Ginkgo biloba and Nitric Oxide

NO is a neuronal messenger molecule whose overproduction can initiate neurotoxic events under pathological conditions. NO production has clearly been linked to neurodegeneration in animal models of ischemia and in vitro cultured cells. The final cellular pathways that lead from 

Ginko biloba reduces the formation of nitric oxide and peroxynitrite Metallothionein 

The precise mechanisms underlying the neuroprotective effects of EGb 761, particularly with respect to ischemia, have yet to be clearly established, but they have been reported to be associated with either its terpenoid or its flavonoid fractions. The present evidence indicates that EGb 761, 

The production of superoxide anions is one of the major factors involved in NO toxicity because superoxide anions can react with NO to form the highly toxic free-radical peroxynitrite. A pivotal role for superoxide anions in NO-related insults is emphasized by results showing that transgenic mice overexpressing superoxide dismutase (SOD) are resistant to brain ischemia. Superoxide can protect against SNP-induced toxicity. Thus, the superoxide-scavenging properties of EGb 761 are likely to explain, at least in part, its ability to block cell death and the increase in reactive oxygen species accumulation induced by the two NO donors used here, SNP and SIN-1. 

EGb 761 might also directly scavenge peroxynitrites and inhibit lipid peroxidation because it has been reported both to block the cytotoxicity induced by peroxynitrites and inhibit cyclosporine-A-induced peroxidation. This hypothesis is supported by the finding that the purported anti-ischemic agent ebselen completely protected and rescued hippocampal cells against SNP-induced toxicity. In contrast, the hydroxyl radical scavenging properties of EGb 761 do not seem able to account for its protective effects because catalase failed to display any neuroprotective properties in this model. 

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