Efficient Extraction of Ursolic Acid from Natural Materials Using Alcohol-based DES Solvents

To enable the efficient extraction of ursolic acid, a non-polar bioactive compound, the applicability of alcohol-based deep eutectic solvents (DESs) was investigated. A series of DESs were prepared by combining a fixed hydrogen bond acceptor, choline chloride (ChCl), with various hydrogen bond donors (HBDs) such as glycerol, ethylene glycol, 1,3-propanediol, 1,2-propylene glycol, and 1,4-butanediol at different molar ratios. To evaluate their potential as green solvents, the cytotoxicity of the alcohol-based DESs was assessed, and the 1,2-propylene glycol-based DESs exhibited the lowest cytotoxicity. Due to the high viscosity of DESs, direct solubility measurements of ursolic acid were limited; thus, the COSMO-SAC model was employed to predict solubility and guide the screening of suitable DESs. Computational results suggested that DESs containing 1,2-propylene glycol and 1,4-butanediol provided superior solubility for ursolic acid. Based on both cytotoxicity and predicted solubility, the DES composed of ChCl and 1,2-propylene glycol at a 1:4 molar ratio was identified as the most biocompatible solvent system. Using this DES, ursolic acid was successfully extracted from rosemary and apple peel. Experimental validation confirmed that PG-based DES (ChCl:1,2-propylene glycol = 1:4) exhibited a solubility 70% lower for ursolic acid than pure ethanol. This study supports a strategic shift toward sustainable extraction technologies using DESs and provides a foundation for future research on their industrial applicability.