Planta Med 2005; 71(12): 1167-1170
DOI: 10.1055/s-2005-873147
Letter
© Georg Thieme Verlag KG Stuttgart · New York

Anti-Inflammatory Activity of 20(S)-Protopanaxadiol: Enhanced Heme Oxygenase 1 Expression in RAW 264.7 Cells

Sung Hee Lee1 , Geom Seog Seo2 , Geonil Ko1 , Jae Baek Kim3 , Dong Hwan Sohn1
  • 1College of Pharmacy, Medicinal Resources Research Institute, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
  • 2Department of Internal Medicine, Wonkwang University Medical School, Iksan, Jeonbuk, Republic of Korea
  • 3Wonkwang Pharmaceutical Co. Ltd., Iksan, Jeonbuk, Republic of Korea
Further Information

Publication History

Received: December 19, 2004

Accepted: June 27, 2005

Publication Date:
23 November 2005 (online)

Abstract

20(S)-Protopanaxadiol (PPD) is one of the metabolites of ginsenosides from Panax ginseng. In this study, we demonstrate that PPD inhibits the increase in lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expression through inactivation of nuclear factor-κB by preventing degradation of inhibitory factor-κBα. PPD also induces heme oxygenase 1 (HO-1) expression in RAW 264.7 cells, at the mRNA and protein levels, in the presence and absence of LPS. This effect is associated with suppression of LPS-induced nitric oxide (NO) production and iNOS expression. The HO-1 inducer hemin is associated with the suppression of LPS-induced NO production in a dose-dependent manner, and the HO-1 inhibitor tin protoporphyrin attenuates the inhibitory activity of PPD on LPS-induced NO production. These results provide evidence for the role of HO-1 in the inhibition of LPS-induced NO production by PPD.

References

  • 1 Wink D A, Mitchell J B. Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide.  Free Radic Biol Med. 1998;  25 434-56
  • 2 Lin H Y, Juan S H, Shen S C, Hsu F L, Chen Y C. Inhibition of lipopolysaccharide-induced nitric oxide production by flavonoids in RAW264.7 macrophages involves heme oxygenase-1.  Biochem Pharmacol. 2003;  66 1821-32
  • 3 Cavicchi M, Gibbs L, Whittle B J. Inhibition of inducible nitric oxide synthase in the human intestinal epithelial cell line, DLD-1, by the inducers of heme oxygenase 1, bismuth salts, heme, and nitric oxide donors.  Gut. 2000;  47 771-8
  • 4 Datta P K, Koukouritaki S B, Hopp K A, Lianos E A. Heme oxygenase-1 induction attenuates inducible nitric oxide synthase expression and proteinuria in glomerulonephritis.  J Am Soc Nephrol. 1999;  10 2540-50
  • 5 Popovich D G, Kitts D D. Mechanistic studies on protopanaxadiol, Rh2, and ginseng (Panax quinquefolius) extract induced cytotoxicity in intestinal Caco-2 cells.  J Biochem Mol Toxicol. 2004;  18 143-9
  • 6 Bae E A, Choo M K, Park E K, Park S Y, Shin H Y, Kim D H. Metabolism of ginsenoside R(c) by human intestinal bacteria and its related antiallergic activity.  Biol Pharm Bull. 2002;  25 743-7
  • 7 Popovich D G, Kiyys D D. Structure-function relationship exists for ginsenosides in reducing cell proliferation and inducing apoptosis in the human leukemia (THP-1) cell line.  Arch Biochem Biophys. 2002;  406 1-8
  • 8 Xie Q W, Kashiwabara Y, Nathan C. Role of transcription factor NF-κB/Rel in induction of nitric oxide synthase.  J Biol Chem. 1994;  269 4705-8
  • 9 Rice N R, Ernst M K. In vivo control of NF-κB activation by IκBα.  EMBO J. 1993;  12 4685-95
  • 10 May M J, Ghosh S. Signal transduction through NF-κB.  Immunol Today. 1998;  19 80-8
  • 11 Datta P K, Koukouritaki S B, Hopp K A, Lianos E A. Heme oxygenase-1 induction attenuates inducible nitric oxide synthase expression and proteinuria in glomerulonephritis.  J Am Soc Nephrol. 1999;  10 2540-50
  • 12 Sato K, Balla J, Otterbein L, Smith R N, Brouard S, Lin Y. et al . Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants.  J Immunol. 2001;  166 4185-94
  • 13 Lee T S, Tsai H L, Chau L Y. Induction of heme oxygenase-1 expression in murine macrophages is essential for the anti-inflammatory effect of low dose 15-deoxydelta-12,14-prostaglandin J2.  J Biol Chem. 2003;  278 19 325-30
  • 14 Naughton P, Hoque M, Green C J, Foresti R, Motterlini R. Interaction of heme with nitroxyl or nitric oxide amplifies heme oxygenase-1 induction: involvement of the transcription factor Nrf2.  Cell Mol Biol (Noisy-le-grand). 2002;  48 885-94
  • 15 Lee S H, Seo G S, Sohn D H. Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase by butein in RAW 264.7 cells.  Biochem Biophys Res Commun. 2004;  323 125-32

Prof. Dong Hwan Sohn

College of Pharmacy

Medicinal Resources Research Institute

Wonkwang University

Iksan

Jeonbuk 570-749

Republic of Korea

Phone: +82-63-850-6822

Fax: +82-63-854-6038

Email: dhsohn@wonkwang.ac.kr