Ultrasound-assisted temperature-responsive deep eutectic solvents for simultaneous extraction and separation of the alkaloid components from the white pepper

In this study, eighteen LCST-type temperature-responsive deep eutectic solvents (TRDESs) were developed for the ultrasound-assisted extraction of alkaloids from white pepper, using piperine (PIP) as the indicator. After optimization, the best conditions were identified as lidocaine/valeric acid (1:1) as the solvent, a solid‑to‑liquid ratio of 1:40 mg/mL, 75°C, and 30 min of ultrasound, achieving a PIP yield of 33.7502 mg/g. By utilizing the temperature‑responsive behavior of TRDES, PIP was separated solely by adjusting temperature and water content, without additional reagents, resulting in a crude extract containing 122.3 μg/mg of PIP. Subsequent analysis confirmed that the TRDES‑based ultrasound‑assisted extraction did not affect the antioxidant or anti‑diabetic (α‑glucosidase and α‑amylase inhibitory) activities of the extract. The TRDES system also showed good reusability, retaining over 85% of its initial extraction efficiency after five cycles. Density functional theory calculations revealed that ultrasound‑assisted extraction proceeds via hydrogen bonding between lidocaine/valeric acid and the five‑membered ring of PIP. With a high GAPI score of 82, this method offers a clearly greener and more sustainable alternative to conventional extraction techniques. This work integrates the novel green solvent TRDES with ultrasound‑assisted extraction, laying a key foundation for developing environmentally friendly processes in natural product preparation.