Neuroprotective abilities of resveratrol and other red wine constituents against nitric oxide-related toxicity in cultured hippocampal neurons

1 Animal and epidemiological studies suggest that polyphenol constituents o f red wine possess antioxidant activities that favour protection against ca rdiovascular disease - the so-called. 'French paradox' - and possibly, cent ral nervous system disorders such as Alzheimer's disease (AD) and ischaemia . 2 In the present study, the potential of three major red wine derived-polyp henols to protect against toxicity induced by the nitric oxide free radical donors sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1) was examined in cultured rat hippocampal cells. 3 Both co- and post-treatments with either the stilbene resveratrol (5-25 m uM) or the flavonoids quercetin (5-25 muM) and (+)-catechin (1-10 muM) were capable of attenuating hippocampal cell death and intracellular reactive o xygen species accumulation produced by SNP (100 muM and 1 mM, respectively) . However, among the phenolic compounds tested, only the flavonoids afforde d significant protection against 5 mM SIN-1-induced toxicity. 4 The effects of phenolic constituents were shared by Trolox (100 muM), a v itamin E analogue, but not by selective inhibitors of cyclo-oxygenases (COX ) and lipoxygenases (LOX). 5 Among the phenolic compounds tested, only quercetin (10 muM) inhibited 10 0 muM SNP-stimulated protein kinase C (PKC) activation, whereas none of the m were able to attenuate nitrite accumulation caused by SNP (100 muM). 6 Taken together, these data suggest that the neuroprotective abilities of quercetin, resveratrol, and (+)-catechin result from their antioxidant prop erties rather than their purported inhibitory effects on intracellular enzy mes such as COX, LOX, or nitric oxide synthase. Quercetin, however, may als o act via PKC to produce its protective effects.