Glycolytic overload promotes accumulation of the highly reactive dicarbonyl compounds, resulting in harmful conditions called dicarbonyl stress. Methylglyoxal (MG) is a highly reactive dicarbonyl species and its accumulation plays a crucial pathophysiological role in diabetes and its vascular complications. MG cytotoxicity is mediated by reactive oxygen species (ROS) generation, a key event underlying the intracellular signaling pathways leading to inflammation and apoptosis. The identification of compounds able to inhibit ROS signaling pathways and counteract the MG-induced toxicity is a crucial step for developing new therapeutic strategies in the treatment of diabetic vascular complications. In this study, the effect of genistein, a natural soybean isoflavone, has been evaluated on MG-induced cytotoxicity in human endothelial cells. Our results show that genistein is able to counteract the MG-induced apoptosis by restraining ROS production, thus inhibiting the MAPK signaling pathways and caspase-3 activation. These findings identify a beneficial role for genistein, providing new insights for its potential clinical applications in preserving endothelial function in diabetic vascular complications.

Annurca apple extract is gaining growing attention for its beneficial properties, particularly its outstanding antioxidant activity. Using a combination of biophysical, cell, and molecular biology techniques, this study investigates the sustainable valorization of Annurca apple by-products at different ripening stages and their role in the formation of advanced glycation end-products (AGEs), as well as in protection against AGE-related cytotoxicity. AGEs are a class of compounds formed by non-enzymatic reactions between reducing sugars and proteins, lipids, or nucleic acids. They can be produced endogenously or ingested through dietary sources and tobacco smoke. AGEs accumulate in nearly all mammalian tissues and are linked to various health issues, such as diabetes and its related complications, cardiovascular disease, and neurodegenerative disorders. Our data show that Annurca apple by-products at different ripening stages differentially counteract AGEs’ formation by inhibiting protein glycation and protect against AGE-induced cytotoxicity in endothelial cells. In particular, the extracts reduce AGE-induced reactive oxygen species (ROS) production, thereby inhibiting MAPK signaling pathways and caspase-3 activation. Moreover, ripening significantly enhances the concentration of bioactive compounds and the extent of cellular protection. This study highlights new beneficial properties of Annurca apple extracts and suggests that adopting nutritional interventions may support health and potentially reduce the risk of complications associated with AGE accumulation.

Oleuropein and hydroxytyrosol, two major polyphenolic compounds extracted from the olive tree (Olea europaea), have involved significant consideration scientific interest due to their strong pharmacological properties, including anticancer, antioxidant, an-ti-inflammatory, and antidiabetic effects. These compounds play a crucial role in modu-lating oxidative stress, neutralizing free radicals, and protecting against cellular damage, thereby contributing to neuroprotection, cardiovascular health, and metabolic regula-tion. Their anticancer potential has been widely demonstrated through their ability to inhibit tumor progression, induce apoptosis, and in various tumor models they boost the efficiency of chemotherapy, including breast and hepatocellular carcinoma. Addi-tionally, their anti-inflammatory activity is attributed to the regulation of cytokines, suppression of NF-κB signaling, and modulation of immune responses, which could be beneficial in managing chronic inflammatory and autoimmune diseases. Moreover, their role in diabetes management has been extensively studied, showing their ability to im-prove insulin sensitivity, regulate glucose metabolism, and reduce lipid accumulation in hepatic and adipose tissues, thus preventing metabolic complications. Despite extensive preclinical evidence supporting the therapeutic benefits of these compounds, their clin-ical translation remains challenging due to issues related to bioavailability, stability, and optimal dosage. Future research should focus on improving their pharmacokinetic properties, developing advanced drug delivery systems, and carrying out extensive clinical trials to confirm their safety and effectiveness in humans. The integration of these compounds into functional foods, nutraceuticals, and pharmaceutical formula-tions holds immense promise for preventive and therapeutic applications, potentially offering natural alternatives to conventional therapeutic agents for managing metabolic, inflammatory, and degenerative diseases.