Development of Naringin Extract from Pomelo Peel Using Natural Deep Eutectic Solvent System as Green Technology for Antidiabetic Purpose: Box-Behnken design approach

Diabetes remains a critical public health issue, intensifying the demand for safe, affordable, and eco-friendly therapeutic alternatives. Pomelo peel, rich in the flavonoid naringin, offers promising antidiabetic potential. This study introduces a novel green extraction approach using natural deep eutectic solvents (DES), offering a safer alternative to organic solvents. Among six Thai pomelo cultivars, Khao Nam Phueng exhibited the highest naringin content (4.28% w/w dry weight), significantly surpassing Khao Yai (2.74% w/w DW). Regional variation was also observed: peels from Nakhon Pathom yielded 4.01%, compared to only 1.62% from Pathum Thani. Seasonal decline was evident, with early-harvest fruit showing nearly double the naringin content of late-season samples. Initial screening identified choline chloride:citric acid (1:1) as the most effective DES, extracting 0.19%w/w DW naringin, followed by malic acid (0.18% w/w DW) and oxalic acid (0.13%w/w DW). Optimization using Box–Behnken design improved yield to 0.28% w/w. The extract displayed potent α-glucosidase inhibition (IC₅₀=9.99 µg/mL) and strong antioxidant activity (FRAP=192.3 FEAC/µg DW). Antiglycation activity was moderate (IC₅₀=104.75 µg/mL), lower than pure naringin (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 only slight degradation (0.24–0.25% w/w). This work demonstrates a novel, scalable method to valorize agro-industrial pomelo peel waste into standardized, high-quality antidiabetic extracts using sustainable DES technology. These findings support broader applications of DES in green phytopharmaceutical development and highlight cultivar and harvest timing as key factors in maximizing bioactive compound recovery.