The present study investigated the effects of gossypin, 3,3',4',5,7,8-hexahydroxyflavone 8-glucoside, on the toxicity induced by oxidative stress or beta-amyloid (Abeta) in primary cultured rat cortical cells. The antioxidant properties of gossypin were also evaluated by cell-free assays. Gossypin was found to inhibit the oxidative neuronal damage induced by xanthine/xanthine oxidase or by a glutathione depleting agent, D,L-buthionine (S,R)-sulfoximine. In addition, gossypin significantly attenuated the neurotoxicity induced by Abeta(25-35). Furthermore, gossypin dramatically inhibited lipid peroxidation initiated by Fe2+ and ascorbic acid in rat brain homogenates. It also exhibited potent radical scavenging activity generated from 1,1-diphenyl-2-picrylhydrazyl. These results indicate that gossypin exerts neuroprotective effects in the cultured cortical cells by inhibiting oxidative stress- and Abeta-induced toxicity, and that the antioxidant properties of gossypin may contribute to its neuroprotective actions.