Treatment of Ischemic Stroke With Wenyang Huayu Formula: Network Pharmacology Analysis and Experimental Validation

Abstract

Context: Wenyang Huayu formula (WYHYF) is a prescription useful for treating stroke. Objective: To evaluate the mechanism of WYHYF in the treatment of ischemic stroke. Materials and methods: Network pharmacology analysis was performed to identify the chemical components and potential targets of WYHYF related to cerebral ischemia-reperfusion. The Cytoscape software and STRING database were used to draw a “drug component target disease” and protein interaction network diagram, respectively. Metascape database was used for gene enrichment analysis, and Autodock vina software was used for molecular docking to determine the pathways and targets of WYHYF. Finally, the pathways and targets were verified in vivo in rats. Results: We identified 277 drug targets and 3777 disease targets of WYHYF. Enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes pathways yielded 222 entries. The results of molecular docking showed that the core components and core proteins had a good binding ability. Validation analysis in the animal model indicated that stigmasterol, C-homoerythrin, luteolin, and other components in WYHYF influence the effects of the Toll-like receptor 4(TLR4)/NF-κB signal pathway on IL-6, IL-1β, and tumor necrosis factor-alpha-α and exert neuroprotective effects, relieve reperfusion injury, and inhibit apoptosis and inflammation. Discussion and conclusions: WYHYF affects ischemic stroke through the interactions of multiple components, targets, and pathways. The mechanism may involve the TLR4/NF-κB signal pathway to inhibit apoptosis, reduce inflammation, and promote angiogenesis.