Rotundic acid ameliorates non-alcoholic steatohepatitis via SREBP-1c/ SCD1 signaling pathway and modulating gut microbiota

Abstract

Non-alcoholic steatohepatitis (NASH) is a devastating form of non-alcoholic fatty liver disease (NAFLD) with distinguished hallmarks of steatosis and inflammation. Rotundic acid (RA) is a natural pentacyclic triterpene compound extracted from the bank of Ilex rotunda Thunb with a wide range of biological activities. The aim of the study is to evaluate the pharmacological effect and action mechanism of RA on NASH in vitro and in vivo. RA has weak lipid lowering ability in rat primary hepatocytes, significantly decreases serum LDL level, hepatic TG and TC levels and lipid droplets, reduces NAS compared with the NASH group, and alleviates hepatic inflammation. RA also enhances the recovery of intestinal bacterial community and intestinal-derived short-chain fatty acid caused by high food diet (HFD). Further investigation shows that RA protects against HFD-induced NASH via downregulating the expression of SREBP-1c/SCD1 signaling pathway and improving gut microbiota. These findings imply that RA might be helpful for the alleviation of NASH.

Keywords: Gut microbiota; NASH; RA; SCD1; SCFA; SREBP-1c.