Revealing inhibitory activity of luteolin from Vietnamese Jatropha Podagrica Hook against Staphylococcus aureus by integrating in vitro and in silico approaches.

Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) are increasingly prevalent pathogens associated with multidrug-resistant infections in both hospital and community. In this study, we evaluated the antibacterial activity of Jatropha podagrica Hook. extracts collected from Vietnam against S. aureus and MRSA. Among various plant parts, the root extract exhibited the most potent activity, with an MBC/MIC ratio of 2.0, indicating bactericidal properties. To elucidate the mechanism of action and identify potential bioactive constituents, a virtual screening of 43 phytochemicals from J. podagrica was performed against sortase A (SrtA), a key virulence factor of S. aureus, using molecular docking. Among them, luteolin demonstrated the highest binding affinity (ΔG = - 9.3 kcal/mol) and formed multiple stable interactions with catalytically important residues such as His120, Cys184, and Arg197. Further molecular dynamics simulations over 100 ns confirmed the structural stability of the luteolin-SrtA complex, with minimal RMSD fluctuation and sustained hydrogen bonding throughout the simulation. Protein-ligand contact analysis revealed consistent interactions involving hydrogen bonds, hydrophobic contacts, and π-alkyl interactions, supporting a well-anchored and dynamically stable binding pose. In addition, in vitro experiments results showed that luteolin inhibited the growth of S. aureus and MRSA at a MIC of 31.25 µg/mL and showed a bacteriostatic profile with an MBC/MIC ratio > 4.0. This study provides the first comprehensive report on the antibacterial potential of J. podagrica from Vietnam, and highlights luteolin as a promising lead compound targeting bacterial virulence through SrtA inhibition, supporting its further development as an adjunctive or alternative anti-MRSA therapeutic agent.