Protective effects and mechanisms of Yi Qi Huo Xue Fang in cerebral ischemic stroke based on network pharmacology and experimental verification

Abstract

Ethnopharmacological relevanceYi Qi Huo Xue Fang (YQHXF) is an effective formula for treating cerebral ischemic stroke (CIS). However, its active ingredients and mechanism of action remain unclear. Aim of the studyThis study aimed to reveal the mechanism of action of YQHXF in the treatment of ischemic stroke based on network pharmacology and experimental validation. Materials and methodsThis study identified the chemical components in YQHXF and the components absorbed by rat serum based on UPLC-Q-TOF/MS technology and used network pharmacology to predict key candidate targets. A protein-protein-interaction (P-P-I) network was constructed using String 11.0 database and Cytoscape, and R software for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Finally, molecular docking combined with animal experiments was used to verify network pharmacology results. ResultsThis study identified and confirmed 36 chemical components of YQHXF and five chemical ingredients that were absorbed into the blood of rats and screened 66 key candidate targets. All targets in the P-P-I network were mainly related to inflammation and vascular processes. KEGG enrichment results revealed that these 66 key candidate targets were primarily involved in the “AGE-RAGE signaling pathway,” “TNF-α signaling pathway, and “T cell receptor signaling pathway.” Molecular docking results revealed that Prostaglandin-endoperoxidase synthase 2(PTGS-2), Nitric oxide synthase, endothelial (NOS3), and peroxisome proliferator-activated receptor gamma (PPARG) were more stably bound to their active ingredients. Animal experiments demonstrated that YQHXF promoted M2 polarization, inhibited M1 polarization in microglia, and promoted angiogenesis, which may be related to the PPARG pathway. ConclusionThis study revealed the key active components and effective targets of YQHXF, identified the mechanism of action of YQHXF, laid the foundation for further research on YQHXF, and provided ideas for developing new drugs for CIS.