Cordycepin protects against cerebral ischemia/reperfusion injury in vivo and in vitro

Cordycepin protects against cerebral ischemia/reperfusion injury in vivo and in vitro
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DOI:
10.1016/j.ejphar.2011.04.052
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发表时间:
2011-08-16
影响因子:
5
通讯作者:
Guo, Lianjun
Guo, Lianjun
中科院分区:
医学2区
文献类型:
--
作者:
Cheng, Zhenyong;He, Wei;Guo, Lianjun

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虫草素(Cordycepin,3 '-deoxyadenosine)是蛹虫草(Cordyceps militaris)中的一种生物活性成分,具有抗炎、抗氧化、抗癌等多种药理作用。目前对虫草素的神经保护作用及其分子机制知之甚少。在这项研究中,虫草素的神经保护潜力在小鼠缺血后15分钟的双侧颈总动脉闭塞和4小时的再灌注。在小鼠脑片上观察虫草素对缺氧缺糖(OGD)损伤的影响。结果表明,虫草素对脑缺血后神经元变性和脑片损伤有保护作用。采用高效液相色谱法(HPLC)检测缺血再灌注组大鼠脑匀浆上清液中谷氨酸、天冬氨酸等兴奋性氨基酸含量的变化。结果表明,虫草素能显著降低细胞外谷氨酸和天冬氨酸的水平。虫草素还能提高超氧化物歧化酶(SOD)活性,降低丙二醛(MDA)含量,减轻氧化程度。缺血再灌注后,炎症反应的关键酶基质金属蛋白酶-3(MMP-3)的表达明显增加,而虫草素能明显抑制其表达。总之,我们的体内和体外研究表明,虫草素能够发挥强有力的脑缺血/再灌注后的神经保护功能。(C)2011 Elsevier B. V.保留所有权利。
Cordycepin, (3'-deoxyadenosine), a bioactive compound of Cordyceps militaris, has been shown to exhibit many pharmacological actions, such as anti-inflammatory, antioxidative and anticancer activities. Little is known about the neuroprotective action of cordycepin as well as its molecular mechanisms. In this study, cordycepin was investigated for its neuroprotective potential in mice with ischemia following 15 min of the bilateral common carotid artery occlusion and 4 h of reperfusion. The effect of cordycepin was also studied in mice brain slices treated with oxygen-glucose deprivation (OGD) injury. Our results showed that cordycepin was able to prevent postischemic neuronal degeneration and brain slice injury. Excitatory amino acids such as glutamate and aspartate in brain homogenized supernatant, which were increased in ischemia/reperfusion group, were detected by high performance liquid chromatography (HPLC). The results showed that cordycepin was able to decrease the extracellular level of glutamate and aspartate significantly. Moreover, cordycepin was able to increase the activity of superoxide dismutase (SOD) and decrease the level of malondialdehyde (MDA), ameliorating the extent of oxidation. Furthermore, matrix metalloproteinase-3 (MMP-3), a key enzyme involved in inflammatory reactions, was markedly increased after ischemia reperfusion, whereas cordycepin was able to inhibit its expression obviously. In conclusion, our in vivo and in vitro study showed that cordycepin was able to exert a potent neuroprotective function after cerebral ischemia/reperfusion. (C) 2011 Elsevier B.V. All rights reserved.