VALORIZATION OF BY-PRODUCTS FROM AGRI-FOOD SUPPLY CHAINS FOR THE DEVELOPMENT OF FUNCTIONAL INGREDIENTS AND NUTRACEUTICAL

The integration of sustainable practices, advanced analytical methodologies, and the valorization of bioactive compounds derived from agri-food supply chains is crucial for addressing global challenges in health, industry, and environmental management. This doctoral research explores the potential of agro-industrial by-products, focusing on their transformation into valuable resources through eco-friendly processes and state-of-art analytical characterization. A significant component of this research is the study of bergamot by-products. A scalable, eco-friendly extraction process was developed to obtain phytochemically complex materials rich in flavonoids and other bioactive compounds, such as stachydrine. This bergamot-derived extract demonstrated promising anti-inflammatory and antioxidant properties, which resulted to be helpful in treating obesity in an animal model and related physiological dysfunctions, offering a sustainable and efficient approach to valorize industrial residues. By avoiding conventional chemical purification steps and focusing on preserving bioactive compounds, this research highlights the potential of bergamot in nutraceutical applications, including the prevention of oxidative stress and inflammation-related conditions. The study also focuses on the valorization of white grape skins (WGS), a by-product of grappa production, which were transformed into VITUVA®, an industrial-scale extract with a balanced polyphenol profile. Employing green and water-based extraction methods, the study underscores the scalability, safety, and environmental compatibility of this approach. Advanced LC-HRMS profiling identified metabolites such as flavonoids and phenolic acids, linked to the extract's significant anti-inflammatory activity (via NF-κB modulation) and antioxidant properties, despite a limited NRF2 activation. These findings highlight the dual potential of VITUVA® in addressing inflammation and oxidative stress, opening the way for its application in the nutraceutical field and cosmetics. In parallel, this research investigates the parahormetic mechanisms underlying the health-protecting effects of grape seed procyanidins. These compounds demonstrated a remarkable capacity to modulate redox signaling and mitigate oxidative damage through the conversion into species, such as 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, that acts as electrophiles and thus activating Nrf2 pathway. By focusing on their hormetic effects, this study highlights the delicate balance between beneficial and potentially adverse responses at different doses, a crucial aspect for future therapeutic applications. Additionally, pre-ADMET evaluations of 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, the main bioactive metabolite derived from proanthocyanidins consumption, provided valuable insights into its pharmacokinetic profile, safety, and bioactivity, further supporting the potential in nutraceutical and pharmaceutical contexts of proanthocyanidins. Overall, this doctoral research bridges the principles of circular economy, green chemistry, and advanced omics techniques, demonstrating how the transformation of industrial by-products into high-value compounds can drive innovation while reducing environmental impact. By integrating environmental oversight with scientific discovery, the findings contribute to a sustainable model for industrial processes and pharmaceutical development. Future directions involve not only exploring the application of products such as VITUVA®, grapeseed procyanidins and bergamot-derived extracts in cosmetic formulations and nutraceuticals but also continuing studies to elucidate the mechanisms of action of bergamot compounds and grape-derived polyphenols. These efforts aim to definitively establish their role in advancing the circular economy and sustainability within the domain of raw materials for nutraceutical and cosmetic use, highlighting their phytochemical value alongside their eco-sustainability potential.