Sustainable strategies to obtain bioactive compounds from citrus peels by supercritical fluid extraction, ultrasound-assisted extraction, and natural deep eutectic solvents

• An optimization of UAE-NaDES extraction of bioactive polyphenols from citrus peels was performed. • ChCl:TA provided the highest polyphenols recovery from grapefruit and lemon peels. • ChCl:Gly was the most efficient NaDES to obtain polyphenols from lime peels. • SC-CO 2 allowed to obtain anticholinergic terpenoids from citrus peels. • A sequential SC-CO 2 + UAE-NaDES extraction provided a wide exploitation of this residue. This work proposes a sustainable sequential extraction of bioactive terpenoids and phenolic compounds from grapefruit, lime, and lemon peels using supercritical CO 2 extraction (SC-CO 2 ) and ultrasound-assisted extraction (UAE) with natural deep eutectic solvents (NaDES). NaDES screening demonstrated that Choline Chloride:Tartaric acid (1:2) for grapefruit and lemon peels, and Choline Chloride:Glycerol (1:2) for lime peels with 50% water yielded the highest phenolic contents. Cryogenic grinding (CR) and SC-CO 2 pretreatments before UAE-NaDES did not improve phenolic recovery compared to direct UAE-NaDES. Pretreatments reduced particle size and increased surface tension, lowering UAE-NaDES efficiency. The direct UAE-NaDES extracts showed the highest phenolic diversity, with naringin in grapefruit and hesperidin in lime and lemon peels as the major compounds identified by HPLC-QTOF-MS. However, SC-CO 2 obtained before UAE-NaDES presented higher anticholinergic capacity and a rich terpenoid profile identified by GC-Q-MS. Results demonstrate the potential of this sequential strategy for a more holistic exploitation of citrus peels.