Ginsenoside Rp(1), a Ginsenoside Derivative, Blocks Promoter Activation of iNOS and COX-2 Genes by Suppression of an IKK beta-mediated NF-kappa B Pathway in HEK293 Cells

Abstract

Ginsenoside (G) Rp(1) is a ginseng saponin derivative with anti-cancer and anti-inflammatory activities. In this study, we examined the mechanism by which G-Rp(1) inhibits inflammatory responses of cells. We did this using a strategy in which DNA constructs containing cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) promoters were transfected into HEK293 cells. G-Rp(1) strongly inhibited the promoter activities of COX-2 and iNOS; it also inhibited lipopolysaccharide induced upregulation of COX-2 and iNOS mRNA levels in RAW264.7 cells. In HEK293 cells G-Rp(1) did not suppress TANK binding kinase 1-, Toll-interleukin-1 receptor-domain-containing adapter-inducing interferon-beta (TRIF)-, TRIF-related adaptor molecule (TRAM)-, or activation of interferon regulatory factor (IRF)-3 and nuclear factor (NF)-kappa B by the myeloid differentiation primary response gene (MyD88)-induced. However, G-Rp(1) strongly suppressed NF-kappa B activation induced by I kappa B kinase (IKK)beta in HEK293 cells. Consistent with these results, G-Rp(1) substantially inhibited IKK beta-induced phosphorylation of I kappa B alpha and p65. These results suggest that G-Rp(1) is a novel anti-inflammatory ginsenoside analog that can be used to treat IKK beta/NF-kappa B-mediated inflammatory diseases.