Ultrasound-assisted natural deep eutectic solvents for the extraction of flavonoids from Zanthoxylum bungeanum Maxim leaves: COSMO-RS screening, process optimization, and α-glucosidase inhibition mechanism.

This study developed an ultrasound-assisted natural deep eutectic solvent (UAE-NADES) method guided by COSMO-RS for extracting flavonoids from Zanthoxylum bungeanum Maxim leaves. Betaine-urea with 33% water was identified as the optimal solvent. Under optimized conditions, the flavonoid yield reached 224.28 mg RE/g DW, exceeding that of conventional solvents, mainly due to hydrogen bonding and ultrasonic disruption. HPD600 macroporous resin effectively purified the extract, with its adsorption governed by pseudo-second-order kinetics that highlighted surface interactions. Additionally, the NADES used in the extraction showed satisfactory recyclability. The purified extract exhibited strong antioxidant activity and α-glucosidase inhibition. Spectroscopic and molecular docking revealed spontaneous binding via hydrogen bonds and hydrophobic interactions. Quercitrin displayed the strongest inhibition and binding affinity among five flavonoid monomers, acting as the key active component responsible for mixed-type inhibition and enzyme conformational changes. This sustainable strategy facilitates the valorization of Z. bungeanum leaves for functional food and nutraceutical applications.