Isotschimgine alleviates nonalcoholic steatohepatitis and fibrosis via FXR agonism in mice

• DOI: 10.1002/ptr.7055
• Publication Date: 2021-03-30T23:30:45Z
• Authors: Junxiao Li; Chuhe Liu; Zhenyu Zhou; Baokai Dou; Jinwen Huang; Leilei Huang; Peiyong Zheng; Shengjie Fan; Cheng Huang
• Keywords: Obeticholic acid; Farnesoid X receptor; Steatosis; Steatohepatitis; Hepatic fibrosis

Farnesoid X receptor (FXR) agonist obeticholic acid (OCA) has emerged as a potential therapy for nonalcoholic fatty liver disease (NAFLD). However, the side effects of OCA may limit its application in clinics. We identified previously that isotschimgine (ITG) is non‐steroidal FXR selective and potent therapeutic on NAFLD mice. Here, we aimed to evaluate ITG steatohepatitis (NASH) fibrosis used methionine choline deficient (MCD) diet‐induced NASH mice, bile duct ligation (BDL), carbon tetrachloride (CCl 4 )‐treated hepatic mice investigate NASH, fibrosis, cholestatic injury. Our results showed improved steatosis inflammation MCD diet‐fed well alleviated CCl ‐treated Furthermore, attenuated serum levels, reduced vacuolization, inflammatory infiltration, parenchymal necrosis, collagen accumulation BDL Mechanistically, increased expression target genes. These data suggest an be developed novel or primary biliary cholangitis.