Methyl helicterilate ameliorates alcohol-induced hepatic fibrosis by modulating TGF-ß1/Smads pathway and mitochondria-dependent pathway.

ABSTRACT

This study aimed to investigate the effect and underlying mechanism of Methyl helicterilate from Helicteres angustifolia (MHHA) on alcohol-induced hepatic fibrosis. The results showed that MHHA treatment markedly alleviated alcohol-induced liver injury and notably reduced collagen deposition in liver tissue. It significantly enhanced the activity of alcohol dehydrogenase and aldehyde dehydrogenase. Moreover, MHHA treatment markedly decreased the content of inflammatory cytokines, alleviated collagen accumulation, and inhibited the expression of TGF-ß1 and Smad2/3 in liver tissue. The experiments in cells showed that MHHA significantly inhibited HSC activation by blocking TGF-ß1/Smads signaling pathway. Additionally, it notably induced HSC apoptosis by modulating the mitochondria-dependent pathway. The present study demonstrates that MHHA treatment significantly ameliorates alcoholic hepatic fibrosis and the underlying mechanism may be ascribed to the inhibition of the TGF-ß1/Smads pathway and regulation of the mitochondria-mediated apoptotic pathway.