Molecular mechanisms of baicalin antibacterial based on network pharmacology, molecular docking, and molecular dynamics

Aims:This study explores the antibacterial potential of baicalin, an active compound derived from Scutellaria baicalensis, focusing on its mechanisms of action against carbapenem-resistant Acinetobacter baumannii and other pathogens in the context of rising antibiotic resistance.Methodology and results: A total of 175 potential baicalin targets were identified using database SEA, SwissTargetPrediction, and GeneCards, of which 106 overlapped with known antibacterial targets.Protein-protein interaction (PPI) network analysis revealed critical targets such as AKT1, NFKB1, BCL2, MYC, and TNF.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that baicalin impacts pathways involved in inflammation and apoptosis, particularly TNF and IL-17 signaling pathways.Molecular docking revealed strong binding of baicalin to AKT1 and TNF.However, molecular dynamics (MD) simulations showed that while the AKT1-baicalin complex remained stable, the TNF-baicalin interaction was unstable due to high solvation energy.This suggests that baicalin influences TNF signaling pathways rather than relying on stable direct binding to TNF.Conclusion, significance and impact of study: Baicalin exhibits promising antibacterial properties by targeting molecular pathways that regulate inflammation and cell survival, offering dual benefits of pathogen clearance and immune modulation.These findings support the potential development of baicalin-based antimicrobial therapies, addressing the urgent need for novel solutions in the fight against antibiotic resistance.