An Anxiolytic-Like Effect ofGinkgo bilobaExtract and Its Constituent, Ginkgolide-A, in Mice

Abstract

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.

Chronic administration of a Ginkgo biloba leaf extract facilitates acquisition but not performance of a working memory task

“…It is noteworthy that the highest doses tested here (25 mg/kg) significantly increased the time required to complete the maze, suggesting that some non-memorial effects may occur following high dose parenteral Ginkgo administration. Suppression of motor activity by a single oral dose of G. biloba extract (500 and 1,000 mg/kg but not 250 mg/kg) have also been reported elsewhere (Kuribara et al 2003).…”

GABA‐modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence

“…In anxiety rodent models, ginkgolides A, B, C, and bilobalide (individually and combined) were tested using the EPM paradigm with mice (Kuribara, Weintraub, Yoshihama, & Maruyama, ). The study found significant dose‐dependent relationships between ginkgolide A with reductions in anxiety (i.e., increased open arm time).…”

Prescriptions of Chinese Herbal Medicines for Insomnia in Taiwan during 2002

“…Several individual Chinese herbs not included in our top 10 commonly used regimens are still used for the treatment of insomnia in clinical practice. Some of these Chinese herbs have been reported to have anxiolytic-like effects, including Corydalis turtschaninovii (Yan-hu-suo) [43], Ginkgo biloba (Bai-guo) [44], Gardenia jasminoides (Zhi-zi) [45], and Gastrodia elata (Tian-ma) [46]. Others have been reported to have hypnotic effects, such as Stephania tetrandra (Fang-ji) [28].…”