Natural deep eutectic extract of onion peel obtained by different extraction methods: bioaccessibility and cytotoxicity

Onion peel, a major by-product of onion processing, is a rich source of flavonoids and other phenolic compounds that have been associated with antioxidant and anti-inflammatory potential. In this study, the efficiency of ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), ultrasound–enzyme-assisted extraction (UEAE), and enzyme–ultrasound-assisted extraction (EUAE) using a choline chloride/lactic acid-based natural deep eutectic solvent (ChCl–La NADES) was investigated and compared with conventional extraction (CE; 80% methanol) for the recovery of bioactive compounds from onion peel. The resulting extracts were evaluated in terms of total phenolic content (TPC), total antioxidant capacity (TAC), individual phenolic composition, cytotoxicity, and in vitro digestion behavior, with methanolic extracts serving as references. Among all extraction approaches, UEAE exhibited the highest efficiency, yielding significantly greater TPC (2581 ± 38 mg GAE/100 g), TAC (11,625 ± 2360 mg TE/100 g by CUPRAC and 5616 ± 744 mg TE/100 g by DPPH), and total individual phenolics (380.11 ± 0.06 mg/100 g). The UEAE-derived extract was further assessed for cytotoxicity using Caco-2 cell lines, demonstrating low toxicity, with an EC₅₀ value exceeding 1%. Moreover, this extract showed enhanced phenolic retention during in vitro digestion compared to conventional extracts. Overall, the UEAE–NADES approach represents an effective and green strategy for producing an onion peel extract with high bioactivity and non-cytotoxicity within the tested range. These findings highlight its strong potential for application in functional foods, nutraceuticals, and pharmaceutical formulations, contributing to the sustainable valorization of agri-food by-products.