Ginsenoside 25-OCH3-PPD promotes activity of LXRs to ameliorate P2X7R-mediated NLRP3 inflammasome in development of hepatic fibrosis

OBJECTIVE 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 LXRs pathway. METHODS C57 BL/6 mice were received intraperitoneal TAA to induce hepatic fibrosis, and treated with 25-OCH_3-PPD or equal volume of saline. The regulation of AA against hepatic fibrosis was also detected in activated HSCs. RESULTS 25-OCH_3-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; regulates PI3K/Akt and LKB1/AMPK-SIRT1. 25-OCH_3-PPD also facilitates LX25 Rs and FXR activities decreased by TAA stimulation. 25-OCH3-PPD also decreasesα-SMA via regulation of LXRs and P2X7R-NLRP3 in vitro.CONCLUSION Current data suggest the possibility that 25-OCH_3-PPD promotes activity of LXRs to ameliorate P2X7 R-mediated NLRP3 inflammasome in the development of hepatic fibrosis.