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

Acta Pharmaceutica Sinica. B
Hongxuan FengHaiyan Zhang

Abstract

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 ...Continue Reading

Citations

May 7, 2021·Medicinal Research Reviews·Qing-Zhang TuoPeng Lei
Aug 14, 2021·Acta Pharmaceutica Sinica. B·Chenglong GaoTao Pang
Jan 8, 2020·Journal of Medicinal Chemistry·Linghao HuJian Li
Sep 19, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Roland Seifert, Bastian Schirmer

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Methods Mentioned

BETA
fluorescence microscopy
ELISA
Protein Assay
flow cytometry
antibody array

Software Mentioned

Image studio
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ImagePro Plus
pheatmap
Excel
PathScan®
ARRIVE
NetworKIN

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