title: Ginsenoside Rp1, a Ginsenoside Derivative, Blocks Promoter Activation of iNOS and COX-2 Genes by Suppression of an IKKβ-mediated NF-кB Pathway in HEK293 Cells.
abstract: Ginsenoside (G) Rp1 is a ginseng saponin derivative with anti-cancer and anti-inflammatory activities. In this study, we examined the mechanism by which G-Rp1 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-Rp1 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-Rp1 did not suppress TANK binding kinase 1-, Toll-interleukin-1 receptor-domain-containing adapter-inducing interferon-β (TRIF)-, TRIFrelated adaptor molecule (TRAM)-, or activation of interferon regulatory factor (IRF)-3 and nuclear factor (NF)-кB by the myeloid differentiation primary response gene (MyD88)-induced. However, G-Rp1 strongly suppressed NF-кB activation induced by IкB kinase (IKK)β in HEK293 cells. Consistent with these results, G-Rp1 substantially inhibited IKKβ-induced phosphorylation of IкBɑ and p65. These results suggest that G-Rp1 is a novel anti-inflammatory ginsenoside analog that can be used to treat IKKβ/NF-кB-mediated inflammatory diseases.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Korea.
authors.forename: Ting
authors.initials: T
authors.lastname: Shen
authors.forename: Jaehwi
authors.initials: J
authors.lastname: Lee
authors.forename: Myung Hwan
authors.initials: MH
authors.lastname: Park
authors.forename: Yong Gyu
authors.initials: YG
authors.lastname: Lee
authors.forename: Ho Sik
authors.initials: HS
authors.lastname: Rho
authors.forename: Yi-Seong
authors.initials: YS
authors.lastname: Kwak
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
authors.forename: Yung Chul
authors.initials: YC
authors.lastname: Park
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
keywords: Cyclooxygenase 2; Ginsenoside Rp1; Nitric oxide synthase type II; Nuclear factor-кB; Panax ginseng; Promoter activity