Ginsenoside 25-OCH3-PPD Promotes Activity of LXRs To Ameliorate P2X7R-Mediated NLRP3 Inflammasome in the Development of Hepatic Fibrosis,Journal of Agricultural and Food Chemistry

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Ginsenoside 25-OCH3-PPD Promotes Activity of LXRs To Ameliorate P2X7R-Mediated NLRP3 Inflammasome in the Development of Hepatic Fibrosis
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2018-06-22 00:00:00 , DOI: 10.1021/acs.jafc.8b01982
Xin Han ₁ , Jian Song ₁ , Li-Hua Lian ₁ , You-Li Yao ₁ , Dan-Yang Shao ₁ , Ying Fan ₁ , Li-Shuang Hou ₁ , Ge Wang ₁ , Shuang Zheng ₁ , Yan-Ling Wu ₁ , Ji-Xing Nan _{1,

2}

Affiliation

Ginseng is widely used in energy drinks, dietary supplements, and herbal medicines, and its pharmacological actions are related with energy metabolism. As an important modulating energy metabolism pathway, liver X receptors (LXRs) can promote the resolving of hepatic fibrosis and inflammation. The present study aims to evaluate the regulation of 25-OCH₃-PPD, a ginsenoside isolated from Panax ginseng, against hepatic fibrosis and inflammation in thioacetamide (TAA)-stimulated mice by activating the LXRs pathway. 25-OCH₃-PPD decreases serum ALT/AST levels and improves the histological pathology of liver in TAA-induced mice; attenuates transcripts of pro-fibrogenic markers associated with hepatic stellate cell activation; attenuates the levels of pro-Inflammatory cytokines and blocks apoptosis happened in liver; inhibits NLRP3 inflammasome by affecting P2X7R activation; and regulates PI3K/Akt and LKB1/AMPK-SIRT1. 25-OCH₃-PPD also facilitates LX25Rs and FXR activities decreased by TAA stimulation. 25-OCH₃-PPD also decreases α-SMA via regulation of LXRs and P2X7R-NLRP3 in vitro. Our data suggest the possibility that 25-OCH₃-PPD promotes activity of LXRs to ameliorate P2X7R-mediated NLRP3 inflammasome in the development of hepatic fibrosis.

中文翻译：

人参皂苷25-OCH ₃ -PPD促进LXRs改善肝纤维化发展中P2X7R介导的NLRP3炎性体的活性。

人参被广泛用于能量饮料，膳食补充剂和草药中，其药理作用与能量代谢有关。作为重要的调节能量代谢途径，肝X受体（LXR）可以促进肝纤维化和炎症的解决。本研究旨在通过激活LXRs途径评估从人参中分离出的人参皂甙25-OCH ₃ -PPD对硫代乙酰胺（TAA）刺激的小鼠肝纤维化和炎症的调节作用。25-OCH ₃-PPD降低了TAA诱导的小鼠的血清ALT / AST水平并改善了肝脏的组织病理学；减弱与肝星状细胞激活相关的促纤维化标记物的转录本；减弱促炎细胞因子的水平并阻断肝脏中发生的细胞凋亡；通过影响P2X7R激活来抑制NLRP3炎性体；并调节PI3K / Akt和LKB1 / AMPK-SIRT1。25-OCH ₃ -PPD还有助于通过TAA刺激降低LX25R和FXR活性。25-OCH ₃ -PPD在体外还通过调节LXRs和P2X7R-NLRP3降低α-SMA 。我们的数据表明，25-OCH ₃ -PPD可能促进LXRs改善肝纤维化发展中P2X7R介导的NLRP3炎性小体的活性。

更新日期：2018-06-22

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