Curcumin protects ANIT-induced cholestasis through signaling pathway of FXR-regulated bile acid and inflammation.
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.
The MOE Key Laboratory for Standardization of Chinese Medicines and the Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Fan
F
Yang
The MOE Key Laboratory for Standardization of Chinese Medicines and the Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Xiaowen
X
Tang
The MOE Key Laboratory for Standardization of Chinese Medicines and the Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Lili
L
Ding
The MOE Key Laboratory for Standardization of Chinese Medicines and the Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Yue
Y
Zhou
The MOE Key Laboratory for Standardization of Chinese Medicines and the Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Qiaoling
Q
Yang
The MOE Key Laboratory for Standardization of Chinese Medicines and the Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Junting
J
Gong
The MOE Key Laboratory for Standardization of Chinese Medicines and the Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Guangyun
G
Wang
The MOE Key Laboratory for Standardization of Chinese Medicines and the Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Zhengtao
Z
Wang
The MOE Key Laboratory for Standardization of Chinese Medicines and the Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.|Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Li
L
Yang
D015058:1-Naphthylisothiocyanate / Q000633:toxicity*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002779:Cholestasis / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D003474:Curcumin / Q000737:chemistry*; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
D015058:1-Naphthylisothiocyanate; D001647:Bile Acids and Salts; D003474:Curcumin; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated