Functional Mechanism of Tongmai Granule in Treating Ischemic Stroke Based on Network Pharmacology and Experimental Validation
Objective The mechanism of Tongmai Granules in the treatment of ischemic stroke was investigated by network pharmacology and verified in vivo.Methods The chemical constituents and their corresponding targets of Salviae miltiorrhizae radix et rhizome,Chuanxiong rhizome and Puerariae lobatae radix were searched through TCMSP database and TCMIP database.The related targets of ischemic stroke(IS)were collected in GeneCards database,Drugbank database,TTD database and OMIM database.The intersection of chemical composition targets and IS targets is drawn by Venn diagram.The network diagram of drug-potential active ingredient-targets was constructed by STRING database and Cytoscape.DAVID database was used to perform the enrichment analysis of key targets.An IS rat model was established by MCAO method.The IS rats were administered with low,medium and high dose of Tongmai Granules for 1 week.The efficacy and mechanism of Tongmai Granules were verified by Longa score and immunofluorescence staining.Results Through network pharmacological analysis,87 potential active components of Tongmai granules were obtained.The key targets were IL-6,AKT1,TNF,ACTB and VEGFA.The possible mechanism was related to MAPK signaling pathway,PI3K-Akt signaling pathway,TNF signaling pathway,IL-17 signaling pathway and other signaling pathways.The results of animal experiments showed that compared with the model group,Tongmai Granules could significantly reduce the neurological deficit score of IS rats(P<0.05),significantly shrink the infarct of brain tissue,effectively improve the pathological manifestations of brain tissue,change the activation state of microglia,significantly reduce the expression levels of IL-6 and TNF-α(P<0.05),and significantly increase the expression levels of IL-4 and IL-10(P<0.05).Conclusion Tongmai Granules can inhibit the expression of inflammatory factors and improve nerve function injury,the mechanism of which may be related to the regulation of microglia-mediated inflammatory response.
NETL
NSTL
万方数据
维普
