In this study, an efficient natural deep eutectic solvent (NADES, 30 mL/100 mL water content) was identified and coupled with ultrasonication to extract phenolic compounds from broccoli leaves (BLs). A NADES prepared using choline chloride and 1,2-propylene glycol (ChCl-PG) at a molar ratio of 1:2 provided the highest extraction rate. Phenolic extraction conditions were optimized using single-factor experiments coupled with response surface methodology. The optimal parameters were as follows: solvent-to-solid ratio, 36.35 mL/g; extraction temperature, 49.5 °C; extraction time, 31.4 min; and ultrasonic power, 383 W. Under these parameters, the phenolic yield was 4.91 mg/g. Quantitative analysis revealed that neochlorogenic acid was the most abundant phenolic compound, followed by ferulic acid, erucic acid, quinic acid, chlorogenic acid, and caffeic acid. Furthermore, the isolation of broccoli leaf phenolics (BLPs) using ultrasonication-assisted extraction coupled with ChCl-PG (UAE + ChCl-PG) yielded a higher total phenolic content than other extraction methods. These BLPs also had greater antioxidant activity (DPPH, ABTS assay) and inhibitory effects against S. aureus, E. coli, and Salmonella. DSC, FT-IR, and SEM results further validated the synergistic efficiency of the new phenolic extraction process. Accordingly, this study offers an efficient and green alternative strategy for extracting phenolic compounds from plant by-products.
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