Tags

Type your tag names separated by a space and hit enter

Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-κB pathway.
Chem Biol Interact. 2018 Mar 25; 284:32-40.CB

Abstract

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 downregulation 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-κB 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-IκBα 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-κB signaling pathway. Our findings suggested that Iso could be a potential agent for I/R brain injury.

Authors+Show Affiliations

Department of Neurology, The First People's Hospital of Shangqiu, Shangqiu, China. Electronic address: daiyysq@yeah.net.Department of Neurology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China.Department of Neurology, The First People's Hospital of Shangqiu, Shangqiu, China.Department of Laboratory Medicine, The First People's Hospital of Shangqiu, Shangqiu, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29454613

Citation

Dai, Yunyi, et al. "Isoquercetin Attenuates Oxidative Stress and Neuronal Apoptosis After Ischemia/reperfusion Injury Via Nrf2-mediated Inhibition of the NOX4/ROS/NF-κB Pathway." Chemico-biological Interactions, vol. 284, 2018, pp. 32-40.
Dai Y, Zhang H, Zhang J, et al. Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-κB pathway. Chem Biol Interact. 2018;284:32-40.
Dai, Y., Zhang, H., Zhang, J., & Yan, M. (2018). Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-κB pathway. Chemico-biological Interactions, 284, 32-40. https://doi.org/10.1016/j.cbi.2018.02.017
Dai Y, et al. Isoquercetin Attenuates Oxidative Stress and Neuronal Apoptosis After Ischemia/reperfusion Injury Via Nrf2-mediated Inhibition of the NOX4/ROS/NF-κB Pathway. Chem Biol Interact. 2018 Mar 25;284:32-40. PubMed PMID: 29454613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-κB pathway. AU - Dai,Yunyi, AU - Zhang,Haojie, AU - Zhang,Jianping, AU - Yan,Mingguang, Y1 - 2018/02/16/ PY - 2017/11/10/received PY - 2018/01/15/revised PY - 2018/02/13/accepted PY - 2018/2/20/pubmed PY - 2018/3/28/medline PY - 2018/2/19/entrez KW - Apoptosis KW - Ischemia/reperfusion KW - Isoquercetin KW - NADPH oxidase 4 KW - NF-E2-related factor 2 KW - Oxidative stress SP - 32 EP - 40 JF - Chemico-biological interactions JO - Chem Biol Interact VL - 284 N2 - 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 downregulation 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-κB 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-IκBα 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-κB signaling pathway. Our findings suggested that Iso could be a potential agent for I/R brain injury. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/29454613/Isoquercetin_attenuates_oxidative_stress_and_neuronal_apoptosis_after_ischemia/reperfusion_injury_via_Nrf2_mediated_inhibition_of_the_NOX4/ROS/NF_κB_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(17)31226-7 DB - PRIME DP - Unbound Medicine ER -