Suksawat T.Boonthaworn N.Junseedeechai Y.Kitisripanya T.Chewchinda S.Aneklaphakij C.Mahidol University2025-10-112025-10-112025-10-01Journal of Pharmaceutical Innovation Vol.20 No.5 (2025)18725120https://repository.li.mahidol.ac.th/handle/123456789/112488Diabetes remains a critical public health issue, driving demand for safe, affordable, and eco-friendly therapeutic alternatives. Pomelo peel, rich in the flavonoid naringin, shows promising antidiabetic potential. This study introduces a green extraction approach using natural deep eutectic solvents (NADESs), providing a safer alternative to conventional organic solvents. Among six Thai pomelo cultivars, Khao Nam Phueng contained the highest naringin content (4.28% w/w dry weight), significantly exceeding Khao Yai (2.74%w/w DW). Regional variation was observed, with peels from Nakhon Pathom yielding 4.01% DW versus 1.62% DW from Pathum Thani. A seasonal decline was noted, as early-harvest fruit had nearly twice the naringin of late-season samples. Initial NADES screening identified choline chloride: citric acid (1:1) as most effective, extracting 0.19%w/w DW naringin, followed by malic acid (0.18% w/w DW) and oxalic acid (0.13% w/w DW). Box-Behnken optimization improved the yield to 0.28% w/w. The extract exhibited potent α-glucosidase inhibition (IC₅₀=9.99 µg/mL) and strong antioxidant activity, as measured by the ferric reducing antioxidant power (FRAP) assay (192.3 TE/µg DW). Antiglycation activity was moderate (IC₅₀=104.75 µg/mL), lower than naringin standard (IC₅₀=36.77 µg/mL), likely due to solvent-matrix interactions. Predictive response surface models showed high accuracy, and the extract remained chemically stable over six months with minimal degradation (0.24–0.25% w/w DW). In conclusion, this study presents a scalable, green method to valorize pomelo peel waste into bioactive antidiabetic extracts. The findings support broader NADES applications and highlight cultivar and harvest timing as critical to maximizing recovery.Pharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1007/s12247-025-10084-72-s2.0-10501780134419398042