AMPK-Regulated Autophagy Contributes to Ursolic Acid Supplementation-Alleviated Hepatic Steatosis and Liver Injury in Chronic Alcohol-Fed Mice.

Abstract

Alcoholic liver disease (ALD) is a chronic liver disease caused by long-term heavy consumption of alcohol. The pathogenesis of ALD is complex, and there is no effective clinical treatment at present. Ursolic acid (UA), a general triterpenoid with multiple biological roles, is widely distributed in plants. This study aims to explore the therapeutic effect and potential mechanisms of UA that protect against liver injury and hepatic steatosis in an ALD mouse model. In this study, we analyzed the lipid accumulation and the effect of UA treatment in a mouse model of ALD; AML12 and HepG2 cells were used to study the biological effect and potential mechanisms of UA on ethanol-induced hepatotoxicity. The morphologic and histological detections showed that UA significantly reduced alcohol-induced liver injury and hepatic steatosis. In addition, UA dramatically ameliorated alcohol-induced metabolic disorders, oxidative stress, and inflammation. Furthermore, UA treatment activated autophagy via the AMPK-ACC pathway to protect hepatocytes from lipotoxicity. Thus, these findings demonstrate that UA treatment alleviates alcoholic-induced liver injury by activating autophagy through the AMPK-ACC pathway. Therefore, UA may represent a promising candidate for the treatment of ALD.