Coumarin derivatives protect against ischemic brain injury in rats
Coumarin derivatives protect against ischemic brain injury in rats
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DOI：
10.1016/j.ejmech.2013.04.015
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发表时间：
2013-09-01
影响因子：
6.7
通讯作者：
Liu, Gang
中科院分区：
文献类型：
--
作者：
Sun, Mingna;Hu, Jinfeng;Liu, Gang
神经保护策略在缺血性脑损伤的治疗中具有重要意义。对我们的现货香豆素衍生物进行筛选，确定化合物1具有神经保护活性。随后，进行了结构优化，最终发现了有效化合物20。该化合物显著减轻了体外培养的大鼠肾上腺嗜铬细胞瘤细胞系因缺氧缺糖而造成的损伤。此外，化合物20对大脑中动脉闭塞大鼠有明显的神经保护作用，可减少脑梗塞面积和脑含水量，改善神经功能，抑制大脑皮质和海马区神经元丢失和神经病理改变。药代动力学研究表明，化合物20具有透过大鼠血脑屏障的作用。(C)2013年爱思唯尔·马森公司。版权所有。
Neuroprotection strategies are of great importance in the treatment of ischemic brain injury. Screening of our in-stock coumarin derivatives identified compound 1 as exhibiting neuroprotective activity. Subsequently, a structural optimization was carried out, which led to the discovery of the potent compound 20. This compound significantly attenuated the damage in a cell line derived from a pheochromocytoma of the rat adrenal medulla induced by oxygen glucose deprivation in vitro. Furthermore, compound 20 exhibited clear neuroprotection in middle cerebral artery occlusion rats by reducing infarct size and brain-water content, improving neurological function, and suppressing neuronal loss and neuropathological changes in the cortex and hippocampus. Pharmacokinetic evaluation indicated that compound 20 could penetrate the blood brain barrier of rats. (C) 2013 Elsevier Masson SAS. All rights reserved.