2,3,5,4'?tetrahydroxy?stilbene?2?O?β?D?glucoside attenuates methionine and choline?deficient diet?induced non?alcoholic fatty liver disease Abstract. Previous studies have suggested that 2,3,5,4'-tetrahydroxy-stilbene-2-O?β?D-glucoside (TSG) prevents progression of non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet. The present study aimed to evaluate whether TSG could reverse NAFLD induced by a methionine and choline?deficient (MCD) diet and identify the possible mechanism of action. C57BL6/J mice were fed a MCD diet and were treated with TSG, fenofibrate, and resveratrol for 9 weeks. Regulatory effects of several cytokines and enzymes, including Nod-like receptor protein 3, apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), caspase-1, interleukin (IL)-18, IL-1β, and gut microbiota balance were investigated. TSG significantly reduced NAFLD biochemical indexes, including total cholesterol, triglyceride, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, aspartate aminotransferase and free fatty acid. Middle dosage (TSG.M, 35 mg/kg) of TSG reduced the expression of ASC and caspase-1. Furthermore, TSG displayed gut microbiota regulatory effects on MCD-induced NAFLD mice. The results of the present study suggested that TSG prevented the occurrence and development of MCD diet-induced NAFLD. The data further indicated that TSG may serve as a promising lead compound that may aid with intervention in NAFLD therapy.