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.
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.
Oh
G S
GS
Medicinal Resources Research Center of Wonkwang University, Iksan, Chonbuk 570-749, South Korea.
Pae
H O
HO
Choi
B M
BM
Seo
E A
EA
Kim
D H
DH
Shin
M K
MK
Kim
J D
JD
Kim
J B
JB
Chung
H T
HT
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D024202:Electrophoretic Mobility Shift Assay; D036145:Ginsenosides / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000187:drug effects*; D012502:Sapogenins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
D036145:Ginsenosides; D007527:Isoenzymes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012502:Sapogenins; D014315:Triterpenes; C081552:protopanaxatriol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases