Single-cell RNA-seq reveals the piperlongumine is a potential drug for ischemic stroke.

Abstract

Ischemic stroke is a cerebrovascular disease that can cause long-term neurological impairment, dementia, or death. It is the third most common cause of disability and the second leading cause of death worldwide. The aim of this study was to explore the underlying molecular mechanisms and potentially effective therapeutic drugs for ischemic stroke. Single-cell seq data (GSE174574) were downloaded from the Gene Expression Omnibus (GEO) database, and dimensionality reduction clustering was performed after quality control. Eighteen cell clusters were identified, which were annotated into 9 cell types according to specific marker genes. In addition, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) enrichment analysis showed that apoptosis was significantly increased after ischemic brain injury, while p53 signaling pathway, TNF-a signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway may play an important role in ischemic stroke. Furthermore, Connectivity Map (CMap) analysis and molecular docking suggested that piperlongumine might be an effective drug for the treatment of ischemic stroke by binding to the proteins encoded by Actb and Cflar. Finally, in vitro and in vivo experiments conformed the effectiveness of piperlongumine. This study provided new ideas for the treatment of ischemic stroke.