Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-kappa B pathway
机构：[a]Department of Neurology, The First People's Hospital of Shangqiu, Shangqiu, China[b]Department of Neurology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China重点科室诊疗科室神经病学中心神经病学中心首都医科大学附属天坛医院[c]Department of Laboratory Medicine, The First People's Hospital of Shangqiu, Shangqiu, China
Isoquercetin (Iso) has been found to have neuroprotective effects against cerebral ischemic stroke. However, the exact molecular mechanism underlying its neuroprotective ability remains unclear. In this study, we aimed to evaluate the neuroprotective effects of Iso in primary culture of rat hippocampal neurons exposed to oxygen and glucose deprivation and reperfusion (OGD/R) injury and in rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R) injury. We found that rats treated with Iso exhibited a lower degree of infarct volume, and brain water content than the vehicle-treated rats. Treatment with Iso also improved the neurological deficits in MCAO/R rats as shown by the decreased modified neurological severity score. Iso treatment decreased the reactive oxygen species (ROS) and malondialdehyde (MDA) production, and increased the activity of superoxide dismutase (SOD) and catalase (CAT) in brains of MCAO/R rats and primary culture of rat hippocampal neurons exposed to OGD/R. Iso treatment prevents I/R-induced neuronal apoptosis in vivo and in vitro as indicated by increased cell viability and decreased number of TUNEL-positive cells, accompanying with down-regulation of cleaved caspase-3 protein and upregulation of Bcl-2 protein. Moreover, Nrf2 knockdown weakened the anti-apoptotic and anti-oxidant activities of Iso in primary culture of rat hippocampal neurons exposed to OGD/R. Interestingly, we found that Iso could induce Nrf2 translocation from cytoplasm to nucleus in primary culture of rat hippocampal neurons exposed to OGD/R. Iso activated the NOX4/ROS/NF-kappa B signaling pathway in in vivo and in vitro cerebral I/R injury models. Nrf2 knockdown blocked the inhibitory effect of Iso on protein expression of NOX4, p-I kappa B alpha and p-p65 in primary culture of rat hippocampal neurons exposed to OGD/R. All the data suggested that Iso protected against oxidative stress and neuronal apoptosis in in vivo and in vitro cerebral I/R injury models via Nrf2-mediated inhibition of the NOX4/ROS/NF-kappa B signaling pathway. Our findings suggested that Iso could be a potential agent for I/R brain injury.
基金：
Henan Province Science and Technology Plan Project [152102310029]; Henan Province Science and Technology Tackling Plan Project [132102310490]
第一作者机构：[a]Department of Neurology, The First People's Hospital of Shangqiu, Shangqiu, China[*1]Department of Neurology, The First People's Hospital of Shangqiu, No. 292 Kaixuan Nan Road, Suiyang District, Shangqiu City, 476100, China.
通讯作者：
通讯机构：[a]Department of Neurology, The First People's Hospital of Shangqiu, Shangqiu, China[*1]Department of Neurology, The First People's Hospital of Shangqiu, No. 292 Kaixuan Nan Road, Suiyang District, Shangqiu City, 476100, China.
推荐引用方式(GB/T 7714)：
Yunyi Dai,Haojie Zhang,Jianping Zhang,et al.Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-kappa B pathway[J].CHEMICO-BIOLOGICAL INTERACTIONS.2018,284:32-40.doi:10.1016/j.cbi.2018.02.017.
APA：
Yunyi Dai,Haojie Zhang,Jianping Zhang&Mingguang Yan.(2018).Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-kappa B pathway.CHEMICO-BIOLOGICAL INTERACTIONS,284,
MLA：
Yunyi Dai,et al."Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-kappa B pathway".CHEMICO-BIOLOGICAL INTERACTIONS 284.(2018):32-40
