Pii: S0304-3940(01)02028-6

Flavonoids are a group of low molecular weight polyphenolic compounds derived from plants. 5,7-dihydroxy-8methoxy ̄avone (Wogonin), a ̄avonoid originated from the root of Scutellaria baicalensis Georgi, has been shown to exert various anti-in ̄ammatory 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 in ̄ammatory activation and this auto-regulatory process may be negatively affected by exogenous factors possessing anti-in ̄ammatory 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-g, and tumor necrosis factor-a induced NO production followed by cell death. Pretreatment of C6 cells with wogonin before LPS and cytokine treatment dosedependently 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-kB) 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-kB-mediated iNOS induction. q 2001 Elsevier Science Ireland Ltd. All rights reserved.