title: Ganoderma lucidum inhibits inducible nitric oxide synthase expression in macrophages.
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 microg/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.
authors.affiliation: Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Connie W H
authors.initials: CW
authors.lastname: Woo
authors.forename: Ricky Y K
authors.initials: RY
authors.lastname: Man
authors.forename: Yaw L
authors.initials: YL
authors.lastname: Siow
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Choy
authors.forename: Eric W Y
authors.initials: EW
authors.lastname: Wan
authors.forename: Chak S
authors.initials: CS
authors.lastname: Lau
authors.forename: Karmin
authors.initials: K
authors.lastname: O
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D009566:Nitrates / Q000032:analysis / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics; D009573:Nitrites / Q000032:analysis / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020940:Reishi / Q000737:chemistry*; D013481:Superoxides / Q000032:analysis / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D009566:Nitrates; D009573:Nitrites; D010936:Plant Extracts; D012333:RNA, Messenger; D013481:Superoxides; D052247:Nitric Oxide Synthase Type II; D013755:Tetradecanoylphorbol Acetate