Green Extraction of Phenolic Compounds from Blueberry (Vaccinium corymbosum L.) By-Products Using Natural Deep Eutectic Solvents for Cosmetic Applications ^†

The valorization of agri-food by-products generated during juice extraction represents a key strategy within circular economy frameworks, as it reduces the environmental impact of waste disposal while creating added value and improving the food supply chain. In this work, five betaine-based natural deep eutectic solvents (NaDES) differing in their hydrogen-bond donors, namely citric acid, lactic acid, acetic acid, glycerol, and ethylene glycol, were used for the green extraction of blueberry pomace, a largely underutilized by-product that is nevertheless rich in bioactive compounds. The extracts were characterized by liquid chromatography coupled with diode-array and tandem mass spectrometric detection, allowing targeted profiling of anthocyanins and non-anthocyanin phenolics, including phenolic acids, flavonoids, and phenolic aldehydes. The extraction performance of NaDES was benchmarked against conventional solvents (water and ethanol) to evaluate differences in selectivity and efficiency toward distinct phenolic classes. Antioxidant capacity was determined using DPPH and ABTS radical scavenging assays. Among the NaDES systems, the betaine–citric acid NaDES extract exhibited notable phenolic recovery together with marked radical scavenging activity. After evaluating its inhibitory activity against elastase and tyrosinase, enzymes involved in the skin aging process, the selected NaDES extract was incorporated into a natural-based antiaging cosmetic formulation, and its main physicochemical properties were assessed to verify suitability for topical application. This study demonstrated that the use of NaDES represents an environmentally friendly and sustainable approach to transform blueberry by-products into high-value, safe, and ready-to-use cosmetic functional ingredients without the need for solvent removal.