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標題: Inhibition of nitric oxide production by quercetin in endotoxin/cytokine-stimulated microglia
作者: Kao, T.K.
Ou, Y.C.
Raung, S.L.
Lai, C.Y.
Liao, S.L.
Chen, C.J.
關鍵字: Flavonoid;Lipid raft;Microglia;Nitric oxide;Quercetin;kappa-b kinase;necrosis-factor-alpha;inflammatory responses;signal-transduction;cerebral-ischemia;oxidative stress;interferon-gamma;gene-expression;lipid rafts;flavonoids
Project: Life Sciences
期刊/報告no:: Life Sciences, Volume 86, Issue 9-10, Page(s) 315-321.
Aims: Flavonoids possess several biological and pharmacological activities. Quercetin, a naturally occurring flavonoid, has been shown to down-regulate inflammatory responses and provide neuroprotection. However, the mechanisms underlying the anti-inflammatory properties of quercetin are poorly understood. In the present study, we investigated the modulatory effect of quercetin against neuroinflammation. Main methods: We herein describe a potential regulatory mechanism by which quercetin suppresses nitric oxide (NO) production by lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-stimulated BV-2 microglial cells. The underlying regulatory cascades were approached by biochemical and pharmacological strategies. Key findings: Quercetin produced an inhibitory effect on inducible nitric oxide synthase (iNOS) expression and NO production. Biochemical studies revealed that the anti-inflammatory effect of quercetin was accompanied by the down-regulation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, Akt, Src, Janus kinase-1, Tyk2, signal transducer and activator of transcription-1, and NF-kappa B. In addition, quercetin scavenged free radicals and produced inhibitory effects on serine/threonine and tyrosine phosphatase activities. Intriguingly, the accumulation of lipid rafts, which is the critical step for signaling, was disrupted by quercetin. Significance: The data indicate that the anti-inflammatory action of quercetin may be attributable to its raft disrupting and anti-oxidant effects. These distinct mechanisms work in synergy to down-regulate iNOS expression and NO production. (C) 2010 Elsevier Inc. All rights reserved.
ISSN: 0024-3205
DOI: 10.1016/j.lfs.2009.12.014
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