[6]-Gingerol inhibits nitric oxide synthesis in activated J774.1 mouse macrophages and prevents peroxynitrite-induced oxidation and nitration reactions.
Reactive nitrogen species (RNS), such as nitric oxide (NO) and its derivatives, e.g. peroxynitrite (ONOO-), have been proposed as being able to influence signal transduction and cause DNA damage, contributing to carcinogenic processes. In this study, the effect of [6]-gingerol, a pungent phenolic compound present in ginger (Zingiber officinale Roscoe), on NO synthesis in lipopolysaccharide (LPS)-activated J774.1 macrophages was tested, and the protective ability of this compound against peroxynitrite-mediated oxidation and nitration reactions were evaluated. [6]-Gingerol exhibited dose-dependent inhibition of NO production and significant reduction of inducible NO synthase (iNOS) in LPS-stimulated J774.1 cells. Moreover, [6]-gingerol effectively suppressed peroxynitrite-induced oxidation of dichlorodihydrofluorescein, oxidative single strand breaks in supercoiled pTZ 18U plasmid DNA, and formation of 3-nitrotyrosine in bovine serum albumin (BSA) and J774.1 cells. Our results indicate that [6]-gingerol is a potent inhibitor of NO synthesis and also an effective protector against peroxynitrite-mediated damage.
Ippoushi
Katsunari
K
National Institute of Vegetable and Tea Science, National Agricultural Research Organization, Ano, Mie 514-2392, Japan. ippoushi@affrc.go.jp
Azuma
Keiko
K
Ito
Hidekazu
H
Horie
Hideki
H
Higashio
Hisao
H
D000818:Animals; D002396:Catechols; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005233:Fatty Alcohols / Q000494:pharmacology*; D005452:Fluoresceins / Q000378:metabolism; D020939:Zingiber officinale; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000494:pharmacology
D002396:Catechols; D005233:Fatty Alcohols; D005452:Fluoresceins; D008070:Lipopolysaccharides; C065013:2',7'-dichlorodihydrofluorescein; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C007845:gingerol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse