Ali Mahzari,
RMIT University, Australia
Title: The therapeutic effects of matrine for MCD-induced NASH are associated with upregulation of HSP72 and suppression of mTOR
Biography
Biography: Ali Mahzari,
Abstract
Non-alcoholic steatohepatitis (NASH) is an advanced stage of the metabolic syndrome in liver with serious consequences largely because of hepatic injury, inflammation and fibrosis. Matrine (MW: 248) is used as a prescribed hepatoprotective drug in humans and it has been shown by us to decrease hepatosteatosis and glucose intolerance in high fat-fed mice (Bri J Pharmacol 172:4303,2015). Here, we investigated whether matrine exerts therapeutic efficacy for NASH by attenuating hepatic injury, inflammation and fibrosis. The study was performed in methionine choline-deficient (MCD) diet-fed mice for 6 weeks with or without the treatment with matrine (100 mg/kg/d). Compared with untreated MCD-fed mice, matrine markedly reduced hepatic injury (indicated by ALT level, p<0.05), inflammation (indicated by TNFα, CD68 and inflammasome NLRP3, all p<0.05). Along with these effects, matrine inhibited MCD-induced increases in fibrogenesis (as indicated by the expression levels of TGFβ, Smad3 and type I collagen (all p<0.05). Further examination revealed that matrine resecured MCD-suppressed heat shock protein 72 (HSP72, a protective chaperon protein against cell toxicity) and inhibited MCD-activated mTOR (a key master regulator triggering pathogenic pathways leading to NASH). Our findings indicate that matrine attenuated MCD-induced NASH by a new mechanism involving the upregulation of HSP72 and inhibition of mTOR. This hepatoprotective drug may be repurposed for the treatment of NASH.