Systematic understanding of mechanism of Shenfu decoction improve the prognosis of ischemic stroke using a network pharmacology and animal experiment approach.

Objective: To explore the active compounds and the mechanism of Shenfu decoction (, SFD) against ischemic stroke (IS) through network pharmacology and animal experiments.

Methods: SFD components were retrieved from the Traditional Chinese Medicine (TCM) database. The Online Mendelian Inheritance in Man (OMIM), Comparative Toxicogenomics Database (CTD) and Therapeutic Target Database (TTD) database were used to retrieve the IS-related disease targets. The herb-compound-target network was built by Cytoscape 3.7.1 software. The core targets were obtained using protein-protein interaction (PPI) network. The core targets of SFD were further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We then performed molecular docking between the hub proteins and key active compounds. Finally, we conducted animal experiments to verify the regulation of SFD on apoptosis following IS.

Results: There were 221 corresponding targets and 25 components related to Chinese medicine throughout the compound-target network. The core targets of SFD in the treatment of IS was tumor protein P53 (Tp53), mitogen-activated protein kinase 3 (MAPK3), MAPK1, heat shock proteins 90AA1 and alpha serine/threonine-protein kinase1. There were 221 GO items in GO function enrichment analysis and 106 signaling pathways in KEGG, mainly including negative regulation of the apoptosis process, vascular endothelial growth factor signaling pathways, NOD-like receptor signaling pathway, etc. Among them, Tp53, MAPK3, and MAPK1 were docked with small molecule compounds. Through animal research, we confirmed the effect of SFD on apoptosis following stroke.

Conclusion: This study demonstrates that SFD can treat IS through multiple targets and pathways, and provides new perspectives for exploring the core targets and mechanisms of SFD against IS.