Flavonoid-Rich Cyperus esculentus Extracts Disrupt Cellular and Metabolic Functions in Staphylococcus aureus

The escalating threat of antibiotic resistance, particularly from <i>Staphylococcus aureus</i> (<i>S. aureus</i>), has become a critical challenge in both public health and animal husbandry. The extensive use of conventional antibiotics in livestock production accelerates the emergence of resistant strains, heightening risks to food safety and human health. Although plant-derived bioactive compounds are increasingly recognized as promising alternatives to synthetic antimicrobials, the mechanisms underlying their efficacy-and the potential for synergistic action among different plant parts-remain poorly understood. In particular, the antibacterial interactions among extracts from different tissues of <i>Cyperus esculentus</i> L. (<i>C. esculentus</i>), a plant rich in flavonoids and phenolics, have yet to be systematically evaluated. Here, we investigated the antibacterial properties and mechanisms of ethanol extracts from the tubers, stems-leaves and their mixture of <i>C. esculentus</i> against <i>S. aureus</i>. Using Oxford cup diffusion assays, scanning electron microscopy (SEM), bacterial growth kinetics, and untargeted metabolomics, we assessed both phenotypic inhibition and metabolic disruption. The mixed extract exhibited the strongest antibacterial effect, producing a 26.15 mm inhibition zone-approximately 7% greater than that of single-part extracts-and induced cell wall rupture and disintegration as observed by SEM. Growth curve analyses revealed time-dependent bacterial suppression, while metabolomic profiling identified 845 differential metabolites, indicating disturbances in amino acid, lipid, and nucleotide metabolism. Flavonoids such as acacetin, diosmetin, naringenin, and silybin A were identified as principal active compounds contributing to these effects.