Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages

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 invest...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Chuanrui Ma, Jiaqing Xiang, Guixiao Huang, Yaxi Zhao, Xinyu Wang, Han Wu, Kewei Jiang, Zhen Liang, Lin Kang, Guangyan Yang, Shu Yang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	cholestasis pterostilbene SIRT1 FXR p53 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/2f6b7998610b4b7dbe7599cf68119b5f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2f6b7998610b4b7dbe7599cf68119b5f
record_format	dspace
spelling	oai:doaj.org-article:2f6b7998610b4b7dbe7599cf68119b5f2021-12-01T01:29:06ZPterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages1663-981210.3389/fphar.2021.785403https://doaj.org/article/2f6b7998610b4b7dbe7599cf68119b5f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.785403/fullhttps://doaj.org/toc/1663-9812Background 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.Chuanrui MaChuanrui MaJiaqing XiangGuixiao HuangYaxi ZhaoXinyu WangHan WuKewei JiangZhen LiangLin KangLin KangGuangyan YangShu YangShu YangFrontiers Media S.A.articlecholestasispterostilbeneSIRT1FXRp53Therapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cholestasis pterostilbene SIRT1 FXR p53 Therapeutics. Pharmacology RM1-950
spellingShingle	cholestasis pterostilbene SIRT1 FXR p53 Therapeutics. Pharmacology RM1-950 Chuanrui Ma Chuanrui Ma Jiaqing Xiang Guixiao Huang Yaxi Zhao Xinyu Wang Han Wu Kewei Jiang Zhen Liang Lin Kang Lin Kang Guangyan Yang Shu Yang Shu Yang Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages
description	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.
format	article
author	Chuanrui Ma Chuanrui Ma Jiaqing Xiang Guixiao Huang Yaxi Zhao Xinyu Wang Han Wu Kewei Jiang Zhen Liang Lin Kang Lin Kang Guangyan Yang Shu Yang Shu Yang
author_facet	Chuanrui Ma Chuanrui Ma Jiaqing Xiang Guixiao Huang Yaxi Zhao Xinyu Wang Han Wu Kewei Jiang Zhen Liang Lin Kang Lin Kang Guangyan Yang Shu Yang Shu Yang
author_sort	Chuanrui Ma
title	Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages
title_short	Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages
title_full	Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages
title_fullStr	Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages
title_full_unstemmed	Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages
title_sort	pterostilbene alleviates cholestasis by promoting sirt1 activity in hepatocytes and macrophages
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2f6b7998610b4b7dbe7599cf68119b5f
work_keys_str_mv	AT chuanruima pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT chuanruima pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT jiaqingxiang pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT guixiaohuang pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT yaxizhao pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT xinyuwang pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT hanwu pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT keweijiang pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT zhenliang pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT linkang pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT linkang pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT guangyanyang pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT shuyang pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages AT shuyang pterostilbenealleviatescholestasisbypromotingsirt1activityinhepatocytesandmacrophages
_version_	1718405950617944064

Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages

Ejemplares similares