Deep Eutectic Solvents as an Eco-Efficient Alternative for the Sustainable Recovery of Multitarget Alkaloids from Bocconia frutescens

Deep eutectic solvents (DESs) have emerged as sustainable alternatives to conventional organic solvents for the extraction of bioactive natural products. This study developed a green extraction strategy for recovering neuroactive alkaloids from Bocconia frutescens roots using DES-based systems. Thirteen DES formulations were evaluated and compared with conventional aqueous and ethanolic extraction. UHPLC-DAD and UHPLC-ESI-HRMS analyses identified sanguinarine and chelerythrine as the major benzophenanthridine alkaloids present in the extracts. Among the solvents tested, a citric acid–glucose (1:1) DES exhibited the highest extraction efficiency. Extraction parameters were optimized using a Box–Behnken response surface design, evaluating the effects of plant material-to-solvent ratio, temperature, and effect of water addition. Under optimized conditions, alkaloid recovery increased four-fold compared with the central experimental point, reaching a maximum alkaloids concentration of 400.1 ppm. The optimized alkaloid-rich extract displayed potential neuroprotective activity, inhibiting acetylcholinesterase and butyrylcholinesterase with IC50 values of 2.96 and 46.79 μg/mL, respectively. Additionally, the extract strongly inhibited Aβ1–42 aggregation, exhibiting an IC50 value of 0.70 μg/mL. Finally, to assess the greenness of the analytical method here employed, the green analytical procedure index (GAPI) and the analytical greenness metric approach and software (AGREE version 0.5 BETA) were used, and these metrics show that the ecofriendly character is mainly based on factors such as the low sample size, the use of bio-based solvents and the lack of other hazards associated with handling toxic petroleum-derived solvents. These results demonstrate that DES-assisted extraction is an efficient and environmentally sustainable approach for obtaining alkaloid-enriched extracts from B. frutescens and highlight their potential as multitarget agents for Alzheimer’s disease management.