Isotschimgine alleviates nonalcoholic steatohepatitis and fibrosis via FXR agonism in mice.
|
| Abstract |
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 a non-steroidal FXR selective agonist and has potent therapeutic effects on NAFLD in mice. Here, we aimed to evaluate the therapeutic effects of ITG on nonalcoholic steatohepatitis (NASH) and fibrosis in mice. We used methionine and choline deficient (MCD) diet-induced NASH mice, bile duct ligation (BDL), and carbon tetrachloride (CCl4 )-treated hepatic fibrosis mice to investigate the effects of ITG on NASH, fibrosis, and cholestatic liver injury. Our results showed that ITG improved steatosis and inflammation in the liver of MCD diet-fed mice, as well as alleviated fibrosis and inflammation in the liver of CCl4 -treated mice. Furthermore, ITG attenuated serum bile acid levels, and reduced vacuolization, inflammatory infiltration, hepatic parenchymal necrosis, and collagen accumulation in the liver of BDL mice. Mechanistically, ITG increased the expression of FXR target genes. These data suggest that ITG is an FXR agonist and may be developed as a novel therapy for NASH, hepatic fibrosis, or primary biliary cholangitis.
|
|---|---|
| Authors | Junxiao Li, Chuhe Liu, Zhenyu Zhou, Baokai Dou, Jinwen Huang, Leilei Huang, Peiyong Zheng, Shengjie Fan, Cheng Huang |
| Journal | Phytotherapy research : PTR (Phytother Res) Vol. 35 Issue 6 Pg. 3351-3364 (Jun 2021) ISSN: 1099-1573 [Electronic] England |
| PMID | 33784797 (Publication Type: Journal Article) |
| Copyright | © 2021 John Wiley & Sons, Ltd. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!