Molecular Design and Experimental Study of Deep Eutectic Solvents Extraction of Polydatin from Polygonum cuspidatum

As the main constituent of Polygonum cuspidatum, polydatin (PLD) possesses a diverse array of pharmacological activities. However, its poor water solubility and stability pose substantial challenges to its efficient extraction and further development. Deep eutectic solvents (DESs) are highly suitable media tailored to the molecular properties of active ingredients as well as their extraction and developmental requirements. According to the thermodynamic analysis of COSMO-RS, betaine (Bet)-glycerol (Gly) was identified as the optimal DES. And the optimal extraction conditions were established as follows: 28:1 mL/g of liquid-material ratio, 54 min of extraction time, and 246 W of ultrasonic power. The PLD yield was 20.34 ± 0.55 mg/g, which was 2.1-fold higher than that of ethanol extraction. Furthermore, the underlying extraction mechanism is explored by SEM, FT-IR, ¹H NMR, and molecular dynamics simulations. The primary driving force underlying the extraction of PLD via Bet-Gly interactions is hydrogen bonding. And the most negative interaction energy between PLD and Bet-Gly reached -994.72 kcal/mol, whereas the highest hydrogen bond abundance (36.05%) was observed between PLD and Gly. Moreover, the DES-based extract exhibited excellent antioxidant activity, noncytotoxicity, and superior stability, which offer compelling evidence for its safe and effective application in multiple biomedical domains. Hence, this study provided a robust theoretical foundation for advancing the rational design of DES and the sustainable application of excess plant resources.