Prevention by Ginkgo biloba extract (EGb 761) and trolox C of the decrease in synaptosomal dopamine or serotonin uptake following incubation.
Prolonged incubation of synaptosomes in Krebs-Ringer oxygenated medium in the presence of ascorbic acid (10(-4) M) 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 x 10(-6) M) role of ascorbic acid in the decrease of [3H]DA or [3H]5HT uptake was demonstrated. This decrease was potentiated by Fe2+ 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 Fe2+ ions. The decrease in synaptosomal uptake was prevented, in a concentration-dependent manner, by the Ginkgo biloba extract EGb 761 (4-16 micrograms/mL) and the vitamin E analog trolox C (10(-4) M). The terpenic fraction of EGb 761, Bn 52063 (up to 0.5 microgram/mL), did not prevent the reduction of [3H]amine uptake. In contrast, the flavonoidic fraction, Cp 202, was effective (from 1 microgram/mL) and its efficacy was shared by the flavonoid quercetin (from 0.1 microgram/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.
Ramassamy
C
C
Unité de Neuropsychopharmacologie Expérimentale, U.R.A. 1170 du C.N.R.S., Faculté de Médecine et Pharmacie de Rouen, Saint-Etienne du Rouvray, France.
Naudin
B
B
Christen
Y
Y
Clostre
F
F
Costentin
J
J
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D020441:Ginkgo biloba; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium; D000096983:Ginkgo Extract
D001205:Ascorbic Acid; D002839:Chromans; D003676:Deferoxamine; D004298:Dopamine; D010936:Plant Extracts; D011794:Quercetin; D012701:Serotonin; D014316:Tritium; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid