Ultrasound-Assisted Deep Eutectic Solvent Extraction of Polysaccharides: Mechanistic Foundations, Structural Consequences, and Process Optimization.

Ultrasound-assisted deep eutectic solvent (DES) extraction has emerged as a promising green and intensified strategy for recovering natural polysaccharides from plant, algal, fungal, and other biological matrices. By coupling acoustic cavitation with tunable solvent microenvironments, this approach can enhance cell-wall disruption, solvent penetration, mass transfer, and polysaccharide solubilization while reducing reliance on harsh acidic, alkaline, or organic solvents. However, extraction efficiency alone is insufficient to define process quality because ultrasound-assisted DES systems may also reshape the molecular weight distribution, monosaccharide composition, uronic acid or sulfate content, substitution pattern, charge density, conformation, surface morphology, and physicochemical behavior. These structural consequences directly influence downstream bioactivities, including antioxidant, hypoglycemic, prebiotic, anti-inflammatory, and anti-ulcerative colitis effects. This review critically summarizes the mechanistic foundations of ultrasound-DES synergy, analyzes how extraction conditions determine polysaccharide structural outcomes, and highlights the importance of linking structure with functionality. Emerging data-driven approaches, including solvent prescreening, COSMO-RS, and machine learning-assisted process optimization, are also discussed as supporting tools for navigating the multidimensional extraction space. However, their current application to the direct prediction of polysaccharide structural outcomes remains limited. Future progress will require standardized datasets, advanced structural characterization, causal structure-activity validation, and scalable process engineering. Overall, ultrasound-assisted DES extraction should be viewed as a structure-sensitive extraction platform whose performance depends on the coordinated control of solvent properties, acoustic conditions, biomass characteristics, and downstream processing.