Antioxidants

50 pages, 3428 KB

Open AccessReview

Targeting Oxidative Stress in Carcinogenesis: Oleanolic Acid and Its Molecular Pathways

by Andrzej Günther, Maciej Kulawik, Szymon Sip, Przemysław Zalewski, Donata Jarmołowska-Jurczyszyn, Przemysław Stawicki and Barbara Bednarczyk-Cwynar

Antioxidants 2026, 15(1), 67; https://doi.org/10.3390/antiox15010067 (registering DOI) - 4 Jan 2026

Abstract

This narrative review aims to systematize the current knowledge on the dual role of reactive oxygen species and reactive nitrogen species in cancer processes, from their physiological function in redox signaling to their pathological impact in oxidative distress. The mechanisms of biomolecule damage, [...] Read more.

This narrative review aims to systematize the current knowledge on the dual role of reactive oxygen species and reactive nitrogen species in cancer processes, from their physiological function in redox signaling to their pathological impact in oxidative distress. The mechanisms of biomolecule damage, particularly DNA, and deregulation of signaling pathways induced by excessive ROS/RNS concentrations, which promote neoplastic transformation, are presented. The importance of diet and endogenous antioxidants in cancer prevention is also discussed, emphasizing the role of natural antioxidants in prevention and adjunctive therapy. In this context, oleanolic acid emerges as a promising compound with dual action modulating oxidative stress, capable of balancing cellular redox responses. We discuss the most important antioxidant mechanisms of oleanolic acid, the interconnection of oxidative stress with carcinogenesis-related pathways, anticancer mechanisms mediated by oxidative stress modulation, and structural modifications and modern application techniques that improve its bioavailability, as well as future perspectives on oleanolic acid research in the context of its antioxidant and anticancer activity. Overall, available experimental and preclinical data indicate that oleanolic acid, through pleiotropic modulation of oxidative stress and signaling networks, holds promise as an adjuvant agent in cancer prevention and therapy. Full article

(This article belongs to the Special Issue Redox Signaling in Cancer: Mechanisms and Therapeutic Opportunities)

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Graphical abstract

42 pages, 2204 KB

Open AccessReview

Roles of Reactive Oxygen Species in Relationships Between Viral Infections and Alzheimer’s Disease and Related Dementia

by Gunel Ayyubova, Fariha E. Bablu, Nazrin Rahimli, Leyla Aghayeva, Elijah M. Springer, Fada A. Alghenaim and Yuichiro J. Suzuki

Antioxidants 2026, 15(1), 66; https://doi.org/10.3390/antiox15010066 (registering DOI) - 3 Jan 2026

Abstract

Emerging evidence suggests that viral infections may contribute to the onset and progression of Alzheimer’s disease (AD) and other forms of dementia. Understanding the mechanism of viral involvement in the pathogenesis of AD and related dementia (ADRD) could contribute to reducing the burden [...] Read more.

Emerging evidence suggests that viral infections may contribute to the onset and progression of Alzheimer’s disease (AD) and other forms of dementia. Understanding the mechanism of viral involvement in the pathogenesis of AD and related dementia (ADRD) could contribute to reducing the burden caused by these conditions, which affect a large portion of the aging population. Some studies indicate the link between AD and viral infections, notably coronaviruses and herpesviruses. In AD, excessive production of reactive oxygen species (ROS) results in the modifications of lipids, proteins, and nucleic acids, contributing to synaptic dysfunction and cognitive impairments. Experimental evidence suggests that viral infections linked to ADRD induce the cellular production of ROS, possibly contributing to the pathogenesis of these conditions. Despite significant advances in defining the roles of ROS in neurological disorders and viral infections, the specific roles of ROS in virus-associated ADRD have not been thoroughly investigated. The main objective of this review article is to comprehensively provide information on the experimental evidence for the production of ROS by viruses to help the readers investigate the role of ROS in the relationship between viral infections with ADRD. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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20 pages, 5643 KB

Open AccessArticle

A Neutral Polysaccharide from Ginseng Berry Mitigates D-Galactose-Induced Oxidative Stress and Cognitive Deficits Through the Keap1/Nrf2/HO-1/NQO1 Pathway

by Ting Ren, Lina Wang, Jiaxin Zhang, Ruitong Song, Xin Li, Jiayue Gao, Xin Sun and Lili Jiao

Antioxidants 2026, 15(1), 65; https://doi.org/10.3390/antiox15010065 (registering DOI) - 3 Jan 2026

Abstract

Oxidative stress contributes to brain aging processes and is implicated in related functional decline. Developing strategies to mitigate oxidative stress is therefore of significant interest. In this study, a neutral polysaccharide (GBPN) was isolated from ginseng berry. Structural analysis revealed that GBPN (molecular [...] Read more.

Oxidative stress contributes to brain aging processes and is implicated in related functional decline. Developing strategies to mitigate oxidative stress is therefore of significant interest. In this study, a neutral polysaccharide (GBPN) was isolated from ginseng berry. Structural analysis revealed that GBPN (molecular weight 1.52 × 10⁴ Da) is primarily composed of glucose (53.18%), arabinose (24.3%), and galactose (16.75%). Glucose exists in the forms of →4)-Glcp-(1→ (32.95%), →6)-Glcp-(1→ (13.81%), and →4,6)-Glcp-(1→ (3.70%), while arabinose exists as →1)-Araf (9.73%), →1)-Arap (5.82%), →2)-Arap-(1→ (0.66%), →5)-Araf-(1→ (7.62%), and →3,5)-Araf-(1→ (1.69%) forms, while galactose exists in the forms of →1)-Galp (3.58%), →3)-Galp-(1→ (1.59%), and →3,6)-Galp-(1→ (12.67%). GBPN adopts a triple-helix conformation and exhibits a curled lamellar appearance. Functionally, GBPN exhibited strong 2,2-diphenyl-1-picrylhydrazyl radical, hydroxyl radical scavenging activity, and iron ion chelation capacity. It can activate the antioxidant system in D-galactose-induced aging-like mice, and simultaneously enhance their learning and memory abilities. Mechanistic analysis revealed that these effects are associated with the kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 pathway. These findings suggest that ginseng berry polysaccharides like GBPN hold promise as potential agents for alleviating oxidative stress and cognitive deficits in aging-related contexts. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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Graphical abstract

24 pages, 1465 KB

Open AccessReview

Melatonin at the Crossroads of Oxidative Stress, Immunity, and Cancer Therapy

by Elena Lavado-Fernández, Cristina Pérez-Montes, Miguel Robles-García, Adrián Santos-Ledo and Marina García-Macia

Antioxidants 2026, 15(1), 64; https://doi.org/10.3390/antiox15010064 (registering DOI) - 3 Jan 2026

Abstract

Melatonin, an ancient and evolutionarily conserved indolamine, has long attracted attention for its multifunctional roles in redox homeostasis. More recently, it has been studied in relation to immune regulation and cancer biology. Beyond its well-known circadian function, melatonin modulates oxidative stress by directly [...] Read more.

Melatonin, an ancient and evolutionarily conserved indolamine, has long attracted attention for its multifunctional roles in redox homeostasis. More recently, it has been studied in relation to immune regulation and cancer biology. Beyond its well-known circadian function, melatonin modulates oxidative stress by directly scavenging reactive oxygen and nitrogen species and by upregulating antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. At the same time, it exerts wide-ranging immunomodulatory functions by influencing both innate and adaptive immune responses. All these actions converge within the tumor microenvironment, where oxidative stress and immune suppression drive cancer progression. Although the antitumoral effects of melatonin have traditionally been interpreted through its actions on T cells and NK cells, recent studies identify macrophages as an underappreciated and pivotal target. Notably, melatonin influences macrophage polarization, favoring antitumor M1 phenotypes over pro-tumoral M2 states, while attenuating chronic inflammation and restoring mitochondrial function. This review summarizes current knowledge on melatonin’s antioxidant and immunoregulatory mechanisms, highlighting its impact on the tumor immune microenvironment, with a particular focus on the growing recognition of macrophages as a compelling new axis through which melatonin may exert anticancer effects. Full article

(This article belongs to the Special Issue Redox Regulation of Immune and Inflammatory Responses)

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16 pages, 2789 KB

Open AccessReview

Experimental Models of Acute Lung Injury to Study Inflammation and Pathophysiology: A Narrative Review

by Akinori Cardozo Nagato, Pedro Alves Machado-Junior, Samuel Santos Valenca, Remo Castro Russo and Frank Silva Bezerra

Antioxidants 2026, 15(1), 63; https://doi.org/10.3390/antiox15010063 - 2 Jan 2026

Abstract

Acute lung injury (ALI) is characterized by acute respiratory insufficiency, including tachypnea, cyanosis refractory to oxygen, decreased lung compliance, and diffuse alveolar infiltrates, which is a condition associated with high morbidity and mortality that usually results in the development of multiple organ dysfunction. [...] Read more.

Acute lung injury (ALI) is characterized by acute respiratory insufficiency, including tachypnea, cyanosis refractory to oxygen, decreased lung compliance, and diffuse alveolar infiltrates, which is a condition associated with high morbidity and mortality that usually results in the development of multiple organ dysfunction. Acute lung injury in humans is histopathologically characterized by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury, such as LPS-induced ALI, hyperoxia-induced ALI, and ventilator-induced lung injury (VILI). Here we will show selected preclinical mice models used as proof of concept to test new drugs in vivo with anti-inflammatory properties, discussing their particularities and clarifying the context of use. Full article

(This article belongs to the Special Issue The OxInflammation Process and Tissue Repair)

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Graphical abstract

16 pages, 2337 KB

Open AccessArticle

Autofluorescence Profiling of Virgin Olive Oil: Impact of Rosemary and Basil Flavoring During Storage

by Enrique J. Díaz-Montaña, Ramón Aparicio-Ruiz, Noelia Tena, Ana Lobo-Prieto, Diego L. García-González and María Teresa Morales

Antioxidants 2026, 15(1), 62; https://doi.org/10.3390/antiox15010062 - 1 Jan 2026

Abstract

The consumption of virgin olive oil has been associated with a broad spectrum of beneficial effects. These health outcomes are attributed not only to its high monounsaturated fatty acid content but also to its bioactive components. Nowadays, the flavoring of olive oil has [...] Read more.

The consumption of virgin olive oil has been associated with a broad spectrum of beneficial effects. These health outcomes are attributed not only to its high monounsaturated fatty acid content but also to its bioactive components. Nowadays, the flavoring of olive oil has gained popularity to improve its antioxidant properties, modify its sensory characteristics, and enhance its oxidative stability. This study explores spectrofluorometry as a fast, non-destructive, and eco-friendly tool to monitor oxidation and predict shelf life in virgin olive oils (VOOs). Both unflavored and flavored rosemary and basil samples were studied. Over nine months of storage, monthly autofluorescence measurements at 330 nm excitation revealed dynamic spectral changes. These changes were mapped into three distinct emission zones (I, II, and III), providing a spectral fingerprint of oil freshness and stability. Autofluorescence analysis revealed that oxidation-related emission increased while pigment-related emission decreased over time, especially within the first five months. Rosemary and basil flavoring slowed degradation due to antioxidant migration from the herbs. It is proposed that a ratio between the fluorescence intensity of Zone III/Zone II of the spectrum of less than 0.6 indicates oils stored for more than three months. Full article

(This article belongs to the Special Issue Lipid Peroxidation, Vegetable Oil Oxidation, and the Role of Plant Extracts in Enhancing Oxidative Stability)

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Graphical abstract

40 pages, 2183 KB

Open AccessReview

Anthocyanins and Metabolic Disease: A New Frontier in Precision Nutrition

by Giuseppe T. Patanè, Ruben J. Moreira, Maria de Almeida-Santos, Stefano Putaggio, Davide Barreca, Pedro F. Oliveira and Marco G. Alves

Antioxidants 2026, 15(1), 61; https://doi.org/10.3390/antiox15010061 - 1 Jan 2026

Abstract

Metabolic syndrome (MetS) represents a global health challenge mainly driven by chronic low-grade inflammation and persistent oxidative stress (OS). Current therapeutic and nutritional strategies often fail to resolve these interconnected core pathologies due to the multifactorial nature of MetS. Anthocyanins (ACNs), a class [...] Read more.

Metabolic syndrome (MetS) represents a global health challenge mainly driven by chronic low-grade inflammation and persistent oxidative stress (OS). Current therapeutic and nutritional strategies often fail to resolve these interconnected core pathologies due to the multifactorial nature of MetS. Anthocyanins (ACNs), a class of potent dietary flavonoids, offer significant promise due to their established pleiotropic effects, including robust antioxidant activity through modulation of the Nrf2/ARE pathway, anti-inflammatory effects via NF-κB suppression, and overall support for glucose and lipid homeostasis. However, the therapeutic efficacy of ACNs is characterized by interindividual variability, which is intrinsically linked to their low systemic bioavailability. This heterogeneity in the response is due to the complex interplay between genetic polymorphisms affecting absorption, distribution, metabolism, and excretion (ADME), as well as the specific biotransformation capacity of the gut microbiome. This review proposes that achieving the full clinical potential of ACNs requires moving beyond conventional nutritional advice. We propose that precision nutrition, which integrates multi-omics data (e.g., genomics, metagenomics, and metabolomics), can determine the individual phenotype, predict functional metabolic response, and tailor safer and effective ACN-rich interventions. This integrated, multifactorial approach is essential for optimizing the antioxidant and metabolic benefits of ACNs for the prevention and management of MetS and its associated pathologies. Full article

(This article belongs to the Special Issue Antioxidant Therapy for Obesity-Related Diseases)

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12 pages, 1663 KB

Open AccessArticle

NADPH Oxidase 1 Mediates Endothelial Dysfunction and Hypertension in a Murine Model of Obesity

by Caleb A. Padgett, Joshua T. Butcher, Sebastian Larion, James D. Mintz, David J. R. Fulton and David W. Stepp

Antioxidants 2026, 15(1), 60; https://doi.org/10.3390/antiox15010060 - 1 Jan 2026

Abstract

Obesity is a foremost risk factor for the development of cardiovascular disease, a hallmark of which is chronic vascular inflammation and overproduction of reactive oxygen species (ROS). NADPH oxidases (NOX) are central mediators of ROS overproduction in the obese vasculature, yet a complete [...] Read more.

Obesity is a foremost risk factor for the development of cardiovascular disease, a hallmark of which is chronic vascular inflammation and overproduction of reactive oxygen species (ROS). NADPH oxidases (NOX) are central mediators of ROS overproduction in the obese vasculature, yet a complete understanding of the mechanism underlying their dysregulation in obesity remains poorly understood. Herein, we investigated the contribution of NOX1 in obesity-associated hypertension and evaluated the therapeutic potential of pharmacologically targeting NOX1 using the novel inhibitor GKT771. In obese db/db mice, NOX1 deletion ameliorated hypertension independent of metabolic improvements such as weight loss or improved glucose handling. Furthermore, NOX1 deletion improved renal sodium handling with no compensatory upregulation of other NOX isoforms. Importantly, treatment with the NOX1-specific inhibitor GKT771 rescued endothelial function in obese mice, restoring microvascular function to levels observed in lean controls. These data highlight the importance of NOX1 as a driver of endothelial dysfunction in obesity and suggest that NOX1 inhibition may offer a novel therapeutic strategy for obesity-associated endothelial dysfunction and its downstream cardiovascular complications. Full article

(This article belongs to the Special Issue NADPH Oxidases (NOXs))

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26 pages, 7584 KB

Open AccessArticle

Neuroprotective Effect of D-Pinitol Against MPTP-Induced Parkinsonism in C57BL/6J Mice

by María del Carmen Juárez-Vázquez, María Leonor González-Rivera, Ramsés Maximiliano Ramírez-Martínez, Athzirys Alejandra Melecio-Hernández, Juan C. Jiménez-Cruz, Gabriela Josefina López-González, Juan Carlos Barragán-Gálvez, Juan Ramón Zapata-Morales, Judit A. Aviña-Verduzco and Angel Josabad Alonso-Castro

Antioxidants 2026, 15(1), 59; https://doi.org/10.3390/antiox15010059 - 1 Jan 2026

Abstract

Parkinson’s disease is the second most common neurodegenerative disease in the world. Natural products can offer a possible option of neuroprotective agents for preventing neurodegenerative diseases. D-Pinitol is a cyclic polyol with anxiolytic and antidepressant effects in acute assays. This work aimed to [...] Read more.

Parkinson’s disease is the second most common neurodegenerative disease in the world. Natural products can offer a possible option of neuroprotective agents for preventing neurodegenerative diseases. D-Pinitol is a cyclic polyol with anxiolytic and antidepressant effects in acute assays. This work aimed to evaluate the effects of D-Pinitol (10, 50, and 100 mg/kg p.o.) in a chronic reserpine-induced depression model (19 days), using the forced swimming and tail suspension tests in female Balb/c mice, and the neuroprotective effects in an MPTP-induced Parkinsonism model (30 days) in male C57bL/6 mice, using behavioral tests such as wire grip, rotarod, catalepsy, and others. D-Pinitol showed low antidepressant-like effects in the reserpine-induced chronic depression model, compared to amitriptyline (25 mg/kg p.o.). D-Pinitol protected MPTP-treated mice from motor impairment with similar effects to those shown by L-Dopa (25 mg/kg p.o.) as evaluated in different behavioral tests. The inhibition of oxidative stress markers, increase in dopamine levels, and avoidance of apoptosis in neuronal cells were the mechanisms by which D-Pinitol protects MPTP-treated mice from motor impairment. Full article

(This article belongs to the Section Natural and Synthetic Antioxidants)

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18 pages, 2958 KB

Open AccessArticle

Targeting Arginase 1 but Not Arginase 2 Protects from Myocardial Ischemia–Reperfusion Injury via Nitric Oxide Signaling by Red Blood Cells in Type 2 Diabetes

by Jiangning Yang, Yahor Tratsiakovich, Renhai Cao, Ali Mahdi, Gianluigi Pironti, Tong Jiao, Rawan Humoud, Eftychia Kontidou, John Tengbom, Aida Collado, Zhichao Zhou, Yihai Cao, Eleonore Köhler, Adam E. Mullick and John Pernow

Antioxidants 2026, 15(1), 58; https://doi.org/10.3390/antiox15010058 - 1 Jan 2026

Abstract

Background: Arginase influences cardiac tolerance to ischemia–reperfusion by modulating nitric oxide (NO) signaling. In type 2 diabetes (T2D), elevated arginase activity may worsen ischemic injury through red blood cells (RBCs), but the specific roles of arginase isoforms are unclear. Methods: C57BL/6 and db/db [...] Read more.

Background: Arginase influences cardiac tolerance to ischemia–reperfusion by modulating nitric oxide (NO) signaling. In type 2 diabetes (T2D), elevated arginase activity may worsen ischemic injury through red blood cells (RBCs), but the specific roles of arginase isoforms are unclear. Methods: C57BL/6 and db/db mice were pretreated with ARG1 or ARG2 antisense oligonucleotides (ASO) for six weeks. Conditional ARG1 knockout (ARG1^fl/fl/Tie2Cre^tg/−) and wild-type littermates were also studied. Mice underwent coronary artery ligation and reperfusion in vivo for infarct size assessment. In ex vivo experiments, buffer-perfused hearts were subjected to global ischemia–reperfusion with or without RBCs to evaluate recovery of left ventricular developed pressure (LVDP). Results: ARG1 knockdown, but not ARG2, improved post-ischemic recovery of LVDP in isolated hearts. RBCs from ARG1 ASO-treated mice enhanced recovery in wild-type hearts, while ARG1 knockout reduced infarct size compared with controls. Cardioprotection was abolished by NO synthase inhibition. RBCs from male and female ARG1 knockout mice improved LVDP recovery compared with RBCs from wild-type mice. In T2D mice, impaired recovery was restored by ARG1 ASO or RBCs from ARG1 ASO-treated T2D mice. Conclusions: Arginase 1, but not arginase 2, limits cardiac tolerance to ischemia–reperfusion and contributes to increased vulnerability in T2D. Full article

(This article belongs to the Special Issue Blood Cells and Redox Homeostasis in Health and Disease, 2nd Edition)

17 pages, 2001 KB

Open AccessReview

Dietary Supplements in Pregnancy and Postpartum: Evidence, Safety Challenges and a Precision Nutrition Framework (GAPSS)

by Jibing Chen, Mingyu Duan, Zhiting Zhu, Rui Su and Jie Cai

Antioxidants 2026, 15(1), 57; https://doi.org/10.3390/antiox15010057 - 1 Jan 2026

Abstract

Maternal undernutrition remains a major modifiable risk factor for adverse pregnancy outcomes. Dietary supplements are widely used to bridge nutritional gaps, but their efficacy, safety, and quality control remain controversial. This review critically evaluates the mechanisms, clinical evidence, and quality assurance of key [...] Read more.

Maternal undernutrition remains a major modifiable risk factor for adverse pregnancy outcomes. Dietary supplements are widely used to bridge nutritional gaps, but their efficacy, safety, and quality control remain controversial. This review critically evaluates the mechanisms, clinical evidence, and quality assurance of key supplements (folic acid, iron, vitamin D, calcium, iodine, omega-3 PUFA, choline, and multiple micronutrients) specifically in pregnant and postpartum women. We highlight that while folic acid (400–800 µg/d) and iron supplementation reduce neural tube defects by >70% and maternal anaemia by 30–50%, respectively, high-dose antioxidant cocktails (vitamins C + E) have shown no benefit and potential harm in large RCTs. Up to 18–40% of commercially available prenatal supplements contain undeclared pharmaceuticals, heavy metals, or incorrect dosages, underscoring the urgent need for advanced analytical methods (LC-MS/MS, HRMS, NMR). We propose the GAPSS (Genotype–Analytics–Physiology–Safety–Sustainability) framework for future personalised maternal nutrition. Rigorous, pregnancy-specific quality control combined with biomarker-guided supplementation is essential to maximise benefits and minimise risks. Full article

(This article belongs to the Topic Oxidative Stress and Diet: The Health Implications of Advanced Glycation and Lipid Oxidation End-Products)

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21 pages, 1192 KB

Open AccessArticle

Fecal Metabolomic Insights into Memory-Associated Pathways Modulated by Bacopa monnieri, Mixed Thai Berry, and Combined Extracts in Rats Under Chronic Unpredictable Mild Stress

by Kalyarut Phumlek, Nitra Nuengchamnong, Phichsinee Rerkshanandana, Sutisa Nudmamud-Thanoi, Worawut Chaiyasaeng, Nathareen Chaiwangrach, Wiyada Khangkhachit, Plaiyfah Janthueng, Wanfrutkon Waehama, Kornkanok Ingkaninan and Prapapan Temkitthawon

Antioxidants 2026, 15(1), 56; https://doi.org/10.3390/antiox15010056 - 1 Jan 2026

Abstract

Chronic stress impairs cognition through gut–brain axis dysregulation and metabolic imbalance. This study applied untargeted fecal metabolomics to investigate the cognitive and metabolic effects of Bacopa monnieri (L.) Wettst (Brahmi), mixed Thai berry, and their combined extracts in rats exposed to chronic unpredictable [...] Read more.

Chronic stress impairs cognition through gut–brain axis dysregulation and metabolic imbalance. This study applied untargeted fecal metabolomics to investigate the cognitive and metabolic effects of Bacopa monnieri (L.) Wettst (Brahmi), mixed Thai berry, and their combined extracts in rats exposed to chronic unpredictable mild stress. Cognitive performance was evaluated using the novel object recognition test. Fecal metabolites were profiled using LC-ESI-QTOF-MS, followed by data preprocessing and multivariate statistical analysis. Orthogonal partial least squares regression was applied to identify metabolites associated with the recognition index, and pathway enrichment analysis was subsequently performed to interpret biological relevance. All interventions were associated with improved recognition performance and treatment-related metabolic modulation. Biosynthesis of unsaturated fatty acids was consistently enriched across treatment groups, indicating a shared involvement of lipid remodeling. Treatment-specific responses were also observed: Brahmi was associated with linoleic and alpha-linolenic acid metabolism; mixed Thai berry extract demonstrated dose-dependent modulation of lipid metabolism, with low-dose supplementation additionally yielding amino-acid-derived metabolites; and bile acid-related signaling was uniquely detected in the low-dose combined extract group. These findings demonstrate that fecal metabolomics can capture distinct metabolic signatures associated with herbal extract-induced cognitive improvement and highlight lipid remodeling as a shared metabolic feature across interventions under chronic stress. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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25 pages, 804 KB

Open AccessReview

Phagocyte NADPH Oxidase NOX2-Derived Reactive Oxygen Species in Antimicrobial Defense: Mechanisms, Regulation, and Therapeutic Potential—A Narrative Review

by George Țocu, Bogdan Ioan Ștefănescu, Loredana Stavăr Matei and Lavinia Țocu

Antioxidants 2026, 15(1), 55; https://doi.org/10.3390/antiox15010055 - 31 Dec 2025

Abstract

ROS derived from NADPH oxidase, particularly NOX2, are central to antimicrobial defense, coupling direct pathogen killing with redox signaling that shapes inflammation. This narrative review integrates recent advances on NOX2 structure, assembly, and spatiotemporal control in phagocytes, and outlines how ROS interact with [...] Read more.

ROS derived from NADPH oxidase, particularly NOX2, are central to antimicrobial defense, coupling direct pathogen killing with redox signaling that shapes inflammation. This narrative review integrates recent advances on NOX2 structure, assembly, and spatiotemporal control in phagocytes, and outlines how ROS interact with NF-κB, MAPK, and Nrf2 networks to coordinate microbicidal activity and immune modulation. We summarize evidence that both ROS deficiency, as in chronic granulomatous disease, and uncontrolled excess, as in sepsis and severe COVID-19, drive clinically significant pathology, emphasizing the need for precise redox balance. Emerging therapeutic strategies include selective NOX2 inhibitors that limit pathological oxidative bursts, redox-modulating peptides that disrupt upstream activation cues, and Nrf2 activators that enhance endogenous antioxidant capacity, with attention to dosing challenges that preserve host defense while mitigating tissue injury. Key gaps remain in biomarker standardization, real-time in vivo ROS monitoring, and translation from animal models to patients, motivating personalized, combination approaches to redox medicine in infectious diseases. Full article

(This article belongs to the Special Issue Reactive Oxygen Species (ROS): Key Components in Infection Control, Wound Healing, and Cancer Therapy)

23 pages, 2969 KB

Open AccessReview

Dynamic Oxidative States: Interplay of Aging, Metabolic Stress, and Circadian Rhythms in Modulating Stroke Severity

by Jui-Ming Sun, Jing-Shiun Jan, Cheng-Ta Hsieh, Rajeev Taliyan, Chih-Hao Yang, Ruei-Dun Teng and Ting-Lin Yen

Antioxidants 2026, 15(1), 54; https://doi.org/10.3390/antiox15010054 - 31 Dec 2025

Abstract

Oxidative stress is a defining feature of stroke pathology, but the magnitude, timing and impact of redox imbalance are not static. Emerging evidence indicates that physiological contexts, such as aging, metabolic stress, and circadian disruption, continuously reshape oxidative status and determine the brain’s [...] Read more.

Oxidative stress is a defining feature of stroke pathology, but the magnitude, timing and impact of redox imbalance are not static. Emerging evidence indicates that physiological contexts, such as aging, metabolic stress, and circadian disruption, continuously reshape oxidative status and determine the brain’s vulnerability to ischemic and reperfusion injury. This review integrates recent insights into how these intrinsic modulators govern the transition from adaptive physiological redox signaling to pathological oxidative stress during stroke. Aging compromises mitochondrial quality control and blunts NRF2-driven antioxidant responses, heightening susceptibility to ROS-driven damage. Metabolic dysfunction, as seen in obesity and diabetes, amplifies oxidative burden through NADPH oxidase activation, lipid peroxidation, and impaired glutathione recycling, further aggravating post-ischemic inflammation. Circadian misalignment, meanwhile, disrupts the rhythmic expression of antioxidant enzymes and metabolic regulators such as BMAL1, REV-ERBα, and SIRT1, constricting the brain’s temporal window of resilience. We highlight convergent signaling hubs, NRF2/KEAP1, SIRT–PGC1α, and AMPK pathways, as integrators of these physiological inputs that collectively calibrate redox homeostasis. Recognizing oxidative stress as a dynamic, context-dependent process reframes it from a static pathological state to a dynamic outcome of systemic and temporal imbalance, offering new opportunities for time-sensitive and metabolism-informed redox interventions in stroke. Full article

(This article belongs to the Special Issue Antioxidants, Metabolic Regulation and Stroke)

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9 pages, 1930 KB

Open AccessCommunication

Unveiling Resveratrone: A High-Performance Antioxidant Substance

by Eunhak Lim, Kyung-Eun Gil and Kyoung-Chan Park

Antioxidants 2026, 15(1), 53; https://doi.org/10.3390/antiox15010053 - 31 Dec 2025

Abstract

Resveratrone is a novel compound that was inadvertently discovered by photo-conversion of natural compound resveratrol. Although resveratrol, a representative antioxidant and anti-aging compound, is widely used to promote human health, the benefits of resveratrone have been little studied and remain largely unknown. Since [...] Read more.

Resveratrone is a novel compound that was inadvertently discovered by photo-conversion of natural compound resveratrol. Although resveratrol, a representative antioxidant and anti-aging compound, is widely used to promote human health, the benefits of resveratrone have been little studied and remain largely unknown. Since resveratrone has a completely different molecular structure from resveratrol, it has a high possibility of possessing different effects to resveratrol. In this study, the various effects of resveratrone on skin health were revealed, including outstanding antioxidants, whitening, anti-wrinkle, skin regeneration, anti-acne, and so on. Moreover, resveratrone has been confirmed to be an excellent ingredient for skin health because it shows higher performance than resveratrol in most areas. Full article

(This article belongs to the Section Natural and Synthetic Antioxidants)

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29 pages, 8236 KB

Open AccessArticle

Enriched Environment Ameliorates Cerebral Ischemia–Reperfusion Injury via Dopamine–H₂S Axis-Mediated Dual Mitophagy Activation

by Bao Zhou, Haocheng Qin, Pengkun Yang, Na Ren, Lu Sun, Zhengran Ding, Zhong He, Shuai Zhang, Zijian Hua, Ya Zheng, Ce Li, Shenyi Kuang, Yulian Zhu and Kewei Yu

Antioxidants 2026, 15(1), 52; https://doi.org/10.3390/antiox15010052 - 30 Dec 2025

Abstract

Cerebral ischemia–reperfusion injury triggers mitochondrial dysfunction and oxidative stress, exacerbating neuronal apoptosis. Emerging evidence highlights hydrogen sulfide (H₂S) as a gasotransmitter modulating redox balance, autophagy, and apoptosis. This study investigates the neuroprotective mechanisms of Enriched Environment (EE) against ischemic injury, focusing [...] Read more.

Cerebral ischemia–reperfusion injury triggers mitochondrial dysfunction and oxidative stress, exacerbating neuronal apoptosis. Emerging evidence highlights hydrogen sulfide (H₂S) as a gasotransmitter modulating redox balance, autophagy, and apoptosis. This study investigates the neuroprotective mechanisms of Enriched Environment (EE) against ischemic injury, focusing on mitochondrial dynamics and H₂S-mediated pathways. Using MCAO mice and OGD/R-treated SH-SY5Y neurons, interventions targeting H₂S synthesis, hypoxia-inducible factor 1-alpha (HIF-1α), and mitophagy were implemented. Behavioral, histological, and molecular analyses demonstrated EE significantly improved neurological outcomes, suppressed apoptosis, and attenuated oxidative damage (reduced MDA, elevated MnSOD/glutathione). Mechanistically, EE enhanced mitophagy via dual pathways: canonical PINK1/parkin-mediated mitochondrial clearance, corroborated by transmission electron microscope and LC3B/parkin colocalization, and non-canonical HIF-1α/BNIP3L axis activation. Transcriptomic and Co-immunoprecipitation (Co-IP) data revealed EE upregulated endogenous H₂S biosynthesis post-injury by promoting dopamine-induced calcium influx, which activated calmodulin-dependent signaling to stimulate cystathionine β-synthase/γ-lyase expression. Pharmacological blockade of H₂S synthesis or HIF-1α abolished mitochondrial protection, confirming H₂S as a central mediator. Notably, H₂S exerted antiapoptotic effects by restoring mitochondrial integrity through synergistic mitophagy activation and oxidative stress mitigation. These findings propose a novel neuroprotective cascade: EE-induced dopaminergic signaling potentiates H₂S production, which coordinates PINK1/parkin and HIF-1α/BNIP3L pathways to eliminate dysfunctional mitochondria, thereby preserving neuronal homeostasis. This study elucidates therapeutic potential of EE via H₂S-driven mitochondrial quality control, offering insights for ischemic brain injury intervention. Full article

(This article belongs to the Special Issue Antioxidant Therapies, Mitochondrial Function, and Transplantation Strategies: Mechanisms and Emerging Therapeutics)

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16 pages, 286 KB

Open AccessArticle

Oxidative Stress and Inflammatory Biomarkers in Aqueous Humor and Blood of Patients with Leber’s Hereditary Optic Neuropathy

by Berta Sánchez-Fernández, Pablo Zamorano-González, Elisa Martín-Montañez, Carmen Alba-Linero, Francisca Rius-Díaz, María García-Fernandez, Rafael Luque-Aranda and Ignacio García-Basterra

Antioxidants 2026, 15(1), 51; https://doi.org/10.3390/antiox15010051 - 30 Dec 2025

Abstract

Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder that causes visual impairment due to the degeneration of retinal ganglion cells. Oxidative stress (OS) and inflammatory cytokines have been implicated in its pathophysiology. We investigated, for the first time, the presence of OS [...] Read more.

Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder that causes visual impairment due to the degeneration of retinal ganglion cells. Oxidative stress (OS) and inflammatory cytokines have been implicated in its pathophysiology. We investigated, for the first time, the presence of OS biomarkers and inflammatory cytokines in the aqueous humor and peripheral blood of LHON patients compared to controls, aiming to identify potential clinical biomarkers for diagnosis and disease monitoring. A total of 38 participants were enrolled in a single-center, retrospective observational study, including 17 genetically confirmed LHON patients from different Spanish regions and 21 controls. OS biomarkers and inflammatory cytokines were quantified using spectrophotometry and fluorimetry techniques. Statistical analyses were performed to compare groups and to assess the discriminatory performance of biomarkers in identifying affected individuals. Compared to controls, LHON patients exhibited significantly higher levels of AOPP, LOOH, nitrotyrosine, GPX, GRD, and OX/AntiOX ratio in both aqueous humor and serum. Among these, serum LOOH levels and the OX/AntiOX ratio were the most reliable for identifying patients affected, with high sensitivity and specificity. However, additional data on serum IL-1ra are required to confirm its potential as an effective classifier. These findings highlight novel candidate biomarkers for the diagnosis and monitoring of LHON progression. Full article

(This article belongs to the Special Issue Oxidative Stress in Eye Diseases)

21 pages, 4370 KB

Open AccessArticle

Ultrasound-Assisted Extraction of Bioactive Compounds from Strawberry Pomace: Optimization and Bioactivity Assessment

by Milena Terzić, Biljana Lončar, Mirjana Petronijević, Sanja Panić, Aleksandra Cvetanović Kljakić, Jelena Arsenijević, Gokhan Zengin and Slavica Ražić

Antioxidants 2026, 15(1), 50; https://doi.org/10.3390/antiox15010050 - 30 Dec 2025

Abstract

The growing production of strawberry-based foods generates large quantities of pomace, a phenolic-rich by-product with high valorization potential. This study aimed to optimize ultrasound-assisted extraction (UAE) of strawberry pomace and to evaluate the bioactivity of the resulting extracts. The greenness assessment using the [...] Read more.

The growing production of strawberry-based foods generates large quantities of pomace, a phenolic-rich by-product with high valorization potential. This study aimed to optimize ultrasound-assisted extraction (UAE) of strawberry pomace and to evaluate the bioactivity of the resulting extracts. The greenness assessment using the AGREEprep metric yielded a score of 0.68/1, confirming the environmental friendliness of the process. Under the optimized UAE conditions (20 min, 50 °C, solid-to-liquid ratio 1:20 g/mL), the extract exhibited the highest total phenolic (16.49 mg GAE/g) and flavonoid contents (2.10 mg RE/g). The optimized extract showed strong antioxidant activity, with DPPH, ABTS, CUPRAC, and FRAP values of 32.70, 46.76, 57.29, and 38.90 mg TE/g, respectively. Enzyme inhibition was particularly pronounced against tyrosinase (55.45 mg KAE/g), while moderate inhibition of acetylcholinesterase and butyrylcholinesterase was also observed. Artificial neural network (ANN) modeling demonstrated excellent predictive performance (R² > 0.99) and enabled effective optimization of extraction parameters. These findings confirm UAE as an efficient and sustainable approach for strawberry pomace valorization and highlight ANN-based optimization as a robust tool for developing multifunctional bioactive extracts for food, nutraceutical, and pharmaceutical applications. Full article

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18 pages, 6193 KB

Open AccessArticle

The Protective Efficacy of Total Alkaloids from Nelumbinis Plumula on Irradiation-Induced Oxidative Stress Damage in Human Umbilical Vein Endothelial Cells

by Junyu Bu, Ziming Xia, Jinrui Zhang, Longhui Yan, Yiming Luo, Zhiyan Zhang, Min Li, Shuchen Liu and Ying Tian

Antioxidants 2026, 15(1), 49; https://doi.org/10.3390/antiox15010049 - 30 Dec 2025

Abstract

A high-purity alkaloid-enriched extract (NPAE) was developed from Nelumbinis Plumula. Beyond quantifying its representative alkaloids and total alkaloid content, this study revealed the novel radioprotective role of NPAE against radiation-induced oxidative stress in human umbilical vein endothelial cells (HUVECs). Pretreatment with NPAE significantly [...] Read more.

A high-purity alkaloid-enriched extract (NPAE) was developed from Nelumbinis Plumula. Beyond quantifying its representative alkaloids and total alkaloid content, this study revealed the novel radioprotective role of NPAE against radiation-induced oxidative stress in human umbilical vein endothelial cells (HUVECs). Pretreatment with NPAE significantly attenuated H₂O₂-induced oxidative stress and suppressed irradiation-induced pyroptosis, primarily through restoration of redox homeostasis and inhibition of inflammasome activation. Mechanistic investigations showed that NPAE downregulated the expression of GSDMD-N and cleaved caspase-1, while reducing the secretion of proinflammatory cytokines (IL-18 and IL-1β). These results demonstrate that NPAE effectively alleviates oxidative damage and prevents pyroptosis in endothelial cells, highlighting its potential as a promising phytotherapeutic agent for protection against ionizing radiation injury. Full article

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