Cardioprotective and anti-oxidant effects of the terpenoid constituents of Ginkgo biloba extract (EGb 761).
Hemodynamic and electron spin resonance analyses were used to assess the in vivo and in vitro cardioprotective and antioxidant effects of therapeutically relevant doses of Ginkgo biloba extract (EGb 761) and its terpenoid constituents (ginkgolides A and B, bilobalide) in the rat. Significant anti-ischemic effects, indicating improved myocardial functional recovery, were observed after repeated (15-day) oral treatments 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 hearts in the presence of the ginkgolides A and B (both at 0.05 microgram/ml) or bilobalide (0.15 microgram/ml), but not EGb 761 (5 micrograms/ml), significantly improved all hemodynamic parameters. Post-ischemic levels of the 5,5-dimethyl-1-pyrroline N-oxide (DMPO)/hydroxyl radical spin-adduct (DMPO-OH) in coronary effluents were significantly decreased after in vivo oral treatments or after in vitro perfusion with EGb 761 or the terpenes, the most effective compound being ginkgolide A. As the presence of the terpenes did not influence the formation of the superoxide/DMPO adduct or DMPO-OH in acellular tests with superoxide and hydroxyl radical generators, their cardioprotective effects appear to involve an inhibition of free radical formation rather than direct free radical scavenging.
Pietri
S
S
Unité Mixte de Recherche 6517 du Centre National de la Recherche Scientifique, Université d'Aix-Marseille I, Marseille, France.
Maurelli
E
E
Drieu
K
K
Culcasi
M
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D005343:Fibrinolytic Agents / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology; D020441:Ginkgo biloba; D046934:Ginkgolides; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007783:Lactones / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy; D010477:Perfusion; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000494:pharmacology*; D000096983:Ginkgo Extract
D000975:Antioxidants; D003497:Cyclic N-Oxides; D003517:Cyclopentanes; D004224:Diterpenes; D005343:Fibrinolytic Agents; D016166:Free Radical Scavengers; D005663:Furans; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D013729:Terpenes; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C069977:2,2-dimethyl-5-hydroxy-1-pyrrolidinyloxy; C045856:ginkgolide B; C073710:bilobalide