Differential effects of natural polyphenols on neuronal survival in primary cultured central neurons against glutamate- and glucose deprivation-induced neuronal death
Differential effects of natural polyphenols on neuronal survival in primary cultured central neurons against glutamate- and glucose deprivation-induced neuronal death
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DOI：
10.1016/s0006-8993(03)03197-4
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发表时间：
2003-10-03
期刊：
影响因子：
2.9
通讯作者：
Lee, YH
中科院分区：
文献类型：
--
作者：
Lee, HH;Yang, LL;Lee, YH
缺血性损伤后中枢神经系统的神经元损伤被认为是谷氨酸毒性和葡萄糖剥夺的结果。本研究以原代培养的大鼠脑神经元为模型，研究了黄芩苷、黄芩素和汉黄芩素对谷氨酸/NMDA（Glu/NMDA）刺激和葡萄糖剥夺的神经保护作用。通过乳酸脱氢酶（LDH）释放测定坏死来评估细胞死亡，并且通过3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑（MTT）还原活性测定来评估线粒体活性。结果表明，黄芩苷和黄芩素作用24 h后均能抑制培养神经元LDH的释放，汉黄芩素作用2 h后显著增加LDH的释放，24 h后导致神经元死亡。Glu/NMDA处理显著增加LDH释放，并以NMDA受体依赖性方式适度降低MTT还原活性。黄芩苷和黄芩素均能显著抑制Glu/NMDA诱导的LDH释放，其中黄芩素的抑制作用强于黄芩苷。Glu/NMDA引起的细胞内钙离子浓度升高也被黄芩苷和黄芩素显著减弱。黄芩苷和黄芩素不影响谷氨酸受体结合活性，但黄芩素适度降低Glu/NMDA诱导的一氧化氮（NO）的产生。在葡萄糖剥夺（GD）实验中，黄芩素对GD诱导的LDH释放有明显的保护作用，而对NO的产生无明显影响。这些结果表明，黄芩素是最有效的化合物中的三个多酚测试在防止谷氨酸和GD诱导的神经毒性，而黄芩苷是唯一有效的防止谷氨酸毒性。汉黄芩素可能对大脑有神经毒性作用。(C)2003 Elsevier B. V.保留所有权利。
Neuronal injury in the central nervous system following ischemic insult is believed to result from glutamate toxicity and glucose deprivation. In this study, polyphenols isolated from Scutellaria baicalensis Georgi, including baicalin, baicalein, and wogonin, were investigated for their neuroprotective effects against glutamate/NMDA (Glu/NMDA) stimulation and glucose deprivation in primary cultured rat brain neurons. Cell death was accessed by lactate dehydrogenase (LDH) release assay for necrosis, and mitochondrial activity was accessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction activity assay. It was found that both baicalin and baicalein decreased LDH release of the cultured neurons after 24 h treatment, whereas wogonin profoundly increased LDH release after 2 h treatment and resulted in neuronal death after 24 h. Glu/NMDA treatment profoundly increased LDH release and moderately decreased MTT reduction activity in an NMDA receptor-dependent manner. Both baicalin and baicalein significantly reduced Glu/NMDA-increased LDH release, in which baicalein is much more potent than baicalin. Glu/NMDA-increased intracellular calcium was also significantly attenuated by baicalin and baicalein. Baicalin and baicalein did not affect glutamate receptor binding activity, but baicalein did moderately decrease Glu/NMDA-induced nitric oxide (NO) production. In the glucose deprivation (GD) study, baicalein but not baicalin showed significant protective effects on the GD-increased LDH release, without affecting the GD-induced NO production, in cultured rat brain neurons. These results suggest that baicalein is the most effective compound among three polyphenols tested in preventing neurotoxicity induced by both glutamate and GD, whereas baicalin was only effective in preventing glutamate toxicity. Wogonin might have a neurotoxic effect on the brain. (C) 2003 Elsevier B.V. All rights reserved.