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

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Abstract
Deep eutectic solvents (DESs) have emerged as sustainable alternatives to conventional or-ganic 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 conven-tional aqueous and ethanolic extraction. UHPLC-DAD and UHPLC-ESI-HRMS analyses iden-tified 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 com-pared with the central experimental point, reaching a maximum alkaloids concentration of 400.1 ppm. The optimized alkaloid-rich extract displayed potent neuroprotective activity, in-hibiting 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. These results demonstrate that DES-assisted extraction is an effi-cient and environmentally sustainable approach for obtaining alkaloid-enriched extracts from B. frutescens and highlight their potential as multitarget neuroprotective agents for Alzheimer's disease management.

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