20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear factor-kappaB in RAW 264.7 macrophages stimulated with lipopolysaccharide

Cancer Lett. 2004 Mar 8;205(1):23-9. doi: 10.1016/j.canlet.2003.09.037.

Abstract

Ginsenosides from Panax ginseng are metabolized by human intestinal bacteria after oral administration of ginseng extract. 20(S)-Protopanaxatriol (PPT) is one of the major metabolites of ginsenosides. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important enzymes that mediate inflammatory processes. Improper up-regulation of iNOS and/or COX-2 has been associated with the pathogenesis of inflammatory diseases and certain types of human cancers. Here, we investigated whether PPT could modulate iNOS and COX-2 expressions in RAW 264.7 macrophages stimulated with the endotoxin lipopolysaccharide (LPS). We found that PPT blocked the increase in LPS-induced iNOS and COX-2 expressions through inactivation of nuclear factor-kappaB by preventing I-kappaBalpha phosphorylation and degradation. Thus, it may be possible to develop PPT as a useful agent for chemoprevention of cancer or inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Cyclooxygenase 2
  • Electrophoretic Mobility Shift Assay
  • Ginsenosides / metabolism
  • Isoenzymes / biosynthesis
  • Isoenzymes / drug effects*
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • NF-kappa B / drug effects*
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase / drug effects*
  • Nitric Oxide Synthase Type II
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Sapogenins / pharmacology*
  • Triterpenes / pharmacology*

Substances

  • Ginsenosides
  • Isoenzymes
  • Lipopolysaccharides
  • NF-kappa B
  • Sapogenins
  • Triterpenes
  • protopanaxatriol
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases