School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, China.
College of Medicine, Southwest Jiaotong University, Chengdu, China.
Pharmacology. 2019;104(5-6):320-331. doi: 10.1159/000502401. Epub 2019 Aug 30.
Cerebral ischemia/reperfusion (I/R) injury causes a larger population of disable patients and deaths annually. Three Tibetan prescriptions have been applied in alleviating the I/R injury for a 1,000 years. Interestingly, ellagic acid (EA) is one of the commonly dominated phytochemicals in these 3 prescriptions. Therefore, it is noteworthy to evaluate the association between the pharmacodynamics effects of EA and I/R injury alleviation. In this study, we reveal that the EA can effectively reduce the infarction area, and prevent the neuron from apoptosis and damage in permanent middle cerebral artery occlusion rat model. The results of the histopathological study indicate that alleviation of brain damage is positively correlated with the EA dose. Further by biochemical analysis, it indicates that the EA can alleviate the brain damage by the anti-inflammatory and anti-oxidative response mediated by EA. The upregulation of zonula occludens-1 and down-regulation of Aquaporin 4 and matrix metalloprotein 9 (MMP-9) in injured brain tissues after being treated with EA suggested that the reconstruction of brain-blood-barrier (BBB), which can further prevent the brain from further injury by the other xenobiotics. In addition, EA will not activate the coagulation factors XII to induce coagulation formation during the treatment process. Therefore, EA is a promising candidate oral drug for I/R injury therapy.
脑缺血/再灌注(I/R)损伤每年导致大量残疾患者和死亡。三种藏药已被应用于缓解 I/R 损伤 1000 年。有趣的是,鞣花酸(EA)是这三种处方中常见的主导植物化学物质之一。因此,评估 EA 的药效作用与缓解 I/R 损伤之间的关联是值得注意的。在这项研究中,我们发现 EA 可有效减少梗死面积,并可防止永久性大脑中动脉闭塞大鼠模型中的神经元凋亡和损伤。组织病理学研究结果表明,脑损伤的缓解与 EA 剂量呈正相关。通过生化分析进一步表明,EA 通过 EA 介导的抗炎和抗氧化反应来缓解脑损伤。用 EA 处理后损伤脑组织中紧密连接蛋白-1(zonula occludens-1)的上调和水通道蛋白 4(Aquaporin 4)和基质金属蛋白酶 9(MMP-9)的下调表明,血脑屏障(BBB)的重建可以进一步防止其他外源性物质对大脑的进一步损伤。此外,EA 在治疗过程中不会激活凝血因子 XII 诱导凝血形成。因此,EA 是一种有前途的 I/R 损伤治疗口服药物候选物。