Nowadays, bioactive natural products play key roles in drug development due to their safety profile and strong antioxidant power. Vanillin is a natural phenolic compound found in several vanilla beans and widely used for food, cosmetic, and pharmaceutical products. Besides its industrial applications, vanillin possesses several beneficial effects for human health, such as antioxidant activity in addition to anti-inflammatory, anti-mutagenic, anti-metastatic, and anti-depressant properties. Moreover, vanillin exhibits neuroprotective effects on multiple neurological disorders and neuropathophysiological conditions. This study reviews the mechanisms of action by which vanillin prevents neuroinflammation and neurodegeneration in vitro and in vivo systems, in order to provide the latest views on the beneficial properties of this molecule in chronic neurodegenerative diseases and neuropathophysiological conditions.

Doxorubicin (Dox) is a highly effective chemotherapeutic agent employed in the handling of hematological and solid tumors. The effective use of Dox in cancer therapy has been seriously limited due to its well-known cardiotoxic side effects, mainly mediated by oxidative damage. Therefore, the identification of an effective and safe antagonist against Dox-induced cardiotoxicity remains a challenge. In this respect, as plant polyphenols have attracted considerable interest due to their antioxidant properties and good safety profile, hydroxytyrosol (HT), the major phenolic compound in olive oil, could be a potential candidate due to its remarkable antioxidant and anticancer powers. In this study, the effect of HT was tested on Dox-induced cardiotoxicity by using a combination of biochemical and cellular biology techniques. Interestingly, HT was able to counteract Dox-induced cytotoxicity in cardiomyocytes by acting on the SOD2 level and the oxidative response, as well as on apoptotic mechanisms mediated by Bcl-2/Bax. At the same time, HT did not to interfere with the antitumorigenic properties of Dox in osteosarcoma cells. This study identifies new, beneficial properties for HT and suggests that it might be a promising molecule for the development of additional therapeutic approaches aimed at preventing anthracycline-related cardiotoxicity and improving long-term outcomes in antineoplastic treatments.

Hydroxytyrosol (HT), the major phenolic compound in olive oil, is attracting increasing interest for its beneficial properties including a notable antioxidant and anti-inflammatory power. In this study, using a combination of biophysical and cell biology techniques, we have tested the role of HT in the formation of advanced glycation end-products (AGEs). AGEs have a key role in clinical sciences as they have been associated to diabetes, neurodegenerative and cardiovascular diseases. In addition, as the incidence of Alzheimer’s disease (AD) is strongly increased in diabetic patients, AGE formation is supposed to be involved in the development of the pathological hallmarks of AD. Our data show that HT selectively inhibits protein glycation reaction in human insulin, and it is able to counteract the AGE-induced cytotoxicity in human neurotypical cells by acting on SIRT1 level and oxidative stress, as well as on inflammatory response. This study identifies new beneficial properties for HT and suggests it might be a promising molecule in protecting against the AGE-induced toxicity, a key mechanism underlying the development and progression of neurodegenerative disorders.

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.

The development of functional staple foods with improved metabolic properties represents a practical dietary strategy for the prevention of type 2 diabetes. This study investigated the effects of incorporating sprouted fenugreek (Trigonella foenum-graecum L.) into wheat-based flatbread (chapatti) on postprandial glycemic and insulinemic responses in healthy adults. Wheat (cv. Galaxy 2013) and fenugreek seeds were germinated for up to 96 h and analyzed for nutritional composition and antioxidant activity. Composite flours containing 0%, 2.5%, 5%, and 7.5% sprouted fenugreek were formulated and evaluated for sensory acceptability. Eighteen healthy participants (18–25 years; BMI 21–22.5 kg/m²) consumed chapattis containing 7.5% sprouted fenugreek or control white flour in a ran-domized crossover design. Blood glucose and serum insulin were measured at 0, 30, 60, and 120 min postprandially. Sprouting significantly increased protein, dietary fiber, and antioxidant capacity in both wheat and fenugreek (p < 0.001). Total phenolic content in wheat increased from 55.82 to 110.17 mg GAE/100 g after 96 h of germination, accompa-nied by a significant rise in DPPH radical scavenging activity. The formulation containing 7.5% sprouted fenugreek showed the highest sensory acceptability (7.52/9). Fenu-greek-supplemented chapattis significantly reduced postprandial glucose and insulin re-sponses (p < 0.05) compared with control. Incorporation of 7.5% sprouted fenugreek into wheat flatbread improves nutritional quality while attenuating glycemic and insulinemic responses, suggesting a practical dietary strategy for metabolic health and diabetes pre-vention.