<![CDATA[The increasing resistance of acne-associated bacteria necessitates the exploration of alternative antibacterial agents from natural sources. This study evaluated the antibacterial potential of Euodia hortensis leaf essential oil against Cutibacterium acnes and Staphylococcus aureus using an integrated in vitro and in silico approach. GC–MS analysis identified menthofuran (47.73%), limonene (18.17%), evodone (17.45%), and viridiflorol (6.58%) as the predominant constituents, with oxygenated monoterpenes and sesquiterpenes as the major chemical classes. Antibacterial activity assessed by disc diffusion assay at 5% concentration showed moderate inhibition, with inhibition zones of 10.75 ± 0.24 mm against C. acnes and 10.60 ± 0.50 mm against S. aureus. Molecular docking analysis based on binding affinity values demonstrated that limonen-10-yl acetate exhibited the strongest interaction with C. acnes lipase (−7.3 kcal/mol), exceeding that of clindamycin (−6.6 kcal/mol), while limonene showed the highest affinity toward tyrosyl-tRNA synthetase (−7.0 kcal/mol). Viridiflorol and caryophyllene oxide also displayed favorable binding energies. These interaction patterns support a multitarget antibacterial mechanism involving inhibition of protein synthesis and bacterial virulence factors. Overall, E. hortensis leaf essential oil shows promise as a natural antibacterial candidate for skin infections, although further in vivo, toxicity, and formulation studies are required.]]>
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