Deep eutectic solvents (DESs) are promising green solvents for the extraction of compounds from food byproducts. Hazelnut (Corylus avellana L.) is one of the most commonly cultivated tree nuts worldwide. The skin represents one of the major byproducts of the hazelnut industry and accounts for 2.5% of the total hazelnut kernel weight. It is a rich source of phenolic compounds like flavan-3-ols, flavonols, dihydrochalcones, and phenolic acids. In this work, fifteen DESs based on choline chloride and betaine, with different compositions, were studied in order to test their phenolic compounds extraction efficiency through the determination of their total concentration via Folin–Ciocalteu assay. A qualitative analysis of extracted phenolic compounds was assessed by HPLC with UV and MS detection. Using the DES with the best extraction efficiency, a new ultrasound-assisted solid liquid extraction (UA-SLE) method was optimized though the response surface methodology (RSM), taking into account some extraction parameters. Efficient recovery of extracted phenolic compounds was achieved using a 35% water solution of choline chloride and lactic acid (molar ratio 1:2) as an extraction solvent, working at 80 °C and with a solid-to-solvent ratio of 1:25 gmL⁻¹. The optimized conditions made it possible to recover 39% more phenolic compounds compared to a classic organic solvent.

The advanced glycation end-products (AGEs) arise from non-enzymatic reactions of sugar with protein side chains, some of which are oxido-reductive in nature. Enhanced production of AGEs plays an important role in the pathogenesis of diabetic complications as well as in natural aging, renal failure, oxidative stress, and chronic inflammation. The aim of this work is to study antiglycation effects of polyphenol compounds extracted by hazelnut skin that represents an example of polyphenols-rich food industry by-product, on AGEs formation. AGEs derived from incubation of bovine serum albumin (BSA) and methylglyoxal (MGO) were characterized by fluorescence. The phenolics identification and total polyphenol content in hazelnut skin extracts were analyzed by HPLC-MS and the Folin–Ciocalteu method, respectively. Antioxidant efficacy was evaluated by monitoring total antioxidant activity to assess the ABTS radical scavenging activity of samples by TEAC assay and oxygen radical absorbance capacity (ORAC) assay, expressed as millimoles of Trolox equivalents per gram of sample. Data here presented suggest that phenolic compounds in hazelnut skin have an inhibitory effect on the BSA-AGEs model in vitro, and this effect is concentration-dependent. The putative role of the hazelnut skin antioxidative properties for hindering AGEs formation is also discussed. Because of AGEs contribution to the pathogenesis of several chronic diseases, foods enriched, or supplements containing natural bioactive molecules able to inhibit their production could be an interesting new strategy for supporting therapeutic approaches with a positive effect on human health.