Department of Pharmacology, Goethe University of Frankfurt, Germany.
J Pharm Pharm Sci. 2010;13(4):607-14. doi: 10.18433/j31c7q.
PURPOSE. Bilobalide is an active constituent of Ginkgo biloba and has shown neuroprotective effects in mice with cerebral ischemia. In the present study, we investigated brain permeability of bilobalide (i) in healthy mice and (ii) in mice before or after stroke. METHODS. We have used in vivo microdialysis and LC-MS to estimate extracellular levels of bilobalide. 10 mg/kg of bilobalide was given by i.p. injection to control mice, and 60 minutes before and after middle cerebral artery occlusion (MCAO). RESULTS. Bilobalide was already detectable in brain striatal microdialysates 10 min after i.p. administration and reached maximum levels (19 ng/mL, corresponding to 0.92 µM) after 40 min. Maximum plasma bilobalide levels were 5.9 µM. After an ischemic insult, the drug could be dialysed with similar efficiency as in control mice indicating slow elimination from the ischemic brain. When the drug was given after MCAO, availability in the brain was low, but measurable, at approx. 10% of control values. CONCLUSIONS. Our data demonstrate that bilobalide easily crosses the blood brain barrier and reaches extracellular concentrations in the brain that allow efficient interaction with target molecules such as neurotransmitter receptors. Availability of the drug in ischemic tissue is high when given before ischemia, but severely limited after MCAO.
目的。银杏内酯是银杏叶的一种活性成分，已显示出对脑缺血小鼠的神经保护作用。在本研究中，我们研究了银杏内酯（i）在健康小鼠和（ii）在中风前或中风后的脑通透性。
方法。我们使用体内微透析和 LC-MS 来估计银杏内酯的细胞外水平。通过腹腔注射给予 10 mg/kg 的银杏内酯给对照组小鼠，在大脑中动脉闭塞（MCAO）前 60 分钟和后。
结果。银杏内酯在腹腔给药后 10 分钟即可在纹状体微透析液中检测到，并在 40 分钟后达到最大水平（19 ng/mL，对应于 0.92 µM）。最大血浆银杏内酯水平为 5.9 µM。在缺血性损伤后，药物可以以与对照小鼠相似的效率被透析出来，表明其从缺血性大脑中缓慢消除。当药物在 MCAO 后给予时，大脑中的可用性较低，但可测量，约为对照值的 10%。
结论。我们的数据表明，银杏内酯很容易穿过血脑屏障，并达到大脑中的细胞外浓度，从而允许与神经递质受体等靶分子进行有效相互作用。在给予缺血前，药物在缺血组织中的可用性较高，但在 MCAO 后严重受限。
