This article reviews the synergistic effects of antioxidant-enriched functional foods and exercise in improving metabolic health, focusing on the underlying molecular mechanisms. The review incorporates evidence from PubMed, SCOPUS, Web of Science, PsycINFO, and reference lists of relevant reviews up to 20 December 2024, highlighting the central role of the Nrf2 pathway. As a critical regulator of oxidative stress and metabolic adaptation, Nrf2 mediates the benefits of these interventions. This article presents an innovative approach to understanding the role of Nrf2 in the regulation of oxidative stress and inflammation, highlighting its potential in the prevention and treatment of various diseases, including cancer, neurodegenerative disorders, cardiovascular and pulmonary diseases, diabetes, inflammatory conditions, ageing, and infections such as COVID-19. The novelty of this study is to investigate the synergistic effects of bioactive compounds found in functional foods (such as polyphenols, flavonoids, and vitamins) and exercise-induced oxidative stress on the activation of the Nrf2 pathway. This combined approach reveals their potential to improve insulin sensitivity and lipid metabolism and reduce inflammation, offering a promising strategy for the management of chronic diseases. However, there are significant gaps in current research, particularly regarding the molecular mechanisms underlying the interaction between diet, physical activity, and Nrf2 activation, as well as their long-term effects in different populations, including those with chronic diseases. In addition, the interactions between Nrf2 and other critical signalling pathways, including AMPK, NF-κB, and PI3K/Akt, and their collective contributions to metabolic health are explored. Furthermore, novel biomarkers are presented to assess the impact of these synergistic strategies, such as the NAD⁺/NADH ratio, the GSH ratio, and markers of mitochondrial health. The findings provide valuable insights into how the integration of an antioxidant-rich diet and regular exercise can improve metabolic health by activating Nrf2 and related molecular pathways and represent promising strategies for the prevention and treatment of metabolic disorders. Further studies are needed to fully understand the therapeutic potential of these interventions in diseases related to oxidative stress, such as cardiovascular disease, neurodegenerative disease, diabetes, and cancer.

Stroke is the second leading cause of death worldwide, and its incidence is rising rapidly. Acute ischemic stroke is a subtype of stroke that accounts for the majority of stroke cases and has a high mortality rate. An effective treatment for stroke is to minimize damage to the brain’s neural tissue by restoring blood flow to decreased perfusion areas of the brain. Many reports have concluded that both oxidative stress and excitotoxicity are the main pathological processes associated with ischemic stroke. Current measures to protect the brain against serious damage caused by stroke are insufficient. For this reason, it is important to investigate oxidative and antioxidant strategies to reduce oxidative damage. This review focuses on studies assessing the concentration of oxidative stress biomarkers and the level of antioxidants (enzymatic and non-enzymatic) and their impact on the clinical prognosis of patients after stroke. Mechanisms related to the production of ROS/RNS and the role of oxidative stress in the pathogenesis of ischemic stroke are presented, as well as new therapeutic strategies aimed at reducing the effects of ischemia and reperfusion.

This narrative review provides an analysis of the role of nitric oxide (NO) and its precursors, particularly L-arginine, in vascular regulation and health, with an emphasis on findings from our experimental research in animal models. NO serves as a critical mediator of vascular function, contributing to vasodilation, the regulation of blood flow, and the prevention of thrombosis. As a primary precursor of NO, L-arginine is essential for maintaining endothelial integrity, modulating mitochondrial function, and reducing oxidative damage. This review synthesises the data and contextualises these findings within the physiological challenges faced by blood donors, such as repeated blood donation and associated oxidative stress. It examines the effects of L-arginine supplementation on mitochondrial respiration, lipid peroxidation, and microsomal oxidation in different conditions, including differences in age, gender, and dietary interventions. The mechanisms by which L-arginine enhances NO production, improves vascular elasticity, and alleviates endothelial dysfunction caused by reduced NO bioavailability are also investigated. By integrating experimental findings with insights from the existing literature, this review provides a perspective on the potential of L-arginine supplementation to address the specific physiological needs of blood donors. It highlights the importance of personalised nutritional approaches in enhancing donor recovery and vascular resilience. In addition, this review assesses the wider implications of L-arginine supplementation in mitigating oxidative stress and preserving vascular function. The interplay between NO bioavailability, dietary factors, and physiological adaptation in blood donors is highlighted, along with the identification of current knowledge gaps and recommendations for future research. By presenting both original experimental evidence and a critical synthesis of the literature, this article highlights the therapeutic potential of NO precursors, particularly L-arginine, in promoting vascular health in the context of blood donation.

The review summarises the data of the last 50 years on the effectiveness of the amino acid L-arginine in therapeutic practice in conditions accompanied by different-origin hypoxia. The aim of this review was to analyse the literature and our research data on the role of nitric oxide in the modulation of individual physiological reactivity to hypoxia. The review considers the possibility of eliminating methodological conflicts in the case of L-arginine, which can be solved by taking into account individual physiological reactivity (or the hypoxia resistance factor). Considerable attention is paid to genetic and epigenetic mechanisms of adaptation to hypoxia and conditions of adaptation in different models. The article presents data on the clinical effectiveness of L-arginine in cardiovascular system diseases (hypertension, atherosclerosis, coronary heart disease, etc.) and stress disorders associated with these diseases. The review presents a generalised analysis of techniques, data on L-arginine use by athletes, and the ambiguous role of NO in the physiology and pathology of hypoxic states shown via nitric oxide synthesis. Data on the protective effects of adaptation in the formation of individual high reactivity in sportsmen are demonstrated. The review demonstrates a favourable effect of supplementation with L-arginine and its application depending on mitochondrial oxidative phosphorylation processes and biochemical indices in groups of individuals with low and high capacity of adaptation to hypoxia. In individuals with high initial anti-hypoxic reserves, these favourable effects are achieved by the blockade of NO-dependent biosynthesis pathways. Therefore, the methodological tasks of physiological experiments and the therapeutic consequences of treatment should include a component depending on the basic level of physiological reactivity.

This narrative review presents the role of antioxidants in regulating the gut microbiota and the impact on the gut–brain axis, with a particular focus on neurodegenerative diseases, such as Alzheimer’s (AD) and Parkinson’s disease (PD). These diseases are characterised by cognitive decline, motor dysfunction, and neuroinflammation, all of which are significantly exacerbated by oxidative stress. This review elucidates the contribution of oxidative damage to disease progression and explores the potential of antioxidants to mitigate these pathological processes through modulation of the gut microbiota and associated pathways. Based on recent studies retrieved from reputable databases, including PubMed, Web of Science, and Scopus, this article outlines the mechanisms by which antioxidants influence gut health and exert neuroprotective effects. Specifically, it discusses how antioxidants, including polyphenols, vitamins, and flavonoids, contribute to the reduction in reactive oxygen species (ROS) production and neuroinflammation, thereby promoting neuronal survival and minimising oxidative damage in the brain. In addition, the article explores the role of antioxidants in modulating key molecular pathways involved in oxidative stress and neuroinflammation, such as the NF-κB, Nrf2, MAPK, and PI3K/AKT pathways, which regulate ROS generation, inflammatory cytokine expression, and antioxidant responses essential for maintaining cellular homeostasis in both the gut and the central nervous system. In addition, this review explores the complex relationship between gut-derived metabolites, oxidative stress, and neurodegenerative diseases, highlighting how dysbiosis—an imbalance in the gut microbiota—can exacerbate oxidative stress and contribute to neuroinflammation, thereby accelerating the progression of such diseases as AD and PD. The review also examines the role of short-chain fatty acids (SCFAs) produced by beneficial gut bacteria in modulating these pathways to attenuate neuroinflammation and oxidative damage. Furthermore, the article explores the therapeutic potential of microbiota-targeted interventions, including antioxidant delivery by probiotics and prebiotics, as innovative strategies to restore microbial homeostasis and support brain health. By synthesising current knowledge on the interplay between antioxidants, the gut–brain axis, and the molecular mechanisms underlying neurodegeneration, this review highlights the therapeutic promise of antioxidant-based interventions in mitigating oxidative stress and neurodegenerative disease progression. It also highlights the need for further research into antioxidant-rich dietary strategies and microbiota-focused therapies as promising avenues for the prevention and treatment of neurodegenerative diseases.

It has been demonstrated that prolonged exposure to stress engenders a plethora of neuropsychiatric, immune and metabolic disorders. However, its pathophysiology transcends the conventional hypothalamic–pituitary–adrenal (HPA) axis. This review addresses the central question of how integrated neural and microbial pathways regulate stress responses and resilience. We present a model in which the parasympathetic nervous system (particularly the vagus nerve) and the gut microbiota interact to form a bidirectional neuroimmune network that modulates the HPA axis, immune function, neurotransmitter balance, and metabolic adaptation. Key molecular pathways include nitric oxide synthesis via the classical nitric oxide synthase (NOS)-dependent and microbiota-mediated nitrate–nitrite routes, inducible nitric oxide synthase (iNOS) regulation, nuclear factor erythroid 2-related factor 2 (Nrf2) signalling, lysosomal function, autophagy and the cholinergic anti-inflammatory reflex. Other pathways include the gamma-aminobutyric acid (GABA) and serotonin (5-HT) systems, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signalling, polyamine metabolism and peroxisome proliferator-activated receptor gamma (PPARγ). Intermittent hypoxia training (IHT) enhances mitochondrial function, oxidative stress responses, autonomic balance and gut microbiota composition. This promotes parasympathetic activity and stress resilience that is tailored to the individual. These adaptations support the concept of personalised stress response profiles based on hypoxic adaptability. Clinical implications include combining IHT with vagus nerve stimulation, probiotics, dietary strategies, and stress reduction techniques. Monitoring vagal tone and microbiota composition could also serve as predictive biomarkers for personalised interventions in stress-related disorders. This integrative framework highlights the therapeutic potential of targeting the parasympathetic system and the gut microbiota to modulate stress.