Treatment of Ischemic Stroke with Wenyang Huayu Formula: network pharmacology analysis and experimental validation

Abstract Objective To explore the mechanism of Wenyang Huayu Formula in the treatment of ischemic stroke based on network pharmacology, molecular docking and experimental verification. Methods The chemical components and potential targets in Wenyang Huayu Formula were obtained by network pharmacology, and the targets related to the pathological process of cerebral ischemia-reperfusion were obtained, and the "drug-component-target-disease" was drawn by Cytoscape software,protein interaction network map was drawn based on STRING database.Gene enrichment analysis was using the Metascape database, and the Autodock vina software was using for molecular docking to determine the pathways and targets of Wenyang Huayu Formula, which were verified by vivo experiments in rats. Results 277 drug targets and 3777 disease targets of Wenyang Huayu Formula were retrieved. The core components were Quercetin, kaempferol, luteolin, etc., and the core targets were AKT1, TP53, IL6, CASP3, IL1β, etc.Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis yielded 222 entries, involving Cellular senescence, TNF signaling pathway, Toll-like receptor signaling pathway, etc. Molecular docking results showed that the core component and the core protein had good binding energy. Vivo experiments results shown that: Stigmasterol, C-Homoerythrinan, luteolin and other components in Wenyang Huayu Formula may act on targets such as IL-6, IL-1β and TNF-α through the TLR4/NF-κB signaling pathway, and play roles in neural protection, reduce reperfusion injury, inhibit apoptosis, anti-inflammatory and other effects. Conclusion The mechanism of ischemic stroke by Wenyang Huayu Formula was the result of multi-component, multi-target and multi-channel interaction, and its mean mechanism may inhibit cell apoptosis, reduce inflammation and promote blood vessels through the TLR4/NF-κB signaling pathway.