Prevention by Ginkgo biloba extract (EGb 761) and trolox C of the decrease in synaptosomal dopamine or serotonin uptake following incubation

Abstract

Prolonged incubation of synaptosomes in Krebs-Ringer oxygenated medium in the presence of ascorbic acid (10 −4M) led, after 20 min, to a decrease in [ 3H]dopamine (DA) (synaptosomes prepared from the striatum) and [ 3H]serotonin (5HT) (synaptosomes prepared from the cortex) uptake. The decrease was progressive and uptake was virtually abolished after a 60 min incubation period. A concentration-dependent (from 5 × 10 −6 M) role of ascorbic acid in the decrease of [ 3H]DA or [ 3H]5HT uptake was demonstrated. This decrease was potentiated by Fe 2+ ions and prevented by the ferrous chelating agent desferrioxamine. Thus, the progressive decrease in synaptosomal uptake of either [ 3H]DA or [ 3H]5HT could depend on the generation of free radicals by the association of ascorbic acid with Fe 2+ ions. The decrease in synaptosomal uptake was prevented, in a concentration-dependent manner, by the Ginkgo biloba extract EGb 761 (4–16 μg/mL) and the vitamin E analog trolox C (10 −4 M). The terpenic fraction of EGb 761, Bn 52063 (up to 0.5 μg/mL), did not prevent the reduction of [ 3H]amine uptake. In contrast, the flavonoidic fraction, Cp 202, was effective (from 1 μg/mL) and its efficacy was shared by the flavonoid quercetin (from 0.1 μg/mL). The prolongation of the ability of synaptosomes to take up [ 3H]amine elicited by EGb 761, in particular its flavonoidic fraction, as well as by trolox C could be due to their free radical scavenger properties.