Differential neuroprotective activity of two different grape seed extracts.

Differential neuroprotective activity of two different grape seed extracts.
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DOI:
10.1371/journal.pone.0014575
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发表时间:
2011-01-24
期刊:
影响因子:
3.7
通讯作者:
Takeda S
Takeda S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Narita K;Hisamoto M;Okuda T;Takeda S

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谷氨酸兴奋性毒性是脑缺血等神经毒性损伤过程中发生的主要事件之一。我们从两个不同的品种中制备了葡萄籽提取物,含有大量的多酚,但白藜芦醇很少。他们的神经保护作用进行了研究,使用原代培养的新生小鼠海马神经元处理兴奋毒性浓度的谷氨酸。Koshu是一种白色的葡萄属植物,在暴露于毒性浓度的谷氨酸(1.0 ng/ml)的培养海马神经元中,可减轻Erk 1/2的急性失活和树突回缩。相比之下,麝香贝利A,一个红色的,杂交品种(麝香亨伯格×贝利),没有显示出任何神经保护作用。与脑源性神经营养因子和其他神经保护性细胞因子不同,Koshu提取物不诱导Akt磷酸化。Koshu提取物还增加谷氨酸中毒后24小时的神经元存活率。通过液相色谱/飞行时间质谱法对两种样品之间的多酚进行比较,表明Koshu具有较高量的低分子量多酚沿着几种Koshu特异性矢车菊苷配质低聚物。这些数据表明,在海马神经元中存在多酚的高亲和力分子靶,其以不同于BDNF的方式诱导神经保护作用,以及低分子量多酚和/或矢车菊苷配质低聚物对于神经保护的重要性。
Glutamate excitotoxicity is one of the major events that takes place during various neurotoxic injuries such as brain ischemia. We prepared grape seed extracts, from two different varieties, containing high amounts of polyphenols but little resveratrol. Their neuroprotective effects were investigated using primary culture of neonatal mouse hippocampal neurons treated with an excitotoxic concentration of glutamate. Koshu, a white, local variety of V. vinifera, alleviated the acute inactivation of Erk1/2 and dendrite retraction in cultured hippocampal neurons exposed to a toxic concentration of glutamate (1.0 ng/ml). By contrast, Muscat Bailey A, a red, hybrid variety (Muscat Humburg × Bailey), failed to show any neuroprotective effect. Unlike brain-derived neurotrophic factor and other neuroprotective cytokines, Koshu extract did not induce Akt phosphorylation. Koshu extract also augmented neuron survival rate 24 hours after glutamate toxicity. The comparison of polyphenols between the two samples by liquid chromatography/time-of-flight mass spectrometry demonstrated that Koshu had higher amounts of low molecular weight polyphenols along with several Koshu-specific procyanidin oligomers. These data suggest the presence of high affinity molecular targets for polyphenols in hippocampal neurons, which induce neuroprotective effects in a manner different from BDNF, and the importance of low molecular weight polyphenols and/or procyanidin oligomers for neuroprotection.
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