Celastrus orbiculatus Thunb. ameliorates high-fat diet-induced non-alcoholic fatty liver disease in guinea pigs

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 7α-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.