MicroRNA-451 and Genistein AmeliorateNonalcoholic Steatohepatitis in Mice....................Abstract: Effective, targeted therapy for chronic liver disease nonalcoholic steatohepatitis (NASH)is imminent. MicroRNAs (miRNAs) are a potential therapeutic target, and natural productsthat regulate miRNA expression may be a safe and effective treatment strategy for liver disease.Here, we investigated the functional role of miR-451 and the therapeutic effects of genistein inthe NASH mouse model. MiR-451 was downregulated in various types of liver inflammation,and subsequent experiments showed that miR-451 regulates liver inflammation via IL1β. Genisteinis a phytoestrogen with anti-inflammatory and anti-oxidant effects. Interestingly, we found thatthe anti-inflammatory effects of genistein were related to miR-451 and was partially antagonizedby the miR-451 inhibitor. MiR-451 overexpression or genistein treatment inhibited IL1β expressionand inflammation. Taken together, this study shows that miR-451 has a protective effect on hepaticinflammation, and genistein can be used as a natural promoter of miR-451 to ameliorate NASH.