Isoquercetin Ameliorates Cerebral Impairment in Focal Ischemia Through Anti-Oxidative, Anti-Inflammatory, and Anti-Apoptotic Effects in Primary Culture of Rat Hippocampal Neurons and Hippocampal CA1 Region of Rats
Isoquercetin Ameliorates Cerebral Impairment in Focal Ischemia Through Anti-Oxidative, Anti-Inflammatory, and Anti-Apoptotic Effects in Primary Culture of Rat Hippocampal Neurons and Hippocampal CA1 Region of Rats
复制标题
异槲皮素通过大鼠海马神经元和海马 CA1 区原代培养物的抗氧化、抗炎和抗凋亡作用改善局灶性缺血性脑损伤
DOI：
10.1007/s12035-016-9806-5
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发表时间：
2017-04-01
影响因子：
5.1
通讯作者：
Ding, Fei
中科院分区：
文献类型：
--
作者：
Wang, Cai-Ping;Shi, Yun-Wei;Ding, Fei
缺血性中风是一种主要的残疾和死亡原因，由于其狭窄的治疗时间窗。神经保护剂是抢救急性缺血脑组织和延长治疗时间窗的一种有前途的策略。在这项研究中，我们的目的是评估异槲皮素在（1）大鼠海马神经元原代培养中暴露于氧和葡萄糖剥夺和再灌注（OGD/R）损伤和（2）大鼠短暂大脑中动脉闭塞和再灌注（MCAO/R）中的神经保护作用。损伤。结果显示，异槲皮素后处理可减少缺血再灌注损伤后的梗死面积、凋亡细胞数量、氧化应激和炎症反应。异槲皮素可能通过抑制Toll样受体4（TLR4）、核因子-κ B的活化而发挥神经保护作用（NF-κ B）和半胱天冬酶-1; ERK 1/2、JNK 1/2和p38丝裂原活化蛋白激酶（MAPK）的磷酸化;以及肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1 β）和IL-6的分泌。此外，异槲皮素还通过调节cAMP反应元件结合蛋白（CREB）、Bax、Bcl-2和caspase-3，有效减轻海马神经元凋亡。我们的报告为异槲皮素改善缺血性卒中患者脑损伤的治疗作用和潜在机制提供了新的考虑。作为一种有效的抗炎和抗氧化化合物，具有神经保护能力，异槲皮素用于治疗人类缺血性中风和相关疾病时的有益作用值得进一步研究。
Ischemic stroke is a major disability and cause of death worldwide due to its narrow therapeutic time window. Neuroprotective agent is a promising strategy to salvage acutely ischemic brain tissue and extend the therapeutic time window for stroke treatment. In this study, we aimed to evaluate the neuroprotective effects of isoquercetin in (1) primary culture of rat hippocampal neurons exposure on oxygen and glucose deprivation and reperfusion (OGD/R) injury and (2) rats subjected to transient middle cerebral artery occlusion and reperfusion (MCAO/R) injury. The results showed that isoquercetin post-treatment reduced the infarct size, number of apoptotic cells, oxidative stress, and inflammatory response after ischemia and reperfusion injury. The underlying mechanism study indicated that the neuroprotective effects of isoquercetin were elicited via suppressing the activation of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-kappa B) and caspase-1; the phosphorylation of ERK1/2, JNK1/2, and p38 mitogen-activated protein kinase (MAPK); and the secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6. In addition, isoquercetin also effectively alleviated hippocampus neuron apoptosis by regulation of cyclic AMP responsive element-binding protein (CREB), Bax, Bcl-2, and caspase-3. Our report provided new considerations into the therapeutic action and the underlying mechanisms of isoquercetin to improve brain injury in individuals who have suffered from ischemic stroke. As a potent anti-inflammatory and anti-oxidative compound with neuroprotective capacities, the beneficial effects of isoquercetin when used to treat ischemic stroke and related diseases in humans warrant further studies.