Neuroprotective effects of Ginkgo biloba constituents

Abstract

The neuroprotective effects of Ginkgo biloba extract (EGb 761) and some of its constituents were tested by using the mouse and the rat model of focal cerebral ischemia, the rat model of global cerebral ischemia and primary cultures of neurons obtained from newborn rat hippocampi and chick embryo telencephalic hemispheres. In the models of focal ischemia, 2 days after occlusion of the middle cerebral artery the infarct area on the mouse brain surface and the infarct volume of the rat brain were measured. The infarct area on the mouse brain was dose-dependently (5–20 mg/kg, s.c.) reduced by bilobalide administered 60 min before ischemia. When administered immediately after ischemia, 10 mg/kg bilobalide also diminished the infarct area. The same dose of bilobalide administered to rats 60 min before occluding the middle cerebral artery reduced the cortical and the total infarct volume significantly. Ginkgolide A (50 mg/kg, s.c.) and ginkgolide B (100 mg/kg, s.c.) also had cerebroprotective effects in the mouse model of focal cerebral ischemia, but ginkgolides C and J did not. EGb 761 (2 × 100 mg/kg,i.v.) increased the cerebral blood flow after 10 min of global ischemia in rats but neuroprotection was not demonstrable. Ginkgolide B (1 μM) and bilobalide (10 μM) were shown to protect cultured rat hippocampal neurons against damage caused by glutamate. Bilobalide (0.1 μM) also enhanced the percentage of viable neurons in primary cultures from chick embryo hemispheres when damaged with 1 mM cyanide. The results demonstrate different types of neuroprotective and cerebrovascular effects of the Ginkgo biloba extract and some of its constituents.