Numerous natural antioxidants commonly found in our daily diet have demonstrated significant benefits for human health and various diseases by counteracting the impact of reactive oxygen and nitrogen species. Their chemical properties enable a range of biological actions, including antihypertensive, antimicrobial, anti-inflammatory, anti-fibrotic, and anticancer effects. Despite promising outcomes from preclinical studies, ongoing debate persists regarding their reproducibility in human clinical models. This controversy largely stems from a lack of understanding of the pharmacokinetic properties of these compounds, coupled with the predominant focus on monotherapies in research, neglecting potential synergistic effects arising from combining different antioxidants. This study aims to provide an updated overview of natural antioxidants, operating under the hypothesis that a multitherapeutic approach surpasses monotherapy in efficacy. Additionally, this study underscores the importance of integrating these antioxidants into the daily diet, as they have the potential to prevent the onset and progression of various diseases. To reinforce this perspective, clinical findings pertaining to the treatment and prevention of non-alcoholic fatty liver disease and conditions associated with ischemia and reperfusion phenomena, including myocardial infarction, postoperative atrial fibrillation, and stroke, are presented as key references.

Acute myocardial infarction (AMI) is one of the main causes of mortality worldwide. Currently, the most effective treatment is percutaneous coronary angioplasty (PCA). However, paradoxically, the restoration of blood flow induces myocardial reperfusion injury (MRI), contributing up to 50% of the final infarct size. Oxidative stress, characterized by a burst of reactive oxygen species (ROS) following reperfusion, plays a fundamental role in its pathophysiology, causing inflammation, endothelial dysfunction, and cell death mainly through autophagy, apoptosis, ferroptosis, necroptosis, and pyroptosis. To mitigate these injury mechanisms, numerous antioxidant strategies have been evaluated using both in vitro and in vivo models with promising results, but limited benefit when tested in humans. Several antioxidants have biological properties that counteract ROS-induced damage by acting as ROS scavengers, metal chelators, and antioxidant enzyme enhancers. In this review, we focus on the mechanisms by which oxidative stress induces cell death after AMI and highlight the most promising therapeutic antioxidant agents that could provide comprehensive protection against MRI. A multitarget cardioprotective strategy, combining interventions with strong preclinical evidence, could provide a more effective approach for reducing MRI. Our study aims to bridge the gap between basic and clinical research and explore the potential clinical applications of antioxidants.

The central nervous system is essential for maintaining homeostasis and controlling the body’s physiological functions. However, its biochemical characteristics make it highly vulnerable to oxidative damage, which is a common factor in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). ALS is a leading cause of motor neuron disease, characterized by a rapidly progressing and incurable condition. ALS often results in death from respiratory failure within 3–5 years from the onset of the first symptoms, underscoring the urgent need to address this medical challenge. The aim of this study is to present available data supporting the role of oxidative stress in the mechanisms underlying ALS and to discuss potential antioxidant therapies currently in development. These therapies aim to improve the quality of life and life expectancy for patients affected by this devastating disease.

Brain radiation is a crucial tool in neuro-oncology for enhancing local tumor control, but it can lead to mild-to-profound and progressive impairments in cognitive function. Radiation-induced brain injury is a significant adverse effect of radiotherapy for cranioencephalic tumors, primarily caused by indirect cellular damage through the formation of free radicals. This results in late neurotoxicity manifesting as cognitive impairment due to free radical production. The aim of this review is to highlight the role of different substances, such as drugs used in the clinical setting and antioxidants such as ascorbate, in reducing the neurotoxicity associated with radiation-induced brain injury. Currently, there is mainly preclinical and clinical evidence supporting the benefit of these interventions, representing a cost-effective and straightforward neuroprotective strategy.