An anxiolytic-like effect of Ginkgo biloba extract and its constituent, ginkgolide-A, in mice

J Nat Prod. 2003 Oct;66(10):1333-7. doi: 10.1021/np030122f.


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.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / administration & dosage
  • Anti-Anxiety Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Benzodiazepines
  • Caffeine / administration & dosage
  • Caffeine / pharmacology
  • Cyclopentanes / pharmacology
  • Diazepam / pharmacology
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification*
  • Diterpenes / pharmacology
  • Dose-Response Relationship, Drug
  • Furans / pharmacology
  • Ginkgo biloba / chemistry*
  • Ginkgolides
  • Lactones / chemistry
  • Lactones / isolation & purification*
  • Lactones / pharmacology
  • Male
  • Maze Learning / drug effects*
  • Mice
  • Mice, Inbred Strains
  • Molecular Structure
  • Motor Activity / drug effects
  • Phenobarbital / pharmacology
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Plants, Medicinal / chemistry*
  • Sleep / drug effects


  • Anti-Anxiety Agents
  • Cyclopentanes
  • Diterpenes
  • Furans
  • Ginkgolides
  • Lactones
  • Plant Extracts
  • Benzodiazepines
  • ginkgolide C
  • Caffeine
  • ginkgolide B
  • bilobalide
  • Diazepam
  • ginkgolide A
  • Phenobarbital