Innovative microwave-assisted extraction with biobased solvents to enhance the recovery of bioactive extractable and non-extractable polyphenols from lemon peels.

This study develops, for the first time, a sustainable method to extract extractable (EPPs) and non-extractable polyphenols (NEPs) from lemon peels using microwave-assisted extraction (MAE) with biobased solvents. A simplex-centroid design optimized EPPs extraction using γ-valerolactone (GVL), ethyl acetate (EtAc), and cyclopentyl methyl ether (CPME) (59.4:37:3.6, v/v/v, 6 min, 50 °C), yielding extracts with strong antioxidant and anti-inflammatory properties. NEPs were recovered from the lemon peels EPPs residue for the first time by testing different natural deep eutectic solvents (NADES) combined with MAE. Choline Chloride: Citric Acid (1:2) with 50 % ethanol was selected as the best solvent, with optimized MAE conditions of 57.3 % ethanol, 57.8 min, and 68 °C. These NEPs extracts exhibited superior bioactivity compared to conventional acid and alkaline hydrolyses. UHPLC-DAD-Orbitrap-MS identified key bioactive compounds responsible for anti-inflammatory (e.g., limocitrin) and antioxidant capacity (e.g. syringetin). Sustainable extracts also demonstrated interesting anticarcinogenic properties while maintaining the viability of healthy cell lines.