<![CDATA[Staphylococcus aureus is a major Gram-positive microorganism implicated in a wide range of skin infections. The increasing prevalence of antimicrobial resistance among S. aureus emphasizes the need for the development of novel therapeutic interventions. This study evaluated the antibacterial efficacy and analysis the molecular mechanism of Marsdenia tinctoria R.Br. (Tarum Areuy) leaf aqueous extract against S. aureus through integrated in vitro and network pharmacology analyzed. The aqueous extract was prepared by infusion, and its metabolite profile was characterized using UPLC-HRMS. Antibacterial activity was quantitatively investigated using the agar well diffusion method against S. aureus ATCC 6538. Network pharmacology identified ten secondary metabolites with antibacterial potential, seven of which exhibited pharmacokinetic properties that met the established bioavailability criteria (BOILED-Egg method). Protein-protein interaction (PPI) analysis indicated that fifteen key proteins interact with the seven compounds, with quercetin identified as the major bioactive compound activating specific bacterial pathways (SAV0081 and pkrC) in S. aureus. The highest antibacterial effect was observed at an 8% extract concentration with an inhibition zone of 17.03 ± 1.78 mm. Overall, these results confirm that the aqueous extract of M. tinctoria leaves contains potential metabolites as antibacterials that could be further developed as therapeutic agents for the treatment of S. aureus infections.]]>
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