Schwarzkopf T M, Hagl S, Eckert G P, Klein J
Pharmakologisches Institut für Naturwissenschaftler, Goethe Universittit Frankfurt am Main, Germany.
Pharmazie. 2013 Jul;68(7):584-9.
Bilobalide, an active constituent of Ginkgo biloba, is known to have neuroprotective properties, but its mode of action remains unclear. In this study, bilobalide significantly reduced brain damage in mice (indicated by TTC staining) when given before transient middle cerebral artery occlusion (tMCAO). As measured by microdialysis in the ischemic striatum, local perfusion with bilobalide (10 microM) reduced ischemia-induced glutamate release by 70% while glucose levels were not affected. Mitochondria isolated from ischemic brain showed a decrease of respiration compared to non-ischemic controls. Treatment with bilobalide (10 mg/kg) before tMCAO improved respiratory capacity of complex I significantly when measured ex vivo. In addition, mitochondrial swelling induced ex vivo by calcium was used to estimate opening of the mitochondrial permeability transition pore. In this assay, the changes induced by tMCAO were completely reversed when mice had received pretreatment with bilobalide. We conclude that neuroprotection by bilobalide involves a mechanism in which the drug reverses ischemia-induced changes in mitochondria, leading to a reduction of glutamate release.
白果内酯是银杏叶的一种活性成分，已知具有神经保护特性，但其作用方式尚不清楚。在本研究中，白果内酯在短暂性大脑中动脉闭塞（tMCAO）前给药时，能显著减少小鼠的脑损伤（通过TTC染色显示）。通过对缺血纹状体进行微透析测量，用白果内酯（10微摩尔）局部灌注可使缺血诱导的谷氨酸释放减少70%，而葡萄糖水平不受影响。与非缺血对照组相比，从缺血脑中分离出的线粒体显示呼吸作用降低。在tMCAO前用白果内酯（10毫克/千克）治疗，离体测量时可显著改善复合体I的呼吸能力。此外，用钙在离体条件下诱导线粒体肿胀来评估线粒体通透性转换孔的开放情况。在该试验中，当小鼠接受白果内酯预处理时，tMCAO诱导的变化完全逆转。我们得出结论，白果内酯的神经保护作用涉及一种机制，即该药物可逆转缺血诱导的线粒体变化，从而减少谷氨酸释放。
