Ursolic acid protects hepatocytes against lipotoxicity through activating autophagy via an AMPK pathway

Ursolic acid is a naturally occurring pentacyclic triterpenoid in many plants, such as medicinal herbs and food, and was previously found to be an effective phytochemical that protected against high-fat diet-induced hepatic steatosis and liver injury. However, the molecular mechanisms are not fully determined. The present study examined the protective role of ursolic acid against saturated fatty acid-induced lipotoxicity. We found that ursolic acid protected HepG2 (hepatocellular carcinoma, human) cells against palmitate-induced cell death and mitochondrial dysfunction. The protective activity was the result of ursolic acid-induced autophagy, and an autophagy inhibitor prevented this protective effect. Ursolic acid activated/phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and reduced phosphorylation of mammalian target of rapamycin. AMPK gene knockdown by siRNA transfection abolished the protective effect of ursolic acid. Ursolic acid induced autophagy in HepG2 cells to protect against palmitate-induced cell death via an AMPK/mTOR pathway. (C) 2015 Elsevier Ltd. All rights reserved.