Preconditioning with Ginkgo biloba (EGb 761®) provides neuroprotection through HO1 and CRMP2.
Preconditioning with Ginkgo biloba (EGb 761®) provides neuroprotection through HO1 and CRMP2.
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DOI：
10.1016/j.nbd.2012.01.006
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发表时间：
2012-04
影响因子：
6.1
通讯作者：
Shah, Zahoor A.
中科院分区：
文献类型：
--
作者：
Nada, Shadia E.;Shah, Zahoor A.
关键词：
银杏叶/EGb 761®（EGb 761）是一种受欢迎的标准化天然提取物，在全球范围内用于治疗许多疾病。虽然EGb 761据称具有过多的益处，但在此，我们有兴趣研究EGb 761及其组分的神经保护特性，并确定核因子E2（Nrf 2）/血红素加氧酶1（HO 1）诱导的红细胞蛋白反应介体蛋白2（CRMP 2）通路是否有助于神经保护。小鼠用EGB 761或其成分之一（白果内酯、银杏内酯A、银杏内酯B和无萜物质[TFM]）预处理7天，然后进行短暂大脑中动脉闭塞（tMCAO）和48小时再灌注。除TFM外，所有成分均显著减少梗死体积和神经功能缺损。接下来，我们研究了EGb 761在原代神经元中的抗氧化和神经突发生特性。与溶剂处理的细胞相比，EGb 761预处理显著增强了暴露于叔丁基过氧化氢（t-BuOOH）、过氧化氢（H2 O2）和N-甲基-D-天冬氨酸（NMDA）的神经元的存活。白果内酯和银杏内酯A也保护细胞免受NMDA诱导的兴奋性毒性。免疫荧光和Western blot分析显示，EGb 761预处理显著增加了t-BuOOH诱导的氧化应激过程中Nrf 2、HO 1、GAPDH、β-actin、CRMP 2和组蛋白H3的蛋白表达水平。这些结果表明，EGb 761不仅具有抗氧化活性，而且具有促神经生的潜力。证明这种可能的药物发现的影响可能证明有益于中风和缺血性脑损伤。
Ginkgo biloba/EGb 761® (EGb 761) is a popular and standardized natural extract used worldwide for the treatment of many ailments. Although EGb 761 is purported to have a plethora of benefits, here, we were interested to study the neuroprotective properties of EGb 761 and its components and determine whether nuclear factor E2 (Nrf2)/heme oxygenase 1 (HO1) induction of the collapsin response mediator protein 2 (CRMP2) pathway contributes to neuroprotection. Mice were pretreated with EGb 761 or one of its constituents (bilobalide, ginkgolide A, ginkgolide B, and terpene free material [TFM]) for 7 days and then subjected to transient middle cerebral artery occlusion (tMCAO) and 48 h of reperfusion. All components except TFM significantly reduced infarct volumes and neurologic deficits. Next, we examined the antioxidant and neuritogenic properties of EGb 761 in primary neurons. Compared with vehicle-treated cells, pretreatment with EGb 761 significantly enhanced the survival of neurons exposed to tertiary butylhydroperoxide (t-BuOOH), hydrogen peroxide (H2O2), and N-methyl-D-aspartate (NMDA). Bilobalide and ginkgolide A also protected cells against NMDA-induced excitotoxicity. Immunofluorescence and Western blot analysis showed that EGb 761 pretreatment significantly increased the protein expression levels of Nrf2, HO1, GAPDH, β-actin, CRMP2, and histone H3 during t-BuOOH-induced oxidative stress. These findings suggest that EGb 761 not only has antioxidant activity but also neuritogenic potential. Demonstrating such effects for possible drug discovery may prove beneficial in stroke and ischemic brain injury.
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影响因子：
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作者：
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