Brochet D, Chermat R, DeFeudis F V, Drieu K
Psypharm SA, Route de Port Brillet, La Brulatte, France.
Gen Pharmacol. 1999 Sep;33(3):249-56. doi: 10.1016/s0306-3623(99)00018-x.
A mouse model of barbital-induced narcosis was used to examine the effects of single intraperitoneal injections of an extract of Ginkgo biloba (EGb 761), an extract devoid of terpene trilactones (CP 205), and three terpene trilactone constituents of the extract (ginkgolides A and B, bilobalide). Administration of sodium barbital (180 mg/kg, IP) to the mice caused narcosis, measured as a loss in righting reflex. Single injections of EGb 761 (25 and 50 mg/kg), given 60 min prior to sodium barbital, significantly shortened barbital-induced sleeping time, whereas these same doses of CP 205 were ineffective. Single injections of ginkgolide B (1 mg/kg) and bilobalide (2 and 5 mg/kg) significantly shortened sleeping time, whereas ginkgolide A was ineffective. The effects of ginkgolide B and bilobalide were reflected as increases in latency to onset of sleep and those of EGb 761, ginkgolide B, and bilobalide were correlated with decreases in the number of mice that slept. At the behavioral level, these potent in vivo effects of EGb 761, ginkgolide B, and bilobalide resemble those of certain antidepressants. At the molecular level, it is hypothesized that interactions with the picrotoxinin/TBPT site of GABA-regulated Cl- channels of the CNS may be involved. This information appears useful in explaining the clinically observed "vigilance-enhancing" and "antidepressant-like" actions of EGb 761.
采用巴比妥诱导麻醉的小鼠模型，研究单次腹腔注射银杏叶提取物（EGb 761）、不含萜类三内酯的提取物（CP 205）以及该提取物的三种萜类三内酯成分（银杏内酯A和B、白果内酯）的效果。给小鼠腹腔注射戊巴比妥钠（180 mg/kg）可导致麻醉，以翻正反射消失来衡量。在戊巴比妥钠给药前60分钟单次注射EGb 761（25和50 mg/kg）可显著缩短巴比妥诱导的睡眠时间，而相同剂量的CP 205则无效。单次注射银杏内酯B（1 mg/kg）和白果内酯（2和5 mg/kg）可显著缩短睡眠时间，而银杏内酯A无效。银杏内酯B和白果内酯的作用表现为睡眠开始潜伏期延长，EGb 761、银杏内酯B和白果内酯的作用与睡眠小鼠数量减少相关。在行为水平上，EGb 761、银杏内酯B和白果内酯在体内的这些显著作用类似于某些抗抑郁药。在分子水平上，据推测可能涉及与中枢神经系统GABA调节的Cl-通道的印防己毒素/TBPT位点的相互作用。这些信息似乎有助于解释临床上观察到的EGb 761的“增强警觉”和“类抗抑郁”作用。
