3-methylquercetin and Non-alcoholic-Fatty-Liver-Disease

Nonalcoholic steatohepatitis (NASH) is the most severe and progressive form of nonalcoholic fatty liver disease (NAFLD), which can lead to life-threatening conditions, however, there is still no approved drug for the treatment of NASH. In this study we used human-like NASH mouse model and treated orally with isorhamnetin at a dose of 50 mg/kg to analyze the effect of isorhamnetin on the progression of NASH. NASH-induced mice represented severe steatosis with inflammation, and fibrosis in liver accompanied with high level of liver injury markers in serum. Isorhamnetin treatment reduced intrahepatic lipid accumulation and TG content by inhibiting de novo lipogenic pathway in NASH-induced mice. Consistent with this, isorhamnetin-treated NASH mice showed improved liver injury markers, reduced collagen deposition as well as decreased gene expression of fibrogenic markers. Taken together, here we showed for the first time that synthesized isorhamnetin alleviates pathologic features of NASH and thus can potentially contribute to NASH drug development.

Topics: Animals; Body Weight; Lipogenesis; Liver; Liver Cirrhosis; Macrophages; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Organ Size; Oxidation-Reduction; Quercetin

Studies on peroxisome proliferator-activated receptor (PPAR)-γ ligands have been focused on agonists. However, PPARγ activation may induce obesity and nonalcoholic fatty liver disease (NAFLD), one of the most challenging medical conditions. Here, we identified that isorhamnetin, a naturally occurring compound in fruits and vegetables and the metabolite of quercetin, is a novel antagonist of PPARγ. Isorhamnetin treatment inhibited the adipocyte differentiation induced by the PPARγ agonist rosiglitazone, reduced obesity development and ameliorated hepatic steatosis induced by both high-fat diet treatment and leptin deficiency. Our results suggest that dietary supplement of isorhamnetin may be beneficial to prevent obesity and steatosis and PPARγ antagonists may be useful to treat hepatic steatosis.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Cell Differentiation; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Gene Expression Regulation; Humans; Leptin; Metabolic Diseases; Mice; Models, Molecular; Molecular Conformation; Non-alcoholic Fatty Liver Disease; Obesity; PPAR gamma; Protein Binding; Quercetin; Transcriptional Activation

To investigate the potential effect of Ginkgo biloba extract (GBE) on the prevention and treatment of nonalcoholic fatty liver disease (NAFLD).. Male Wistar rats were divided into 4 groups (the control group, GBE group, high-fat diet [HFD] group and HFD + GBE group). The human hepatocellular carcinoma cell line (HepG2) was treated with GBE and its flavonoid ingredients. The fatty acid composition of the rat liver was analyzed with gas chromatography/time-of-flight mass spectrometry (GC/TOFMS). Triglyceride contents of both the rat liver and HepG2 cells were measured by enzymatic colorimetric method. The expressions of fatty acid metabolism-related genes were analyzed with real-time reverse transcription-polymerase chain reaction (RT-PCR). The protein expression and enzymatic activity were subsequently measured.. In rat livers, GBE reduced the elevations of hepatic triglyceride contents caused by HFD and the increased hepatic fatty acids were differentially affected by GBE. Notably, the expression and total activity of the fatty acid β-oxidation rate-limiting enzyme, carnitine palmitoyltransferase 1a (CPT1A), were also promoted with GBE ingestion. In HepG2 cells, GBE and its ingredients, quercetin, kaempferol and isorhamnetin, could decrease the cellular triglyceride content and upregulate the expression and total activity of CPT1A, respectively.. The triglyceride-lowering effect of GBE on the HFD rat liver is closely associated with the increased expression and activity of CPT1A, and the flavonoid ingredients are the major contributors of GBE.

Topics: Animals; Carnitine O-Palmitoyltransferase; Dietary Fats; Fatty Acids; Fatty Liver; Gene Expression Regulation, Enzymologic; Ginkgo biloba; Hep G2 Cells; Humans; Kaempferols; Male; Non-alcoholic Fatty Liver Disease; Phytotherapy; Plant Extracts; Quercetin; Rats; Rats, Wistar; Triglycerides; Up-Regulation