Exploration of antibacterial mechanism of palmatine based on network pharmacology,molecular docking,and molecular dynamics
AIM To study the antibacterial mechanism of palmatine based on network pharmacology,molecular docking,and molecular dynamics.METHODS The drug targets of palmatine were predicted through the Swiss Target Prediction website,and the potential antibacterial targets of palmatine were obtained by mapping them with the antibacterial targets retrieved from GeneCards and OMIM databases.Protein-protein interaction network was constructed using STRING database and Cytoscape software and key targets were screened.The DAVID database was used to carry out Gene Ontology(GO)functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of potential targets,and visual processing was performed to build the"Component-Target-Pathway"network of palmatine.The binding of palmatine to key targets was validated through molecular docking and molecular dynamics simulations.In vitro antibacterial experiments were conducted to verify the antibacterial activity of palmatine.RESULTS A total of 28 critical anti-bacterial targets of palmatine were screened and enriched to 199 GO entries and 105 related pathways."Ingredients-Target-Pathway"network showed that MAPK8,RAC1,and STAT3 were key anti-bacterial targets.The molecular docking results indicated that palmatine had an excellent binding effect with key targets MAPK8 and RAC1.Molecular dynamics studies found that there were hydrogen bonds and hydrophobic interactions between palmatine and proteins,enabling stable binding of palmatine to target proteins.In vitro antibacterial experiments showed that palmatine had strong inhibitory activity against Staphylococcus aureus and Candida albicans,and it had synergistic effects when combined with positive drugs.CONCLUSION Palmatine may exert its antibacterial effects by inhibiting the gene expression of MAPK8 and RAC 1 through endocrine resistance and signaling pathways such as PI3K-Akt and FoxO.
network pharmacologypalmatinemolecular dockingmolecular dynamic simulationantibacterial test
万方数据
维普
