Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages

Ma, Chuanrui1,2; Xiang, Jiaqing3; Huang, Guixiao4; Zhao, Yaxi5; Wang, Xinyu3; Wu, Han3; Jiang, Kewei3; Liang, Zhen3; Kang, Lin3,6; Yang, Guangyan3; Yang, Shu3,7

2021-11-25

10.3389/fphar.2021.785403

FRONTIERS IN PHARMACOLOGY   影响因子和分区

1663-9812

Background and purpose: FXR is a promising target for the treatment of human cholestatic liver disease (CLD). SIRT1 is a deacetylase which promotes FXR activity through deacetylating FXR. Pterostilbene (PTE) is an activator of SIRT1. However, the role of PTE in cholestasis has so far not been investigated. We examined whether PTE treatment alleviate liver injury in DDC or ANIT-induced experimental cholestasis, and explored the underlying mechanisms.Experimental approach: Mice with DDC- or ANIT-induced cholestasis were treated with different dose of PTE. Primary hepatocytes and bone marrow derived macrophages were used in vitro to assess the molecular mechanism by which PTE may improve CLD. Identical doses of UDCA or PTE were administered to DDC- or ANIT-induced cholestasis mice.Key results: PTE intervention attenuated DDC or ANIT-induced cholestasis. PTE inhibited macrophage infiltration and activation in mouse liver through the SIRT1-p53 signaling pathway, and it improved hepatic bile metabolism through the SIRT1-FXR signaling pathway. Compare with UDCA, the same doses of PTE was more effective in improving cholestatic liver injury caused by DDC or ANIT.Conclusion and implications: SIRT1 activation in macrophages may be an effective CLD treatment avenue. Using CLD models, we thus identified PTE as a novel clinical candidate compound for the treatment of CLD.

cholestasis pterostilbene SIRT1 FXR p53

SCI

英语

通讯

National Natural Science Foundation of China (NSFC)[82000824,82003747] ; China Postdoctoral Science Foundation[2020M683179] ; Natural Science Foundation of Shenzhen City[JCYJ20190807145213180]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:000729132500001

FRONTIERS MEDIA SA

Web of Science

1.Tianjin Univ Tradit Chinese Med, First Teaching Hosp, Tianjin, Peoples R China
2.Natl Clin Res Ctr Chinese Med Acupuncture & Moxib, Tianjin, Peoples R China
3.Southern Univ Sci & Technol, Dept Geriatr, Shenzhen Peoples Hosp, Second Clin Med Coll,Affiliated Hosp 1,Jinan Univ, Shenzhen, Peoples R China
4.Shenzhen Univ, Affiliated Hosp 3, Shenzhen, Peoples R China
5.Shenzhen Third Peoples Hosp, Dept TB, Shenzhen, Peoples R China
6.Shenzhen Peoples Hosp, Biobank Natl Innovat Ctr Adv Med Devices, Shenzhen, Peoples R China
7.Jinan Univ, Integrated Chinese & Western Med Postdoctoral Res, Guangzhou, Peoples R China

Ma, Chuanrui,Xiang, Jiaqing,Huang, Guixiao,et al. Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages[J]. FRONTIERS IN PHARMACOLOGY,2021,12.

Ma, Chuanrui.,Xiang, Jiaqing.,Huang, Guixiao.,Zhao, Yaxi.,Wang, Xinyu.,...&Yang, Shu.(2021).Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages.FRONTIERS IN PHARMACOLOGY,12.

Ma, Chuanrui,et al."Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages".FRONTIERS IN PHARMACOLOGY 12(2021).