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

doi:10.1016/j.apsb.2019.08.002

	Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent
	Feng, Hongxuan 1,2; Hu, Linghao 3,4; Zhu, Hongwen 2; Tao, Lingxue 2; Wu, Lei 2; Zhao, Qinyuan 1,2; Gao, Yemi 2; Gong, Qi 2; Mao, Fei 3; Li, Xiaokang 3
刊名	ACTA PHARMACEUTICA SINICA B
	2020-03-01
卷号	10 期号:3 页码:434-446
关键词	Blood-brain barrier Brain ischemia Cell cycle Inflammation Neuroprotection
ISSN号	2211-3835
DOI	10.1016/j.apsb.2019.08.002
通讯作者	Zhou, Hu(zhouhu@simm.ac.cn) ; Li, Jian(jianli@ecust.edu.cn) ; Zhang, Haiyan(hzhang@simm.ac.cn)
英文摘要	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-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 GSK3 beta (glycogen synthase kinase 3 beta) 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. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
资助项目	National Natural Science Foundation of China[81872859] ; National Natural Science Foundation of China[81661148046] ; National Natural Science Foundation of China[81522045] ; National Natural Science Foundation of China[81703507] ; National Special Fund for State Key Laboratory of Bioreactor Engineering (China)[2060204] ; National R&D Projects (China)[ZDYZ2013-1]
WOS关键词	CEREBRAL-ARTERY OCCLUSION ; CELL-CYCLE ; SIGNALING PATHWAY ; ISCHEMIC-STROKE ; PHOSPHORYLATION ; NEUROPROTECTION ; MECHANISMS ; INHIBITORS ; DISCOVERY ; DESIGN
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
WOS记录号	WOS:000518042300004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281337]
专题	中国科学院上海药物研究所
通讯作者	Zhou, Hu; Li, Jian; Zhang, Haiyan
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China 4.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China
推荐引用方式 GB/T 7714	Feng, Hongxuan,Hu, Linghao,Zhu, Hongwen,et al. Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent[J]. ACTA PHARMACEUTICA SINICA B,2020,10(3):434-446.
APA	Feng, Hongxuan.,Hu, Linghao.,Zhu, Hongwen.,Tao, Lingxue.,Wu, Lei.,...&Zhang, Haiyan.(2020).Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent.ACTA PHARMACEUTICA SINICA B,10(3),434-446.
MLA	Feng, Hongxuan,et al."Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent".ACTA PHARMACEUTICA SINICA B 10.3(2020):434-446.