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

Abstract

Diabetes 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.