摘要Background:QiShenYiQi(QSYQ)is commonly accepted to treat ischemic stroke(IS)in clinical settings,yet the underlying mechanism of action of QSYQ is largely unknown.Methods:By combining systems pharmacology with experimental assessment,we examined the key targets,bioactive components,and mechanisms of QSYQ against IS.Results:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform predicted a total number of 254 targets that were potentially related to QSYQ,whereas 699 targets associated with IS were gathered from Therapeutic Target Database,Comparative Toxicogenomics Database,Gene Cards,Online Mendelian Inheritance in Man,and National Center for Biotechnology Information databases,and 83 of these targets overlap with QSYQ-related targets.Importantly,through the analysis of Gene Ontology functional annotation,Kyoto Encyclopedia of Genes and Genomes pathway enrichment,and protein-protein interaction network,we identified 20 related signaling pathways along with 4 hub genes.Subsequently,our molecular docking results revealed that QSYQ might interact with PTGS2,PTGS1,SCN5A,and HSP90AB1.We observed dose-dependent beneficial effects of QSYQ in significantly improving neurological function and alleviating histopathological damage in middle cerebral artery occlusion model,while decreasing infarct volume.Notablely,QSYQ markedly downregulates tumor necrosis factor-α,interleukin-6,and interleukin-1 beta.Overall,this study demonstrates the synergetic effects of QSYQ on regulating multi-targets in IS through inhibiting inflammatory processes and neuronal apoptosis,these findings may expand the understanding of QSYQ and provide guidance for its clinical application in treating IS.Conclusion:Current study reveals the protective roles of QSYQ against IS through modulating PTGS2/PTGS1/SCN5A/HSP90AB1 and TNF signaling pathways.