Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside Rp1, a Ginsenoside Derivative, Blocks Promoter Activation of iNOS and COX-2 Genes by Suppression of an IKKβ-mediated NF-κB Pathway in HEK293 Cells

  • Shen, Ting (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Lee, Jae-Hwi (College of Pharmacy, Chung-Ang University) ;
  • Park, Myung-Hwan (Ambo Institute) ;
  • Lee, Yong-Gyu (College of Biomedical Science, Kangwon National University) ;
  • Rho, Ho-Sik (R & D Center, AmorePacific Corporation) ;
  • Kwak, Yi-Seong (Korea Ginseng Corporation Central Research Institute) ;
  • Rhee, Man-Hee (College of Veterinary Medicine, Kyungpook National University) ;
  • Park, Yung-Chul (College of Forest and Environmental Sciences, Kangwon National University) ;
  • Cho, Jae-Youl (Department of Genetic Engineering, Sungkyunkwan University)
  • Received : 2010.12.31
  • Accepted : 2011.03.30
  • Published : 2011.06.29
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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.

Keywords

References

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