Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages.
Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages.
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DOI：
10.3389/fphar.2021.785403
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发表时间：
2021
影响因子：
5.6
通讯作者：
Yang S
中科院分区：
文献类型：
--
作者：
Ma C;Xiang J;Huang G;Zhao Y;Wang X;Wu H;Jiang K;Liang Z;Kang L;Yang G;Yang S
背景和目的：FXR是一个很有前途的治疗胆汁淤积性肝病（CLD）的靶点。SIRT 1是一种脱乙酰酶，通过脱乙酰化FXR促进FXR活性。Pterostilbene（PTE）是SIRT 1的激活剂。然而，PTE在胆汁淤积中的作用迄今尚未研究。我们研究了PTE治疗是否减轻DDC或ANIT诱导的实验性胆汁淤积的肝损伤，并探讨了潜在的机制。 实验方法：用不同剂量的PTE治疗DDC或ANIT诱导的胆汁淤积小鼠。体外使用原代肝细胞和骨髓源性巨噬细胞来评估PTE可改善CLD的分子机制。对DDC或ANIT诱导的胆汁淤积小鼠给予相同剂量的UDCA或PTE。 关键结果：PTE干预减弱DDC或ANIT诱导的胆汁淤积。PTE通过SIRT 1-p53信号通路抑制小鼠肝脏巨噬细胞浸润和活化，通过SIRT 1-FXR信号通路改善肝脏胆汁代谢。与UDCA相比，相同剂量的PTE对DDC或ANIT所致胆汁淤积性肝损伤的改善作用更明显。 结论和影响：SIRT 1激活巨噬细胞可能是一种有效的CLD治疗途径。因此，使用CLD模型，我们将PTE鉴定为治疗CLD的新型临床候选化合物。
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.
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DOI：
10.1002/hep.27744
发表时间：
2015-08
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Ghonem NS;Assis DN;Boyer JL
通讯作者：
Boyer JL
影响因子：
13.5
作者：
Kulkarni, Supriya R.;Soroka, Carol J.;Hagey, Lee R.;Boyer, James L.
通讯作者：
Boyer, James L.
影响因子：
14.9
作者：
Chanda D;Xie YB;Choi HS
通讯作者：
Choi HS
影响因子：
16.6
作者：
El Kasmi KC;Vue PM;Anderson AL;Devereaux MW;Ghosh S;Balasubramaniyan N;Fillon SA;Dahrenmoeller C;Allawzi A;Woods C;McKenna S;Wright CJ;Johnson L;D'Alessandro A;Reisz JA;Nozik-Grayck E;Suchy FJ;Sokol RJ
通讯作者：
Sokol RJ
影响因子：
13.5
作者：
Garcia-Rodriguez, Juan L.;Barbier-Torres, Lucia;Fernandez-Alvarez, Sara;Gutierrez-de Juan, Virginia;Monte, Maria J.;Halilbasic, Emina;Herranz, Daniel;Alvarez, Luis;Aspichueta, Patricia;Marin, Jose J. G.;Trauner, Michael;Mato, Jose M.;Serrano, Manuel;Beraza, Naiara;Luz Martinez-Chantar, Maria
通讯作者：
Luz Martinez-Chantar, Maria