hyperoside and Non-alcoholic-Fatty-Liver-Disease

Non-alcoholic fatty liver disease (NAFLD) results from increased hepatic total cholesterol (TC) and total triglyceride (TG) accumulation. In our previous study, we found that rats treated with hyperoside became resistant to hepatic lipid accumulation.. The present study aims to investigate the possible mechanisms responsible for the inhibitory effects of hyperoside on the lipid accumulation in the liver tissues of the NAFLD rats.. Label-free proteomics and metabolomics targeting at bile acid (BA) metabolism were applied to disclose the mechanisms for hyperoside reducing hepatic lipid accumulation among the NAFLD rats.. In response to hyperoside treatment, several proteins related to the fatty acid degradation pathway, cholesterol metabolism pathway, and bile secretion pathway were altered, including ECI1, Acnat2, ApoE, and BSEP, etc. The expression of nuclear receptors (NRs), including farnesoid X receptor (FXR) and liver X receptor α (LXRα), were increased in hyperoside-treated rats' liver tissue, accompanied by decreased protein expression of catalyzing enzymes in the hepatic. Taken together, the results suggest that hyperoside could improve the condition of NAFLD by regulating the cholesterol metabolism as well as BAs metabolism and excretion. These findings contribute to understanding the mechanisms by which hyperoside lowers the cholesterol and triglyceride in NAFLD rats.

Topics: Animals; Bile Acids and Salts; Cholesterol; Lipid Metabolism; Non-alcoholic Fatty Liver Disease; Quercetin; Rats

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and a systemic pro-inflammatory response. To date, no medications for NAFLD have been approved by relevant governmental agencies. Emerging evidence indicates that innate immune mechanisms are pivotal drivers of inflammation and other pathological manifestations observed in NAFLD. Hyperoside, a flavonoid compound mainly found in medicinal plants, has many biological effects, but the role of hyperoside in the physiological process of NAFLD is poorly defined. This study demonstrated that hyperoside exerts protective effects against high-fat diet (HFD)-induced NAFLD and regulates macrophage polarization in an Nr4A1-dependent manner. After 16 weeks on a HFD, hepatic steatosis, insulin resistance, and inflammatory responses were significantly ameliorated in hyperoside-treated HFD-fed wild-type mice, and hyperoside facilitated the polarization of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 subtype. Nr4A1 was found to be upregulated in hyperoside-treated HFD-fed mice, and hyperoside did not improve HFD-induced NAFLD or regulate macrophage polarization in Nr4A1-deficient mice. In conclusion, hyperoside may have therapeutic potential in preventing the pathological progression of NAFLD.

Topics: Animals; Diet, High-Fat; Liver; Liver Cirrhosis; Macrophages; Male; Mice, Inbred C57BL; Mice, Knockout; Non-alcoholic Fatty Liver Disease; Nuclear Receptor Subfamily 4, Group A, Member 1; Quercetin