Ginsenoside 25-OCH3-PPD Promotes Activity of LXRs To Ameliorate P2X7R-Mediated NLRP3 Inflammasome in the Development of Hepatic Fibrosis

J Agric Food Chem. 2018 Jul 11;66(27):7023-7035. doi: 10.1021/acs.jafc.8b01982. Epub 2018 Jul 2.

Abstract

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.

Keywords: Ginsenoside 25-OCH3-PPD; LXRs; P2X7R; hepatic fibrosis; inflammation.

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Apoptosis / drug effects
  • Cytokines / genetics
  • Cytokines / metabolism
  • Ginsenosides / pharmacology*
  • Inflammasomes / drug effects*
  • Inflammasomes / metabolism
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism
  • Liver X Receptors / metabolism*
  • Male
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Receptors, Purinergic P2X7 / metabolism*
  • Sirtuin 1 / metabolism
  • Thioacetamide / toxicity

Substances

  • 25-methoxylprotopanaxadiol
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Ginsenosides
  • Inflammasomes
  • Liver X Receptors
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Receptors, Purinergic P2X7
  • Thioacetamide
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Stk11 protein, mouse
  • AMP-Activated Protein Kinases
  • Sirt1 protein, mouse
  • Sirtuin 1