Article

Molecular and Cellular Biochemistry

, Volume 275, Issue 1, pp 165-171

Ganoderma lucidum inhibits inducible nitric oxide synthase expression in macrophages

  • Connie W. H. WooAffiliated withDepartment of Physiology, University of Manitoba
  • , Ricky Y. K. ManAffiliated withNational Centre for Agri-Food Research in Medicine, St. Boniface Hospital Research Centre, University of Manitoba
  • , Yaw L. SiowAffiliated withDepartment of Physiology, University of ManitobaDepartment of Pharmacology, University of Hong KongCentre for Research and Treatment of Atherosclerosis, University of Manitoba
  • , Patrick C. ChoyAffiliated withCentre for Research and Treatment of Atherosclerosis, University of Manitoba
  • , Eric W. Y. WanAffiliated withNational Centre for Agri-Food Research in Medicine, St. Boniface Hospital Research Centre, University of Manitoba
  • , Chak S. LauAffiliated withDepartment of Medicine, University of Hong Kong
  • , Karmin OAffiliated withDepartment of Physiology, University of ManitobaDepartment of Pharmacology, University of Hong KongDepartment of Animal Science, University of ManitobaLaboratory of Integrative Biology, St. Boniface Hospital Research Centre Email author 

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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.

Keywords

herbal medicine inducible nitric oxide synthase nitric oxide oxidative stress