Investigation of luteolin's antibacterial mechanism against staphylococcus aureus through network pharmacology and molecular docking approaches
Shijia Lu, Tianjiao Cui, Shaofeng Wu, Yibo Wang, Hao Li, Xue Yang, Guanjie Li, Yifan Li, Huaying Du, Mengjia Yan, Jinle Wang, Xumeng Shi, Jingran Lu, Linpu Liu, Xinyang Liu, Siyu Zhang, Jinwen Sima · In Silico Research in Biomedicine · 2025
This research endeavors to systematically investigate the molecular mechanisms through which luteolin exerts inhibitory effects on Staphylococcus aureus. This will be achieved by employing an integrative approach that combines network pharmacology, molecular docking, in vitro experimentation, and molecular dynamics simulation techniques. Initially, the antibacterial targets of luteolin were identified utilizing a comprehensive database, followed by the construction of a protein-protein interaction network to isolate eight key targets. Subsequently, pathway enrichment analysis, Gene Ontology (GO) biological process analysis, molecular docking, and molecular dynamics simulations were performed to elucidate the biological mechanisms through which luteolin exerts its inhibitory effects on Staphylococcus aureus. Finally, the antibacterial efficacy of luteolin against Staphylococcus aureus was evaluated. Luteolin disrupts DNA replication, energy metabolism, and cell membrane integrity by inhibiting DNA topology, ATP, and metal ion binding. In vitro tests confirmed its bactericidal effect on Staphylococcus aureus with a specific MBC/MIC ratio. This study introduces a quantitative model linking luteolin's multi-target binding energy to its concentration effect, offering a basis for developing new antibacterial agents from natural flavonoids.