Fan Yang1, Yao Wang2, Gang Li3, Juan Xue4, Zhi-Lin Chen5, Feng Jin6, Lei Luo7, Xuan Zhou5, Qian Ma8, Xin Cai6, Hua-Rong Li9, Lei Zhao5. 1. Department of Hepatology, Hubei Provincial Hospital of Chinese Medicine, Wuhan, China. 2. Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, China. 3. Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, China. 4. Department of Gastroenterology, Hubei Province Hospital of Integrated Traditional Chinese and Western Medicine, Wuhan, China. 5. Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 6. Department of Neurosurgery, Affiliated Hospital of Jining Medical University and Shangdong Provincial Key Laboratory of Stem Cells and Neuro-oncology, Jining, Shandong, China. 7. School of First Clinical Medicine, Hubei University of Chinese Medicine, Wuhan, China. 8. School of Life Science, Hubei University, Wuhan, China. 9. Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract
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.
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.
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