Network Pharmacology-Based Prediction and Experimental Validation of the Targets and Mechanism of Tilianin Action Against Myocardial Infarction

Abstract

Tilianin is a flavonoid glycoside with potential applications in the prevention and treatment of myocardial infarction, but its specific targets and pharmacological mechanisms are unclear. Therefore, in this study, a reverse screening and molecular docking approach was used to predict the pharmacological targets and mechanisms of tilianin on myocardial infarction based on network pharmacology and experimental validation. Firstly, we screened various databases to obtain potential core targets of tilianin. Secondly, we used protein–protein interaction, gene ontology, Kyoto Encyclopedia of Genes and Genomes, and ClueGO to correlate the key targets before molecular docking of new target genes. Finally, the gene expression of tilianin in HL-1 cells was experimentally validated with quantitative real-time polymerase chain reaction and immunofluorescence. The result showed that tilianin may significantly modulate pro-inflammatory effects in the tumor necrosis factor-α signaling pathway, which activates and regulates various cellular activities. Molecular docking revealed that protein kinase B1, proto-oncogene cellular sarcoma, tumor necrosis factor-α, matrix metalloproteinase-9, nitric oxide synthetase 2, mitogen-activated protein kinase 14 and phosphatase and tensin homolog-induced kinase 1 may be the key targets for the systematic regulatory effect of tilianin against myocardial infarction. Finally, quantitative real-time polymerase chain reaction and immunofluorescence results showed that tilianin significantly influences the expression of the key genes in myocardial infarction. Using network bioinformatic analysis, molecular docking techniques, and experimental validation, we predicted and preliminarily validated potential target sites for tilianin. These findings provide a new perspective for further exploration of the mechanism of action of tilianin in myocardial infarction therapy. Meanwhile, this study provides an objective basis for further experimental studies in the future.