Article date: March 2018
By: Fan Yang, Yao Wang, Gang Li, Juan Xue, Zhi‐Lin Chen, Feng Jin, Lei Luo, Xuan Zhou, Qian Ma, Xin Cai, Hua‐Rong Li, Lei Zhao in Volume 175, Issue 5, pages 810-829
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.
DOI: 10.1111/bph.14126
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