Abstract
RESULTS ACHIEVED The project successfully developed and characterized a broad panel of extracts obtained from agro-food and marine waste through environmentally compatible approaches. Chemical analyses confirmed that the selected biomasses are rich in phenolic compounds and other secondary metabolites with antioxidant, anti-inflammatory and antimicrobial potential, demonstrating the feasibility of converting residual materials into biologically active preparations. In the neuroinflammation research line, oleocanthal, an olive-derived secoiridoid, was evaluated in lipopolysaccharide-activated BV-2 microglial cells. Oleocanthal reduced the production of pro-inflammatory cytokines, downregulated inflammatory gene expression, attenuated oxidative stress and enhanced microglial phagocytic activity. Proteomic analysis showed that it counteracted the lipopolysaccharide-induced modulation of 31 proteins, including gelsolin, clathrin, ACOD1 and several 14-3-3 protein isoforms. These findings identify previously unrecognized molecular targets and provide a strong rationale for the future recovery of oleocanthal and related secoiridoids from olive-processing by-products. Tomato-skin and pomegranate-peel extracts obtained through green procedures were tested in human primary gingival epithelial cells exposed to an inflammatory stimulus. The extracts strengthened cellular antioxidant defences, including increased SOD1 expression, and reduced inflammatory mediators such as TNF-α and MCP-1. Their antioxidant, anti-inflammatory and antibacterial activities support the use of food-waste-derived compounds in oral-care applications and suggest broader relevance for limiting peripheral inflammatory processes. Citrus-processing waste was valorised using Natural Deep Eutectic Solvents. The resulting extracts showed a high polyphenol content, with hesperidin as the predominant compound. In human keratinocytes, the extracts reduced intracellular hydrogen peroxide, promoted wound closure and partially protected against genotoxic damage. These results indicate antioxidant and regenerative properties relevant to skin resilience and demonstrate the potential of citrus waste as a sustainable source of functional ingredients. A chestnut by-product extract was chemically characterized and investigated in the human MNNG osteosarcoma cell line. The results showed preliminary anti-inflammatory and pro-apoptotic effects. Proteomic and pathway analyses indicated inhibition of TEAD1, a transcription factor that cooperates with YAP1 in tumour-cell growth and migration, together with activation of the ferroptosis pathway and reduced abundance of proteins involved in mitochondrial dynamics, cell adhesion and membrane organization, including TOMM20 and CD63. These findings support the potential of chestnut waste-derived compounds to modulate cancer-related survival pathways. Additional phytochemical, in vitro and in silico studies on Chaetomorpha linum, saffron tepals, hemp leaves and sweet-cherry waste identified bioactive profiles with antioxidant, anti-inflammatory and antimicrobial properties. Collectively, these studies expanded the range of residual biomasses that may be repurposed for nutraceutical, pharmaceutical and cosmeceutical development. Simulated gastrointestinal digestion and membrane-permeability experiments were performed on Castanea sativa and Chaetomorpha linum materials. The fractions recovered after membrane passage did not retain measurable antioxidant activity, suggesting limited stability and/or recovery of active compounds under the tested conditions. This result led to the adoption of a complementary experimental strategy based on direct testing of selected extracts in cellular and in vivo models and highlighted the importance of considering bioaccessibility and stability during product development. In vivo validation was conducted in wild-type Drosophila melanogaster. Chaetomorpha linum produced a statistically significant, dose-dependent extension of median lifespan in males, whereas females showed no lifespan extension and displayed toxicity at the highest concentration. This marked sex-specific response identifies dose, sex and biological context as critical determinants of efficacy and opens new research perspectives on metabolic and longevity-related pathways. Overall, the project generated mechanistic and proof-of-concept evidence supporting the valorisation of bio-waste as a source of compounds able to modulate inflammation, oxidative stress, cancer-cell survival and longevity. The work also revealed relevant limitations, particularly concerning post-digestion stability and sex-dependent responses, which will guide dose optimization, formulation strategies and future translational validation. The results were disseminated through peer-reviewed Open Access publications, presentations at national and international scientific meetings, doctoral and degree theses, and the coordination of the Special Issue “Agri-Food Wastes as Natural Source of Bioactive Antioxidants—Third Edition”. The project also supported the training and professional development of young researchers and strengthened interdisciplinary collaboration among the three Research Units. The project was funded by the European Union – NextGenerationEU under the National Recovery and Resilience Plan (NRRP), Mission 4, Component 2, Investment 1.1, PRIN 2022, project code 2022LW54KC. ABSTRACT The project “Bio-waste products as a source of nutraceuticals to target the common trait of inflammation in cancer and neurodegeneration” (PRIN 2022, Prot. 2022LW54KC) addressed two major health challenges—cancer and neurodegenerative diseases—through a sustainable strategy based on the valorization of agro-food and marine bio-waste. Although these diseases have distinct clinical manifestations, they share pathogenic features, including aging, oxidative stress and chronic inflammation. The project, therefore, aimed to identify low-cost, eco-sustainable nutraceutical molecules and bio-waste-derived extracts capable of modulating inflammatory pathways relevant to cancer progression and neurodegeneration. The research was conducted by the Universities of Bologna, Siena, and Camerino through an integrated approach combining green extraction, phytochemical characterization, in vitro digestion, cellular and animal models, proteomics, bioinformatics, and computational analysis. Selected residual biomasses and bioactives included olive-derived compounds, tomato skins, pomegranate peels, citrus-processing waste, chestnut by-products, the invasive macroalga Chaetomorpha linum, saffron tepals, hemp leaves and sweet-cherry processing waste. Environmentally friendly extraction procedures, including water-based methods and Natural Deep Eutectic Solvents, were developed or optimized to recover phenolic compounds and other bioactive molecules while reducing the use of hazardous solvents and supporting circular-economy principles. The biological activity of selected compounds and extracts was investigated in models relevant to neuroinflammation, oral and skin inflammation, cancer-cell survival, and organismal longevity. Particular attention was devoted to oxidative stress, inflammatory signaling, apoptosis, ferroptosis, and other pathways involved in cell survival and tissue homeostasis. The overall objective was to generate proof-of-concept evidence that low-value biological residues can be transformed into high-value bioactive ingredients with potential nutraceutical, pharmaceutical, and cosmeceutical applications.
Dettagli del progetto
Responsabile scientifico: Silvana Hrelia
Strutture Unibo coinvolte:
Dipartimento di Scienze per la Qualità della Vita
Coordinatore:
Università degli Studi di CAMERINO(Italy)
Contributo totale di progetto: Euro (EUR) 193.616,00
Contributo totale Unibo: Euro (EUR) 70.396,00
Durata del progetto in mesi: 24
Data di inizio
05/10/2023
Data di fine:
28/02/2026
