Lu Yong-Ming, Pan Jian, Zhang Wen-Na, Hui Ai-Ling, Guo Wen-Qiang, Huang Li, Zhu Qin-Jun, Chen Yan
School of Life Sciences, Anhui University, Hefei 230601, China.
Engineering Research Center of Bio-Process, Hefei University of Technology, Ministry of Education, Hefei 230009, China.
Fitoterapia. 2015 Oct;106:110-4. doi: 10.1016/j.fitote.2015.08.012. Epub 2015 Aug 29.
Ginkgolide B, one of the important components of Ginkgo biloba extracts, has been revealed to exhibit great potential in therapy of cerebrovascular diseases. However the lack of permeability greatly limited it from further clinical application. Based on the prediction model for blood brain barrier (BBB) permeation, herein a potential brain-targeting analog ginkgolide B cinnamate (GBC) was successfully synthesized and characterized. After intravenous administration of GBC or GB, liquid chromatography tandem mass spectrometry (LC-MS/MS) was conducted to determine the analog in rat plasma and brain. The results showed that GBC had a significant increase in BBB permeability. A significant 1.61-times increase in half-life was observed for GBC and the drug targeting index (DTI) value was calculated to be 9.91. The experiment results matched well with the predicted one, which revealed that BBB permeability prediction model combined with in vivo study could be used as a quick, feasible and efficient tool for brain-targeting drug design.
银杏内酯B是银杏叶提取物的重要成分之一，已被证明在脑血管疾病治疗中具有巨大潜力。然而，其通透性不足极大地限制了它的进一步临床应用。基于血脑屏障（BBB）渗透预测模型，本文成功合成并表征了一种潜在的脑靶向类似物肉桂酸银杏内酯B（GBC）。静脉注射GBC或GB后，采用液相色谱串联质谱（LC-MS/MS）法测定大鼠血浆和脑中的类似物。结果表明，GBC的血脑屏障通透性显著增加。GBC的半衰期显著增加了1.61倍，药物靶向指数（DTI）值计算为9.91。实验结果与预测结果吻合良好，表明血脑屏障通透性预测模型与体内研究相结合可作为一种快速、可行且高效的脑靶向药物设计工具。
