Hydrophobic deep eutectic solvents as sustainable media for ultrasound-assisted extraction of triterpenoids: a mechanistic and experimental study on Salvia officinalis L.

This work demonstrates that hydrophobic deep eutectic solvents (HDESs) function as environmentally benign and high-performing media for extracting triterpenoids from Salvia officinalis L. under ultrasound conditions. Among screened HDESs, menthol-lactic acid (Men-LA) and menthol-camphor (Men-CP) exhibited the highest extraction efficiencies. Response surface method optimization yielded triterpenoid levels of 77.27 mg g-1 for Men-LA and 72.76 mg g-1 for Men-CP, representing increases of about two to six times compared with traditional organic solvents. Kinetic modeling showed that extraction followed a second-order model, with activation energies indicating a solubilization-controlled mechanism for Men-LA and a mixed diffusion-solubilization mechanism for Men-CP. Computational analyses (ESP and IRI) revealed that strong hydrogen bonding and van der Waals interactions between solvent components and triterpenoid molecules stabilized the solute-solvent complexes, resulting in lower binding energies than ethanol. These interactions mainly involved the carboxyl/hydroxyl groups of oleanolic and ursolic acids as primary polar sites, which engaged in hydrogen bonding with polar sites of the solvent components, while van der Waals contacts were mainly associated with the pentacyclic triterpenoid cores and the hydrophobic moieties of the solvents. Coupling Men-LA with D-101 macroporous resins enabled high triterpenoid recovery (97.11%), elevated triterpenoid content (71.89%), and stable solvent recyclability (>95%), while Men-CP combined with HP-20 also performed efficiently, achieving 94.15% recovery, 68.86% content, and recyclability above 95%. The triterpenoid-rich extracts exhibited strong antioxidant and α-glucosidase inhibitory activities, surpassing those obtained with ethanol, while displaying distinct cytotoxic profiles across different cancer cell lines. Molecular docking confirmed that oleanolic acid and ursolic acid bind stably to the α-glucosidase active site, supporting their strong inhibitory effects. Overall, this integrated experimental and computational investigation highlights HDESs as a mechanistically informed and recyclable green platform for the sustainable extraction of lipophilic bioactives such as triterpenoids.