title: Quercetin ameliorates ischemia/reperfusion-induced cognitive deficits by inhibiting ASK1/JNK3/caspase-3 by enhancing the Akt signaling pathway.
abstract: Cerebral ischemia/reperfusion (I/R) is a major cause of severe disability and death all worldwide. However, therapeutic options to minimize the detrimental effects of cerebral I/R injury are limited. Recent research has demonstrated that quercetin mediates neuroprotective effects associated with the activation of the Akt signaling pathway in the cerebral I/R brain. Therefore, the aim of this study was to further investigate the mechanisms of cognitive deficits induced by cerebral I/R injury and the effects of quercetin on these mechanisms. First, we assessed anxiety-like behavioral and cognitive impairment using the open field test and the Morris water maze test, respectively. Next, we examined the severity of apoptosis by staining hippocampal neurons by the Cresyl violet method. Third, we used western blot analysis to investigate the expression of total and phosphorylated Akt, ASK1, JNK3, c-Jun and caspase-3 after I/R injury. Our results revealed that mice subjected to bilateral common carotid occlusion exhibited severe anxiety-like behavior, learning and memory impairment, cell damage and apoptosis. These severe effects were attenuated by administration of quercetin. Further, western blot analysis revealed that quercetin increased p-Akt expression and decreased p-ASK1, p-JNK3 and cleaved caspase-3 expression after cerebral I/R injury and led to inhibition of neuronal apoptosis. Conversely, treatment with LY294002 (a selective inhibitor of Akt1) reversed the effects of quercetin. In conclusion, these findings highlight the important role of quercetin in protecting against cognitive deficits and inhibiting neuronal apoptosis via the Akt signaling pathway. We believe that quercetin might prove to be a useful therapeutic component in treating cerebral I/R diseases in the near future.
authors.affiliation: Department of Clinical Laboratory, Suqian First Hospital, Jiangsu Province Hospital at Suqian, Suqian, Jiangsu, 223800, PR China. Electronic address: yanghua2016@sohu.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Pei
authors.affiliation: Department of Clinical Laboratory, Suqian First Hospital, Jiangsu Province Hospital at Suqian, Suqian, Jiangsu, 223800, PR China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Suqian First Hospital, Jiangsu Province Hospital at Suqian, Suqian, Jiangsu, 223800, PR China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Clinical Laboratory, Suqian First Hospital, Jiangsu Province Hospital at Suqian, Suqian, Jiangsu, 223800, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Pharmacy, Suqian First Hospital, Jiangsu Province Hospital at Suqian, Suqian, Jiangsu, 223800, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University, Shanghai, 200040, PR China. Electronic address: hsfayongzhang@163.com.
authors.forename: Fayong
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D003072:Cognition Disorders / Q000503:physiopathology* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism; D018696:Neuroprotective Agents; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011794:Quercetin / Q000008:administration & dosage*; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D011794:Quercetin; D048057:Mitogen-Activated Protein Kinase 10; D051057:Proto-Oncogene Proteins c-akt; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Akt; Apoptosis; Cerebral ischemia/reperfusion (I/R) injury; Quercetin