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KMID : 0352720110350020200
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Journal of Ginseng Research
2011 Volume.35 No. 2 p.200 ~ p.208
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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
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Shen Ting
Lee Jae-Hwi
Park Myung-Hwan
Lee Yong-Gyu
Rho Ho-Sik
Kwak Yi-Seong
Rhee Man-Hee
Park Yung-Chul
Cho Jae-Youl
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Abstract
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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-b (TRIF)-, TRIF-related adaptor molecule (TRAM)-, or activation of interferon regulatory factor (IRF)-3 and nuclear factor (NF)-κB by the myeloid differentiation primary response gene (MyD88)-induced. However, G-Rp₁ strongly suppressed NF-κB activation induced by Iκβ kinase (IKK)β in HEK293 cells. Consistent with these results, G-Rp₁ substantially inhibited IKKβ-induced phosphorylation of Iκβα and p65. These results suggest that G-Rp₁ is a novel anti-inflammatory ginsenoside analog that can be used to treat IKKβ/NF-κB-mediated inflammatory diseases.
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KEYWORD
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Panax ginseng, Ginsenoside Rp₁, Cyclooxygenase 2, Nitric oxide synthase type Ⅱ, Promoter activity, Nuclear factor-κB
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