Rosmarinic acid mediated neuroprotective effects against H2O2-induced neuronal cell damage in N2A cells
Rosmarinic acid mediated neuroprotective effects against H2O2-induced neuronal cell damage in N2A cells
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DOI：
10.1016/j.lfs.2014.07.010
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发表时间：
2014-09-15
期刊：
影响因子：
6.1
通讯作者：
Prakash, H. S.
中科院分区：
文献类型：
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作者：
Ghaffari, Hadi;Venkataramana, M.;Prakash, H. S.
目的：氧化应激在包括神经退行性疾病在内的几种疾病中起着关键作用。本研究的目的是证明迷迭香酸（rosmarinic acid，RA）在预防氧化应激相关的神经元细胞株死亡中的作用。主要方法：在本研究中，我们利用H2 O2诱导的N2 A小鼠神经母细胞瘤细胞的氧化攻击证明了RA的直接神经保护作用。使用MU、乳酸脱氢酶、线粒体膜电位（MMP）、细胞内ROS和彗星试验评价RA中和H2 O2诱导的毒性的机制。通过RT-PCR.Key发现：本文中提出的结果表明，H2 O2诱导的N2 A细胞的细胞毒性被RA治疗抑制在分子水平上的脑神经元标志物的上调。此外，RA在减弱乳酸脱氢酶、线粒体膜电位和细胞内ROS的破坏方面非常有效。RA预处理可显著预防遗传毒性（3.7倍，p < 0.01），并促进酪氨酸羟化酶（TH）的上调（4.5倍，p < 0.01），脑源性神经营养因子（BDNF）基因（5.4倍，p < 0.01）对抗N2 A细胞中H2 O2诱导的细胞毒性。我们的研究结果表明，N2 A细胞是合适的细胞模型，以评估RA的神经保护作用，并建议RA可能作为一种潜在的代理人，用于预防几种人类神经退行性疾病引起的氧化应激。(C)2014爱思唯尔公司All rights reserved.
Aims: Oxidative stress plays a key role in several ailments including neurodegenerative conditions. The aim of the study was to demonstrate the effect of rosmarinic acid (RA) in preventing oxidative stress related death of neuronal cell lines.Main methods: In the present study, we demonstrated direct neuroprotective effect of RA using H2O2-induced oxidative challenge in N2A mouse neuroblastoma cells. The mechanism of neutralization of H2O2-induced toxicity by RA was evaluated using MU, lactate dehydrogenase, mitochondrial membrane potential (MMP), intracellular ROS, and comet assays. Up-regulation of brain neuronal markers at molecular level was performed by RT-PCR.Key findings: Results presented in the paper indicate that H2O2-induced cytotoxicity in N2A cells was suppressed by treatment with RA. Moreover, RA is very effective in attenuating the disruption of lactate dehydrogenase, mitochondrial membrane potential and intracellular ROS. Pretreatment with RA significantly prevents genotoxicity (3.7-fold, p < 0.01) and promotes the up-regulation of tyrosine hydroxylase (TH) (4.5-fold, p < 0.01), and brain-derived neurotrophic factor (BDNF) genes (5.4-fold, p < 0.01) against H2O2-induced cytotoxicity in N2A cells.Significance: Our results revealed that N2A cells are suitable cellular models to evaluate neuroprotective effects of RA, and suggest that RA may potentially serve as an agent for prevention of several human neurodegenerative diseases caused by oxidative stress. (C) 2014 Elsevier Inc. All rights reserved.