Kinsenoside Alleviates 17α-Ethinylestradiol-Induced Cholestatic Liver Injury in Rats by Inhibiting Inflammatory Responses and Regulating FXR-Mediated Bile Acid Homeostasis

作者：Jiaxiong Ming, Qianqian Xu, Limin Gao, Yanfang Deng, Jie Yin, Qun Zhou, Qingyi Tong, Yonghui Zhang · 发表于：Pharmaceuticals · 年份：2021 · DOI：10.3390/ph14050452 · 被引用次数：23 · 研究领域：Drug Transport and Resistance Mechanisms、Drug-Induced Hepatotoxicity and Protection、Chemotherapy-induced organ toxicity mitigation

Cholestasis is an important predisposing factor of liver diseases, such as hepatocyte necrosis, liver fibrosis and primary biliary cirrhosis. In this study, we aimed to investigate the effects of Kinsenoside (KD), a natural active ingredient of Anoectochilus roxburghii, on estrogen-induced cholestatic liver injury in Sprague-Dawley rats and the underlying mechanism. The rats were randomly divided into six groups: control group, model group, low-dose KD group (50 mg/kg body weight, KD-L), medium-dose KD group (100 mg/kg body weight, KD-M), high-dose KD group (200 mg/kg body weight, KD-H) and ursodeoxycholic acid group (40 mg/kg body weight, UDCA). 17α-Ethinylestradiol (EE) was used to establish an experimental animal model of estrogen-induced cholestasis (EIC). The results demonstrated that KD alleviated liver pathologic damage, serum biochemical status and inhibited hepatocellular microstructure disorder and bile duct hyperplasia in EE-induced cholestatic rats. Mechanically, KD alleviated EE-induced cholestatic liver injury by inhibiting inflammatory responses and regulating bile acid homeostasis. Concretely, KD reduced the expression of IL-1β and IL-6 by inhibiting NF-κB p65 to suppress EE-mediated inflammation in rat liver. KD enhanced the expression of FXR and inhibited EE-mediated reduction of FXR in vitro and in vivo. It was the potential mechanism that KD mitigates cholestasis by increasing efflux and inhibiting uptake of bile acids via FXR-mediated induction of bile sa...