Oncotarget

Research Papers:

Chicken bile powder protects against α-naphthylisothiocyanate-induced cholestatic liver injury in mice

Yi-Fei Li, Jia-Sheng Wu, Yuan-Yuan Li, Yan Dai, Min Zheng, Jia-Kai Zeng, Guo-Feng Wang, Tian-Ming Wang, Wen-Kai Li, Xue-Yan Zhang, Ming Gu, Cheng Huang, Li Yang, Zheng-Tao Wang and Yue-Ming Ma _

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Oncotarget. 2017; 8:97137-97152. https://doi.org/10.18632/oncotarget.21385

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Abstract

Yi-Fei Li1,*, Jia-Sheng Wu1,*, Yuan-Yuan Li1, Yan Dai1, Min Zheng1, Jia-Kai Zeng1, Guo-Feng Wang1, Tian-Ming Wang1, Wen-Kai Li1, Xue-Yan Zhang1, Ming Gu2, Cheng Huang2, Li Yang3, Zheng-Tao Wang4 and Yue-Ming Ma1,5

1Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

2School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

3Research Centre for Traditional Chinese Medicine of Complexity Systems, Shanghai University of Traditional Chinese Medicine, Shanghai, China

4Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

5Shanghai Key Laboratory of Compound Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

*These authors have contributed equally to this work

Correspondence to:

Yue-Ming Ma, email: mayueming_117@hotmail.com

Zheng-Tao Wang, email: ztwang@shutcm.edu.cn

Keywords: intrahepatic cholestasis; chicken bile powder; FXR; bile acid; metabolomics

Received: January 27, 2017     Accepted: July 26, 2017     Published: September 27, 2017

ABSTRACT

This study explored the effects of chicken bile powder (CBP), a 2000-year-old Chinese medicine, on α-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. CBP treatment for 14 days significantly ameliorated ANIT-induced changes in serum alanine aminotransferase, aspartate aminotransferase, bile acids, bilirubin, γ-glutamyl transpeptidase, alkaline phosphatase, and liver tissue morphology. Serum metabolomics showed changes in 24 metabolites in ANIT-exposed mice; 16 of these metabolites were reversed by CBP treatment via two main pathways (bile acid biosynthesis and arachidonic acid metabolism). Additionally, CBP administration markedly increased fecal and biliary bile acid excretion, and reduced total and hydrophobic bile acid levels in the livers of cholestatic mice. Moreover, CBP increased liver expression of bile acid efflux transporters and metabolic enzymes. It also attenuated ANIT-induced increases in hepatic nuclear factor-κB-mediated inflammatory signaling, and increased liver expression of the nuclear farnesoid X receptor (FXR) in cholestatic mice. CBP also activated FXR in vitro in HEK293T cells expressing mouse Na+-taurocholate cotransporting polypeptide. It did not ameliorate the ANIT-induced liver injuries in FXR-knockout mice. These results suggested that CBP provided protection from cholestatic liver injury by restoring bile acid homeostasis and reducing inflammation in a FXR-dependent manner.


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