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Effects of corilagin on alleviating cholestasis via farnesoid X receptor‐associated pathways in vitro and in vivo
Author(s) -
Yang Fan,
Wang Yao,
Li Gang,
Xue Juan,
Chen ZhiLin,
Jin Feng,
Luo Lei,
Zhou Xuan,
Ma Qian,
Cai Xin,
Li HuaRong,
Zhao Lei
Publication year - 2018
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14126
Subject(s) - farnesoid x receptor , multidrug resistance associated protein 2 , cholestasis , bile salt export pump , cholesterol 7 alpha hydroxylase , chemistry , biology , medicine , pharmacology , endocrinology , bile acid , biochemistry , nuclear receptor , transporter , transcription factor , atp binding cassette transporter , gene
Background and Purpose The aim of this study was to investigate the ameliorative effects of corilagin on intrahepatic cholestasis induced by regulating liver farnesoid X receptor (FXR)‐associated pathways in vitro and in vivo . Experimental Approach Cellular and animal models were treated with different concentrations of corilagin. In the cellular experiments, FXR expression was up‐regulated by either lentiviral transduction or GW4064 treatment and down‐regulated by either siRNA technology or treatment with guggulsterones. Real‐time PCR and Western blotting were employed to detect the mRNA and protein levels of FXR, SHP1, SHP2, UGT2B4, BSEP, CYP7A1, CYP7B1, NTCP, MRP2 and SULT2A1. Immunohistochemistry was used to examine the expression of BSEP in liver tissues. Rat liver function and pathological changes in hepatic tissue were assessed using biochemical tests and haematoxylin and eosin staining. Results Corilagin increased the mRNA and protein levels of FXR, SHP1, SHP2, UGT2B4, BSEP, MRP2 and SULT2A1, and decreased those of CYP7A1, CYP7B1 and NTCP. After either up‐ or down‐regulating FXR using different methods, corilagin could still increase the mRNA and protein levels of FXR, SHP1, SHP2, UGT2B4, BSEP, MRP2 and SULT2A1 and decrease the protein levels of CYP7A1, CYP7B1 and NTCP, especially when administered at a high concentration. Corilagin also exerted a notable effect on the pathological manifestations of intrahepatic cholestasis, BSEP staining in liver tissues and liver function. Conclusions and Implications Corilagin exerts a protective effect in hepatocytes and can prevent the deleterious activities of intrahepatic cholestasis by stimulating FXR‐associated pathways.