Hazelnut skin: from food waste to nutraceutical source. An investigation on its chemical composition, protective role against Advanced Glycation End-products (AGEs)-induced damage and in silico screening analysis

Bioactive food compounds, like polyphenols, are known for their positive effects on human health. Polyphenols are a large group of secondary metabolites in plants and are, therefore, present in the human diet. Interestingly, it has been reported that long-term consumption of a diet rich in polyphenols has a protective effect against several diseases. In addition to anti-inflammatory properties, many studies have confirmed that different polyphenol substances have antiglycation functions in vivo and in vitro. Advanced glycation end-products (AGEs) derive from spontaneous modification of proteins or amino acids through reducing sugars during Maillard reaction or non-enzymatic glycation. Glycation and the accumulation of AGEs are known to occur during physiological aging, diabetes, chronic diseases and in the development of tumors. Elevated blood glucose or methylglyoxal levels in diabetic patients result in an increase of AGEs. Despite the antidiabetic therapeutic options currently available, new, effective, and safe interventions are urgently required, because diabetes mellitus (DM) is still considered a health emergency. In this work we have characterized polyphenols-rich extract obtained from hazelnut skins, a food waste product. Qualitative and quantitative phenolic compounds contents and antioxidant capability were also determined for further studying their relationship with AGE-inhibitory activity. We have evaluated the possible inhibitory effects on AGEs formation, the cytotoxic effect and capacity of our extract to protect THP-1 derived macrophages from AGEs-induced damage in vitro, demonstrating that hazelnut skin polyphenols extract (HSE) shows positive effect on cell viability. After treatment with AGEs, macrophages express a high level of pro-inflammatory cytokines and reactive oxygen species (ROS), while co-treatment with polyphenol extract led to reduced levels of both TNF-α and IL1-β cytokines and reduced ROS production. To date, our studies suggest that polyphenols-rich extracts have positive effect although further analysis should be conducted to identify the molecular pathway involved in AGEs-polyphenols interaction. Finally, we have characterized the interaction between some compounds in our hazelnut skin extract with glucose transporters of class I (GLUTs) to identify potential GLUT-targeting drugs, based on a combination of structural biology by bioinformatics analysis (molecular docking). Our studies, although preliminary, have revealed a possible interaction between glucose transporters and polyphenols, in agreement with studies in the literature. This research was funded by “Soremartec Italia Srl” (Alba, Cuneo, Italy) to promote a waste product, hazelnut skin, with bioactive potential.