Effect of ginkgolide B on striatal extracellular amino acids in middle cerebral artery occluded rats

Ethnopharmacological relevanceGinkgo biloba leaves are traditionally used in China for its health-promoting properties. There is substantial experimental evidence to support the view that Ginkgo biloba extracts have neuroprotective properties under conditions such as hypoxia/ischemia.Although a number of studies have investigated that ginkgolide B, a purified terpene lactone component extracted from Ginkgo biloba leaves, is available “platelet activating factor (PAF) receptors antagonist”, “antioxidant” with a variety of actions, very little has been performed to explore the effect of ginkgolide B on extracellular amino acids in experimental animal of focal cerebral ischemia/reperfusion. In this study, the effect of ginkgolide B on the striatal extracellular levels of glutamate (Glu), aspartic acid (Asp), glycine (Gly) and γ-aminobutyric acid (GABA) was evaluated in rats undergone middle cerebral artery occlusion (MCAO) for 1 h followed by 23 h reperfusion.Materials and methodsThe Sprague-Dawley (SD) rats received intraperitoneal injections of ginkgolide B dissolved at a dose of 10 mg kg−1 d−1, 20 mg kg−1 d−1, or normal saline (NS) of same volume 3 d before the middle cerebral artery occlusion model establishment. Extracellular concentrations of glutamate, aspartic acid, glycine and GABA in striatum were monitored using in vivo microdialysis and analyzed using high-performance liquid chromatography. Excitotoxic index (EI) was calculated. Twenty-four hours after MCAO, the cerebral infarct volume was detected on 2,3,5-triphenyltetrazolium chloride-stained coronal sections.ResultsThe result showed that administration of ginkgolide B (10 or 20 mg kg−1) before ischemia reduced the ischemia-induced elevation of levels of glutamate, aspartic acid and glycine, increased the elevation of extracellular GABA, decreased the excitotoxic index and diminished the volume of cerebral infarction, although a clear concentration–response relationship was not found.ConclusionsThe present work provides the first evidence that ginkgolide B protects against cerebral ischemic injury by inhibiting excitotoxicity by modulating the imbalance of excitatory amino acids versus inhibitory amino acids, which may support the traditional use of Ginkgo biloba leaves for the treatment of stroke.

Middle cerebral artery occlusion and reperfusion-induced excitotoxicity as well as cerebral infarct in rats were significantly attenuated by pre-treatment with ginkgolide B, an active component extracted from Ginkgo biloba leaves.Figure optionsDownload as PowerPoint slide