Optimization of ultrasound‐assisted extraction using natural deep eutectic solvents for the green production of a polyphenol‐enriched antioxidant extract from ‘Harumanis’ mango ( Mangifera indica L.) leaves

Abstract BACKGROUND ‘Harumanis’ ( Mangifera indica L.) mango leaves are an underutilized agricultural by‐product, rich in polyphenols, with promising antioxidant properties. This study aimed to develop and optimize a green extraction process using ultrasound‐assisted extraction with natural deep eutectic solvents (UAE‐NaDES) to obtain polyphenol‐enriched extracts with enhanced antioxidant activity. Three solvent systems were evaluated, namely choline chloride: glycerol (CCG), choline chloride: 1,2‐propanediol (CCP), and urea: glycerol (UG). The effects of extraction time (20–60 min), temperature (30–70 °C), solid‐to‐liquid ratio (1:20–1:60, w/v), water content (20% to 60%), and hydrogen bond acceptor (HBA)‐to‐hydrogen bond donor (HBD) molar ratio (1:1–1:5) were investigated using single‐factor experiments and subsequently optimized through response surface methodology (RSM). Extraction performance was evaluated based on total phenolic content (TPC), total flavonoid content (TFC), and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging activity. RESULTS The optimized extraction conditions for UG were 29 min, 70 °C, 1:60 (w/v), 40% water, and a 1:3 molar ratio. For CCG, the optimized conditions were 40 min, 43 °C, 1:60 (w/v), 50% water, and a 1:5 molar ratio. For CCP, the optimized conditions were 50 min, 70 °C, 1:60 (w/v), 50% water, and a 1:4 molar ratio. Among the solvent systems that were evaluated, CCP exhibited the highest overall extraction performance, yielding a TPC of 13.49 ± 0.54 μg gallic acid equivalent (GAE) g −1 dry powder and a TFC of 37.50 ± 0.98 μg quercetin equivalent (QE) g −1 dry powder, with a DPPH radical scavenging IC 50 of 527.01 ± 18.45 μg mL −1 . Compared with the single‐factor approach, RSM significantly improved TPC ( P < 0.01) and DPPH radical scavenging activity ( P < 0.001), whereas the improvement in TFC was not statistically significant ( P > 0.05). CONCLUSION Ultrasound‐assisted extraction with natural deep eutectic solvents offers a promising green strategy for valorizing ‘Harumanis’ mango leaves as a source of polyphenol‐rich extracts. The CCP system exhibited the most suitable overall extraction performance and antioxidant activity. The integration of RSM improved TPC and DPPH radical scavenging activity, supporting its application in process optimization. These findings highlight the potential of optimized UAE‐NaDES extraction for producing mango leaf‐derived ingredients for nutraceutical, functional food, and cosmetic applications. © 2026 Society of Chemical Industry.