An anxiolytic-like effect of Ginkgo biloba extract and its constituent, ginkgolide-A, in mice.
The anxiolytic-like effects of Ginkgo biloba extract (GBE) and its four terpenoid components (ginkgolide-A, ginkgolide-B, ginkgolide-C, and bilobalide) were assessed using the elevated plus-maze test in mice. Administration of GBE as a single oral dose (0.5 or 1 g/kg, po) caused a state of suppressed motor activity and, thus, shortened the time spent in the open-sided arms. However, when GBE (0.063-1 g/kg, po) was administered daily for 7 days and the plus-maze test was carried out 24 h after the final administration, the time spent in the open-sided arms was prolonged, with the peak anxiolytic-like effect at 0.125 g/kg. A combination of seven-day administration of GBE (0.125 g/kg) and a single dose of diazepam (1 mg/ kg, po, 10 min before testing) enhanced the anxiolytic-like effect. Flumazenil (0.3 mg/kg, ip, 10 min before testing) blocked the effect of diazepam, but not of GBE. Daily administration of ginkgolide-A (1 or 2 mg/kg, po) resulted in an anxiolytic-like effect by the third treatment, with the maximal effect observed after the fifth administration. Neither ginkgolide-B, ginkgolide-C, nor bilobalide produced any anxiolytic-like effects. At doses higher than 0.5 g/kg, GBE not only inhibited motor activity but also suppressed active avoidance behavior, reduced caffeine-induced stimulation, and enhanced pentobarbital-induced sleep, while ginkgolide-A (up to 20 mg/kg) did not exhibit these effects. Diazepam (1 mg/kg) is known to enhance pentobarbital-induced sleep. These results suggest that GBE produces a significant anxiolytic-like effect following repeated administration and that ginkgolide-A is most likely responsible for this effect. There are also indications that although GBE exerts a sedative effect at comparatively higher doses, ginkgolide-A has a relatively weak tendency to produce benzodiazepine-like side effects.
Center for Cooperative Research, Medical Division, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Hisashi
H
Kuribara
Susan T
ST
Weintraub
Tatsumi
T
Yoshihama
Yuji
Y
Maruyama
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology; D020441:Ginkgo biloba / Q000737:chemistry*; D046934:Ginkgolides; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D012890:Sleep / Q000187:drug effects
D014151:Anti-Anxiety Agents; D003517:Cyclopentanes; D004224:Diterpenes; D005663:Furans; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D001569:Benzodiazepines; C058295:ginkgolide C; D002110:Caffeine; C045856:ginkgolide B; C073710:bilobalide; D003975:Diazepam; C477042:ginkgolide A; D010634:Phenobarbital