Ginsenoside Rp_1, a Ginsenoside Derivative, Blocks Promoter Activation of iNOS and COX-2 Genes by Suppression of an IKKb-mediated NF-kB Pathway in HEK293 Cells

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-b (TRIF)-, TRIFrelated adaptor molecule (TRAM)-, or activation of interferon regulatory factor (IRF)-3 and nuclear factor (NF)-kB by the myeloid differentiation primary response gene (MyD88)-induced. However, G-Rp_1 strongly suppressed NF-kB activation induced by IkB kinase (IKK)b in HEK293 cells. Consistent with these results, G-Rp_1 substantially inhibited IKKb-induced phosphorylation of IkBa and p65. These results suggest that G-Rp_1 is a novel anti-inflammatory ginsenoside analog that can be used to treat IKKb/NF-kB-mediated inflammatory diseases.