Antioxidants

22 pages, 2458 KB

Open AccessArticle

Betulinic Acid-Enriched Dillenia indica L. Bark Extract Attenuates UVB-Induced Skin Aging via KEAP1-Mediated Antioxidant Pathways

by Bo-Rim Song, Sunghwan Kim and Sang-Han Lee

Antioxidants 2025, 14(9), 1144; https://doi.org/10.3390/antiox14091144 - 22 Sep 2025

Viewed by 529

Abstract

The bark of Dillenia indica L. is a rich source of phenolic and triterpenoid compounds, including betulinic acid (BA), known for their antioxidant and anti-aging properties. This study investigated the antioxidant potential of a BA-enriched extract through a multidisciplinary approach combining computational, experimental, [...] Read more.

The bark of Dillenia indica L. is a rich source of phenolic and triterpenoid compounds, including betulinic acid (BA), known for their antioxidant and anti-aging properties. This study investigated the antioxidant potential of a BA-enriched extract through a multidisciplinary approach combining computational, experimental, and cell-based evaluations. Molecular docking and molecular dynamics simulations revealed that BA binds stably to Kelch-like ECH-associated protein 1 (KEAP1), suggesting activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Extraction conditions were optimized using response surface methodology (RSM) and artificial neural network (ANN) modeling, yielding the maximum total phenolic content (TPC; 85.33 ± 2.26 mg gallic acid equivalents/g) and total flavonoid content (TFC; 75.60 ± 1.66 mg catechin equivalents/g), with ANN demonstrating superior predictive performance compared to RSM. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) confirmed the presence of BA in the optimized extract. Simulated gastrointestinal digestion revealed reductions in TPC, TFC, and radical scavenging activity during the gastric phase. In ultraviolet B (UVB)-irradiated human keratinocyte (HaCaT) cells, the optimized extract significantly reduced intracellular reactive oxygen species (ROS) and upregulated the KEAP1-Nrf2-heme oxygenase-1 (HO-1) pathway, confirming its antioxidant mechanism. These findings highlight the extract’s stability, bioactivity, and mechanistic efficacy, supporting its application as a nutraceutical ingredient for combating oxidative stress and skin aging. Full article

(This article belongs to the Special Issue Antioxidants and Oxidative Stress in Skin Health and Diseases)

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23 pages, 1267 KB

Open AccessArticle

Dysregulated Expression of Canonical and Non-Canonical Glycolytic Enzyme Isoforms in Peripheral Blood from Subjects with Alcohol Use Disorder and from Individuals with Acute Alcohol Consumption

by Maura Rojas-Pirela, Daniel Salete-Granado, Diego Andrade-Alviárez, Alejandro Prieto-Rojas, Cristina Rodríguez, María-Lourdes Aguilar-Sánchez, David Puertas-Miranda, María-Ángeles Pérez-Nieto, Vanessa Rueda-Cala, Candy Pérez, Wilfredo Quiñones, Paul A. M. Michels, Ángeles Almeida and Miguel Marcos

Antioxidants 2025, 14(9), 1143; https://doi.org/10.3390/antiox14091143 - 22 Sep 2025

Viewed by 530

Abstract

Glycolysis is primarily involved in ATP production but also modulates oxidative stress. Chronic alcohol consumption is correlated with an increased incidence of multiple diseases, including cancer and neurodegenerative diseases (NDDs), though the underlying mechanisms remain unclear. Guided by a literature review and bioinformatics [...] Read more.

Glycolysis is primarily involved in ATP production but also modulates oxidative stress. Chronic alcohol consumption is correlated with an increased incidence of multiple diseases, including cancer and neurodegenerative diseases (NDDs), though the underlying mechanisms remain unclear. Guided by a literature review and bioinformatics analysis, we evaluated the expression of 22 genes encoding various isoforms of seven glycolytic enzymes (GEs) in the peripheral blood of patients with alcohol use disorder (AUD), individuals with acute alcohol consumption (AAC), and their respective control groups using qPCR. In parallel, we evaluated the expression of selected genes coding for GEs linked to NDDs, as well as astrocytic markers in primary mouse astrocyte cultures exposed to ethanol. Thirteen GE-related genes, including non-canonical isoforms, were significantly dysregulated in AUD patients; notably, eight of these genes showed similar alterations in individuals with AAC. Several enzymes encoded by these genes are known to be regulated by oxidative stress. Ethanol-exposed astrocytes also showed altered expression of glycolytic genes associated with NDDs and astrocyte function. These findings indicate that glycolytic dysregulation is driven by ethanol intake, regardless of exposure duration or organic damage, highlighting a link between ethanol-driven redox imbalance and glycolytic remodeling, which could contribute to organ damage. Full article

(This article belongs to the Special Issue Alcohol-Induced Oxidative Stress in Health and Disease, 2nd Edition)

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38 pages, 2022 KB

Open AccessReview

Beyond Antioxidants: How Redox Pathways Shape Cellular Signaling and Disease Outcomes

by Abdallah Alhaj Sulaiman and Vladimir L. Katanaev

Antioxidants 2025, 14(9), 1142; https://doi.org/10.3390/antiox14091142 - 22 Sep 2025

Viewed by 1023

Abstract

Cellular redox pathways are critical regulators of various biological processes, including the intricate modulation of intracellular signaling pathways. This review explores how major redox enzymes—such as catalase, superoxide dismutases, glutathione peroxidases, thioredoxins, and peroxiredoxins—interact with key cellular signaling pathways, including receptor tyrosine kinase, [...] Read more.

Cellular redox pathways are critical regulators of various biological processes, including the intricate modulation of intracellular signaling pathways. This review explores how major redox enzymes—such as catalase, superoxide dismutases, glutathione peroxidases, thioredoxins, and peroxiredoxins—interact with key cellular signaling pathways, including receptor tyrosine kinase, mTORC1/AMPK, Wnt/β-catenin, TGF-β/SMAD, NF-κB, Hedgehog, Notch, and GPCR signaling. By investigating mechanisms such as ROS-mediated activation, cysteine oxidation, spatial enzyme localization, and phosphatase regulation, we demonstrate the extensive influence of redox balance on cellular signaling dynamics. Understanding these redox-dependent interactions provides insights into pathophysiological conditions ranging from cancer to fibrosis, offering novel therapeutic opportunities. Full article

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

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21 pages, 4454 KB

Open AccessArticle

Modulation of Pulmonary Inflammation and the Redox Pathway In Vitro and In Vivo by Fumaric Ester

by Aline Pontes de Oliveira, Alexsandro Tavares Figueiredo-Junior, Priscilla Cristine de Oliveira Mineiro, Evelyn Caribé Mota, Carolinne Souza de Amorim, Helber da Maia Valenca, Aline Cristina Casimiro de Albuquerque Gomes, Sabrina Sodré de Souza Serra, Pedro Leme Silva, Christina Maeda Takiya, João Alfredo de Moraes, Samuel Santos Valenca and Manuella Lanzetti

Antioxidants 2025, 14(9), 1141; https://doi.org/10.3390/antiox14091141 - 22 Sep 2025

Viewed by 461

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary inflammation and the destruction of the pulmonary parenchyma (emphysema), with only symptomatic treatment available. Molecules with antioxidant and anti-inflammatory properties, such as dimethyl fumarate (DMF), have shown therapeutic potential. This study evaluated the [...] Read more.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary inflammation and the destruction of the pulmonary parenchyma (emphysema), with only symptomatic treatment available. Molecules with antioxidant and anti-inflammatory properties, such as dimethyl fumarate (DMF), have shown therapeutic potential. This study evaluated the effects of DMF and its metabolite, monomethyl fumarate (MMF), on pulmonary inflammation induced by cigarette smoke (in vitro) and porcine pancreatic elastase (PPE) in mice (in vivo). In vitro, human pulmonary epithelial cells (PC-9) were treated with MMF at concentrations of 10, 30, and 100 µM and exposed to cigarette smoke extract (CSE) to assess cell viability, oxidative stress (ROS), lipid peroxidation, and nitrite production. In vivo, C57BL/6 mice were treated with DMF (30 and 100 mg/kg) during and after the induction of emphysema by PPE. ROS levels, total cell count in bronchoalveolar lavage fluid (BALF), lung histology, and the expression of oxidative stress proteins (SOD1 and HO-1) were analyzed. MMF reduced oxidative stress and lipid peroxidation under in vitro conditions. In vivo, DMF reduced ROS levels, inflammation, and prevented lung damage, such as alveolar enlargement. The expression of SOD1 and HO-1 was modulated by DMF treatment. The results suggest that DMF could be an effective therapeutic alternative for COPD, reducing oxidative stress and inflammation. Full article

(This article belongs to the Special Issue Redox Regulation in COPD: Therapeutic Implications of Antioxidants)

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20 pages, 3197 KB

Open AccessArticle

Sheng Mai San Mitigates Heat Stress-Induced Myocardial Injury by Coordinated Regulation of the Keap1-Nrf2-HO-1 and Stub1-HSF1 Signaling Pathways

by Jiaqi Dong, Qian Ma, Rong Yang, Xiaosong Zhang, Yongli Hua, Peng Ji, Wanling Yao, Ziwen Yuan and Yanming Wei

Antioxidants 2025, 14(9), 1140; https://doi.org/10.3390/antiox14091140 - 22 Sep 2025

Viewed by 568

Abstract

Heat stress (HS), a pervasive environmental stressor, significantly disrupts systemic physiological homeostasis, posing substantial threats to human and animal health. Sheng Mai San (SMS), a classic Traditional Chinese Medicine (TCM) formula, exerts its therapeutic effects by replenishing qi (the vital energy governing physiological [...] Read more.

Heat stress (HS), a pervasive environmental stressor, significantly disrupts systemic physiological homeostasis, posing substantial threats to human and animal health. Sheng Mai San (SMS), a classic Traditional Chinese Medicine (TCM) formula, exerts its therapeutic effects by replenishing qi (the vital energy governing physiological functions) and nourishing yin (the material basis responsible for moistening and cooling actions). This formula demonstrates significant efficacy in astringing sweating and preventing collapse. However, its precise molecular mechanisms against HS-induced myocardial injury remain incompletely elucidated. This study initially employed physicochemical analytical methods to determine the contents of total polysaccharides, saponins, and flavonoids in SMS and evaluated its antioxidant activity. Subsequently, both in vitro and in vivo rat models of HS were established to systematically assess the alterations in reactive oxygen species (ROS), antioxidant enzymes (GSH, SOD, CAT), and heat shock proteins (HSP70, HSP90) following SMS intervention, thereby investigating HS-induced myocardial injury and the protective effects of SMS. Furthermore, Western blot, immunofluorescence, and qRT-PCR techniques were utilized to quantitatively analyze key molecules in the Keap1-Nrf2-HO-1 and Stub1-HSF1 signaling pathways. The results demonstrated that total polysaccharides were the most concentrated in SMS, followed by total saponins. This formula exhibited potent free radical scavenging capacity against DPPH, ABTS, and OH⁻, along with significant reducing activity. HS-induced myocardial injury reached its peak severity at 6-12 h post-stress exposure. SMS intervention effectively suppressed excessive ROS generation, enhanced the activities of antioxidant enzymes (GSH, SOD, and CAT), and downregulated HSP70 and HSP90 mRNA expression levels, thereby significantly mitigating cardiomyocyte damage. Mechanistic investigations revealed that SMS conferred cardioprotection through dual modulation of the Keap1-Nrf2-HO-1 and Stub1-HSF1 signaling pathways. This study not only provides a novel TCM-based therapeutic strategy for preventing and treating HS-related cardiovascular disorders but also establishes a crucial theoretical foundation for further exploration of SMS’s pharmacological mechanisms and clinical applications. Full article

(This article belongs to the Special Issue Exploring Biomarkers of Oxidative Stress in Health and Disease)

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Graphical abstract

26 pages, 3122 KB

Open AccessReview

Biomedical Applications of Humic Substances: From Natural Biopolymers to Therapeutic Agents

by Yana Gvozdeva, Petya Peneva and Plamen Katsarov

Antioxidants 2025, 14(9), 1139; https://doi.org/10.3390/antiox14091139 - 21 Sep 2025

Viewed by 1013

Abstract

Humic substances, which include humic acid and fulvic acid, are natural biopolymers formed from the decomposition of organic matter. There is growing interest in them because of their diverse potential in the biomedical field. Their complex structures, rich in various functional groups, provide [...] Read more.

Humic substances, which include humic acid and fulvic acid, are natural biopolymers formed from the decomposition of organic matter. There is growing interest in them because of their diverse potential in the biomedical field. Their complex structures, rich in various functional groups, provide antioxidant, anti-inflammatory, antimicrobial, antiviral, and immunomodulatory properties. Recent studies demonstrate that humic substances can scavenge reactive oxygen species, modulate cytokine production, inhibit viral fusion, promote wound healing, and enhance gut microbiota balance. Humic acid and fulvic acid also exhibit anticancer activity by inducing apoptosis in tumor cells, while protecting healthy tissues from oxidative stress. Furthermore, their chelating capacity underlies detoxifying activity and heavy metal binding effects. Despite promising research, variability in composition and potential cytotoxicity under certain conditions emphasize the need for standardized extraction methods and rigorous preclinical evaluation. This review offers a comprehensive overview of the biological effects of humic substances, exploring the mechanisms behind their actions and their potential biomedical applications. It highlights both the benefits and the limitations associated with their use in drug delivery systems. Full article

(This article belongs to the Special Issue Bioactive Compounds: Antioxidant, Antibacterial, Anti-inflammatory Modulation)

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37 pages, 1326 KB

Open AccessReview

Mitochondrial DNA Dysfunction in Cardiovascular Diseases: A Novel Therapeutic Target

by Mi Xiang, Mengling Yang, Lijuan Zhang, Xiaohu Ouyang, Alexey Sarapultsev, Shanshan Luo and Desheng Hu

Antioxidants 2025, 14(9), 1138; https://doi.org/10.3390/antiox14091138 - 21 Sep 2025

Viewed by 1208

Abstract

Cardiovascular diseases hinge on a vicious, self-amplifying cycle in which mitochondrial deoxyribonucleic acid (mtDNA) dysfunction undermines cardiac bioenergetics and unleashes sterile inflammation. The heart’s reliance on oxidative phosphorylation (OXPHOS) makes it exquisitely sensitive to mtDNA insults—mutations, oxidative lesions, copy-number shifts, or aberrant methylation—that [...] Read more.

Cardiovascular diseases hinge on a vicious, self-amplifying cycle in which mitochondrial deoxyribonucleic acid (mtDNA) dysfunction undermines cardiac bioenergetics and unleashes sterile inflammation. The heart’s reliance on oxidative phosphorylation (OXPHOS) makes it exquisitely sensitive to mtDNA insults—mutations, oxidative lesions, copy-number shifts, or aberrant methylation—that impair ATP production, elevate reactive oxygen species (ROS), and further damage the mitochondrial genome. Damaged mtDNA fragments then escape into the cytosol, where they aberrantly engage cGAS–STING, TLR9, and NLRP3 pathways, driving cytokine storms, pyroptosis, and tissue injury. We propose that this cycle represents an almost unifying pathogenic mechanism in a spectrum of mtDNA-driven cardiovascular disorders. In this review, we aim to synthesize the pathophysiological roles of mtDNA in this cycle and its implications for cardiovascular diseases. Furthermore, we seek to evaluate preclinical and clinical strategies aimed at interrupting this cycle—bolstering mtDNA repair and copy-number maintenance, reversing pathogenic methylation, and blocking mtDNA-triggered innate immune activation—and discuss critical gaps that must be bridged to translate these approaches into precision mitochondrial genome medicine for cardiovascular disease. Full article

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

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35 pages, 1359 KB

Open AccessReview

The Dual Role of NOX4 in Cardiovascular Diseases: Driver of Oxidative Stress and Mediator of Adaptive Remodeling

by Pauline Labbé, Eric Thorin and Nathalie Thorin-Trescases

Antioxidants 2025, 14(9), 1137; https://doi.org/10.3390/antiox14091137 - 19 Sep 2025

Viewed by 693

Abstract

NADPH oxidase 4 (NOX4) plays a crucial role in regulating cardiac function and pathology through its involvement in oxidative stress, fibrosis, and maladaptive remodeling. Studies have demonstrated that NOX4 is upregulated in response to various cardiovascular stressors, including heart failure, myocardial infarction, arrhythmias, [...] Read more.

NADPH oxidase 4 (NOX4) plays a crucial role in regulating cardiac function and pathology through its involvement in oxidative stress, fibrosis, and maladaptive remodeling. Studies have demonstrated that NOX4 is upregulated in response to various cardiovascular stressors, including heart failure, myocardial infarction, arrhythmias, and diabetes. This upregulation contributes to detrimental processes like fibrosis, hypertrophy, and inflammation, which are hallmarks of cardiovascular diseases. Inhibition or knockout of NOX4 has shown promise in mitigating these pathological changes, suggesting that NOX4 represents a potential therapeutic target for treating heart disease. However, NOX4’s role is not entirely negative. It also plays a protective role in the heart, supporting myocardial remodeling and angiogenesis and regulating cardiac energy metabolism. Its constitutive ROS production and ability to respond to environmental cues like hypoxia help maintain cellular homeostasis and facilitate adaptive responses to stress. The impact of NOX4 on cardiac health depends not only on its expression level but also on the nature of the stress, the duration of activation, and the balance between protective signaling and oxidative injury. Collectively, the findings suggest that NOX4 functions as a redox sensor, modulating cellular responses to fluctuations in oxidative stress by signaling the need to re-establish redox homeostasis. The ultimate impact of cardiac NOX4 activity, whether protective or deleterious, is highly context-dependent and should not be evaluated through a singular interpretative framework. In conclusion, NOX4 is a dual-function enzyme that can both exacerbate and protect against cardiac pathology, making it a promising, though complex, therapeutic target for various cardiovascular diseases. Full article

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

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24 pages, 702 KB

Open AccessReview

Impact of Maternal High-Fat Diet on Offspring Cardiovascular–Kidney–Metabolic Health: Spotlight on Oxidative Stress

by Chien-Ning Hsu, Chih-Kuang Chen, Chih-Yao Hou, Yu-Wei Chen, Guo-Ping Chang-Chien, Shu-Fen Lin and You-Lin Tain

Antioxidants 2025, 14(9), 1136; https://doi.org/10.3390/antiox14091136 - 19 Sep 2025

Cited by 1 | Viewed by 874

Abstract

Cardiovascular–kidney–metabolic syndrome (CKMS) encompasses interconnected cardiovascular, renal, and metabolic disorders, including obesity, hypertension, and type 2 diabetes. Oxidative stress is increasingly recognized as a central driver of this multi-organ dysfunction. Among maternal influences, exposure to a high-fat diet (HFD) during pregnancy and lactation [...] Read more.

Cardiovascular–kidney–metabolic syndrome (CKMS) encompasses interconnected cardiovascular, renal, and metabolic disorders, including obesity, hypertension, and type 2 diabetes. Oxidative stress is increasingly recognized as a central driver of this multi-organ dysfunction. Among maternal influences, exposure to a high-fat diet (HFD) during pregnancy and lactation consistently predisposes offspring to CKMS-related phenotypes in animal models. While oxidative stress is implicated as a key mediator, its precise role in developmental programming remains unclear, and comparing the differences in its role between overt CKMS and CKM programming is critical. Critical gaps include whether oxidative stress acts uniformly or in an organ- and time-specific manner, which signals initiate long-term redox alterations, and whether these effects are reversible. Furthermore, its interactions with other programming pathways—such as renin–angiotensin system activation, epigenetic dysregulation, gut microbiota imbalance, and altered nutrient sensing—remain insufficiently explored. This review uniquely highlights maternal HFD-induced oxidative stress as a mechanistic axis of CKMS programming and delineates unresolved questions that limit translation. By integrating evidence across organ systems and proposing priorities for multi-organ profiling, refined models, and longitudinal human studies, we outline a forward-looking agenda for the field. Ultimately, clarifying how maternal HFD and oxidative stress shape offspring CKMS risk is essential to inform targeted antioxidant strategies to reduce the intergenerational transmission of CKMS risk. Full article

(This article belongs to the Special Issue High-Fat Diet-Induced Oxidative Stress)

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19 pages, 1268 KB

Open AccessArticle

Sex- and Ethnic-Specific Associations of Serum Lipids with Risk of 12 Cancers: Findings from 506,381 Adults in Two Large Cohorts

by Minh Nguyen Thien, Ji Woo Baek, Yeun Soo Yang and Sun Ha Jee

Antioxidants 2025, 14(9), 1135; https://doi.org/10.3390/antiox14091135 - 19 Sep 2025

Viewed by 582

Abstract

The contribution of serum lipids to carcinogenesis, including their effects on inflammation and oxidative stress, remains debated due to inconsistent evidence across populations. This study aimed to elucidate sex- and ethnic-specific associations between serum lipid indices and the risk of 12 common cancers [...] Read more.

The contribution of serum lipids to carcinogenesis, including their effects on inflammation and oxidative stress, remains debated due to inconsistent evidence across populations. This study aimed to elucidate sex- and ethnic-specific associations between serum lipid indices and the risk of 12 common cancers in two large, distinct populations. We conducted a pooled analysis of 506,381 participants from the UK Biobank (UKB) and the Korean Cancer Prevention Study-II (KCPS-II) cohort, with median follow-ups of 12.0 and 13.0 years, respectively. Multivariable-adjusted Cox hazards models were used to estimate hazard ratios (HRs) for the association between baseline lipids and cancer incidence. In the UKB, a one-standard deviation (1-SD) increase in HDL-C was associated with a decreased overall cancer risk (HR 0.982, 95% CI: 0.969–0.995); meanwhile, a 1-SD increase in LDL-C was associated with an increased risk (HR 1.021, 1.009–1.034); higher HDL-C was linked to an increased risk of cervical cancer (HR 1.167, 1.019–1.337) and prostate cancer (HR 1.025, 1.001–1.049). These associations were not significant in the KCPS-II. The association between serum lipids and cancer risk is substantially modified by sex and ethnicity, suggesting that universal lipid-based prevention strategies may be inappropriate and underscoring the need for population-specific research. Full article

(This article belongs to the Special Issue Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Cancer)

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34 pages, 2161 KB

Open AccessReview

Does the Maternal Gut Microbiome Influence the Outcome of Perinatal Asphyxia?

by Vlad-Petru Morozan, Mara I. Ionescu, Carmen M. D. Zahiu, Ana Maria Catrina, Andreea Racoviță, Ana-Teodora Chirilă, Ioana-Alexandra Dogaru, Cristian Ciotei, Gratiela Gradisteanu Pircalabioru and Ana-Maria Zăgrean

Antioxidants 2025, 14(9), 1134; https://doi.org/10.3390/antiox14091134 - 19 Sep 2025

Viewed by 1487

Abstract

This review explores the maternal gut microbiome’s role in shaping neonatal neurodevelopmental outcomes following perinatal asphyxia (PA), a leading cause of infant mortality and disability with limited therapeutic options beyond hypothermia. We synthesized current evidence on microbiome-mediated neuroprotective mechanisms against hypoxic-ischemic brain injury. [...] Read more.

This review explores the maternal gut microbiome’s role in shaping neonatal neurodevelopmental outcomes following perinatal asphyxia (PA), a leading cause of infant mortality and disability with limited therapeutic options beyond hypothermia. We synthesized current evidence on microbiome-mediated neuroprotective mechanisms against hypoxic-ischemic brain injury. The maternal microbiome influences fetal development through bioactive metabolites (short-chain fatty acids, indole derivatives) that cross the placental barrier, bacterial antigen regulation, and infant microbiome colonization. These pathways activate multiple protective mechanisms: anti-inflammatory signaling via NF-κB suppression and regulatory T cell expansion; antioxidant defenses through Nrf2 activation; neural repair via BDNF upregulation and neurogenesis; and oxytocin system modulation. Animal models demonstrate that maternal dysbiosis from high-fat diet or antibiotics exacerbates PA-induced brain damage, increasing inflammatory markers and hippocampal injury. Conversely, probiotic supplementation, dietary fiber, and specific interventions (omega-3, resveratrol) reduce neuroinflammation and oxidative injury. Human studies link maternal dysbiosis-associated conditions (obesity, gestational diabetes) with adverse pregnancy outcomes, though direct clinical evidence for PA severity remains limited. Understanding the maternal microbiome-fetal brain axis opens therapeutic avenues, including prenatal probiotics, dietary modifications, and targeted metabolite supplementation to prevent or mitigate PA-related neurological sequelae, potentially complementing existing neuroprotective strategies. Full article

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

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18 pages, 3356 KB

Open AccessArticle

Retinoprotective Effects of Abscisic Acid in Ischemic Retinopathy Mouse Model

by Inez Bosnyak, Agnes Nagy, Dorottya Molitor, Balazs Meresz, Edina Szabo, Dora Reglodi, Tamas Atlasz and Alexandra Vaczy

Antioxidants 2025, 14(9), 1133; https://doi.org/10.3390/antiox14091133 - 19 Sep 2025

Viewed by 908

Abstract

The prevalence of hypoxia-caused eye diseases is increasing, but effective, non-invasive treatment options are not available. Abscisic acid (ABA) is a plant hormone with anti-inflammatory and antioxidant effects. ABA is also present in various mammalian tissues and plays an important role in metabolic [...] Read more.

The prevalence of hypoxia-caused eye diseases is increasing, but effective, non-invasive treatment options are not available. Abscisic acid (ABA) is a plant hormone with anti-inflammatory and antioxidant effects. ABA is also present in various mammalian tissues and plays an important role in metabolic processes. Therefore, we aimed to investigate the potential protective role of ABA eye drops in ischemic retinopathy. Retinal ischemia was induced by permanent unilateral common carotid artery occlusion (UCCAO) in mice. Half of the animals received ABA eye drops two times a day for two weeks. Optical coherence tomography (OCT) was used to follow the changes in retinal thickness. Moreover, immunohistochemistry and molecular biology methods were used to explore the morphological changes and the underlying mechanisms, respectively. Based on OCT measurements, ischemic retinopathy was successfully developed. The decrease in the thickness of numerous retinal layers could be prevented with ABA eye drops. The ganglion cell number decreased significantly after UCCAO in the central and peripheral regions of the retina. ABA treatment could moderate the damage in both regions. Furthermore, our apoptosis array results suggest that ABA regulates the apoptotic pathways under hypoxic conditions. In conclusion, ABA eye drops may represent a new potential therapeutic option for the treatment of ischemic retinopathy. Full article

(This article belongs to the Special Issue Antioxidants and Retinal Diseases—2nd Edition)

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35 pages, 1792 KB

Open AccessReview

Time to Reset: The Interplay Between Circadian Rhythms and Redox Homeostasis in Skeletal Muscle Ageing and Systemic Health

by Elizabeth Sutton and Vanja Pekovic-Vaughan

Antioxidants 2025, 14(9), 1132; https://doi.org/10.3390/antiox14091132 - 18 Sep 2025

Viewed by 1514

Abstract

Skeletal muscle plays vital roles in locomotion, metabolic regulation and endocrine signalling. Critically, it undergoes structural and functional decline with age, leading to a progressive loss of muscle mass and strength (sarcopenia) and contributing to a systemic loss of tissue resilience to stressors [...] Read more.

Skeletal muscle plays vital roles in locomotion, metabolic regulation and endocrine signalling. Critically, it undergoes structural and functional decline with age, leading to a progressive loss of muscle mass and strength (sarcopenia) and contributing to a systemic loss of tissue resilience to stressors of multiple tissue systems (frailty). Emerging evidence implicates misalignments in both the circadian molecular clock and redox homeostasis as major drivers of age-related skeletal muscle deterioration. The circadian molecular clock, through core clock components such as BMAL1 and CLOCK, orchestrates rhythmic gene, protein and myokine expression impacting diurnal regulation of skeletal muscle structure and metabolism, mitochondrial function, antioxidant defence, extracellular matrix organisation and systemic inter-tissue communication. In parallel, the master redox regulator, NRF2, maintains cellular antioxidant defence, tissue stress resistance and mitochondrial health. Disruption of either system impairs skeletal muscle contractility, metabolism, and regenerative capacity as well as systemic homeostasis. Notably, NRF2-mediated redox signalling is clock-regulated and, in turn, affects circadian clock regulation. Both systems are responsive to external cues such as exercise and hormones, yet studies do not consistently include circadian timing or biological sex as key methodological variables. Given that circadian regulation shifts with age and differs between sexes, aligning exercise interventions with one’s own chronotype may enhance health benefits, reduce adverse side effects, and overcome anabolic resistance with ageing. This review highlights the essential interplay between circadian and redox systems in skeletal muscle homeostasis and systemic health and argues for incorporating personalised chrono-redox approaches and sex-specific considerations into future experimental research and clinical studies, aiming to improve functional outcomes in age-related sarcopenia and broader age-related metabolic and musculoskeletal conditions. Full article

(This article belongs to the Special Issue Antioxidant Response in Skeletal Muscle)

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10 pages, 1146 KB

Open AccessCommunication

Superoxide Dismutase Gene Family in Chili Pepper (Capsicum annuum L.): Molecular Characterization and Involvement in Redox Regulation Under Chilling Stress

by Seo Hyeon Ban, Chae Eun Song, Seung Hee Eom and Tae Kyung Hyun

Antioxidants 2025, 14(9), 1131; https://doi.org/10.3390/antiox14091131 - 18 Sep 2025

Viewed by 478

Abstract

Chilling stress is a major abiotic factor that limits chili pepper (Capsicum annuum L.) cultivation by disrupting redox homeostasis, thereby impairing growth and fruit productivity. Superoxide dismutases (SODs), which catalyze the conversion of superoxide radicals into hydrogen peroxide and oxygen, serve as [...] Read more.

Chilling stress is a major abiotic factor that limits chili pepper (Capsicum annuum L.) cultivation by disrupting redox homeostasis, thereby impairing growth and fruit productivity. Superoxide dismutases (SODs), which catalyze the conversion of superoxide radicals into hydrogen peroxide and oxygen, serve as key components of the plant antioxidant defense system. However, the SOD gene family in chili pepper has not been comprehensively characterized. Therefore, this study aimed to characterize the SOD gene family in chili pepper and investigate their responses to chilling stress. We identified nine putative CaSOD genes and classified them into CZSOD, FeSOD, and MnSOD clades based on phylogenetic relationships and conserved domain architecture. Bioinformatic analyses revealed variation in physicochemical properties and predicted subcellular localizations, suggesting functional diversification. Transcriptome profiling indicated tissue-specific expression, with several CaSODs preferentially expressed in fruits and floral buds, while qRT-PCR analysis demonstrated that six CaSODs were transcriptionally induced under chilling stress. Functional validation in Nicotiana benthamiana leaves showed that transient expression of four selected CaSODs significantly enhanced SOD activity in an isoform-specific manner. Future studies should validate these genes across diverse chili pepper cultivars under field conditions and assess their potential for integration into breeding programs. Collectively, these findings provide new insights into the molecular and functional diversity of CaSODs, highlight their role in maintaining redox balance under chilling stress, and provide useful genetic resources for breeding stress-tolerant chili pepper and related crops. Full article

(This article belongs to the Special Issue Antioxidant Systems in Plants)

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17 pages, 4154 KB

Open AccessArticle

Hydrogen Gas Mitigates Acute Hypoxia-Induced Oxidative and Inflammatory Brain Injuries in Medaka (Oryzias latipes)

by Eriko Sato, Naohiro Shimamura, Chikako Saiki, Katsuhisa Sunada, Nobuhiko Miwa and Li Xiao

Antioxidants 2025, 14(9), 1130; https://doi.org/10.3390/antiox14091130 - 18 Sep 2025

Viewed by 753

Abstract

Hypoxia-induced oxidative stress and inflammation in the brain are critical contributors to neurological disorders. Hydrogen gas has emerged as a therapeutic agent with potent antioxidant and anti-inflammatory properties. In this study, we evaluated the protective effects of hydrogen against acute hypoxia-induced brain injuries [...] Read more.

Hypoxia-induced oxidative stress and inflammation in the brain are critical contributors to neurological disorders. Hydrogen gas has emerged as a therapeutic agent with potent antioxidant and anti-inflammatory properties. In this study, we evaluated the protective effects of hydrogen against acute hypoxia-induced brain injuries in medaka. Fish were exposed to hypoxia and then recovered in water bubbled with air, hydrogen, or ozone. LOX-1 hypoxia probe imaging and HIF-1α immunostaining showed persistent tissue hypoxia in the air and ozone groups, which was significantly reduced by hydrogen treatment. Histological analysis revealed extensive vascular congestion in the midbrain after hypoxia, which was markedly alleviated by hydrogen. TUNEL assay demonstrated that hydrogen suppressed hypoxia-induced neuronal apoptosis. Immunohistochemistry and ELISA showed elevated levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and proinflammatory markers (COX-2, IL-6, TNF-α) in the brains of air- and ozone-treated fish; these increases were significantly attenuated by hydrogen. ORAC assay confirmed that hydrogen restored brain antioxidant capacity. Behavioral analysis further demonstrated that hydrogen treatment improved locomotor activity and stabilized respiratory function. These results indicate that hydrogen protects medaka against hypoxia-induced oxidative and inflammatory injuries and may represent a promising therapeutic strategy for hypoxia-related neurological disorders. Full article

(This article belongs to the Special Issue Hydrogen and Oxidative Stress: Implications for Health and Longevity)

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18 pages, 9177 KB

Open AccessArticle

Ovary Metal Toxicity Remediation by Agro-Food Waste: Evidence for a Regulatory Mechanism of Oxidative Stress by Banana (Musa cavendish) Peel Extract

by Boma F. Eddie-Amadi, Rubina Vangone, Valeria Guerretti, Harrison A. Ozoani, Kenneth O. Okolo, Dokubo Awolayeofori, Tamuno-Boma Odinga-Israel, Kpobari W. Nkpaa, Emidio M. Sivieri, Orish E. Orisakwe and Giulia Guerriero

Antioxidants 2025, 14(9), 1129; https://doi.org/10.3390/antiox14091129 - 18 Sep 2025

Cited by 1 | Viewed by 549

Abstract

Banana (Musa cavendish) peel, usually discarded as waste, is a polyphenol-rich source with antioxidant and chelating properties. This study evaluated its ability to mitigate ovarian toxicity induced by a heavy metal mixture (HMM) consisting of Hg, Mn, Pb, and Al in [...] Read more.

Banana (Musa cavendish) peel, usually discarded as waste, is a polyphenol-rich source with antioxidant and chelating properties. This study evaluated its ability to mitigate ovarian toxicity induced by a heavy metal mixture (HMM) consisting of Hg, Mn, Pb, and Al in female rats. Animals received the HMM with or without banana peel extract at 200, 400, and 800 mg/kg dosages for 60 days. Co-treatment dose-dependently reduced ovarian metal accumulation, attenuated oxidative and nitrosative stress (MDA, NO), restored antioxidant enzyme activities (SOD, CAT, GSH, GPx), and modulated pro-inflammatory (IL-6, TNF-α), apoptotic (Caspase-3), and transcriptional factors (NF-κB, Nrf2). The gonadal endocrine profile also improved gonadotropins (FSH, LH), prolactin (PRL), and progesterone (P), which were normalized at the medium dose (400 mg/kg), and demonstrated a clear dose-related effect. Histological examination further revealed that this dose most effectively improved ovarian tissue. GC–MS analysis identified bioactive compounds including resveratrol, proanthocyanidins, and anthocyanidins, supporting both antioxidant and chelating actions. These findings demonstrate that banana peel extract exerts a dual, dose-dependent protective role in the gonad, limiting metal burden while enhancing redox defenses, and highlight its translational potential as a sustainable agro-food waste product in reproductive toxicology. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—3rd Edition)

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33 pages, 3308 KB

Open AccessReview

Applications of Antioxidant Nanoparticles in Immune-Mediated Inflammatory Diseases

by Hong-Wei Shi, Bo-Cheng Yang, Yun-Qing Ren and Yi Xue

Antioxidants 2025, 14(9), 1128; https://doi.org/10.3390/antiox14091128 - 18 Sep 2025

Viewed by 846

Abstract

Immune-mediated inflammatory diseases (IMIDs) encompass a wide range of disorders, including autoimmune, acute, and chronic inflammatory conditions, which are often characterized by immune dysregulation and excessive oxidative stress. Oxidative stress plays a pivotal role in the initiation and progression of these diseases by [...] Read more.

Immune-mediated inflammatory diseases (IMIDs) encompass a wide range of disorders, including autoimmune, acute, and chronic inflammatory conditions, which are often characterized by immune dysregulation and excessive oxidative stress. Oxidative stress plays a pivotal role in the initiation and progression of these diseases by promoting tissue damage and sustaining inflammation. However, conventional antioxidant therapies are limited by poor bioavailability, inadequate targeting, and short-lived efficacy. In recent years, nano-antioxidants have emerged as a promising therapeutic approach due to their enhanced stability, targeted delivery capabilities, and multifunctional therapeutic effects. This review provides a comprehensive overview of recent advances in the application of nano-antioxidants in the treatment of IMIDs. Their therapeutic roles are categorized into three major groups: autoimmune diseases, acute inflammatory diseases, and chronic inflammatory diseases. In autoimmune disorders such as alopecia areata and multiple sclerosis, nano-antioxidants have demonstrated the ability to reduce oxidative damage, modulate immune responses, and alleviate clinical symptoms. In acute inflammatory conditions, including acute kidney injury and acute liver injury, these nanomaterials exert protective effects by scavenging ROS, mitigating tissue injury, and restoring organ function. In chronic inflammatory diseases such as inflammatory bowel disease and ulcerative colitis, nano-antioxidants contribute to maintaining mucosal integrity, suppressing chronic inflammation, and improving therapeutic outcomes through localized delivery and sustained release. In summary, nano-antioxidants represent a novel and promising therapeutic strategy for the management of IMIDs. Their unique physicochemical properties offer significant advantages over traditional treatments. Further research is needed to optimize their delivery platforms, evaluate long-term safety, and facilitate clinical translation. Full article

(This article belongs to the Special Issue Applications of Antioxidant Nanoparticles, 2nd Edition)

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18 pages, 1837 KB

Open AccessReview

Emerging and Versatile Non-Mammalian Model Organisms for Studying the In Vivo Antioxidant Properties of Food-Derived Bioactive Compounds

by Alejandra Miranda-Carrazco, Verenice Torres-Salas, Rosy G. Cruz-Monterrosa, Monzerrat Rosas-Espejel, Ildefonso Guerrero-Encinas, Javier N. González-González, Luis Quihui-Cota, Andrea M. Liceaga and José E. Aguilar-Toalá

Antioxidants 2025, 14(9), 1127; https://doi.org/10.3390/antiox14091127 - 18 Sep 2025

Viewed by 603

Abstract

In recent years, there has been increased attention to exploring non-mammalian model organisms to study the antioxidant properties of bioactive compounds. These models include both unicellular organisms, such as Escherichia coli and Saccharomyces cerevisiae, and multicellular organisms, such as Caenorhabditis elegans, Drosophila [...] Read more.

In recent years, there has been increased attention to exploring non-mammalian model organisms to study the antioxidant properties of bioactive compounds. These models include both unicellular organisms, such as Escherichia coli and Saccharomyces cerevisiae, and multicellular organisms, such as Caenorhabditis elegans, Drosophila melanogaster, and Danio rerio. In particular, multicellular models have emerged as promising systems due to their ease of establishing systems and maintenance, short duration of experiments, ease of genetic manipulation and genome-wide screening, availability as off-the-shelf models, safety, and cost-effectiveness. Notably, these organisms share a high degree of gene homology with humans, ranging from 65% to 84%, which positions them as powerful platforms for investigating human disease mechanisms. These advantages make them attractive candidates for investigating the potential health benefits of various bioactive compounds before resorting to mammalian models. This review delves into the rationale for utilizing these emerging non-mammalian model organisms during preliminary stages of research, emphasizing their distinct advantages over traditional mammalian models. It also highlights their significant contributions to advancing our understanding of the antioxidant mechanisms of bioactive compounds, shedding light on their potential therapeutic implications for human health. By leveraging these models, researchers can efficiently screen and validate bioactive compounds, laying a robust foundation for subsequent translational studies in mammalian systems. Full article

(This article belongs to the Special Issue Exploring New Frontiers in Oxidative Stress and Antioxidant Research: From Model Organisms to Human Disease)

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19 pages, 1379 KB

Open AccessArticle

The Addition of Marigold Extract to the Diet Improved the Performance of Laying Hens in the Late Laying Period by Increasing Their Antioxidant Capacity, Lipid Metabolism, and Microbial Composition

by Qiyue Yang, Keying Zhang, Jianping Wang, Shiping Bai, Qiufeng Zeng, Huanwei Peng, Yadong Mu, Yue Xuan, Shanshan Li and Xuemei Ding

Antioxidants 2025, 14(9), 1126; https://doi.org/10.3390/antiox14091126 - 17 Sep 2025

Viewed by 499

Abstract

The decrease in the production performance of laying hens during the later laying stage can be attributed to multiple factors, chief among them being oxidative stress and disrupted lipid metabolism. Quercetagetin, the active component of marigold extract, is a flavonoid whose polyhydroxy structure [...] Read more.

The decrease in the production performance of laying hens during the later laying stage can be attributed to multiple factors, chief among them being oxidative stress and disrupted lipid metabolism. Quercetagetin, the active component of marigold extract, is a flavonoid whose polyhydroxy structure has greater antioxidant capacity than other flavonoids. In this study, we determined whether adding marigold extract to the diet can improve the antioxidant capacity and lipid metabolism of late-laying hens to increase their performance. In total, 800 Lohmann laying hens (45 weeks old) were randomly assigned to five treatment groups, each consisting of eight replicates (20 hens per replicate). Throughout the experiment, which lasted 24 weeks, the hens were fed diets containing 0, 200, 400, 600, or 800 mg/kg marigold extract. The results of the study showed that the addition of marigold extract to the feed significantly increased the egg production rate and qualified egg rate and reduced the feed-to-egg ratio; it also reduced the levels of oxidized products in eggs, serum, and liver, and improved the antioxidant capacity of the organism. Mechanistic studies showed that marigold extract could activate the Keap1-Nrf2 signaling pathway and up-regulate the gene expression of CAT, SOD, GPX, and Nrf2. In addition, marigold extract increased HDL and VLDL content in the liver, decreased TC and LDL content, and alteration of the cecal microbial composition. In conclusion, marigold extract showed good application value and potential as a safe and effective antioxidant additive in the late laying stage of laying hens. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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19 pages, 1800 KB

Open AccessArticle

Recovery of SIRT3-SOD2 Axis and Mitophagy by Short-Term Calorie Restriction in Old Rat Soleus Skeletal Muscle

by Rosa Di Lorenzo, Anna Picca, Guglielmina Chimienti, Christiaan Leeuwenburgh, Vito Pesce and Angela Maria Serena Lezza

Antioxidants 2025, 14(9), 1125; https://doi.org/10.3390/antiox14091125 - 17 Sep 2025

Viewed by 503

Abstract

Age-related mitochondrial dysfunction is involved in the progressive loss of mass and strength of skeletal muscle with aging. The effects of a short-term calorie restriction (ST-CR) were assessed in the oxidative skeletal soleus muscle (Sol) from 27-month-old rats and compared with those of [...] Read more.

Age-related mitochondrial dysfunction is involved in the progressive loss of mass and strength of skeletal muscle with aging. The effects of a short-term calorie restriction (ST-CR) were assessed in the oxidative skeletal soleus muscle (Sol) from 27-month-old rats and compared with those of a CR in combination with resveratrol (RSV) (ST-CR + RSV). PGC-1α and PRXIII proteins showed a marked decrease in both ST-CR and ST-CR + RSV rats. The SIRT3 protein presented a very relevant increase in both ST groups. ST-CR and ST-CR + RSV elicited a marked increase in SOD2 protein amount and activity. ST-CR and ST-CR + RSV led to recovery of the SIRT3-SOD2 axis as a fast/early response. ST-CR and ST-CR + RSV did not affect the MFN2 protein, whereas both treatments induced a relevant increase in DRP1 protein. ST-CR and ST-CR + RSV induced a decrease in Parkin protein, suggestive of rescued mitophagy, leading to the elimination of dysfunctional mitochondria. Such a response likely enhanced the fission-mediated elimination of mitochondria, supported by the marked increase in DRP1. MtDNA copy number and TFAM protein were not changed by any ST treatment. The mtDNA oxidative damage level was strongly increased by both ST treatments. All the effects elicited by ST-CR and ST-CR + RSV were specific to the oxidative type fibers. Full article

(This article belongs to the Special Issue Mitochondrial Oxidative Stress in Aging and Disease—2nd Edition)

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34 pages, 1551 KB

Open AccessArticle

Brine Enriched with Olive Wastewater Phenols: A Green Strategy to Reduce Nitrites in Cooked Ham

by Dario Mercatante, Stefania Balzan, Sonia Esposto, Sara Barbieri, Federico Fontana, Luca Fasolato, Vincenzo De Rosa, Maurizio Servili, Agnese Taticchi, Enrico Novelli and Maria Teresa Rodriguez-Estrada

Antioxidants 2025, 14(9), 1124; https://doi.org/10.3390/antiox14091124 - 17 Sep 2025

Viewed by 595

Abstract

This study aimed to evaluate the effects of brine enriched with an olive vegetation water (OVW) extract on the physico-chemical, oxidative, and sensory characteristics of cooked ham during storage, as a strategy to partially or totally replace nitrites. Four brines formulated with different [...] Read more.

This study aimed to evaluate the effects of brine enriched with an olive vegetation water (OVW) extract on the physico-chemical, oxidative, and sensory characteristics of cooked ham during storage, as a strategy to partially or totally replace nitrites. Four brines formulated with different concentrations of nitrites in combination with 200 mg of OVW extract/kg product were tested; the cooked ham samples were sliced, placed in trays, packed in a protective atmosphere, and monitored for 30 days at 4 °C. The results showed that phenolic compounds derived from OVW effectively reduced lipid and protein oxidation, limiting the formation of secondary oxidation products such as thiobarbituric acid reactive substances, volatile aldehydes, and cholesterol oxides. Sensory analysis confirmed that the extract did not negatively affect the organoleptic properties of the ham, while also helping to preserve color stability. These findings suggest that brine enriched with OVW phenols can be a promising green strategy to reduce nitrites in cooked ham, which also promotes the sustainable valorization of olive oil by-products. Full article

(This article belongs to the Special Issue Agri-Food Wastes as Natural Source of Bioactive Antioxidants: Fourth Edition)

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23 pages, 2368 KB

Open AccessArticle

Depolymerization and Nanoliposomal Encapsulation of Grape Seed Condensed Tannins: Physicochemical Characterization, Stability, In Vitro Release and Bioaccessibility

by Carolina F. Morales, Marcela Zamorano, Natalia Brossard, Andreas Rosenkranz and Fernando A. Osorio

Antioxidants 2025, 14(9), 1123; https://doi.org/10.3390/antiox14091123 - 16 Sep 2025

Viewed by 666

Abstract

Condensed tannins from grape seed residues show high antioxidant activity but low oral bioavailability because of their high degree of polymerization and covalent interactions with proteins. This study aimed to improve their bioaccessibility through depolymerization and encapsulation. Depolymerization was carried out using microwave-assisted [...] Read more.

Condensed tannins from grape seed residues show high antioxidant activity but low oral bioavailability because of their high degree of polymerization and covalent interactions with proteins. This study aimed to improve their bioaccessibility through depolymerization and encapsulation. Depolymerization was carried out using microwave-assisted SN1 reactions with gallic acid as a nucleophile under food-grade conditions, mainly producing epicatechin monomers with 99.8% polymer degradation efficiency. Importantly, the inhibition of ABTS●+ and DPPH● radicals remained unaffected (p > 0.05), indicating that depolymerization preserved the antioxidants’ redox function, maintaining about 90% of their inhibition activity. The products were encapsulated in phosphatidylcholine liposomes, which had nanometric sizes and high encapsulation efficiency (83.11%), and remained stable for up to 60 days. In vitro release of nanoliposomal epicatechin in a D1 simulant was less than 10% after 48 h, fitting a Weibull model (β = 0.07), suggesting sub-diffusive transport and demonstrating high bioactive retention capacity in aqueous systems. During in vitro digestion, bioaccessibility of gallic acid and epicatechin reached 95.61 ± 0.58% and 98.56 ± 0.81%, respectively, with a 2333% increase in the bioaccessible mass of flavan-3-ols in native liposomal condensed tannins, which otherwise showed no detectable bioaccessibility. These findings highlight the potential of polyphenols from agro-industrial waste with enhanced bioaccessibility for applications in nutraceuticals and functional foods. Full article

(This article belongs to the Special Issue Antioxidants from Sustainable Food Sources)

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17 pages, 6618 KB

Open AccessArticle

Synechococcus sp. PCC 7002 Performs Anoxygenic Photosynthesis and Deploys Divergent Strategies to Cope with H₂S_n and H₂O₂

by Yafei Wang, Yue Meng, Hongwei Ren, Ranran Huang, Jihua Liu and Daixi Liu

Antioxidants 2025, 14(9), 1122; https://doi.org/10.3390/antiox14091122 - 16 Sep 2025

Viewed by 636

Abstract

Oxygenic and anoxygenic photosynthesis have long been considered defining traits of cyanobacteria. However, whether the important cyanobacterial genus Synechococcus is capable of anoxygenic photosynthesis remains unconfirmed. Here, we report that Synechococcus sp. PCC 7002 is capable of anoxygenic photosynthesis when sulfide (H₂ [...] Read more.

Oxygenic and anoxygenic photosynthesis have long been considered defining traits of cyanobacteria. However, whether the important cyanobacterial genus Synechococcus is capable of anoxygenic photosynthesis remains unconfirmed. Here, we report that Synechococcus sp. PCC 7002 is capable of anoxygenic photosynthesis when sulfide (H₂S) is supplied as the sole electron donor. Combining the targeted deletion of the sulfide: quinone oxidoreductase gene (Δsqr) with 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) mediated the inhibition of photosystem II. We demonstrated that SQR-mediated H₂S oxidation sustains light-dependent CO₂ fixation in the absence of O₂ evolution. Our genome-wide transcriptomic profiling further revealed that polysulfide (H₂S_n) and hydrogen peroxide (H₂O₂) function as distinct signaling molecules in oxygenic and anoxygenic photosynthesis, modulating central carbon and energy metabolism. In central carbon metabolism, H₂S_n markedly upregulates the expression of key genes, including psbA, petC, rbcL, and rbcS, whereas H₂O₂ downregulates these genes. Within energy metabolism, both molecules converge on oxidative phosphorylation by upregulating genes encoding NADH dehydrogenase and ATP synthase. Furthermore, H₂Sₙ treatment uniquely induces sulfur-assimilation and ROS-detoxifying enzymes, conferring a markedly higher tolerance than H₂O₂. These findings provide direct evidence of anoxygenic photosynthesis in the genus Synechococcus and uncover a dual regulatory network that allows Synechococcus sp. PCC 7002 to balance redox homeostasis under fluctuating oxic/anoxic conditions. Full article

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58 pages, 1266 KB

Open AccessReview

Oxidative Stress and Antioxidants in Glioblastoma: Mechanisms of Action, Therapeutic Effects and Future Directions

by Agnieszka Nowacka, Maciej Śniegocki and Ewa Ziółkowska

Antioxidants 2025, 14(9), 1121; https://doi.org/10.3390/antiox14091121 - 15 Sep 2025

Cited by 1 | Viewed by 1434

Abstract

Glioblastoma (GB) is an aggressive and treatment-resistant primary brain tumor with a dismal prognosis. Increasing evidence implicates oxidative stress as a central driver of its pathogenesis, progression, and resistance to therapy. The dynamic interplay between oxidative stress and antioxidant mechanisms is fundamental to [...] Read more.

Glioblastoma (GB) is an aggressive and treatment-resistant primary brain tumor with a dismal prognosis. Increasing evidence implicates oxidative stress as a central driver of its pathogenesis, progression, and resistance to therapy. The dynamic interplay between oxidative stress and antioxidant mechanisms is fundamental to understanding GBM biology and shaping novel therapeutic approaches. This review synthesizes current knowledge on the multifaceted role of redox biology in glioblastoma, highlighting the molecular mechanisms through which oxidative stress influences tumor proliferation, survival, immune evasion, and metabolic adaptation. Particular focus is given to the tumor microenvironment, hypoxia-driven reactive oxygen species, redox-regulating enzymes, and the immunosuppressive conditions fostered by oxidative stress. Antioxidants, in this context, demonstrate a dual role: while they can mitigate oxidative damage, their effects on cancer cells and treatment outcomes vary depending on the therapeutic setting. We further examine emerging strategies that target oxidative pathways, including small-molecule inhibitors, redox-modulating agents, and combinatorial approaches with standard treatments, while also addressing the complexities posed by antioxidant interventions. Preclinical and clinical findings are reviewed to underscore both the opportunities and challenges of exploiting redox vulnerabilities in GB. Ultimately, a deeper understanding of oxidative stress dynamics and antioxidant regulation may guide the development of innovative therapies that overcome resistance and improve outcomes for patients facing this devastating malignancy. Full article

(This article belongs to the Special Issue Antioxidant Phytochemicals for Promoting Human Health and Well-Being)

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19 pages, 2344 KB

Open AccessArticle

PTEN/PKM2/ERα-Driven Glyoxalase 1 Overexpression Sustains PC3 Prostate Cancer Cell Growth Through MG-H1/RAGE Pathway Desensitization Leading to H₂O₂-Dependent KRIT1 Downregulation

by Dominga Manfredelli, Camilla Torcoli, Marilena Pariano, Guido Bellezza, Tiziano Baroni, Vincenzo N. Talesa, Angelo Sidoni and Cinzia Antognelli

Antioxidants 2025, 14(9), 1120; https://doi.org/10.3390/antiox14091120 - 15 Sep 2025

Viewed by 585

Abstract

Glyoxalase 1 (Glo1) functions as a catalyst that neutralizes methylglyoxal (MG), a highly reactive glycating agent predominantly produced during glycolysis—a metabolic pathway upregulated in cancer cells. MG primarily reacts with the amino groups of proteins (especially at arginine residues), leading to the formation [...] Read more.

Glyoxalase 1 (Glo1) functions as a catalyst that neutralizes methylglyoxal (MG), a highly reactive glycating agent predominantly produced during glycolysis—a metabolic pathway upregulated in cancer cells. MG primarily reacts with the amino groups of proteins (especially at arginine residues), leading to the formation of a major advanced glycation end product known as MG-derived hydroimidazolone 1 (MG-H1). We previously demonstrated in PC3 human prostate cancer (PCa) cells that the PTEN/PKM2/ERα axis promotes their aggressive phenotype by regulating the Glo1/MG-H1 pathway. In this study, after confirming our earlier findings, we investigated the downstream mechanisms of the PTEN/PKM2/ERα/Glo1/MG-H1 axis in controlling PC3 cell growth, focusing on the role of RAGE, a high-affinity receptor for MG-H1; hydrogen peroxide (H₂O₂); and Krev interaction trapped 1 (KRIT1), an emerging tumor suppressor. Using genetic approaches and specific inhibitors/scavengers, we demonstrated that the PTEN/PKM2/ERα/Glo1/MG-H1 axis promotes PC3 cell growth—measured by proliferation and etoposide-induced apoptosis resistance—through a mechanism involving MG-H1/RAGE pathway desensitization that leads to H₂O₂-mediated KRIT1 downregulation. These findings support and expand the role of PTEN signaling in PCa progression and shed light on novel mechanistic pathways driven by MG-dependent glycative stress, involving KRIT1, in this still incurable stage of the disease. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic Disorders and Non-Communicable Diseases (NCDs): Molecular Pathways and Genetic Influence)

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20 pages, 2613 KB

Open AccessArticle

Inhibitory Infrared Light Attenuates Mitochondrial Hyperactivity and Accelerates Restoration of Mitochondrial Homeostasis in an Oxygen–Glucose Deprivation/Reoxygenation Model

by Lucynda Pham, Tasnim Arroum, Paul T. Morse, Jamie Bell, Moh H. Malek, Thomas H. Sanderson and Maik Hüttemann

Antioxidants 2025, 14(9), 1119; https://doi.org/10.3390/antiox14091119 - 15 Sep 2025

Viewed by 848

Abstract

Ischemia/reperfusion (I/R) injury following stroke results in increased neuronal cell death due to mitochondrial hyperactivity. Ischemia results in loss of regulatory phosphorylations on cytochrome c oxidase (COX) and cytochrome c of the electron transport chain (ETC), priming COX for hyperactivity. During reperfusion, the [...] Read more.

Ischemia/reperfusion (I/R) injury following stroke results in increased neuronal cell death due to mitochondrial hyperactivity. Ischemia results in loss of regulatory phosphorylations on cytochrome c oxidase (COX) and cytochrome c of the electron transport chain (ETC), priming COX for hyperactivity. During reperfusion, the ETC operates at maximal speed, resulting in hyperpolarization of the mitochondrial membrane potential (ΔΨ_m) and reactive oxygen species (ROS) production. We have shown that COX-inhibitory near-infrared light (IRL) provides neuroprotection in small and large animal models of brain I/R injury. IRL therapy is non-invasive and non-pharmacological and does not rely on blood flow. We identified specific wavelengths of IRL, 750 and 950 nm, that inhibit COX activity. To model the mitochondrial effects following neuronal I/R, SH-SY5Y cells underwent oxygen–glucose deprivation/reoxygenation (OGD/R) ± IRL applied at the time of reoxygenation. Untreated cells exhibited ΔΨ_m hyperpolarization, whereas IRL treated cells showed no significant difference compared to control. IRL treatment suppressed ROS production, decreased the level of cell death, and reduced the time to normalize mitochondrial activity to baseline levels from 4–5 to 2.5 h of reperfusion time. We show that IRL treatment is protective by limiting ΔΨ_m hyperpolarization and ROS production, and by speeding up cellular recovery. Full article

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21 pages, 1447 KB

Open AccessArticle

Multielemental Profile for Seminal Plasma Through Inductively Coupled Plasma–Tandem Mass Spectrometry and Its Relationship with Seminal Parameters, Spermatic Biomarkers, and Oxidative Stress

by Andrea López-Botella, Natalia Cenitagoya-Alonso, Raquel Sánchez-Romero, Paula Sáez-Espinosa, Miranda Hernández-Falcó, María José Gómez-Torres and José Luis Todolí-Torró

Antioxidants 2025, 14(9), 1118; https://doi.org/10.3390/antiox14091118 - 15 Sep 2025

Viewed by 1087

Abstract

The present study investigated the decline in human fertility by analyzing the multielemental profile of seminal plasma and its relationship with seminal parameters and sperm biomarkers. Twenty-nine donor seminal plasma samples were examined using inductively coupled plasma–tandem mass spectrometry (ICP-MS/MS). Method optimization demonstrated [...] Read more.

The present study investigated the decline in human fertility by analyzing the multielemental profile of seminal plasma and its relationship with seminal parameters and sperm biomarkers. Twenty-nine donor seminal plasma samples were examined using inductively coupled plasma–tandem mass spectrometry (ICP-MS/MS). Method optimization demonstrated that robust plasma conditions, including internal standardization and helium (He) collision gas, were essential to achieve reliable quantification. These conditions mitigated matrix effects and spectroscopic interferences, despite lower sensitivity. Elements such as copper (Cu), iron (Fe), manganese (Mn), strontium (Sr), titanium (Ti), vanadium (V), and chromium (Cr) were quantified, and several significant correlations were identified. Specifically, Cu was negatively correlated with seminal volume and positively correlated with sperm concentration and spontaneous acrosome reacted sperm, but negatively correlated with medium mitochondrial membrane potential (MMP); Mn showed negative associations with sperm vitality and medium MMP; Fe showed a negative correlation with motile sperm concentration (4 h); V was positively correlated with acrosome reacted sperm after acrosome reaction induction and with very low/medium MMP, whereas it was negatively associated with tyrosine phosphorylation; and Cr also showed a negative correlation with tyrosine phosphorylation. As, Mo, and Pb were detected in a few samples, limiting correlation analysis. From a functional perspective, elements such as As and Pb, as well as excess Cu or Fe, may contribute to oxidative stress by enhancing reactive oxygen species (ROS) generation and impairing antioxidant defenses. Conversely, essential metals, including Mn and Cu, at physiological concentrations act as cofactors of antioxidant enzymes and play a protective role against oxidative damage. Full article

(This article belongs to the Special Issue Oxidative and Nitrosative Stress in Male Reproduction)

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17 pages, 2585 KB

Open AccessArticle

Novel Hybrid Peptide DEFB126 (1-39)-TP5 Inhibits LPS-Induced Inflammatory Responses and Oxidative Stress by Neutralizing LPS and Blocking the TLR4/MD2-NFκB Signaling Axis

by Yuan Tang, Xuelian Zhao, Zetao Ding, Junyong Wang, Jing Zhang, Yichen Zhou, Marhaba Ahmat, Hao Wang, Yang Zhu, Baseer Ahmad, Zaheer Abbas, Dayong Si, Rijun Zhang and Xubiao Wei

Antioxidants 2025, 14(9), 1117; https://doi.org/10.3390/antiox14091117 - 14 Sep 2025

Viewed by 721

Abstract

Lipopolysaccharide (LPS), an essential structural molecule in the outer membrane of Gram-negative bacteria, is recognized as a principal trigger of inflammatory responses and oxidative stress. Thus, the control and clearance of LPS is essential to inhibit LPS-induced excessive inflammation, oxidative stress, and liver [...] Read more.

Lipopolysaccharide (LPS), an essential structural molecule in the outer membrane of Gram-negative bacteria, is recognized as a principal trigger of inflammatory responses and oxidative stress. Thus, the control and clearance of LPS is essential to inhibit LPS-induced excessive inflammation, oxidative stress, and liver injury. In recent years, some native bioactive peptides, such as human β-defensin 126 (DEFB126) and thymopentin (TP5), have been reported to have inhibitory effects against LPS-induced inflammation and oxidative stress. However, the cytotoxicity, weak stability, and poor biological activity have hindered their practical application and clinical development. The development of novel hybrid peptides is a promising approach for overcoming these problems. In this study, we designed a novel hybrid peptide [DTP, DEFB126 (1-39)-TP5] that combines the active center of DEFB126 and full-length thymopentin (TP5). Compared to the parental peptides, DTP has a longer half-life, lower cytotoxicity, and greater anti-inflammatory and antioxidant activity. The anti-inflammatory and antioxidant effects of DTP were demonstrated in a murine LPS-induced sepsis model, which showed that DTP successfully inhibited the indicators associated with LPS-induced liver injury; decreased the contents of TNF-α, IL-6, and IL-1β; increased the level of glutathione (GSH); and improved the activities of catalase (CAT) and superoxide dismutase (SOD). Furthermore, our study revealed that the anti-inflammatory and antioxidant activities of DTP were associated with LPS neutralization, blockade of LPS binding to the Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD-2) complex, reduction in reactive oxygen species content, and inhibition of the activation of the nuclear factor kappa-B (NF-кB) signaling pathway. These results elucidate the structural and functional properties of the peptide DTP, reveal its underlying molecular mechanisms, and shed light on its potential as a multifunctional agent for applications in agriculture, food technology, and clinical therapeutics. Full article

(This article belongs to the Special Issue Antioxidant Peptides)

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25 pages, 7590 KB

Open AccessArticle

A Study of the Fruits of Catalpa bignonioides Walt.: Evaluation of the Antioxidant, Anti-Inflammatory, and Anti-Cancer Activities in Colorectal Adenocarcinoma Cells in Relation to Phytochemical Profile

by Clizia Bernardi, Thomas Gaslonde, Federica Finetti, Salim Benmaouche, Giulia Macrì, Annabelle Dugay, Claire Cuyamendous, Chouaha Bouzidi, Monica Rosa Loizzo, Philippe Belmont, Rosa Tundis, Lorenza Trabalzini and Brigitte Deguin

Antioxidants 2025, 14(9), 1116; https://doi.org/10.3390/antiox14091116 - 14 Sep 2025

Viewed by 737

Abstract

The chemical profiles and potential anti-inflammatory, antioxidant, and anticancer activities of the aqueous extract and fractions of fresh Catalpa bignonioides fruits were studied. Iridoids, flavonoids, and phenolic compounds represent the main phytochemical classes. Nine of the ten iridoids detected are acyl-iridoids. Significant amounts [...] Read more.

The chemical profiles and potential anti-inflammatory, antioxidant, and anticancer activities of the aqueous extract and fractions of fresh Catalpa bignonioides fruits were studied. Iridoids, flavonoids, and phenolic compounds represent the main phytochemical classes. Nine of the ten iridoids detected are acyl-iridoids. Significant amounts of catalpol and catalposide were found. The antioxidant activity of iridoids was demonstrated by HPTLC analysis coupled with a DPPH derivatization and by applying four in vitro tests, such as DPPH, ABTS, FRAP, and the β-carotene bleaching test. C. bignonioides extract and fractions were also evaluated for their anti-cancer activity using in vitro models of colorectal cancer (HT29 and HCT166 cell lines), and focusing on the effect of the different fractions on inflammation and oxidative stress, key factors that drive the onset and progression of colon cancer. Full article

(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Potential of Plants in Cancer Treatment)

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23 pages, 4376 KB

Open AccessArticle

Integrated Metabolomics and Transcriptomics Reveals Metabolic Pathway Changes in Common Carp Muscle Under Oxidative Stress

by Yongxiang Liu, Bing Li, Yiran Hou, Linjun Zhou, Qiqin Yang, Chengfeng Zhang, Hongwei Li, Jian Zhu and Rui Jia

Antioxidants 2025, 14(9), 1115; https://doi.org/10.3390/antiox14091115 - 14 Sep 2025

Viewed by 873

Abstract

Hydrogen peroxide (H₂O₂), a ubiquitous reactive oxygen species in aquatic ecosystems, has been shown to induce toxicological effects in aquatic animals. However, the molecular mechanisms underlying H₂O₂-mediated alterations in muscle quality and metabolic homeostasis remain [...] Read more.

Hydrogen peroxide (H₂O₂), a ubiquitous reactive oxygen species in aquatic ecosystems, has been shown to induce toxicological effects in aquatic animals. However, the molecular mechanisms underlying H₂O₂-mediated alterations in muscle quality and metabolic homeostasis remain largely unexplored. In this study, we performed integrated metabolomic and transcriptomic analyses to characterize the molecular mechanisms underlying H₂O₂-induced oxidative stress in fish muscle tissue. Common carp (Cyprinus carpio) were randomized into two groups: a control group (0.0 mM H₂O₂) and an H₂O₂-treated group (1.0 mM H₂O₂) for a 14-day exposure. Following the exposure, comprehensive analyses, including fatty acid composition, amino acid profiles, and multi-omics sequencing, were conducted to elucidate the metabolic responses to oxidative stress. The results showed neither the amino acid nor the fatty acid composition exhibited significant modifications following H₂O₂ exposure. Metabolomic profiling identified 83 upregulated and 89 downregulated metabolites, predominantly comprising organic acids and derivatives, lipids and lipid-like molecules. These differential metabolites were associated with histidine and purine-derived alkaloid biosynthesis, glyoxylate and dicarboxylate metabolism pathways. Transcriptomic analysis identified 470 upregulated and 451 downregulated differentially expressed genes (DEGs). GO enrichment analysis revealed that these DEGs were significantly enriched in muscle tissue development and transcriptional regulatory activity. KEGG analysis revealed significant enrichment in oxidative phosphorylation, adipocytokine signaling, and PPAR signaling pathways. The elevated oxidative phosphorylation activity and upregulated adipocytokine/PPAR signaling pathways collectively indicate H₂O₂-induced metabolic dysregulation in carp muscle. Through the integration of metabolomics and transcriptomics, this study offers novel insights into the toxicity of H₂O₂ in aquatic environments, elucidates adaptive mechanisms of farmed fish to oxidative stress, and provides a theoretical basis for developing antioxidant strategies. Full article

(This article belongs to the Special Issue Natural Antioxidants and Aquatic Animal Health—2nd Edition)

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Antioxidants, Volume 14, Issue 9 (September 2025) – 115 articles

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