Isotschimgine alleviates nonalcoholic steatohepatitis and fibrosis via FXR agonism in mice.

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.

Notoginsenoside Fe suppresses diet induced obesity and activates paraventricular hypothalamic neurons.

Obesity has become a major public health challenge worldwide. Energy imbalance between calorie acquisition and consumption is the fundamental cause of obesity. Notoginsenoside Fe is a naturally occurring compound in Panax notoginseng, a herb used in the treatment of cardiovascular diseases in traditional Chinese medicine. Here, we evaluated the effect of notoginsenoside Fe on obesity development induced by high-fat diet in C57BL/6 mice. Our results demonstrated that notoginsenoside Fe decreased food intake and body weight, as well as protected liver structure integrity and normal function. Metabolic cage analysis showed that notoginsenoside Fe also promoted resting metabolic rate. In addition, intracerebroventricular (i.c.v) injection of notoginsenoside Fe induced C-Fos expression in the paraventricular nucleus (PVH) but not the arcuate nucleus (ARC) of the hypothalamus. These results suggest that Fe may reduce body weight through the activation of energy-sensing neurons in the hypothalamus.