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Tectorigenin alleviates intrahepatic cholestasis by inhibiting hepatic inflammation and bile accumulation via activation of PPARg
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  • Jiaqing Xiang,
  • Guangyan Yang,
  • Chuanrui Ma,
  • Linlin Wei,
  • Han Wu,
  • Xiuhua Tao,
  • Lingyun Jiang,
  • Zhen Liang,
  • Lin Kang,
  • shu yang
Jiaqing Xiang
Shenzhen People's Hospital
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Guangyan Yang
Shenzhen People's Hospital
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Chuanrui Ma
First Teaching Hospital of Tianjin University of Traditional Chinese Medicine
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Linlin Wei
Jiangxi Academy of Agricultural Sciences
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Han Wu
Shenzhen People's Hospital
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Xiuhua Tao
Jiangxi Academy of Agricultural Sciences
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Lingyun Jiang
Shenzhen People's Hospital
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Zhen Liang
Shenzhen People's Hospital
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Lin Kang
Shenzhen People's Hospital
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shu yang
Shenzhen People's Hospital
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Abstract

Background and purpose: Increasing evidence has shown that human cholestasis is closely related to hepatic macrophage accumulation and activation. Research has indicated that peroxisome proliferator-activated receptor-g (PPARg) activation exerts liver protection in cholestatic liver disease (CLD), particularly by ameliorating inflammation and fibrosis, thus limiting disease progression. However, existing PPARg agonists, such as troglitazone and rosiglitazone, have significant side effects that impede their clinical application in the treatment of CLD. In this study, we found that tectorigenin (TEC) can alleviate intrahepatic cholestasis in mice by activating PPARg. Experimental approach: Wild-type mice received intragastric administration of a-naphthylisothiocyanate (ANIT) or were fed a diet containing 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to establish an experimental intrahepatic cholestasis model and TEC intervention simultaneously, followed by determination of intrahepatic cholestasis and the involved mechanisms. In addition, PPARg deficient mice were administered ANIT and/or TEC to determine whether TEC exerts its liver protection effect by activating PPARg. Key results: Our results demonstrated that TEC intervention alleviated intrahepatic cholestasis by inhibiting hepatic macrophage recruitment and activation as well as promoting the expression of bile transporters through activating PPARg. Furthermore, our results show that TEC increased bile salt export pump (Bsep) expression through enhanced PPARg binding to the Bsep promoter. We also demonstrated that PPARg deficiency blocked the hepatocyte protective effect of TEC during cholestasis. Conclusions and implications: In conclusion, TEC reduced hepatic macrophage recruitment and activation, and enhanced bile acid export by activating PPARg. Taken together, our results suggest that TEC is a potential drug for the prevention of CLD.

Peer review status:UNDER REVIEW

04 Sep 2020Submitted to British Journal of Pharmacology
06 Sep 2020Assigned to Editor
06 Sep 2020Submission Checks Completed
22 Sep 2020Reviewer(s) Assigned