Green Extraction of Luteolin from Chrysanthemi Indici Flos Using Deep Eutectic Solvents: Mechanistic Insights, Antioxidant Activities, and Synergistic α-Glucosidase Inhibition

Luteolin, a flavonoid, exhibits inhibitory activity against α-glucosidase, an enzyme target relevant to glycemic regulation. This study reports the development of a green extraction process employing deep eutectic solvents (DESs). From a COSMO-SAC (Conductor-like Screening Model for Segment Activity Coefficient)-based screening of 128 candidate DESs, choline chloride/1,4-butanediol was identified as the optimal solvent and experimentally validated. Response surface optimization yielded a maximum luteolin yield of 1.394 mg/g under conditions of 40 mL/g liquid-to-solid ratio, 30% water content, 48 °C, and 30 min, representing 1.37- and 1.34-fold yields of methanol and ethanol, respectively. Molecular dynamic simulations indicated that electrostatic interactions predominantly govern extraction efficiency. Greenness metrics (Modified Green Analytical Procedure Index (MoGAPI) and Analytical GREEnness calculator (AGREE)) confirmed favorable sustainability. The extract displayed notable antioxidant capacity and mixed-type inhibition of α-glucosidase with synergistic potentiation of acarbose. These findings support sustainable luteolin extraction and its further investigation in postprandial glycemic regulation.