimulated LDLR expression, and enhanced LDL-C uptake. Here, we examine whether Q3G supplementation could reverse the hyperlipidemia and hyperinsulinemia of mice fed a high-cholesterol diet, and how it affects hepatic and pancreatic LDLR and PCSK9 expression.. For 12 weeks, mice are fed a low- (0%) or high- (1%) cholesterol diet (LCD or HCD), supplemented or not with Q3G at 0.05 or 0.1% (w/w). Tissue LDLR and PCSK9 is analyzed by immunoblotting, plasma PCSK9 and insulin by ELISA, and plasma cholesterol and glucose by colorimetry. In LCD-fed mice, Q3G has no effect. In HCD-fed mice, it attenuates the increase in plasma cholesterol and insulin, accentuates the decrease in plasma PCSK9, and increases hepatic and pancreatic LDLR and PCSK9. In cultured pancreatic β cells, however, it stimulates PCSK9 secretion.. In mice, dietary Q3G could counter HCD-induced hyperlipidemia and hyperinsulinemia, in part by oppositely modulating hepatic and pancreatic PCSK9 secretion.

Topics: Animals; Cell Line, Tumor; Cholesterol, Dietary; Dietary Supplements; Gene Expression Regulation; Glucose Transporter Type 2; Hyperinsulinism; Hyperlipidemias; Hypolipidemic Agents; Insulin Resistance; Insulin-Secreting Cells; Liver; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Organ Specificity; Pancreas; Proprotein Convertase 9; Quercetin; Receptors, LDL

Quercetin, a major flavonol, present abundantly in apples and onions, is widely studied for ameliorating metabolic syndrome abnormalities. However, quercetin is mainly present in plant food in the form of quercetin glycosides and has been reported for poor gastrointestinal absorption. The present study was designed with the purpose of imparting a lipophilic property to quercetin-3-O-glucoside (QG) by its acylation with eicosapentaenoic acid (EPA) and to study the influence of eicosapentaenoic acid ester of quercetin-3-O-glucoside (QE) on hyperlipidemia and inflammation in vivo and in vitro. QE was more effective in reducing the production of tumor necrosis factor-alpha (TNF-α), prostaglandin 2 (PGE2), cyclo-oxygenase (COX)-2 levels and nuclear expression of nuclear factor-kappa B (NF-кB) compared to the parent compounds (QG and EPA) and commercial drugs, after lipopolysaccharides (LPS) induced inflammation in THP-1 derived macrophages. Serum high-density lipoprotein (HDL)-cholesterol was significantly higher and hepatic total cholesterol concentration was lower in the rats fed high-fat diet supplemented with QE, compared to the high-fat diet with inflammation (HFL). The serum concentrations of C-reactive protein (CRP), interleukin (IL)-6, and interferon-gamma (IFN-γ) were significantly lower in QE treatment group than HFL group. EPA conjugated flavonol, QE, had significant anti-inflammatory and hypolipidemic properties and may be effective for the treatment of obesity-related disorders.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Cholesterol, HDL; Diet, High-Fat; Eicosapentaenoic Acid; Humans; Hyperlipidemias; Hypolipidemic Agents; Inflammation; Macrophages; Male; Quercetin; Rats; Rats, Wistar