Blood brain barrier permeability and therapeutic time window of Ginkgolide B in ischemia-reperfusion injury

被引:66
作者
Fang, Weirong [1 ]
Deng, Yan [1 ]
Li, Yunman [1 ]
Shang, Erxin [2 ]
Fang, Fang [1 ]
Lv, Peng [1 ]
Bai, Li [1 ]
Qi, Yan [1 ]
Yan, Fang [3 ]
Mao, Lishun [4 ]
机构
[1] China Pharmaceut Univ, Dept Physiol, Nanjing 210009, Jiangsu, Peoples R China
[2] Nanjing Univ Chinese Med, Jiangsa Key Lab TCM Formulae Res, Nanjing 210046, Peoples R China
[3] China Pharmaceut Univ, Dept Pharmaceut Anal, Nanjing 210009, Jiangsu, Peoples R China
[4] Jiangsu Kefeiping Pharmaceut Co Ltd, Nanjing 210016, Peoples R China
关键词
Ginkgolide B; Blood brain barrier; Middle cerebral artery occlusion; LC-MS/MS; Therapeutic time window; FOCAL CEREBRAL-ISCHEMIA; TANDEM MASS-SPECTROMETRY; ARTERY OCCLUSION; BILOBA EXTRACT; IN-VITRO; RATS; STROKE; VIVO; NEUROPROTECTION; INHIBITION;
D O I
10.1016/j.ejps.2009.10.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The goal of this study was to estimate the blood brain barrier (BBB) permeability of Ginkgolide B in normal condition and models of ischemia both in vivo and in vitro. A sensitive LC-MS/MS analytical method was developed to determinate accurately the concentration of Ginkgolide B in cell, plasma and brain tissue. The injured rat brain microvessel endothelial cells (RBMECs) induced by Na2S2O4 served as a hypoxia/reoxygenation model in vitro. Intracellular concentration of Ginkgolide B increased in injured cells in a concentration-dependent manner. As a model of in vivo-ischemia/reperfusion, we performed middle cerebral artery occlusion (MCAC)in rats. Concentration of Ginkgolide B in the brain tissues showed higher in cerebral ischemia-reperfused animals than that in normal rats. To evaluate potential clinical effect of Ginkgolide B, we determined therapeutic time window in MCAO rats. Up to i.v. administration at 2 h after reperfusion of rats, Ginkgolide B Could decrease infarction volume and brain edema, exerting significant protective effect in cerebral ischemia injury. In conclusion, Ginkgolide B could pass through BBB, especially after ischemia-reperfusion injury of brain, and might be therapeutically effective for ischemia/reperfusion injury of human brain. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:8 / 14
页数:7
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