基于调控法尼醇X受体的中药治疗肝内胆汁瘀积的研究进展

Research progress on Chinese materia medica in treatment of intrahepatic cholestasis based on FXR-mediated regulation

肝内胆汁瘀积是临床常见病、多发病,其形成机制十分复杂。熊脱氧胆酸和奥贝胆酸是目前FDA批准的仅有的2个用于治疗胆汁瘀积的药物。法尼醇X受体(FXR)是胆汁酸合成和转运的关键调节因子,其高表达对于维持胆汁酸的内环境稳态、降低胆汁酸对肝脏的毒性具有重要意义。中药可以通过多靶点、多途径发挥作用,针对主要发病机制的同时,兼顾次要发病机制,相互协同,在治疗肝内胆汁瘀积方面疗效显著。多种中药及其提取物或有效成分被证明能够通过激活FXR靶点而发挥保肝利胆作用,引起国内外广泛关注。对胆汁酸的体内代谢过程和FXR在肝内胆汁瘀积治疗中的作用进行概述,总结了基于调控FXR的中药治疗肝内胆汁瘀积的研究进展,以期为中药新药的开发提供参考。

Intrahepatic cholestasis is a common disease and the formation mechanisms of this disease are complex. Until now, only two drugs（ursodeoxycholic acid and obeticholic acid） were approved by FDA for the treatment of cholestasis. Farnesoid X receptor（FXR） in cholestasis is an intriguing approach since this receptor is critically involved in the regulation of bile acid homeostasis. FXR serves as a sensor for bile acid and promotes enterohepatic clearance of bile acid by controlling the expression of genes involved in their transport and metabolism. Chinese materia medica（CMM） gained a significant effect in the treatment of intrahepatic cholestasis through multi-target, multi-channel effects, which aimed at major pathogenesis and secondary pathogenesis. Recently, a variety of CMM have been proved to activate FXR targets for the treatment of cholestasis, which has attracted widespread attention at home and abroad. In this paper, we reviewed the metabolism of bile acid, the potential of pharmacological modulators of FXR as novel therapies for cholestatic disorders, and summarized CMM for the treatment of cholestasis based on FXR targets. This paper may provide some theoretical guidance for the development of new drugs and CMM.