Gnetum montanum extract alleviates hepatocellular lipid accumulation through upregulation of SIRT1 and suppression of fatty acid synthesis

Tóm tắt/Abstract

Gnetum montanum Markgr., a traditional Vietnamese medicinal plant rich in bioactive stilbenoids, has been reported to possess antioxidant and metabolic regulatory properties. Previous studies from our group showed that Gnetum montanum extract (GME) protects against ethanol-induced metabolic disturbances. Building on these findings, the present study aimed to clarify the molecular mechanism underlying the effect of GME on alcohol-induced hepatic steatosis using acetaldehyde (ACD)-treated HepG2 cells. The results showed that GME suppressed ACD-induced upregulation of sterol regulatory element-binding protein 1 (SREBP1) and its downstream lipogenic enzymes, including fatty acid synthase (FASN), acetyl-CoA carboxylase 1 (ACC1), and ATP-citrate lyase (ACLY). Additionally, GME restored SIRT1 expression that was impaired by ACD exposure. At the cellular level, GME significantly reduced intracellular lipid droplet formation, triglyceride levels, and malondialdehyde production. Interestingly, pharmacological inhibition using EX-527 and siRNA-mediated knockdown of SIRT1 reversed the inhibitory effects of GME on lipogenesis. These findings suggest that the effects of GME are mediated, at least in part, by SIRT1 induction. Taken together, these findings indicate that GME alleviates hepatic lipid accumulation through modulation of the SIRT1-SREBP1 axis, supporting a potential role of GME in alcohol-associated hepatic steatosis