Planta Med 2009; 75(4): 321-326
DOI: 10.1055/s-0028-1112218
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Ginsenoside Rp1, a Ginsenoside Derivative, Blocks Lipopolysaccharide-Induced Interleukin-1β Production via Suppression of the NF-κB Pathway

Byung Hun Kim1 , Yong Gyu Lee1 , Tae Yoon Park2 , Ho Bang Kim3 , Man Hee Rhee4 , Jae Youl Cho1
  • 1School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University; Chuncheon, Korea
  • 2Ambo Institute, Dogok-dong, Gangnam-ku, Seoul, Korea
  • 3Department of Biological Science, Myongji University, Yongin, Korea
  • 4College of Veterinary Medicine, Kyungpook National University; Daegu, Korea
Further Information

Publication History

Received: June 16, 2008 Revised: November 7, 2008

Accepted: November 17, 2008

Publication Date:
14 January 2009 (online)

Abstract

Ginsenoside Rp1 (G-Rp1) is a ginseng saponin derivative with chemopreventive and anti-cancer activities. In this study, we examined the regulatory activity of G-Rp1 on the production of interleukin (IL)-1β, a pro-inflammatory cytokine managing acute or chronic inflammatory diseases such as septic shock and rheumatoid arthritis, from lipopolysaccharide (LPS)-treated macrophage-like RAW264.7 cells. G-Rp1 dose-dependently inhibited IL-1β production from LPS-treated RAW264.7 cells without altering cell viability. This compound suppressed both mRNA and protein levels of IL-1β. In particular, this compound was found to down-regulate phosphorylation of the inhibitor of κB (IκB) kinase (IKK)/IκBα, and consequent activation of NF-κB, but not the activation of its upstream signaling enzymes such as mitogen-activated protein kinases (MAPK) and p85, a regulatory subunit of phosphoinositide 3-kinase (PI3K). Therefore, these results suggest that G-Rp1 may act as an inhibitor of IL-1β production by inhibiting the NF-κB pathway.

References

  • 1 Gillis C N. Panax ginseng pharmacology: a nitric oxide link?.  Biochem Pharmacol. 1997;  54 1-8
  • 2 Cho J Y, Yoo E S, Baik K U, Park M H, Han B H. In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists.  Planta Med. 2001;  67 213-8
  • 3 Kumar A, Kumar M, Panwar M, Samarth R M, Park T Y, Park M H. Evaluation of chemopreventive action of ginsenoside Rp1.  Biofactors. 2006;  26 29-43
  • 4 Park T Y, Park M H, Shin W C, Rhee M H, Seo D W, Cho J Y. Anti-metastatic potential of ginsenoside Rp1, a novel ginsenoside derivative.  Biol Pharm Bull. 2008;  31 1802-5
  • 5 Bird S, Zou J, Wang T, Munday B, Cunningham C, Secombes C J. Evolution of interleukin-1beta.  Cytokine Growth Factor Rev. 2002;  13 483-502
  • 6 Lee M S, Kim Y J. Signaling pathways downstream of pattern-recognition receptors and their cross talk.  Annu Rev Biochem. 2007;  76 447-80
  • 7 Sekine Y, Yumioka T, Yamamoto T, Muromoto R, Imoto S, Sugiyma K. Modulation of TLR4 signaling by a novel adaptor protein signal-transducing adaptor protein-2 in macrophages.  J Immunol. 2006;  176 380-9
  • 8 Kay J, Calabrese L. The role of interleukin-1 in the pathogenesis of rheumatoid arthritis.  Rheumatology (Oxford). 2004;  43 ( 3) iii2-iii9
  • 9 Lee H J, Hyun E A, Yoon W J, Kim B H, Rhee M H, Kang H K. In vitro anti-inflammatory and anti-oxidative effects of Cinnamomum camphora extracts.  J Ethnopharmacol. 2006;  103 208-16
  • 10 Cho J Y, Baik K U, Jung J H, Park M H. In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. .  Eur J Pharmacol. 2000;  398 399-407
  • 11 Cho J Y, Fox D A, Horejsi V, Sagawa K, Skubitz K M, Katz D R. The functional interactions between CD98, beta1-integrins, and CD147 in the induction of U937 homotypic aggregation.  Blood. 2001;  98 374-82
  • 12 Jung K K, Lee H S, Cho J Y, Shin W C, Rhee M H, Kim T G. Inhibitory effect of curcumin on nitric oxide production from lipopolysaccharide-activated primary microglia.  Life Sci. 2006;  79 2022-31
  • 13 Hardy K, Hunt N H. Effects of a redox-active agent on lymphocyte activation and early gene expression patterns.  Free Radic Biol Med. 2004;  37 1550-63
  • 14 Lee Y G, Lee W M, Kim J Y, Lee J Y, Lee I K, Yun B S. Src kinase-targeted anti-inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7 cells.  Br J Pharmacol. 2008;  154 852-63
  • 15 Nam N H. Naturally occurring NF-kappaB inhibitors.  Mini Rev Med Chem. 2006;  6 945-51
  • 16 Naumann M. Nuclear factor-kappa B activation and innate immune response in microbial pathogen infection.  Biochem Pharmacol. 2000;  60 1109-14
  • 17 Rajapakse N, Kim M M, Mendis E, Kim S K. Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated RAW264.7 cells by carboxybutyrylated glucosamine takes place via down-regulation of mitogen-activated protein kinase-mediated nuclear factor-kappaB signaling.  Immunology. 2008;  123 348-57
  • 18 Sheu M L, Chao K F, Sung Y J, Lin W W, Lin-Shiau S Y, Liu S H. Activation of phosphoinositide 3-kinase in response to inflammation and nitric oxide leads to the up-regulation of cyclooxygenase-2 expression and subsequent cell proliferation in mesangial cells.  Cell Signal. 2005;  17 975-84
  • 19 Hatziieremia S, Gray A I, Ferro V A, Paul A, Plevin R. The effects of cardamonin on lipopolysaccharide-induced inflammatory protein production and MAP kinase and NFkappaB signalling pathways in monocytes/macrophages.  Br J Pharmacol. 2006;  149 188-98
  • 20 Lee Y G, Chain B M, Cho J Y. Distinct role of spleen tyrosine kinase in the early phosphorylation of inhibitor of kappaBalpha via activation of the phosphoinositide-3-kinase and Akt pathways. Int J Biochem Cell Biol, in press
  • 21 Barisic S, Strozyk E, Peters N, Walczak H, Kulms D. Identification of PP2A as a crucial regulator of the NF-kappaB feedback loop: its inhibition by UVB turns NF-kappaB into a pro-apoptotic factor.  Cell Death Differ. 2008;  15 1681-90
  • 22 Park E K, Choo M K, Han M J, Kim D H. Ginsenoside Rh1 possesses antiallergic and anti-inflammatory activities.  Int Arch Allergy Immunol. 2004;  133 113-20
  • 23 Park E K, Shin Y W, Lee H U, Kim S S, Lee Y C, Lee B Y. Inhibitory effect of ginsenoside Rb1 and compound K on NO and prostaglandin E2 biosyntheses of RAW264.7 cells induced by lipopolysaccharide.  Biol Pharm Bull. 2005;  28 652-6
  • 24 Zhang Z, Li X, Lv W, Yang Y, Gao H, Yang J. Ginsenoside Re reduces insulin resistance through inhibition of c-Jun NH2-terminal kinase and nuclear factor-kappaB.  Mol Endocrinol. 2008;  22 186-95

Jae Youl Cho, PhD

School of Bioscience and Biotechnology and

Institute of Bioscience and Biotechnology

Kangwon National University

192–1 Hyoja-2-Dong

Chuncheon 200–701

South Korea

Phone: +82-33-250-6562

Fax: +82-33-253-6560

Email: jaecho@kangwon.ac.kr

Man Hee Rhee, DVM, PhD

College of Veterinary Medicine

Kyungpook National University

Daegu 702–701

South Korea

Phone: +82-53-950-5967

Fax: +82-53-950-5955

Email: rheemh@knu.ac.kr

    >