Curcumin protects ANIT-induced cholestasis through signaling pathway of FXR-regulated bile acid and inflammation

姜黄素通过 FXR 调节胆汁酸和炎症信号通路预防 ANIT 诱导的胆汁淤积

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作者:Fan Yang, Xiaowen Tang, Lili Ding, Yue Zhou, Qiaoling Yang, Junting Gong, Guangyun Wang, Zhengtao Wang, Li Yang

Abstract

Cholestasis is a clinically significant symptom and widely associated with liver diseases, however, there are very few effective therapies for cholestasis. Danning tablet (DNT, a Chinese patent medicine preparation) has been clinically used to treat human liver and gallbladder diseases for more than 20 years in China. However, which ingredients of DNT contributed to this beneficial effect and their mechanistic underpinnings have been largely unknown. In the present study, we discovered that DNT not only demonstrated greater benefits for cholecystitis patients after cholecystectomy surgery in clinic but also showed protective effect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis model in rodent. Curcumin, one major compound derived from DNT, exerted the protective effect against cholestasis through farnesoid X receptor (FXR), which has been focused as potential therapeutic targets for treating cholestasis. The underlying mechanism of curcumin against cholestasis was restoring bile acid homeostasis and antagonizing inflammatory responses in a FXR-dependent manner and in turn contributed to overall cholestasis attenuation. Collectively, curcumin can be served as a potential treatment option for liver injury with cholestasis.

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