Multi-spectroscopic and in silico approaches reveal the α-amylase and α-glucosidase inhibitory mechanism of anacardic acids and their effects on advanced glycation end products Anna Elisabetta Maccarronello, Claudia Sciacca, Nunzio Cardullo, Luana Pulvirenti, Antonella Di Francesco, Vera Muccilli International Journal of Biological Macromolecules, 2026 Anacardic acids (AAs) are a class of alkyl phenols widely distributed in the Anacardiaceae family and known for their diverse biological properties. However, their potential against type 2 diabetes mellitus (T2DM) has never been thoroughly investigated. In this study, a fraction isolated from a Pistacia vera shell extract, enriched in AAs, exhibited potent inhibitory activity against α-amylase (α-Amy) and α-glucosidase (α-Glu). Pure (15:0)-AA and (17:1)-AA also acted as strong inhibitors of both enzymes, displaying IC₅₀ values significantly lower than those of the marketed anti-diabetic drug acarbose. Kinetic and molecular docking analyses identified both AAs as competitive α-Amy and α-Glu inhibitors that interact with the catalytic sites via non-covalent interactions. Fluorescence measurements revealed dynamic quenching upon AA-enzyme binding, while FT-IR and dynamic light scattering analyses demonstrated AA-induced conformational rearrangements and increased size distribution. Beyond their hypoglycaemic potential, (15:0)-AA and (17:1)-AA strongly inhibited the formation of pathogenic advanced glycation end products (AGEs). AAs efficiently reduced fluorescent AGE formation in three distinct glycation models and effectively protected human serum albumin (HSA) from glycation-induced structural alterations, including exposure of hydrophobic domains and amyloid aggregation. Notably, AAs retained substantial antiglycation activity after simulated gastrointestinal digestion. Overall, this work provides the first detailed insights into the hypoglycemic and antiglycation properties of AAs, supporting their potential application as multifunctional natural agents for T2DM management.
Extraction Techniques for Polyphenol-Rich Nutraceuticals Anna Elisabetta Maccarronello, Filipa Teixeira, Vera Muccilli, Francisca Rodrigues Polyphenol Nutraceuticals and Healthcare, 2026 Extraction is the pivotal method for retrieving bioactive compounds, such as polyphenols, from a wide variety of natural sources. These compounds are then harnessed for their valuable functional properties, sought after in several formulations, and, above all, used as nutraceuticals. In this chapter, different extraction techniques, ranging from traditional to the most recently emerged ones, are carefully examined, highlighting their advantages, limitations, and applications in the nutraceutical field. Specifically designed to be effective even at low temperatures and brief extraction times, eco-friendly advanced processes are expected to replace conventional solvent-based extractions, laying the foundations of modern phytotherapy. In this chapter, a special focus has been devoted to natural deep eutectic mixtures, along with scaling-up considerations for a successful transition from laboratory-scale extractions to industrial production to meet the growing demand for natural and functional ingredients in the nutraceutical industry.
Recovery of verbascoside from Lantana camara pruning waste for development of phytosomes with antioxidant and hypoglycemic properties Nunzio Cardullo, Anna Elisabetta Maccarronello, Barbara Melilli, Libera Vitiello, Andrea Antonio Scamporrino, Ana Margarida Silva, Claudia Sciacca, Agata Bącler, Francisca Rodrigues, Vera Muccilli Industrial Crops and Products, 2025 Verbascoside is a phenolic glycoside with various biological properties and is employed in the cosmetic, food, and pharmaceutical industries. However, it suffers from both low bioavailability and chemical stability. This work aims to recover value-added compounds such as verbascoside from Lantana camara crops, a plant naturalized worldwide and considered a risky invasive weed. The extract was then loaded in nanoparticles to improve the physiochemical properties of verbascoside. Firstly, lantana’s twigs were subjected to microwave-assisted extraction by applying a Box–Behnken design. The response surface methodology allows obtaining an extract with total phenolic (222.1 mg GAE/g) and verbascoside (104.2 mg/g) contents, as well as antiradical and antioxidant activities, higher than those previously reported by conventional extraction on lantana twigs. Noteworthy, the new bioactive extract was obtained using greener and more sustainable conditions and methodologies with respect to previously published researches. The extract exhibits promising hypoglycemic properties, with higher inhibitory potency toward α-glucosidase (25.0 µg/mL) compared with α-amylase (65.4 µg/mL), and anti-glycation activity. Cell safety was ascertained (90.1 % on Caco-2, 107.4 % on HT29-MTX) at 62.5 µg/mL, a concentration higher than the effective extract dose. The extract, together with a phosphatidylcholine fraction derived from soy lecithin, was employed for phytosome formulation through a simple, cost-effective, and scalable process. The resulting preparation showed good physical stability when stored at 5 and 25°C for 4 months. The release kinetics from phytosomes revealed the effectiveness of this system in gradually releasing verbascoside, reaching 67.7 % after 7 h. Moreover, phytosomes kept the extract properties. This study demonstrated the feasibility of recoveriyng verbascoside from the pruning of a plant weed, obtaining an extract with promising antioxidant and hypoglycemic properties for developing new products and materials. • A bioactive extract from Lanana camara twigs was obtained applying an algorithm. • The optimized extract was rich in verbascoside (104.2 mg/g) and other phenolics. • Promising antioxidant and hypoglycaemic properties were exhibited by the extract. • A low-cost procedure for high pure phosphatidyl choline (PC) recovery was developed. • Phytosomes obtained with the extract and PC are stable for 4 months at 25 °C.
Exploring the metabolic fate of antioxidant and hypoglycemic compounds from Pistacia vera shells through in vitro simulated digestion and untargeted metabolomics Anna Elisabetta Maccarronello, Nunzio Cardullo, Diana Pinto, Antonella Di Francesco, Maria Gaetana Giovanna Pittalà, Francisca Rodrigues, Vera Muccilli Food Chemistry, 2025 Pistacia vera L. shells (PS) are a sustainable source of health-promoting ingredients. The metabolic fate of a PS extract with antioxidant/antiradical and hypoglycemic properties prepared by microwave-assisted extraction (MAE) was investigated through in vitro gastrointestinal digestion to consider its potential value as nutraceutical ingredient. The results revealed significant changes in the phytochemical profile, bioactivity, and bioaccessibility of the extract during digestion. According to LC-ESI-LTQ-Orbitrap-MS analysis, compounds were mainly preserved in the oral (40.48 μg/mg DW) and gastric (73.67 μg/mg DW) phases, and less in the intestinal phase (13.24 μg/mg DW). α-Amylase inhibitory properties of PS extract remained consistent during digestion, whereas α-glucosidase inhibition and antioxidant/antiradical effects gradually decreased. Multivariate data analysis confirmed the interdependency between phytochemical composition and bioactivity of undigested extract and its digests. This study represents a step forward for developing PS-based functional foods, providing unique insights into the metabolism of PS bioactive constituents under simulated gastrointestinal conditions.
Recent Advances in Microbial Bioconversion as an Approach to Boost Hydroxytyrosol Recovery from Olive Mill Wastewater Irene Maria Zingale, Anna Elisabetta Maccarronello, Claudia Carbone, Cinzia Lucia Randazzo, Teresa Musumeci, Cinzia Caggia Fermentation, 2025 Olive mill wastewater (OMWW) is a highly complex matrix derived from olive oil extraction, containing phenolic compounds, lipids, minerals, and organic acids. Hydroxytyrosol (HT), an outstanding antioxidant and health-promoting phenolic compound, has garnered significant interest as a natural preservative and functional ingredient. Enzymatic hydrolysis, utilizing purified enzymes to cleave glycosidic or ester bonds, and microbial bioconversion, employing whole microorganisms with their intrinsic enzymes and metabolic pathways, are effective biotechnological strategies for fostering the release of HT from its conjugated forms. These approaches offer great potential for the sustainable recovery of HT from OMWW, contributing to the valorization of this environmentally impactful agro-industrial by-product. Processed OMWW can lead to clean-label HT-enriched foods and beverages, capitalizing on by-product valorization and improving food safety and quality. In this review, the most important aspects of the chemistry, technology, and microbiology of OMWW were explored in depth. Recent trends and findings in terms of both enzymatic and microbial bioconversion processes are critically discussed, including spontaneous and driven fermentation, using selected microbial strains. These approaches are presented as economically viable options for obtaining HT-enriched OMWW for applications in the food and nutraceutical sectors. The selected topics aim to provide the reader with a solid background while inspiring and facilitating future research and innovation.
From waste to bioactive compounds: A response surface methodology approach to extract antioxidants from Pistacia vera shells for postprandial hyperglycaemia management Anna Elisabetta Maccarronello, Nunzio Cardullo, Ana Margarida Silva, Antonella Di Francesco, Paulo C. Costa, Francisca Rodrigues, Vera Muccilli Food Chemistry, 2024 Pistacia vera shells, an abundant agricultural by-product, are a rich source of undiscovered bioactive compounds. This study employed a response surface methodology (RSM) approach to optimize the microwave-assisted extraction of antioxidants. The highest total phenolic content, and antioxidant activity were achieved under the optimized extraction conditions (20% ethanol, 1000 W, 135 s, and solvent-to-solid ratio of 27 mL/g). The resulting extract (OPVS-E) included gallic acid derivatives, hydrolysable tannins, flavonoids, fatty acids, and anacardic acids. Remarkably, OPVS-E displayed potent inhibitory activity against α-amylase (IC50 = 2.05 μg/mL) and α-glucosidase (IC50 = 41.07 μg/mL), by far more powerful than the anti-diabetic drug acarbose., OPVS-E exhibited a strong antiradical capacity against reactive oxygen species (ROS) without causing toxicity in intestinal cells (HT29-MTX and Caco-2). These findings introduce OPVS-E as a potential novel dual-action nutraceutical ingredient, able to mitigate postprandial hyperglycemia and counteract the ROS overproduction occurring in type 2 diabetes mellitus.
Green3: A green extraction of green additives for green plastics Vera Muccilli, Anna E. Maccarronello, Carolle Rasoanandrasana, Nunzio Cardullo, Martina S. de Luna, Maria G.G. Pittalà, Paolo M. Riccobene, Sabrina C. Carroccio, Andrea A. Scamporrino Heliyon, 2024 PLA/PBAT bioplastic is a commercial biodegradable plastic employed for packaging and several food and agriculture applications. In this regard, properties such as the antioxidant ability to extend food shelf life and light resistance, are of great interest in the production of packaging and mulching films, respectively. These features are obtained by developing blends with pure chemicals and/or natural products as additives. In the present work blend formulations of PLA/PBAT with a walnut shell extract rich in antioxidants were developed and evaluated for their properties in comparison with classic PLA/PBAT. Specifically, natural additives, and most importantly the production process were purposely selected to i) be green and cost-effective; ii) confer antioxidant properties; and iii) improve material performance. To this aim, a walnut shell extract (EWS) with high antioxidant activity was obtained thanks to a novel green and cost-effective microwave-assisted extraction (MAE) procedure. A response surface methodology was utilized to explore how the total phenolic content (TPC) and antioxidant activity are influenced by varying aqueous ethanol concentration, extraction time, and microwave power. The highest predicted TPC and antioxidant activity were achieved when employing the ideal conditions for Microwave-Assisted Extraction (MAE): using a mixture of 30 % ethanol in water, an irradiation time of 120 s, and a microwave power of 670 W. The optimized EWS was characterized by HPLC-MS determining qualitative and quantitative data with the identification of flavonoids, fatty acids, and anacardic acids among the main components, responsible for antioxidant activity. The resulting EWS powder was melt-mixed at 140C° and 20 RPM with the bio-based PLA/PBAT bioplastic at two different concentrations (0.5 and 1.5 w/w) by forming film specimens. All EWS-based bioplastic films showed increased antioxidant features determined by the DPPH bleaching test, TEAC, and ORAC assays. The films keep the antioxidant capacity even after 7 days of UV-accelerated aging. Remarkably, adding 1.5 % EWS boosted the bioplastic UV light resistance, reducing the abatement of molecular masses by more than 60 % without affecting mechanical properties.
