Asiatic acid from Potentilla chinensis alleviates non-alcoholic fatty liver by regulating endoplasmic reticulum stress and lipid metabolism

Abstract

Endoplasmic reticulum stress (ERS) is induced by accumulation of misfolded proteins, playing a pivotal role during the processes of non-alcoholic fatty liver disease (NAFLD). The present study was to investigate the effect of Asiatic acid from Potentilla chinensis (AAPC) on liver cell lipid metabolism, exploring the underlying mechanism of AAPC against NAFLD. In vivo, the animal NAFLD model was induced by feeding rats with high fat diet (HFD) for 18 weeks, and meanwhile the rats were treated with AAPC from weeks 8 to 18; In vitro experiment, the effect of AAPC on dyslipidemia induced by oleic acid (OA) in hepatic cells (HepG2) was evaluated. The results showed that AAPC significantly decreased lipidosis in rats and in HepG2 cells; it notably alleviated hepatocyte damage and lipid disturbance in rats. Moreover, the cell experiments showed that AAPC strongly inhibited HepG2 cell proliferation. It markedly decreased hepatocyte lipogenesis by regulating the key lipid metabolism-related factors, such as sterol regulatory element-binding protein 1c (SREBP-1c), encoding carboxylase, liver X Receptor Rα (LXRα), fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). The further study elucidated that AAPC treatment significantly alleviated inflammatory response by inhibiting the nuclear factor-kappa B (NF-kB) pathway. Moreover, AAPC significantly alleviated hepatocyte apoptosis and lipid metabolism disorder through reducing the extent of ERS. In conclusion, our study demonstrates that AAPC significantly ameliorates NAFLD by inhibiting the ERS pathway and lipid deposition, which may be a potential natural medicine for the treatment of NAFLD.