文献类型：期刊文献

中文题名：Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent

英文题名：Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent

作者：Hongxuan Feng[1,4];Linghao Hu[2,3];Hongwen Zhu[1];Lingxue Tao[1];Lei Wu[1];Qinyuan Zhao[1,4];Yemi Gao[1];Qi Gong[1];Fei Mao[2];Xiaokang Li[2];Hu Zhou[1];Jian Li[2,3];Haiyan Zhang[1,4]

机构：[1]CAS Key Laboratory of Receptor Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;[2]State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,China;[3]Shanghai Key Laboratory of New Drug Design,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China;[4]University of Chinese Academy of Sciences,Beijing 100049,China

年份：2020

卷号：10

期号：3

起止页码：434

中文期刊名：Acta Pharmaceutica Sinica B

外文期刊名：药学学报（英文版）

收录：CSTPCD;;Scopus;CSCD:【CSCD2019_2020】；PubMed;

基金：supported by the National Natural Science Foundation of China(Nos.81872859,81661148046,81522045,and 81703507);the National Special Fund for State Key Laboratory of Bioreactor Engineering(No.2060204,China);the National R&D Projects for major research instruments(ZDYZ2013-1,China);the Institutional Technology Service Center of Shanghai Institute of Materia Medica,Chinese Academy of Sciences for technical support.

语种：英文

中文关键词：Blood-brain;barrier;Brain;ischemia;Cell;cycle;Inflammation;Neuroprotection

外文关键词：Blood-brain barrier;Brain ischemia;Cell cycle;Inflammation;Neuroprotection

摘要：Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis.Here we demonstrated that post-ischemic treatment with ciclopirox olamine(CPX),a potent antifungal clinical drug,alleviated brain infarction,neurological deficits and brain edema in a classic rat model of ischemic stroke.Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect,which can be further enhanced by multiple doses administration of CPX.CPX also effectively reversed ischemia-induced neuronal loss,glial activation as well as blood-brain barrier(BBB)damage.Employing quantitative phosphoproteomic analysis,130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation(OGD)-exposed SH-SY5 Y cells,which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced.Subsequently,we demonstrated that CPX markedly enhanced the AKT(protein kinase B,PKB/AKT)and GSK3β(glycogen synthase kinase 3β)phosphorylation in OGD-exposed SH-SY5 Y cells,and regulated the cell cycle progression and nitric oxide(NO)release in lipopolysaccharide(LPS)-induced B V-2 cells,which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation.Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries;however,further studies will be needed to clarify the molecular mechanisms involved.
Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis.Here we demonstrated that post-ischemic treatment with ciclopirox olamine(CPX),a potent antifungal clinical drug,alleviated brain infarction,neurological deficits and brain edema in a classic rat model of ischemic stroke.Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect,which can be further enhanced by multiple doses administration of CPX.CPX also effectively reversed ischemia-induced neuronal loss,glial activation as well as blood-brain barrier(BBB) damage.Employing quantitative phosphoproteomic analysis,130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation(OGD)-exposed SH-SY5 Y cells,which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced.Subsequently,we demonstrated that CPX markedly enhanced the AKT(protein kinase B,PKB/AKT) and GSK3β(glycogen synthase kinase 3β) phosphorylation in OGD-exposed SH-SY5 Y cells,and regulated the cell cycle progression and nitric oxide(NO) release in lipopolysaccharide(LPS)-induced B V-2 cells,which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation.Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries;however,further studies will be needed to clarify the molecular mechanisms involved.