CARDIOPROTECTIVE AND ANTIOXIDANT EFFECTS OF THE TERPENOID CONSTITUENTS OF GINKGO-BILOBA EXTRACT (EGB-761)

Hemodynamic and electron spin resonance analyses were used to assess t he in vivo and in vitro cardioprotective and antioxidant effects of th erapeutically relevant doses of Ginkgo biloba extract (EGb 761) and it s terpenoid constituents (ginkgolides A and B, bilobalide) in the rat. Significant anti-ischemic effects, indicating improved myocardial fun ctional recovery, were observed after repeated (15-day) oral treatment s with both EGb 761 (60 mg/kg/day) and ginkgolide A (4 mg/kg/day), as compared to placebo. In vitro pre- and post-ischemic perfusion of hear ts in the presence of the ginkgolides A and B (both at 0.05 mu g/ml) o r bilobalide (0.15 mu g/ml), but not Ebb 761 (5 mu g/ml), significantl y improved all hemodynamic parameters. Post-ischemic levels of the 5,5 -dimethyl-1-pyrroline N-oxide (DMPO)/hydroxyl radical spin-adduct (DMP G-OH) in coronary effluents were Significantly decreased after in vivo oral treatments or after in vitro perfusion with EGb 761 or the terpe nes, the most effective compound being ginkgolide A. As the presence o f the terpenes did not influence the formation of the superoxide/DMPO adduct or DMPG-OH in acellular tests with superoxide and hydroxyl radi cal generators, their cardioprotective effects appear to involve an in hibition of free radical formation rather than direct free radical sca venging. (C) 1997 Academic Press Limited.