Synergistic antibacterial effects and metabolomic insights in Cyperus esculentus L. leaf-stem extracts against Staphylococcus aureus

Introduction: L. (tiger nut) exhibits promising antibacterial properties, yet gaps persist in understanding its specific bioactive components, synergistic mechanisms, and metabolic impact on bacterial pathogens. Methods: . Methods included Kirby-Bauer assays, scanning electron microscopy (SEM), growth curve analysis, response surface optimization, and wide-targeted metabolomics. Results: Key findings revealed: (1) Stem/leaf extracts outperformed tuber extracts in antibacterial activity, with their combination yielding synergistic effects; (2) Flavonoids (naringenin, acacetin, diosmetin, silybin A) demonstrated dose-dependent inhibition, disrupting cell wall/membrane integrity via SEM-confirmed morphological damage; (3) Optimal synergistic mix (2.84 μg/mL naringenin, 2.68 μg/mL acacetin, 3.04 μg/mL diosmetin, 3.08 μg/mL silybin A) achieved potent suppression across bacterial growth phases; (4) Metabolomic perturbations implicated sulfur metabolism, oxidative stress responses, and lipid remodeling in antibiosis. Discussion: stem/leaf extracts as high-value, resource-efficient antibiotic alternatives for animal feed, leveraging synergistic phytochemistry and mechanistic insights to combat antimicrobial resistance.