Skip to main content
SpringerLink
Log in

Ganoderma lucidum inhibits inducible nitric oxide synthase expression in macrophages

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Nitric oxide (NO) is a principal mediator in many physiological and pathological processes. Overproduction of NO via the inducible nitric oxide synthase (iNOS) has cytotoxic effect through the formation of peroxynitrite with superoxide anion. The iNOS is mainly expressed in macrophages and is able to produce large amount of NO. The expression of iNOS is mainly regulated at the transcriptional level. The iNOS-mediated NO production plays a role in the development of atherosclerosis. Ganoderma lucidum (G. lucidum, Linzhi or Reishi) is a traditional herbal medicine which is commonly used as health supplement. Several studies have demonstrated its effectiveness against cancer, immunological disorders and cardiovascular diseases. The objective of the present study was to investigate the effect of G. lucidum on iNOS-mediated NO production in macrophages. Human monocytic cell (THP-1) derived macrophages were incubated with lipopolysaccharide (LPS) for 24 h. Such treatment significantly stimulated NO production (253% versus the control). Such a stimulatory effect was resulted from increased iNOS mRNA expression (270% versus the control) and iNOS activity (169.5% versus the control) in macrophages. The superoxide anion level was also elevated (150% versus the control) in LPS-treated macrophages. Treatment of macrophages with G. lucidum extract (100 μg/ml) completely abolished LPS-induced iNOS mRNA expression and NO production. Such an inhibitory effect of G. lucidum was mediated via its antioxidant action against LPS-induced superoxide anion generation in macrophages. These results suggest that G. lucidum may exert a therapeutic effect against atherosclerosis via ameliorating iNOS-mediated NO overproduction in macrophages.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Shiao M: Natural products of the medicinal fungus Ganoderma lucidum: occurrence, biological activities, and pharmacologial funtions. Chem Rec 3: 172–180, 2003

    Google Scholar 

  2. Miyazaki T, Nishijima M: Studies on fungal polysaccharides. XXVII. Structural examination of a water-soluble, antitumor polysaccharide of Ganoderma lucidum. Chem Pharm Bull 71: 115–124, 1981

    Google Scholar 

  3. Wang SY, Hsu ML, Hsu HC, Tzeng CH, Lee SS, Shiao MS, Ho CK: The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated marophages and T lymphocytes. Int J Cancer 70: 699–705, 1997

    Google Scholar 

  4. Lee SS, Wei YH, Chen CF, Wang SY, Chen KY: Antitumor effects of Ganoderma lucidum. J Chin Med 6: 1–12, 1995

    Google Scholar 

  5. Wasser SP, Weis AL: Medicinal properties of substances occurring in higher Basidiomycetes mushrooms: current perspective (review). Int J Med Mushrooms 1: 31–62, 1999

    Google Scholar 

  6. Lin S, Li C, Lee S, Kan L: Triterpene-enriched extracts from Ganoderma lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating mitogen-activated protein kinases and G2-phase cell cycle arrest. Life Sci 72: 2381–2390, 2003

    Google Scholar 

  7. Zhang HN, Lin ZB: Hypoglycemic effect of Gonaderma lucidum polysaccharides. Acta Pharmacol Sin 25(2): 191–195, 2004

    Google Scholar 

  8. Hsu MJ, Lee SS, Lee ST, Lin WW: Signaling mechanisms of enhanced neutrophil phagocytosis and chemotaxis by the polysaccharide purified from Ganoderma lucidum. Br J Pharmacol 139(2): 289–298, 2003

    Google Scholar 

  9. Zhu M, Chang Q, Wong LK, Chong FS, Li RC: Triterpene antioxidants from Ganoderma lucidum. Phytother Res 13: 529–531, 1999

    Google Scholar 

  10. Mau J, Lin H, Chen C: Antioxidant properties of several medicinal mushrooms. J Agric Food Chem 50: 6072–6077, 2002

    Google Scholar 

  11. Lee J, Kwon H, Jeong H, Lee JW, Lee SY, Baek SJ, Surh Y: Inhibition of lipid peroxidation and oxidative DNA damage by Ganoderma lucidum. Phytother Res 15: 245–249, 2001

    Google Scholar 

  12. Raji L, Baylis C: Glomerular actions of nitric oxide. Kidney Int 48(1): 20–32, 1995

    Google Scholar 

  13. Napoli C, Ignarro LJ: Nitric oxide and atherosclerosis. Nitric Oxide 5: 88–97, 2001

    Google Scholar 

  14. Radi R, Beckman JS, Bush KM, Freeman BA: Peroxynitrite-induced membrane lipid peroxidation: The cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 288: 481–487, 1991

    Google Scholar 

  15. White CR, Brock TA, Chang LT, et al.: Superoxide and peroxynitrite in atherosclerosis. Proc Natl Acad Sci USA 91: 1044–1048, 1994

    Google Scholar 

  16. Estévez A, Jordán J: Nitric oxide and superoxide, a deadly cocktail. Ann N Y Acad Sci 962: 207–211, 2002

    Google Scholar 

  17. Schussheim AE, Fuster V: Antibiotics for myocardial infarction? A possible role of infection in atherogenesis and acute coronary syndromes. Drug 57(3): 283–291, 1999

    Google Scholar 

  18. Rueckschloss U, Duerrschmidt N, Morawietz H: NADPH oxidase in endothelial cells: Impact on atherosclerosis. Antioxid Redox Signal 5(2): 171–180, 2003

    Google Scholar 

  19. Liu S, Adcock IM, Old RW, Barnes PJ, Evans TW: Lipopolysaccharide treatment in vivo induces widespread tissue expression of inducible nitric oxide synthase mRNA. Biochem Biophys Res Commun 196: 1208–1213, 1993

    Google Scholar 

  20. Cheung F, Siow YL, Karmin O: Inhibition by ginkgolides and bilobalide of the production of nitric oxide in macrophages (THP-1) but not in endothelial cells (HUVEC). Biochem Pharmacol 61: 503–510, 2001

    Google Scholar 

  21. Wang G, Siow YL, Karmin O: Homocysteine induces monocyte chemoattractant protein-1 expression by activating NF-kappa B in THP-1 macrophage. Am J Physiol Heart Cir Physiol 280: H2840–H2847, 2001

    Google Scholar 

  22. Kurosaka K, Watanabe N, Kabayashi Y: Production of proinflammatory cytokines by phorbol myristate acetate-treated THP-1 cells and monocyte-derived macrophages after phagocytosis of apoptotic CTLL-2 cells. J Immunol 161: 6245–6249, 1998

    Google Scholar 

  23. Wang N, Tabas I, Winchester R, Ravalli S, Rabbani LE, Tall A: Interleukin 8 is induced by cholesterol loading of macrophage and expressed by macrophage foam cells in human atheroma. J Biol Chem 271: 8837–8842, 1996

    Google Scholar 

  24. Michelakis ED, Archer SL: The measurement of NO in biological systems using chemiluminescene. In: M. Titheradge (ed.). Nitric Oxide Protocols, 1998, pp 111–127

  25. Schmidt H, Kelm M: Determination of nitrite and nitrate by the griess reaction. In: M. Feelisch, J.S. Stamler (eds.). Methods in Nitric Oxide Research, 1996, pp 491–497

  26. Bredti DS, Shmidt H: The Citrulline assay. In: M. Feelisch, J.S. Stamler (eds.). Methods in Nitric Oxide Research. J. Wiley: Chichester, New York, 1996, pp 249–255

  27. Wang G, Siow YL, Karmin O: Homocysteine stimulates nuclear factor kappa B activity and monocyte chemoattractant protein-1 expression in vascular smooth muscle cells: a possible role for protein kinase C. Biochem J 352: 817–826, 2000

    Google Scholar 

  28. Rauen U, Petrat F, Li T, De Groot H: Hypothermia injury/cold-induced apoptosis – evidence of an increase in chelatable iron causing oxidative injury in spite of low O2−/H2O2 formation. FASEB J 14: 1953–1964, 2000

    Google Scholar 

  29. Woo CW, Cheung F, Chan VW, Siow YL, Karmin O: Homocysteine stimulates inducible nitric oxide synthase expression in macrophages: antagonizing effect of ginkgolides and bilobalide. Mol Cell Biochem 243(1–2): 37–47, 2003

    Google Scholar 

  30. Komoda Y, Shimizu M, Sonoda Y, Sato Y: Ganoderic acid and its derivatives as cholesterol synthesis inhibitors. Chem Pharm Bull (Tokyo) 37(2): 531–533, 1989

    Google Scholar 

  31. Kabir Y, Kimura S, Tamura T: Dietary effect of Ganoderma lucidum mushroom on blood pressure and lipid levels in spontaneously hypertensive rats (SHR). J Nutr Sci Vitaminol (Tokyo) 34(4): 433–438, 1998

    Google Scholar 

  32. Tao J, Feng KY: Experimental and clinical studies on inhibitory effect of Ganoderma lucidum on platelet aggregation. J Tongji Med Univ 10(4): 240–243, 1990

    Google Scholar 

  33. Khatri JJ, Johnson C, Magid R, Lessner SM, Laude KM, Dikalov SI, Harrison DG, Sung HJ, Rong Y, Galis ZS: Vascular oxidant stress enhances progression and angiogenesis of experimental atheroma. Circulation 109: 520–525, 2004

    Google Scholar 

  34. Juliet PA, Hayashi T, Daigo S, Matsui-Hirai H, Miyazaki A, Fukatsu A, Funami J, Iguchi A, Ignarro LJ: Combined effect of testosterone and apocynin on nitric oxide and superoxide production in PMA-differentiated THP-1 cells. Biochim Biophys Acta 1693(3): 185–191, 2004

    Google Scholar 

  35. Begarja AA, Wu D, Serafini M, Meydani SN: Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: role of peroxynitrite. Free Radic Biol Med 32(6): 503–511, 2002

    Google Scholar 

  36. Lancel S, Tissier S, Mordon S, Marechal X, Depontieu F, Scherpereel A, Chopin C, Neviere R: Peroxynitrite decomposition catalysts prevent myocardial dysfunction and inflammation in endotoxemic rats. J Am Coll Cardiol 43(12): 2348–2358, 2004

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada

    Connie W. H. Woo, Yaw L. Siow & Karmin O

  2. National Centre for Agri-Food Research in Medicine, St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada

    Ricky Y. K. Man & Eric W. Y. Wan

  3. Department of Pharmacology, University of Hong Kong, Canada

    Yaw L. Siow & Karmin O

  4. Centre for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, Manitoba, Canada

    Yaw L. Siow & Patrick C. Choy

  5. Department of Medicine, University of Hong Kong, Canada

    Chak S. Lau

  6. Department of Animal Science, University of Manitoba, Winnipeg, Manitoba, Canada

    Karmin O

  7. Laboratory of Integrative Biology, St. Boniface Hospital Research Centre, R4032, 351 Tache Avenue, Winnipeg, Manitoba, Canada, R2H 2A6

    Karmin O

Authors
  1. Connie W. H. Woo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ricky Y. K. Man
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yaw L. Siow
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patrick C. Choy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eric W. Y. Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chak S. Lau
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Karmin O
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karmin O.

Additional information

The first two authors contributed equally to the study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Woo, C.W.H., Man, R.Y.K., Siow, Y.L. et al. Ganoderma lucidum inhibits inducible nitric oxide synthase expression in macrophages. Mol Cell Biochem 275, 165–171 (2005). https://doi.org/10.1007/s11010-005-1352-9

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-005-1352-9

Keywords

Search

Navigation