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

Publication date: Available online 14 August 2019Source: Acta Pharmaceutica Sinica BAuthor(s): 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 ZhangAbstractIschemic 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 further 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 ...
Source: Acta Pharmaceutica Sinica B - Category: Cancer & Oncology Source Type: research