Planta Med 2001; 67(2): 122-126
DOI: 10.1055/s-2001-11508
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Nitric Oxide is Involved in the Immunomodulating Activities of Acidic Polysaccharide from Panax ginseng

Kyeong Mee Park1 , Young Sook Kim1 , Tae Cheon Jeong2 , Cheol O. Joe3 , Han Jae Shin1 , You Hui Lee1 , Ki Yeul Nam1 , Jong Dae Park1,*
  • 1 Korea Ginseng & Tobacco Research Institute, Taejon, Korea
  • 2 College of Pharmacy, Yeungnam University, Kyungsan, Korea
  • 3 Korea Advanced Institute of Science and Technology, Taejon, Korea
Further Information

Publication History

February 29, 2000

July 9, 2000

Publication Date:
31 December 2001 (online)

Abstract

The effects of an acidic polysaccharide isolated from the ethanol-insoluble and water-soluble fraction of Panax ginseng C. A. Meyer on immunomodulating activities were investigated. A high output nitric oxide synthase (iNOS) was shown in female BALB/c mice administered intraperitoneally with the acidic polysaccharide from ginseng. Newly synthesized iNOS protein was also observed in peritoneal macrophages cultured with interferon-γ and the acidic polysaccharide. Spleen cells from acidic polysaccharide-treated mice did not proliferate in response to concanavalin A, but restored the responsiveness by the cotreatment of N G-monomethyl-L-arginine (NMMA) with concanavalin A. The treatment of mice with aminoguanidine, a specific iNOS inhibitor, alleviated the acidic polysaccharide-induced suppression of antibody response to sheep red blood cells. Present results suggest that the immunomodulating activities of the acidic polysaccharide were mediated by the production of nitric oxide.

Abbreviations

iNOS:inducible nitric oxide synthase

IFN-γ:interferon-γ

RGAP:red ginseng acidic polysaccharide

Con A:concanavalin A

NMMA:N G-monomethyl-L-arginine

AFC:antibody forming cell

SRBC:sheep red blood cell

AG:aminoguanidine

References

  • 1 Ignarro L J. Nitric oxide-mediated vasorelaxation.  Thromb. Haemost.. 1993;  70 148-51
  • 2 Skaper S D, Facci L, Leon A. Inflammatory mediator stimulation of astrocytes and meningeal fibroblasts induces neuronal degeneration via nitridergic pathway.  J. Neurochem.. 1995;  64 266-76
  • 3 Hibbs J J, Taintor R R, Vavrin Z, Rachlin E M. Nitric oxide: a cytotoxic effector molecule.  Biochem. Biophys. Res. Commun.. 1988;  157 87-94
  • 4 Nathan C. Nitric oxide as a secretory product of mammalian cells.  FASEB J.. 1992;  6 3051-64
  • 5 Green S J, Meltzer M S, Hibbs Jr. J B, Nacy C A. Activated macrophages destroy intracellular Leishmania major amastigotes by an L-arginine-dependent killing mechanism.  J. Immunol.. 1990;  144 278-83
  • 6 Martin J HJ, Edwards S W. Changes in mechanisms of monocyte/macrophage-mediated cytotoxicity during culture. Reactive oxygen intermediates are involved in monocyte-mediated cytotoxicity, whereas reactive nitrogen intermediates are employed by macrophages in tumor cell killing.  J. Immunol.. 1993;  150 3478-86
  • 7 Rojas A, Padrón J, Caveda L, Palacios M, Moncada S. Role of nitric oxide pathway in the protection against lethal endotoxemia by low doses of lipopolysaccharide.  Biochem. Biophys. Res. Commun.. 1993;  191 441-6
  • 8 Albina J E, Abate J A, Henry Jr. W L. Nitric oxide production is required for murine resident peritoneal macrophages to suppress mitogen-stimulated T cell proliferation. Role of IFN-γ in the induction of the nitric oxide-synthesizing pathway.  J. Immunol.. 1991;  147 144-8
  • 9 Al-Ramadi B K, Green J M, Meissler Jr. J J, Eisenstein T K. Immunosuppression induced by attenuated Salmonella: effect of LPS responsiveness on development of suppression.  Micrb. Pathog.. 1992;  12 267-78
  • 10 Lee Y S, Chung I S, Lee I R, Kim K H, Hong W S, Yun Y S. Activation of multiple effector pathways of immune system by the antineoplastic immunostimulator acidic polysaccharide ginsan isolated from Panax ginseng .  Anticancer Res.. 1997;  17 323-32
  • 11 Kim K H, Lee Y S, Jung I S, Park S Y, Chung H Y, Lee I R, Yun Y S. Acidic polysaccharide from Panax ginseng, ginsan, induces Th1 cell and macrophage cytokines and generates LAK cells in synergy with rIL-2.  Planta Med.. 1998;  64 110-5
  • 12 Conrad R E. Induction and collection of peritoneal exudate macrophages.  In: Manual of macrophage methodology. New York; Marcel Dekker 1981: 5-11
  • 13 Klimetzek V, Remold H G. The murine bone marrow macrophage, a sensitive indicator cell for murine migration inhibitory factor and a new method for their harvest.  Cell. Immunol.. 1980;  53 257-66
  • 14 Green L C, Wanger D A, Glogowski J, Skipper P L, Wishnok J S, Tannenbaum S R. Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids.  Anal. Biochem.. 1982;  126 131-8
  • 15 Holsapple M P. The plaque-forming cell (PFC) response in immunotoxicology: an approach to monitoring the primary effector function of B lymphocytes.  In: Methods in Immunotoxicology. Vol. 1 New York; Wiley-Liss 1995: 71-108
  • 16 Holscher S K, Stoker B AD. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines.  Nature. 1981;  291 238-9
  • 17 Lee J C, Gibson C W, Eisenstein T K. Macrophage-mediated mitogenic suppression induced in mice of the C3H lineage by a vaccine strain of Salmonella typhimurium .  Cell. Immunol.. 1985;  91 75-91
  • 18 Al-Ramadi B K, Brodkin M A, Mosser D M, Eisenstein T. Immunosuppression induced by attenuated Salmonella. Evidence for mediation by macrophage precursors.  J. Immunol.. 1991;  146 2737-46
  • 19 Eisenstein T K, Huang D, Meissler Jr. J J, Al-Ramadi B K. Macrophage nitric oxide mediates immunosuppression in infectious inflammation.  Immunobiology. 1994;  191 493-501
  • 20 Macfarlane A S, Schwacha M G, Eisenstein T K. In vivo blockade of nitric oxide with aminoguanidine inhibits immunosuppression induced by an attenuated strain of Salmonella typhimurium, potentiates Salmonella infection, and inhibits macrophage and polymorphonuclear leukocyte influx into the spleen.  Infect. Immun.. 1999;  67 891-8
  • 21 Fehsel K, Kröncke K-D, Meyer K L, Huber H, Wahn V, Kolb-Bachofen V. Nitric oxide induces apoptosis in mouse thymocytes.  J. Immunol.. 1995;  155 2858-65
  • 22 Cui S, Reichner J S, Albina J E. Nitric oxide (NO) induces apoptosis in Con A-stimulated splenocytes.  FASEB J. (Abstract). 1995;  8 4470
  • 23 Chaplin M J, Kennedy J F. Carbohydrate Analysis. Oxford; IRL Press 1994: 2-7

Dr. Jong Dae Park

Department of Biochemical Pharmacology

Korea Ginseng & Tobacco Research Institute

Taejon 305-345

Korea

Email: jdpark@gtr.kgtri.re.kr

Fax: +82-42-861-1949

    >