Inhibition of nitric oxide production by quercetin in endotoxin/cytokine-stimulated microglia.
OBJECTIVE
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.


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.


RESULTS
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-kappaB. 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.


CONCLUSIONS
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.
Kao
Tsung-Kuei
TK
Department of Nursing, Tajen University, Pingtung 907, Taiwan.
Ou
Yen-Chuan
YC
Raung
Shue-Ling
SL
Lai
Ching-Yi
CY
Liao
Su-Lan
SL
Chen
Chun-Jung
CJ
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D011794:Quercetin / Q000494:pharmacology*
D016207:Cytokines; D004731:Endotoxins; D009569:Nitric Oxide; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II