title: 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.
abstract: 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-κB) and caspase-1; the phosphorylation of ERK1/2, JNK1/2, and p38 mitogen-activated protein kinase (MAPK); and the secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), 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.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, No. 19, Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, No. 19, Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Yun-Wei
authors.initials: YW
authors.lastname: Shi
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, No. 19, Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Miao
authors.initials: M
authors.lastname: Tang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, No. 19, Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Xiao-Chuan
authors.initials: XC
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, No. 19, Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, No. 19, Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China. liangxm@dicp.ac.cn.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China. liangxm@dicp.ac.cn.|Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Dalian, Liaoning, 116023, People's Republic of China. liangxm@dicp.ac.cn.
authors.forename: Xin-Miao
authors.initials: XM
authors.lastname: Liang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, No. 19, Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China. zhiweiwang64@gmail.com.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China. zhiweiwang64@gmail.com.|Department of Pharmacology, University of California, Irvine, CA, 92697, USA. zhiweiwang64@gmail.com.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, No. 19, Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China. dingfei@ntu.edu.cn.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China. dingfei@ntu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D007249:Inflammation / Q000188:drug therapy; D007511:Ischemia / Q000188:drug therapy; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; C016527:isoquercitrin; D011794:Quercetin
keywords: Apoptosis; Inflammation; Ischemic stroke; Isoquercetin; Oxidative stress