Total sesquiterpene glycosides from Loquat (Eriobotrya japonica) leaf alleviate high-fat diet induced non-alcoholic fatty liver disease through cytochrome P450 2E1 inhibition

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic steatosis, which affects 20-40% of the population in the world. Loquat (Eriobotrya japonica) Leaf possesses several pharmacological actions. Many sesquiterpene glycosides were reported to be isolated exclusively from the Loquat Leaf, however, their biological activity has been rarely investigated. The present study was designed to evaluate the pharmacological effect of total sesquiterpene glycosides (TSG) in high-fat diet (HFD) induced NAFLD mice with its related mechanisms of action. Mice were fed with a normal diet or HFD for 8 weeks. TSG (25 and 100mg/kg/day), simvastatin (10mg/kg/day) or vehicle were orally administered for last 4 weeks of the 8-week HFD feeding period. From the result, it was showed that TSG significantly reduced the body weight and fat deposition in the liver of NAFLD mice. It also decreased total cholesterol (TC) and triglyceride (TG) contents in the serum. Compared with NAFLD mice, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were increased and decreased after the administration of TSG in a dose of 100mg/kg, respectively. TSG reduced alanine aminotransferase (ALT) activity as well. Finally, TSG was found to suppress the expression of cytochrome P450 2E1 (CYP2E1) and the phosphorylation of c-jun terminal kinase (JNK) in NAFLD mice. In summary, this study demonstrates that TSG reduces oxidative stress by downregulating of CYP2E1 expression and JNK phosphorylation in NAFLD, and alleviates NAFLD ultimately. TSG potentially serves as bioactive compounds for the treatment of NAFLD.

Keywords: C-jun terminal kinase; Cytochrome P450 2E1; Loquat Leaf; Non-alcoholic fatty liver disease; Oxidative stress; Total sesquiterpene glycosides.