Synergistic ultrasound- and vortex-assisted extraction of lobetyolin from Codonopsis tangshen using a supramolecular ternary deep eutectic solvent: yield optimization and antioxidant activity evaluation

Herein, a supramolecular ternary deep eutectic solvent coupled within-situultrasound-assisted extraction (STDES-ISUSE) was developed to extract lobetyolin (LBT) inCodonopsis tangshen. The hydroxypropyl-β-cyclodextrin: lactic acid: glycerol (HP-β-CD: LA: Gly) system stood out to extract LBT among the twenty formulations tested. The optimal extraction conditions-water content of 46% (v/v), liquid/solid ratio of 29 mL/g, ultrasound time of 34 min, ultrasound power of 240 W, and vortex time of 10 min-were established via a hybrid response surface methodology-artificial neural network-genetic algorithm (RSM-ANN-GA) paradigm. Under these conditions, the LBT yield reached 0.613 ± 0.011 mg/g, significantly exceeding that of conventional methods. Twenty compounds were identified via UHPLC-Q-TOF-MS, encompassing two phenolic acids, two polyacetylenic glycosides, five fatty acids, two glycosides, one iridoids, and one alkaloids, while a tailored HPLC method enabled precise LBT quantification. Mechanistic investigations, combining FT-IR corroboration of STDES fabrication, SEM visualization, and MD simulations, collectively revealed that the STDES-ISUSE approach potentiates extraction through synergistic cell-wall disintegration and enhanced LBT solubilization. In vitro antioxidant testing further substantiated the bioactivity of the extracts. In summary, this work delivers a green, high-efficiency extraction protocol for bioactive targets fromC. tangshen, offering a practical route toward sustainable phytochemical recovery and the broader implementation of green extraction practices in natural product research.