Ginsenoside 25-OCH 3 -PPD Promotes Activity of LXRs To Ameliorate P2X7R-Mediated NLRP3 Inflammasome in the Development of Hepatic Fibrosis

• Published in: Journal of agricultural and food chemistry 2018-07, Vol.66 (27), p.7023-7035
• Main Authors: Han, Xin, Song, Jian, Lian, Li-Hua, Yao, You-Li, Shao, Dan-Yang, Fan, Ying, Hou, Li-Shuang, Wang, Ge, Zheng, Shuang, Wu, Yan-Ling, Nan, Ji-Xing
• Format: Article
• Language: English
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.8b01982

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-OCH -PPD, a ginsenoside isolated from Panax ginseng, against hepatic fibrosis and inflammation in thioacetamide (TAA)-stimulated mice by activating the LXRs pathway. 25-OCH -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-OCH -PPD also facilitates LX25Rs and FXR activities decreased by TAA stimulation. 25-OCH -PPD also decreases α-SMA via regulation of LXRs and P2X7R-NLRP3 in vitro. Our data suggest the possibility that 25-OCH -PPD promotes activity of LXRs to ameliorate P2X7R-mediated NLRP3 inflammasome in the development of hepatic fibrosis.