Green ultrasound‑assisted deep eutectic solvent extraction of flavonoid enzyme inhibitors from Blumea aromatica: process optimization, characterization, and mechanistic insights into α‑glucosidase and tyrosinase inhibition.

A green ultrasound-assisted deep eutectic solvent (UAE-DES) method was optimised for extracting flavonoid enzyme inhibitors from Blumea aromatica. Optimal conditions (choline chloride-1,4-butanediol 1:3 molar ratio, 43% water content, 50 mL/g liquid-to-solid ratio, 80 °C ultrasound for 48 min) yielded 3.15% total flavonoids, 45.2% higher than 50% ethanol extraction. Scanning electron microscopy confirmed cell wall disruption. The UAE-DES extract showed the strongest enzyme inhibition among all extracts tested (IC₅₀ 35.872 ± 0.294 µg/mL for α-glucosidase, 9.126 ± 0.285 μg/mL for tyrosinase), though the α-glucosidase inhibition was much weaker than acarbose, while tyrosinase inhibition was comparable to kojic acid. Six flavonoids were identified via UPLC-Q-Orbitrap HRMS, including scutellarein and corylin. Molecular docking revealed strong binding affinities (≤ -5 kcal/mol), with corylin showing the highest binding to both enzymes through hydrogen bonds and van der Waals interactions. This approach supports sustainable discovery of natural enzyme inhibitors for antidiabetic and skin-whitening applications.