The plant flavonoid wogonin suppresses death of activated C6 rat glial cells by inhibiting nitric oxide production.
Flavonoids are a group of low molecular weight polyphenolic compounds derived from plants. 5,7-dihydroxy-8-methoxyflavone (Wogonin), a flavonoid originated from the root of Scutellaria baicalensis Georgi, has been shown to exert various anti-inflammatory effects such as inhibition of nitric oxide (NO) and prostaglandin E2 production in macrophages. Because glial cells have been previously shown to undergo NO-dependent apoptosis upon inflammatory activation and this auto-regulatory process may be negatively affected by exogenous factors possessing anti-inflammatory activities, we examined the effects of wogonin on NO production and activation-induced cell death of C6 rat glial cells. Activation of C6 glial cells with lipopolysaccharide (LPS), interferon-gamma, and tumor necrosis factor-alpha induced NO production followed by cell death. Pretreatment of C6 cells with wogonin before LPS and cytokine treatment dose-dependently inhibited NO production as well as death of activated C6 cells. Wogonin-mediated inhibition of NO production was accompanied by suppression of inducible nitric oxide synthase (iNOS) protein induction and nuclear factor kappa B (NF-kappaB) reporter activity. Wogonin, however, did not affect a NO donor-induced cytotoxicity. Taken together, our results indicate that wogonin inhibits activation-induced death of C6 glial cells by suppressing NO production, and these inhibitory effects of wogonin on NO production are exerted through inhibition of NF-kappaB-mediated iNOS induction.
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Department of Herbal Pharmacology, Graduate School of East-West Medical Science, Kyung Hee University, Hoegi-dong, Tongdaemun-ku, 130-701, Seoul, South Korea.
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D004171:Diploidy; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; C085514:wogonin