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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. 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 TNF���±, 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 TGF���², 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.

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