Roberta Barletta

The European chestnut (Castanea sativa Mill.) industry generates substantial amounts of underutilized biomass, including shells, leaves, and spiny burs. Distinguishing itself from existing literature, this review presents a novel, integrated life-science analysis that redefines these by-products as a complementary ‘bioactive triad’, ranging from metabolic regulators to anti-virulence agents, rather than interchangeable sources of polyphenols. Although traditionally discarded, these by-products are rich sources of polyphenols, ellagitannins, and flavonoids, with promising potential for nutraceutical, cosmetic, and pharmaceutical applications. This review examines recent advances in the valorization of chestnut by-products, focusing on extraction strategies, chemical profiles, and biological activities. Shell valorization has increasingly shifted toward green extraction technologies, such as subcritical water extraction and deep eutectic solvents, which strongly influence bioactive recovery and composition. Chestnut leaves emerge as a sustainable resource enriched in hydrolysable tannins with anti-inflammatory and quorum sensing-inhibitory properties, particularly relevant for dermatological applications. Spiny burs, often the most phenolic-rich fraction, display marked antioxidant activity and the ability to potentiate conventional antibiotics against pathogens such as Helicobacter pylori. Despite these promising features, major challenges remain, including cultivar-dependent chemical variability, the predominance of in vitro evidence, and safety concerns related to the accumulation of potentially toxic elements. Overall, while chestnut by-products represent valuable resources within circular bioeconomy frameworks, their successful industrial and practical translation will require standardized extraction protocols, robust bioavailability assessments, and well-designed in vivo and clinical studies to ensure safety and efficacy.

Agricultural and agro-industrial residues are increasingly recognized as sustainable, low-cost feedstocks for high-performance biomedical materials. This review critically examines the translational potential of polysaccharides, proteins, inorganic compounds, and phytochemical-rich extracts derived from agro-waste, highlighting their chemical features, structure–function relationships, and application-specific readiness. Polysaccharides such as nanocellulose, pectin, and chitosan emerge as the most advanced biopolymer platforms, particularly in wound healing, drug delivery, and 3D-printed scaffolds. Protein-derived materials—including collagen, gelatin, keratin, and soy protein—show strong promise in regenerative medicine, though challenges in mechanical stability and batch reproducibility remain. Inorganic phases such as hydroxyapatite and silica obtained from eggshells, rice husk ash, and marine shells demonstrate high bioactivity, with dental and bone applications approaching clinical translation. Finally, fruit-residue phytochemicals provide multifunctional antioxidant and antimicrobial enhancements to composite systems. By integrating material chemistry, processing strategies, and translational considerations, this review outlines the current state, challenges, and future perspectives for advancing agro-waste-derived biomaterials within a circular bioeconomy.

Background: The accumulation of agri-food waste is a major environmental and economic challenge and converting these by-products into bioactive compounds fits within the circular bioeconomy. This study aimed to evaluate the antimicrobial potential of extracts derived from Cannabis sativa L. leaves (CSE), Crocus sativus tepals (CST), and Prunus avium L. cherry waste (VCE) against four key bacterial species (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa). Methods: Minimum inhibitory concentration (MIC) assays were performed to assess antibacterial activity, while a bioinformatic pipeline was implemented to explore possible molecular targets. Full-proteome multiple sequence alignments across the bacterial strains were used to identify conserved, strain-specific proteins, and molecular docking simulations were applied to predict binding interactions between the most abundant compounds in the extracts and their targets. Results: CSE and CST demonstrated bacteriostatic activity against S. aureus and B. subtilis (MIC = 15.6 mg/mL), while VCE showed selective activity against B. subtilis (MIC = 31.5 mg/mL). CodY was identified as a putative molecular target for CSE and CST, and ChaA for VCE. Docking results supported the possibility of spontaneous binding between abundant extract constituents and the predicted targets, with high binding affinities triggering a strong interaction network with target sensing residues. Conclusions: This study demonstrates the antimicrobial activity of these agri-food wastes and introduces a comprehensive in vitro and in silico workflow to support the bioactivity of these agri-food wastes and repurpose them for innovative, eco-sustainable applications in the biotechnology field and beyond.

This study presents an innovative approach to the sustainable valorization of industrial sweet cherry (Prunus avium L.) waste from the Vignola Region, Italy, transforming what is typically discarded into a high-value bioactive resource. Unlike conventional extractions, our hydroethanolic extract (VCE) was obtained from the entire cherry waste, including the pericarp, pulp, and stone, as generated by industrial processing. This full-fruit extraction strategy represents a novel and efficient use of agricultural by-products, aligning with circular bioeconomy principles. Sweet cherries are known for their phenolic richness, and spectrophotometric assays (TPC, TFC, reducing power, DPPH, and ABTS) confirmed the extract’s antioxidant capacity. In vitro studies using RAW 264.7 macrophages revealed no cytotoxic effects (MTT assay), along with significant anti-inflammatory activity, evidenced by reduced ROS and NO production and downregulation of iNOS and COX-2. Western blotting showed inhibition of NF-κB nuclear translocation and MAPK pathway signaling. Additionally, agarose gel electrophoresis showed protection against oxidative DNA damage. UPLC-MS/MS analysis identified sakuranetin, aequinetin, and dihydrowogonin as the most representative compounds in VCE. Molecular docking simulations revealed strong and specific binding affinities of these compounds to NF-κB p65 and key MAPK targets. These findings highlight whole sweet cherry waste—including the pit—as a potent and sustainable source of bioactive compounds with promising nutraceutical and pharmaceutical applications.

Computational methods have transformed target and drug discovery, significantly accelerating the identification of biological targets and lead compounds. Despite its limitations, in silico molecular docking represents a foundational tool. Molecular Dynamics (MD) simulations, employing accurate force fields, provide near-realistic insights into a compound’s behavior within a biological target. However, docking and MD predictions may be unreliable without precise knowledge of the target binding site. Through MD simulations, we investigated 100 co-crystal structures of biological targets complexed with active compounds, identifying key structural and energy dynamic features that govern target–ligand interactions. Our analysis provides a detailed quantitative description of these parameters, offering critical validation for improving the predictive reliability of docking and MD simulations. This work provides a robust framework for refining early-stage drug discovery and target identification.

Alkaptonuria (AKU) is a rare metabolic disorder characterized by the accumulation of homogentisic acid (HGA), leading to progressive ochronosis and joint degeneration. While much is known about HGA’s role in tissue damage, the molecular mechanisms underlying acute inflammation in AKU remain poorly understood. Serum amyloid A (SAA) proteins are key mediators of the inflammatory response, yet their potential as biomarkers for inflammation in AKU has not been explored. This study investigated the role of the SAA1.1 allele as a biomarker for the severity of acute inflammation in AKU. Data from the ApreciseKUre Precision Medicine Ecosystem were analyzed to assess the relationship between SAA1 allelic variants and inflammatory markers. Molecular dynamics simulations compared the structural dynamics of SAA1.1 and SAA1.2 isoforms, with standard modeling and analysis pipelines employed. Using a clinomics approach, we showed that AKU patients expressing the SAA1.1 allele have significantly higher acute inflammation-related markers. Extensive molecular dynamics simulations revealed that the SAA1.1 isoform lent high structural instability of the C-terminal domain, accelerating the formation of amyloid fibrils and exacerbating the inflammatory condition. These findings would identify the SAA1.1 allele as a novel genetic biomarker for the progression of secondary amyloidosis in AKU and its severity. Furthermore, new molecular insights into the inflammatory mechanisms of AKU were provided, suggesting potential therapeutic approaches aimed at stabilizing SAA1.1 protein and preventing amyloid fibril formation, with significant implications in AKU and precision medicine strategies for SAA-related diseases.

Green chemistry principles are pivotal in driving sustainable and innovative solutions to global health challenges. This study explores a hydroalcoholic extract from Castanea sativa (chestnut) burrs, an underutilized natural resource, as a potent source of antimicrobial compounds against Helicobacter pylori (H. pylori). The extract demonstrated significant bactericidal activity, synergizing effectively with clarithromycin and showing additive effects with metronidazole. Remarkably, combining the extract with clarithromycin and sub-inhibitory concentrations of pantoprazole reduced clarithromycin’s Minimum Bactericidal Concentration (MBC) to just 1.56% of its original value. Mechanistic studies suggest that the extract’s polyphenolic compounds compromise bacterial membrane integrity, enhancing antibiotic uptake, while pantoprazole disrupts bacterial ATPase activity. This research highlights the critical role of natural product extraction within the framework of green chemistry, offering a sustainable and environmentally friendly alternative to synthetic antimicrobials. By harnessing bioactive compounds from plant sources, this approach addresses the pressing issue of antibiotic resistance while promoting the responsible use of natural resources. The findings underscore the transformative potential of green chemistry in developing effective, eco-conscious antimicrobial therapies that align with global sustainability goals.

In an era of escalating environmental challenges, converting organic residues into high-value bioactive compounds provides a sustainable way to reduce waste and enhance resource efficiency. This study explores the potential of the circular bioeconomy through the valorization of agricultural byproducts, with a focus on the antioxidant properties of specific chestnut burr cultivars. Currently, over one-third of food production is wasted, contributing to both humanitarian and environmental crises. Through circular bioeconomy, we can transform biological waste into valuable products for use in fields like food innovation and sustainability. The antioxidant effects of three chestnut cultivars, Bastarda Rossa, Cecio, and Marroni, were assessed through in vitro assays, highlighting their potential to combat oxidative stress—an important factor for health-related applications. The characterization of the three cultivars showed the major presence of ellagic acid and gallic acid in the extract, renowned for their antioxidant activity. In vitro assays evaluated the phenolic and flavonoid content, as well as the antioxidant activity of the three extracts, confirming the cultivar Cecio as the richest in these bioactive compounds and the most performative in antioxidant assays. In vitro antioxidant and oxidative stress recovery assays on SaOS-2, fibroblast, and chondrocyte cell lines displayed a strong antioxidant activity. Furthermore, the cytotoxicity assay demonstrated the safety of all three extracts in the tested human cell lines. In silico docking simulations further validated the biological relevance of these compounds by predicting strong hydrophobic and polar interactions with oxidative stress-related protein targets. Overall, this study demonstrates the antioxidant properties of chestnut byproducts. The findings contribute to the development of functional foods, nutraceuticals, and other applications, underscoring the role of chestnut cultivars in advancing circular bioeconomy practices.

The circular bioeconomy is currently a promising model for repurposing natural sources; these sources include plants due to their abundance of bioactive compounds. This study evaluated the antimicrobial properties of a Chaetomorpha linum extract. Chaetomorpha linum is an invasive macroalga from the Orbetello Lagoon (Tuscany, Italy), which grows in nutrient-rich environments and has been forming extended mats since 2005. The biomass is mechanically harvested and treated as waste, consuming considerable manpower and financial resources. As a potential way to increase the value of such waste, this study found that C. linum extract (CLE) is a source of antimicrobial compounds. The phytochemical characterization of the extract revealed the predominant presence of palmitic acid, a fatty acid with known antimicrobial activity. Based on such findings, four bacterial species of high clinical relevance (Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli) were tested, revealing a notable antibacterial activity of the extract on Enterococcus faecalis (MIC, 32 μg/mL). Computational analyses identified a potential Enterococcus faecalis molecular target for palmitic acid, offering molecular insights on the interaction. This study presents a comprehensive in vitro and in silico approach for drug and target discovery studies by repurposing C. linum as a source of antimicrobial bioactive compounds.

Currently, one-third of global food production, accounting for 1.3 billions tons, goes wasted due to major humanitarian and environmental challenges. In such a scenario, the circular bioeconomy model stands as an innovative solution by promoting sustainable production, utilizing agri-food waste, and converting non-renewable products into valuable resources. Here, the circular bioeconomy concept was applied on a previously obtained chestnut burr extract (agri-food waste) composed of gallic acid, quinic acid, protocatechuic acid, brevifolin carboxylic acid, and ellagic acid to evaluate its antimicrobial activity against four bacterial opportunistic pathogens (Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli). Our results evidenced a modest but measurable antibacterial activity against Enterococcus faecalis, with a minimum inhibitory concentration (MIC) of 64 μg/mL. In silico studies allowed for identifying the potential molecular target, supporting the underlying antibacterial activity of the active principle and providing useful molecular findings regarding their interaction. In this study, we show a robust and comprehensive in vitro and in silico pipeline aimed at the identification of novel antibacterial scaffolds taking advantage of agri-food waste.