Neuroprotective effects of emodin in rat cortical neurons against β-amyloid-induced neurotoxicity
Neuroprotective effects of emodin in rat cortical neurons against β-amyloid-induced neurotoxicity
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DOI：
10.1016/j.brainres.2010.05.079
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发表时间：
2010-08-06
期刊：
影响因子：
2.9
通讯作者：
Hu, Hai-Tao
中科院分区：
文献类型：
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作者：
Liu, Tao;Jin, Hui;Hu, Hai-Tao
大脑中β -淀粉样蛋白（A β）的积累在阿尔茨海默病（AD）的发病机制中起着重要作用。本研究对虎杖大黄素的神经保护作用进行了初步研究。et Zucc对A β(25-35)诱导的皮质神经元细胞死亡的影响。我们发现大黄素预处理可以阻止培养的皮层神经元产生β -淀粉样蛋白诱导的毒性。用磷脂酰肌醇-3-激酶（PI3K）途径抑制剂LY294002或雌激素受体（ER）特异性拮抗剂ICI182780预处理可阻断大黄素的预防作用，但用细胞外信号相关激酶（ERK）抑制剂U0126预处理则不能阻断大黄素的预防作用。此外，我们发现大黄素暴露诱导Akt丝氨酸/苏氨酸激酶活化，并增加Bcl-2的表达水平。此外，应用大黄素24 h能够诱导A β(25-35)抑制的Akt活化，并降低jun - n末端激酶（JNK）的活化，但不影响ERK。有趣的是，在LY294002或ICI182780存在的情况下，Akt和Bcl-2的上调并未发生，这表明大黄素上调的Bcl-2是通过ER和PI3K/Akt途径介导的。综上所述，我们的研究结果表明大黄素是一种有效的神经保护药物，是治疗AD的可行候选药物。(C) 2010 Elsevier B.V.版权所有
Accumulation of beta-amyloid protein (A beta) in the brain plays an important role in the pathogenesis of Alzheimer's disease (AD). In this study, the neuroprotective effect of emodin extracted from the traditional Chinese medicinal herb Polygonum cuspidatum Sieb. et Zucc against A beta(25-35)-induced cell death in cultured cortical neurons was investigated. We found that pre-treatment with emodin prevented the cultured cortical neurons from beta-amyloid-induced toxicity. The preventive effect of emodin was blocked by pre-treatment with a phosphatidylinositol-3-kinase (PI3K) pathway inhibitor LY294002 or an estrogen receptor (ER) specific antagonist ICI182780, but not by pre-treatment with an extracellular signal-related kinases (ERK) inhibitor U0126. Furthermore, we found that emodin exposure induced the activation of the Akt serine/threonine kinase and increased the level of Bcl-2 expression. Moreover, the application of emodin for 24 h was able to induce the activation of A beta(25-35)-suppressed Akt and decrease the activation of the Jun-N-terminal kinases (JNK), but not of ERK. Interestingly, the up-regulation of Akt and Bcl-2 did not occur in the presence of LY294002 or ICI182780, suggesting that emodin-up-regulated Bcl-2 is mediated via the ER and PI3K/Akt pathway. Taken together, our results suggest that emodin is an effective neuroprotective drug and is a viable candidate for treating AD. (C) 2010 Elsevier B.V. All rights reserved.