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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Inhibition of platelet activating factor (PAF)-induced aggregation of human thrombocytes by ginkgolides: considerations on possible bleeding complications after oral intake of Ginkgo biloba extracts.

The special Ginkgo biloba leaf extract EGb 761 is marketed for more then two decades. During this time its therapeutic efficacy and favorable safety profile have been proven in numerous clinical trails as well as by postmarketing surveillance in accordance with German drug regulations. During recent years, however, several cases of hemorrhage have been reported to occur in coincidence with the use of Ginkgo products. Although a clear causality between Ginkgo intake and bleeding could not be established, these observations have generally been explained by the platelet-activating factor (PAF)-antagonistic action of ginkgolides, which represent characteristic constituents of Ginkgo extracts. PAF was originally characterized by inducing aggregation and secretion of serotonin and histamine from rabbit platelets. We now confirmed that induction of aggregation of human platelets by PAF requires at least 200 times higher concentration when compared to rabbit cells. Under the chosen experimental conditions, PAF-mediated aggregation of human platelets was half-maximally inhibited by ginkgolide B, A, C and J at concentrations of 2.5, 15.8, 29.8 and 43.5 microg/ml, respectively. These concentrations are generally more than 100 times higher as the peak plasma values measured after oral intake of EGb 761 at recommended doses between 120 and 240 mg. As PAF is a 'weak' platelet activator, which does not appear to be of importance for primary hemostasis, our results rise serious doubts that the PAF antagonistic effect of ginkgolides could be responsible for hemorrhage in patients taking EGb 761.[1]


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