Green extraction of natural antioxidant polyphenols from Celastrus orbiculatus using ultrasound-assisted deep eutectic solvents: Computational screening, process optimization, and mechanistic insights

COSMO-RS identified Bet-LA as the optimal green solvent for antioxidant recovery. • ANN-GA accurately optimized the non-linear ultrasound-assisted extraction process. • Bet-LA combined with ultrasound increased polyphenol yield by 1.86-fold vs ethanol. • MD simulations and SEM revealed the micro-level synergistic extraction mechanisms. • The green polyphenol extracts exhibited robust in vitro antioxidant capacities. The industrial extraction of bioactive compounds from plant matrices is increasingly shifting towards sustainable and green technologies for pharmaceutical, cosmetic, and functional food applications. In this study, a green and highly efficient strategy combining natural deep eutectic solvents (NADES) with ultrasound-assisted extraction (UAE) was developed to recover antioxidant polyphenols from Celastrus orbiculatus Thunb. To avoid empirical trial-and-error, the conductor-like screening model for realistic solvents (COSMO-RS) was first employed to predict the thermodynamic solubility of representative polyphenols, identifying the betaine-lactic acid (Bet-LA) system as the optimal solvent. Subsequently, an artificial neural network-genetic algorithm (ANN-GA) model was utilized to map and optimize the non-linear extraction parameters. Under optimal conditions (liquid-solid ratio of 33 mL/g, ultrasonic time of 36 min, and power of 520 W), the polyphenol yield reached 22.89 ± 0.41 mg GAE/g DW, representing a 1.86-fold increase over conventional 70% ethanol extraction. UPLC-Q Exactive/MS analysis revealed a significant enrichment of bioactive phenolics, predominantly epicatechin. Furthermore, scanning electron microscopy (SEM) and molecular dynamics (MD) simulations elucidated the extraction mechanisms: ultrasound-induced cavitation aggressively disrupted the plant cell walls, while the dense hydrogen-bonding network of Bet-LA provided superior solvation energy and affinity for the target polyphenols. Crucially, the green Bet-LA extracts exhibited robust in vitro antioxidant capacities (DPPH, ABTS, and FRAP). Overall, this study provides a theoretical and practical framework for the sustainable extraction of plant-derived polyphenols, highlighting their promising potential as natural antioxidants in various bio-based industries. Download: Download high-res image (221KB) Download: Download full-size image