首页|Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent

Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent

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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-SY5Y 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-SY5Y cells,and regulated the cell cycle progression and nitric oxide (NO) release in lipopolysaccharide (LPS)-induced BV-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.

Blood-brain barrierBrain ischemiaCell cycleInflammationNeuroprotection

Hongxuan Feng、Linghao Hu、Hongwen Zhu、Lingxue Tao、Lei Wu、Qinyuan Zhao、Yemi Gao、Qi Gong、Fei Mao、Xiaokang Li、Hu Zhou、Jian Li、Haiyan Zhang

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CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

University of Chinese Academy of Sciences, Beijing 100049, China

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

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This research was supported by the National Natural Science Foundation of ChinaThis research was supported by the National Natural Science Foundation of ChinaNational Special Fund for State Key Laboratory of Bioreactor EngineeringNational Special Fund for State Key Laboratory of Bioreactor EngineeringNational Special Fund for State Key Laboratory of Bioreactor EngineeringNational Special Fund for State Key Laboratory of Bioreactor Engineering

817035072060204Chinathe National R&D Projects

2020

药学学报(英文版)

药学学报(英文版)

CSTPCDCSCDSCI
ISSN：
年,卷(期)：2020.10(3)
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