Unraveling the Antibacterial Mechanisms of Bletilla striata: A Synergistic Approach Combining Network Pharmacology, Molecular Docking, and In Vitro Validation.
INTRODUCTION Bletilla striata, a traditional Chinese medicinal herb, shows promise for treating bacterial infections, but its precise antibacterial mechanisms are not fully understood. MATERIALS AND METHODS An integrated strategy was employed. Network pharmacology identified bioactive compounds from Bletilla striata and predicted antibacterial targets. Molecular docking assessed interactions between key compounds and core targets (ESR1, EGFR, PTGS2, MAPK14), followed by molecular dynamics simulations for the top complex (BJ6-ESR1). In vitro assays evaluated the antibacterial activity, anti-persister effects, and potential for resistance induction of the key compound BJ6 against S. aureus and Gram-negative bacteria. RESULTS Nine bioactive compounds were identified. 4,7-dihydroxy-1-p-hydroxybenzyl-2-methoxy-9,10- dihydrophenanthrene (BJ6) showed the strongest binding to key targets in docking. MD simulations confirmed a stable BJ6-ESR1 complex with a high binding free energy of -39.98 kcal/mol. In vitro, BJ6 exhibited potent activity against S. aureus (MIC = 1~2 μg/mL), significant efficacy against persister cells, and a delayed development of bacterial resistance compared to amoxicillin. DISCUSSION The findings indicate that Bletilla striata, primarily through BJ6, exerts antibacterial effects via multi-component, multi-target interactions, particularly with ESR1, EGFR, PTGS2, and MAPK14. CONCLUSION This study elucidates the molecular basis of Bletilla striata's antibacterial activity, highlighting BJ6 as a key bioactive component.