Antioxidants

21 pages, 2551 KiB

Open AccessArticle

SOD1 Deficiency Reveals Indirect Redox Stress Mechanisms Underlying Vanillin Toxicity in Saccharomyces cerevisiae Yeast

by Sabina Bednarska, Magdalena Kwolek-Mirek, Roman Maslanka, Dominika Graboś, Gabriela Świniuch and Renata Zadrag-Tecza

Antioxidants 2025, 14(7), 842; https://doi.org/10.3390/antiox14070842 (registering DOI) - 9 Jul 2025

Abstract

Vanillin is a compound of great utility, and its production is, among others, based on using microorganisms such as Saccharomyces cerevisiae yeast. The effect of vanillin on cells is not fully understood. It has been demonstrated that vanillin induces oxidative stress; however, evidence [...] Read more.

Vanillin is a compound of great utility, and its production is, among others, based on using microorganisms such as Saccharomyces cerevisiae yeast. The effect of vanillin on cells is not fully understood. It has been demonstrated that vanillin induces oxidative stress; however, evidence also suggests its beneficial effects, including antioxidant and anti-inflammatory properties. For this reason, the present study was designed to elucidate the mechanism of vanillin’s action and to ascertain the extent to which its toxic effect is attributable to oxidative stress. The studies were conducted using wild-type and Δsod1 mutant strains. SOD1 deficiency results in cell hypersensitivity to oxidative factors, thus making the mutant strain a valuable model for investigating various aspects of oxidative stress. Based on an evaluation of cell vitality, Yap1p activation, ROS content, and glutathione and NADP(H) content, it can be concluded that oxidative stress is a secondary effect of metabolic and redox perturbations in cells rather than a direct consequence of vanillin reactivity. Furthermore, alterations observed in the redox couples GSH/GSSG and NADPH/NADP⁺ are one of the reasons for oxidative stress and suggest that vanillin may induce the utilization of NADPH for cellular needs other than antioxidant effects. Full article

(This article belongs to the Special Issue Super Oxide Dismutase (SOD) Isoenzymes and Reactive Oxygen Species (ROS) in Immuno-Pathophysiology)

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17 pages, 4245 KiB

Open AccessArticle

Oxidative Stress and Complement Activation in Aqueous Cells and Vitreous from Patient with Vitreoretinal Diseases: Comparison Between Diabetic ERM and PDR

by Lucia Dinice, Pamela Cosimi, Graziana Esposito, Fabio Scarinci, Andrea Cacciamani, Concetta Cafiero, Luca Placentino, Guido Ripandelli and Alessandra Micera

Antioxidants 2025, 14(7), 841; https://doi.org/10.3390/antiox14070841 (registering DOI) - 8 Jul 2025

Abstract

Background: Epiretinal membrane (ERM) and proliferative diabetic retinopathy (PDR) belong to the group of vitreoretinal diseases, characterized by impairments at both the retina and the vitreous. The non-diabetic and diabetic forms of ERM (no-dERM and dERM) as well as the PDR are caused [...] Read more.

Background: Epiretinal membrane (ERM) and proliferative diabetic retinopathy (PDR) belong to the group of vitreoretinal diseases, characterized by impairments at both the retina and the vitreous. The non-diabetic and diabetic forms of ERM (no-dERM and dERM) as well as the PDR are caused by microvascular disorder, which frequently occurs in association with inflammation and oxidative stress. To better characterize no-dERM, dERM, and PDR at the biomolecular level, we compared the expression of inflammatory, oxidative, lipidic peroxidation products, and complement receptors. Methods: Twenty-seven ocular fluids from patients who underwent phaco-vitrectomy were categorized as no-dERM (9, 4M/5F; 70.4 ± 6.4), dERM (6, 3M/3F; 73.2 ± 4.9), and PDR (6, 5M/1F; 63.7 ± 7.4). Six cataracts (CTR; 3M/3F; 77.7 ± 9.0) were collected for internal control of aqueous cells. Results: In aqueous cells, p65NFkB, iNOS, Nox1/Nox4, and Nrf2 were significantly upregulated, and Keap1 was downregulated in dERM compared with PDR and no-dERM. In aqueous cells, a significant upregulation for C3aR1mRNA, C5aR1mRNA, and CFHmRNA were observed in dERM. In vitreous, C3a, C5b9, and MDA levels were significantly increased in dERM compared with PDR and no-dERM. Conclusions: Inflammatory and ROS products, as well as C3aR1/C5aR1 and soluble MDA, appear of great interest, as their expression in aqueous and vitreous might have potential prognostic and therapeutic values. Full article

(This article belongs to the Special Issue Diabetic Retinopathy and Oxidative Stress: Molecular Mechanisms, Diagnostic Strategies, and Advances in Antioxidant Therapies)

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26 pages, 330 KiB

Open AccessReview

Post-COVID Condition and Neuroinflammation: Possible Management with Antioxidants

by Noemí Cárdenas-Rodríguez, Iván Ignacio-Mejía, César Miguel Mejía-Barradas, Daniel Ortega-Cuellar, Felipe Muñoz-González, Marco Antonio Vargas-Hernández, Exsal Manuel Albores-Méndez, Gabriela Ibáñez-Cervantes, Roberto Medina-Santillán, Aarón Hernández-Ortiz, Elizabeth Herrera-López and Cindy Bandala

Antioxidants 2025, 14(7), 840; https://doi.org/10.3390/antiox14070840 (registering DOI) - 8 Jul 2025

Abstract

Post-COVID condition (PCC) is a complex syndrome characterized by the persistence of diverse symptoms—including respiratory, neurological, and psychiatric manifestations—that last for weeks or months after acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Epidemiological data indicate a higher prevalence among women and [...] Read more.

Post-COVID condition (PCC) is a complex syndrome characterized by the persistence of diverse symptoms—including respiratory, neurological, and psychiatric manifestations—that last for weeks or months after acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Epidemiological data indicate a higher prevalence among women and older adults, with significant impacts on daily functioning. The pathophysiology of PCC is multifactorial, involving immune dysregulation, viral persistence, mitochondrial dysfunction, and oxidative stress, all of which contribute to sustained neuroinflammation. This narrative review examines the clinical features, risk factors, and current evidence on antioxidant-based interventions as potential therapeutic strategies for PCC. A wide range of compounds—including vitamins, polyphenols, and endogenous antioxidants—have shown promise in mitigating neuroinflammation and oxidative damage in both clinical and experimental settings. Antioxidants may help restore redox balance and improve neurological outcomes in affected patients. However, further clinical research is essential to determine their efficacy, safety, and optimal therapeutic protocols. Full article

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36 pages, 848 KiB

Open AccessReview

Oxidative Stress and Inflammation in Hypoxemic Respiratory Diseases and Their Comorbidities: Molecular Insights and Diagnostic Advances in Chronic Obstructive Pulmonary Disease and Sleep Apnea

by Jorge Rodríguez-Pérez, Rosa Andreu-Martínez, Roberto Daza, Lucía Fernández-Arroyo, Ana Hernández-García, Elena Díaz-García, Carolina Cubillos-Zapata, Alicia Lozano-Diez, Aythami Morales, Daniel Ramos, Julián Aragonés, Ángel Cogolludo, Luis del Peso, Francisco García-Río and María J. Calzada

Antioxidants 2025, 14(7), 839; https://doi.org/10.3390/antiox14070839 - 8 Jul 2025

Abstract

In chronic respiratory diseases (CRDs), oxidative stress and inflammation are closely linked, driving disease onset, progression, and comorbidities. Oxidative stress activates inflammatory pathways, while chronic inflammation promotes further reactive oxygen species (ROS) production, creating a vicious cycle leading to airway remodeling, reduced lung [...] Read more.

In chronic respiratory diseases (CRDs), oxidative stress and inflammation are closely linked, driving disease onset, progression, and comorbidities. Oxidative stress activates inflammatory pathways, while chronic inflammation promotes further reactive oxygen species (ROS) production, creating a vicious cycle leading to airway remodeling, reduced lung function, and exacerbations. This review highlights the central roles of inflammation and oxidative stress in chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA). In COPD, chronic hypoxemia associates with emphysema, appearing with disease progression. In OSA, beyond systemic consequences, pulmonary inflammation and oxidative stress contribute to lung injury as well. Although COPD and OSA are distinct conditions, some patients present with “overlap syndrome”, a term used in this review to describe the coexistence of both. This combination poses unique diagnostic and therapeutic challenges. We also examine the role of hypoxia and its transcriptional effects via hypoxia-inducible factors (HIFs) in promoting oxidative stress and inflammation. Finally, we explore how artificial intelligence (AI) offers promising tools to improve diagnosis, monitoring, and management of CRDs and may help elucidate mechanistic links between hypoxia, inflammation, and oxidative stress, contributing to more personalized therapeutic strategies. Full article

(This article belongs to the Special Issue Oxidative Stress and Immune Regulation in Respiratory Diseases)

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18 pages, 2498 KiB

Open AccessArticle

Lemongrass Alleviates Primary Dysmenorrhea Symptoms by Reducing Oxidative Stress and Inflammation and Relaxing the Uterine Muscles

by Sheikh Safeena Sidiq, Qaiser Jabeen, QurratUlAin Jamil, Muhammad Saeed Jan, Iram Iqbal, Fatima Saqib, Mohammed Aufy and Shahid Muhammad Iqbal

Antioxidants 2025, 14(7), 838; https://doi.org/10.3390/antiox14070838 (registering DOI) - 8 Jul 2025

Abstract

Primary dysmenorrhea (PD) is characterized by lower abdominal spasms and painful cramps during menstruation in females with a normal pelvic anatomy. Cymbopogon citratus (DC.) Stapf, commonly known as lemongrass, is consumed in the form of herbal tea around the world. It has been [...] Read more.

Primary dysmenorrhea (PD) is characterized by lower abdominal spasms and painful cramps during menstruation in females with a normal pelvic anatomy. Cymbopogon citratus (DC.) Stapf, commonly known as lemongrass, is consumed in the form of herbal tea around the world. It has been traditionally used for menstrual disorders in several communities. This study aims to evaluate the traditional use of C. citratus for its efficacy in alleviating the symptoms of PD. C. citratus extract (CcE) was chemically characterized using HPLC and GCMS, which indicated the presence of several phenolic compounds and long-chain fatty acids. The anti-inflammatory activity of CcE was assessed by COX-I, COX-II, and 5-LOX enzyme inhibition with IC₅₀ values of 143.7, 91.7, and 61.5 µg/mL, respectively, and showed good total antioxidant capacity and free radical scavenging activity. PD was induced in female Wistar rats by administering estradiol valerate followed by oxytocin to induce PD symptoms. CcE efficacy was assessed at 30, 100, and 300 mg/kg concentrations and compared with ibuprofen. CcE 300 mg/kg reduced abdominal contortions and inflammation in the rat uterus. The inflammatory (COX-II, TNFα and IL-10) and oxidative stress (TAC, TOS, MDA and SOD) markers in uterine tissue homogenate were also improved. An in vivo analgesic assessment through hot-plate, tail-flick, and acetic acid-induced writhing assays showed good analgesic activity by CcE, while ex vivo experiments described tocolytic effects in rat uterine muscles. CcE alleviates PD by its antioxidant, anti-inflammatory, analgesic, and tocolytic effects. Full article

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

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19 pages, 2466 KiB

Open AccessArticle

Agmatine Mitigates Diabetes-Related Memory Loss in Female Mice by Targeting I₂/I₃ Imidazoline Receptors and Enhancing Brain Antioxidant Defenses

by Luis E. Cobos-Puc and Hilda Aguayo-Morales

Antioxidants 2025, 14(7), 837; https://doi.org/10.3390/antiox14070837 - 8 Jul 2025

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Abstract

Cognitive decline is a common complication of diabetes mellitus, driven in part by oxidative stress and impaired glucose–insulin homeostasis. This study examined the neuroprotective effects of agmatine (200 mg/kg intraperitoneally) in female BALB/c diabetic mice. Several receptor pathways were examined using commercially available [...] Read more.

Cognitive decline is a common complication of diabetes mellitus, driven in part by oxidative stress and impaired glucose–insulin homeostasis. This study examined the neuroprotective effects of agmatine (200 mg/kg intraperitoneally) in female BALB/c diabetic mice. Several receptor pathways were examined using commercially available antagonists. Behavioral performance was evaluated using the novel object recognition test. Metabolic parameters, such as glucose and insulin levels, as well as antioxidants, including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), were measured in blood and brain tissue. The diabetic mice exhibited impaired recognition memory (discrimination index = 0.08), hyperglycemia (24.3 mmol/L), decreased insulin levels (38.4 µU/mL), and diminished antioxidant defenses (CAT: 75.4 U/g tissue, SOD: 32.6 U/g tissue, and GSH: 8.3 mmol/g tissue). Agmatine treatment improved cognitive function and reversed the biochemical alterations. However, these effects were reduced when agmatine was co-administered with imidazoline I₂/I₃ receptor antagonists. Correlation analysis revealed that cognitive performance positively correlated with antioxidant enzyme levels and insulin levels and negatively correlated with glucose concentrations. Strong intercorrelations among CAT, SOD, and GSH levels suggest a coordinated antioxidant response. Overall, these results imply that agmatine’s neuroprotective effects are partially mediated by modulation of the oxidative balance and glucose–insulin regulation via imidazoline receptors. Full article

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

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17 pages, 2007 KiB

Open AccessReview

Modulation of Redox-Sensitive Cardiac Ion Channels

by Razan Orfali, Al Hassan Gamal El-Din, Varnika Karthick, Elisanjer Lamis, Vanna Xiao, Alena Ramanishka, Abdullah Alwatban, Osama Alkhamees, Ali Alaseem, Young-Woo Nam and Miao Zhang

Antioxidants 2025, 14(7), 836; https://doi.org/10.3390/antiox14070836 - 8 Jul 2025

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Abstract

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function [...] Read more.

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function and support excitation–contraction coupling. However, when ROS accumulate, they modify a variety of important channel proteins in cardiomyocytes, which commonly results in reducing potassium currents, enhancing sodium and calcium influx, and enhancing intracellular calcium release. These redox-driven alterations disrupt the cardiac rhythm, promote after-depolarizations, impair contractile force, and accelerate the development of heart diseases. Experimental models demonstrate that oxidizing agents reduce repolarizing currents, whereas reducing systems restore normal channel activity. Similarly, oxidative modifications of calcium-handling proteins amplify sarcoplasmic reticulum release and diastolic calcium leak. Understanding the precise redox-dependent modifications of cardiac ion channels would guide new possibilities for targeted therapies aimed at restoring electrophysiological homeostasis under oxidative stress, potentially alleviating myocardial infarction and cardiovascular dysfunction. Full article

(This article belongs to the Special Issue New Insight into Redox Homeostasis and Oxidative Stress in Health and Disease: Focus on Cardiac and Vascular Function)

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22 pages, 17031 KiB

Open AccessArticle

AZU1 as a DNA Methylation-Driven Gene: Promoting Oxidative Stress in High-Altitude Pulmonary Edema

by Qiong Li, Zhichao Xu, Qianhui Gong, Liyang Chen, Xiaobing Shen and Xiaowei Chen

Antioxidants 2025, 14(7), 835; https://doi.org/10.3390/antiox14070835 - 8 Jul 2025

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Abstract

High-altitude pulmonary edema (HAPE) is a severe condition associated with high-altitude environments, and its molecular mechanism has not been fully elucidated. This study systematically analyzed the DNA methylation status of HAPE patients and healthy controls using reduced-representation bisulfite sequencing (RRBS) and 850K DNA [...] Read more.

High-altitude pulmonary edema (HAPE) is a severe condition associated with high-altitude environments, and its molecular mechanism has not been fully elucidated. This study systematically analyzed the DNA methylation status of HAPE patients and healthy controls using reduced-representation bisulfite sequencing (RRBS) and 850K DNA methylation chips, identifying key differentially methylated regions (DMRs). Targeted bisulfite sequencing (TBS) revealed significant abnormalities in DMRs of five genes, azurocidin 1 (AZU1), growth factor receptor bound protein 7 (GRB7), mannose receptor C-type 2 (MRC2), RUNX family transcription factor 3 (RUNX3), and septin 9 (SEPT9). The abnormal expression of AZU1 was validated using peripheral blood leukocytes from HAPE patients and normal controls, as well as rat lung tissue, indicating its potential importance in the pathogenesis of HAPE. To further validate the function of AZU1, we conducted experimental studies using a hypobaric hypoxia injury model in Human Umbilical Vein Endothelial Cells (HUVEC). The results showed that AZU1 was significantly upregulated under hypobaric hypoxia. Knocking down AZU1 mitigates the reduction in HUVEC proliferation, angiogenesis, and oxidative stress damage induced by acute hypobaric hypoxia. AZU1 induces cellular oxidative stress via the p38/mitogen-activated protein kinase (p38/MAPK) signaling pathway. This study is the first to elucidate the mechanism of AZU1 in HAPE via the p38/MAPK pathway, offering novel insights into the molecular pathology of HAPE and laying a foundation for future diagnostic and therapeutic strategies. Full article

(This article belongs to the Topic Cardiovascular Disease in Special Populations: From Basic Science to Clinical Practice)

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27 pages, 3139 KiB

Open AccessArticle

Distinctive Effects of Fullerene C₆₀ and Fullerenol C₆₀(OH)₂₄ Nanoparticles on Histological, Molecular and Behavioral Hallmarks of Alzheimer’s Disease in APPswe/PS1E9 Mice

by Sholpan Askarova, Kseniia Sitdikova, Aliya Kassenova, Kirill Chaprov, Evgeniy Svirin, Andrey Tsoy, Johannes de Munter, Anna Gorlova, Aleksandr Litavrin, Aleksei Deikin, Andrey Nedorubov, Nurbol Appazov, Allan Kalueff, Anton Chernopiatko and Tatyana Strekalova

Antioxidants 2025, 14(7), 834; https://doi.org/10.3390/antiox14070834 - 8 Jul 2025

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Abstract

Fullerenes and fullerenols exhibit antioxidant and anti-inflammatory properties, making them promising candidates for Alzheimer’s disease (AD) therapy. Unlike conventional anti-inflammatory drugs, these compounds have multitargeted effects, including their ability to inhibit amyloid fibril formation. However, few studies have explored their efficacy in high-validity [...] Read more.

Fullerenes and fullerenols exhibit antioxidant and anti-inflammatory properties, making them promising candidates for Alzheimer’s disease (AD) therapy. Unlike conventional anti-inflammatory drugs, these compounds have multitargeted effects, including their ability to inhibit amyloid fibril formation. However, few studies have explored their efficacy in high-validity AD models. Female APPswe/PS1E9 (APP/PS1) mice and their wild-type (WT) littermates were orally administered with fullerene C₆₀ (0.1 mg/kg/day) or fullerenol C₆₀(OH)₂₄ (0.15 mg/kg/day) for 10 months starting at 2 months of age. Behavioral assessments were performed at 12 months of age. Amyloid plaque density and size were analyzed in the brain regions using Congo red staining. The expression of genes related to inflammation and plasticity was examined, and an in vitro assay was used to test the toxicity of fullerenol and its effect on amyloid β peptide 42 (Aβ42)-induced reactive oxygen species (ROS) production. Fullerenol reduced the maximum plaque size in the cortex and hippocampus, decreased the small plaque density in the hippocampus and thalamus, and prevented an increase in glial fibrillary acidic protein (GFAP) positive cell density in the mutants. Both treatments improved cognitive and emotional behaviors and reduced Il1β and increased Sirt1 expression. In vitro, fullerenol was non-toxic across a range of concentrations and reduced Aβ42-induced ROS production in brain endothelial cells and astrocytes. Long-term administration of fullerene or fullerenol improved behavioral and molecular markers of AD in APP/PS1 mice, with fullerenol showing additional benefits in reducing amyloid burden. Full article

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

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31 pages, 4367 KiB

Open AccessArticle

Serine-Driven Metabolic Plasticity Drives Adaptive Resilience in Pancreatic Cancer Cells

by Marcella Bonanomi, Sara Mallia, Mariafrancesca Scalise, Tecla Aramini, Federica Baldassari, Elisa Brivio, Federica Conte, Alessia Lo Dico, Matteo Bonas, Danilo Porro, Cesare Indiveri, Christian M. Metallo and Daniela Gaglio

Antioxidants 2025, 14(7), 833; https://doi.org/10.3390/antiox14070833 - 7 Jul 2025

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Abstract

Pancreatic cancer is one of the most lethal malignancies, in part due to its profound metabolic adaptability, which underlies drug resistance and therapeutic failure. This study explores the metabolic rewiring associated with resistance to treatment using a systems metabolomics approach. Exposure to the [...] Read more.

Pancreatic cancer is one of the most lethal malignancies, in part due to its profound metabolic adaptability, which underlies drug resistance and therapeutic failure. This study explores the metabolic rewiring associated with resistance to treatment using a systems metabolomics approach. Exposure to the redox-disrupting agent erastin revealed key metabolic vulnerabilities but failed to produce lasting growth suppression. Combinatorial treatments with methotrexate or alpelisib significantly impaired proliferation and triggered marked metabolic shifts. Systems-level analyses identified serine metabolism as a central adaptive pathway in resilient cells. Metabolic tracing and gene expression profiling showed increased de novo serine biosynthesis and uptake, supporting redox homeostasis, biosynthetic activity, and epigenetic regulation. Notably, cells that resumed growth after drug withdrawal exhibited transcriptional reprogramming involving serine-driven pathways, along with elevated expression of genes linked to survival, proliferation, and migration. These findings establish serine metabolism as a functional biomarker of metabolic plasticity and adaptive resilience in pancreatic cancer, suggesting that targeting this adaptive axis may enhance therapeutic efficacy. Full article

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

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21 pages, 325 KiB

Open AccessArticle

Antioxidant and Quality Effects of Red Grape Pomace in Barbecued Pork Burgers: Implications for PAH Formation

by María Jesús Petrón, María Jesús Martín-Mateos, Miriam Sánchez-Ordóñez, Belén Godoy and María Rosario Ramírez-Bernabé

Antioxidants 2025, 14(7), 832; https://doi.org/10.3390/antiox14070832 - 7 Jul 2025

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Abstract

The growing concern over the presence of polycyclic aromatic hydrocarbons (PAHs) in grilled meats has intensified the search for natural mitigation strategies. This study evaluates the effect of red grape pomace (RGP), a natural by-product with antioxidant properties, on the lipid stability, color, [...] Read more.

The growing concern over the presence of polycyclic aromatic hydrocarbons (PAHs) in grilled meats has intensified the search for natural mitigation strategies. This study evaluates the effect of red grape pomace (RGP), a natural by-product with antioxidant properties, on the lipid stability, color, fatty acid profile, volatile compounds, and PAHs formation in barbecued pork burgers. Unlike previous studies focusing on polyphenol extracts, this work investigates, for the first time, the direct incorporation of whole RGP stabilized by high hydrostatic pressure (HHP), a method that preserves its bioactive profile and ensures food safety. Incorporation of RGP at different levels (0.5%, 1%, and 3%) demonstrates its potential as a functional ingredient in meat products. Our results show that RGP effectively inhibits lipid oxidation, as indicated by significantly lower malondialdehyde (MDA) levels (p < 0.001) compared to control batches. It also modified the fatty acid profile by reducing saturated fatty acids and increasing the linoleic acid content (up to 15.56% at the 3% level). As the RPG concentration increased, color parameters (lightness, redness, yellowness, chroma, and hue) decreased significantly (p < 0.001), particularly at higher pomace levels (1% and 3%). The RGP did not significantly affect the PAH concentration, indicating its safe use in barbecued products. However, it selectively influenced volatile compounds, decreasing the hydrocarbon levels at higher concentrations, likely due to its antioxidant properties. These findings suggest that stabilized RGP may serve as a natural additive that enhances the nutritional quality and reduces lipid oxidation, without promoting PAH formation in thermally processed meats. Full article

(This article belongs to the Special Issue Natural Antioxidants from Plant-Based By-Products: Mechanisms and Applications in Food Systems)

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20 pages, 7960 KiB

Open AccessArticle

Optimisation of Phenolic Compound Extraction from Agrimonia eupatoria L. Using Response Surface Methodology for Enhanced Yield of Different Phenolics and Maximised Antioxidant Activity

by Justinas Sukackas, Modestas Žilius, Gerda Šaltytė and Lina Raudonė

Antioxidants 2025, 14(7), 831; https://doi.org/10.3390/antiox14070831 - 7 Jul 2025

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Abstract

Agrimonia eupatoria L. is a traditionally used medicinal plant rich in tannin compounds with antioxidant, anti-inflammatory, and antimicrobial activities. This study aimed to optimise the extraction of individual phenolic acids, flavonoids, and tannins from A. eupatoria and maximise their antioxidant activity using response [...] Read more.

Agrimonia eupatoria L. is a traditionally used medicinal plant rich in tannin compounds with antioxidant, anti-inflammatory, and antimicrobial activities. This study aimed to optimise the extraction of individual phenolic acids, flavonoids, and tannins from A. eupatoria and maximise their antioxidant activity using response surface methodology (RSM). A central composite design was applied to evaluate the influence of acetone concentration, solvent ratio, and extraction time on the yield of total phenolics, total radical scavenging and reducing capacities, and individual compounds. Acetone concentration, solvent ratio, and extraction time were varied in a central composite design. The optimal conditions yielded high levels of agrimoniin (9.16 mg/g), total identified phenolics (33.61 mg/g), and strong antioxidant activity. These findings provide a scientific basis for standardising bioactive-rich extracts for nutraceutical and pharmaceutical applications. Full article

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

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24 pages, 5180 KiB

Open AccessArticle

Resolvin D2 Reduces UVB Skin Pathology by Targeting Cytokines, Oxidative Stress, and NF-κB Activation

by Ingrid C. Pinto, Priscila Saito, Camilla C. A. Rodrigues, Renata M. Martinez, Cristina P. B. Melo, Maiara Piva, Clovis M. Kumagai, David L. Vale, Telma Saraiva-Santos, Allan J. C. Bussmann, Marcela M. Baracat, Sandra R. Georgetti, Fabiana T. M. C. Vicentini, Waldiceu A. Verri and Rubia Casagrande

Antioxidants 2025, 14(7), 830; https://doi.org/10.3390/antiox14070830 - 6 Jul 2025

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Abstract

UVB skin pathology is initiated by reactive oxygen species (ROS), differentiating this condition from other inflammatory diseases involving first the immune cell activation by danger or pathogen molecular patterns followed by oxidative stress. Resolvin D2 (RvD2) has been found to reduce inflammation in [...] Read more.

UVB skin pathology is initiated by reactive oxygen species (ROS), differentiating this condition from other inflammatory diseases involving first the immune cell activation by danger or pathogen molecular patterns followed by oxidative stress. Resolvin D2 (RvD2) has been found to reduce inflammation in preclinical models. However, whether or not RvD2 reduces skin pathology caused by UVB irradiation is not yet known. Therefore, the efficacy of RvD2 on skin pathology triggered by UVB irradiation in female hairless mice was assessed. RvD2 (0.3, 1 or 3 ng/mouse, i.p.) was found to protect the skin against UVB inflammation, as observed in the reduction in edema (46%), myeloperoxidase activity (77%), metalloproteinase-9 activity (39%), recruitment of neutrophils/macrophages (lysozyme⁺ cells, 76%) and mast cells (106%), epidermal thickening (93%), sunburn cell formation (68%), collagen fiber breakdown (55%), and production of cytokines such as TNF-α (100%). Considering the relevance of oxidative stress to UVB irradiation skin pathologies, an important observation was that the skin antioxidant capacity was recovered by RvD2 according to the results that show the ferric reducing antioxidant power (68%), cationic radical scavenges (93%), catalase activity (74%), and the levels of reduced glutathione (48%). Oxidative damage was also attenuated, as observed in the reduction in superoxide anion production (69%) and lipid hydroperoxides (71%). The RvD2 mechanism involved the inhibition of NF-κB activation, as observed in the diminished degradation of IκBα (48%) coupled with a reduction in its downstream targets that are involved in inflammation and oxidative stress, such as COX-2 (66%) and gp91^phox (77%) mRNA expression. In conclusion, RvD2 mitigates the inflammatory and oxidative pathologic skin aggression that is triggered by UVB. Full article

(This article belongs to the Special Issue Antioxidants for Skin Health)

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19 pages, 2098 KiB

Open AccessArticle

Influence of an Antioxidant Nanomaterial on Oral Tablet Formulation: Flow Properties and Critical Quality Attributes

by Andrea C. Ortiz, Javiera Carrasco-Rojas, Sofía Peñaloza, Mario J. Simirgiotis, Lorena Rubio-Quiroz, Diego Ruiz, Carlos F. Lagos, Javier Morales and Francisco Arriagada

Antioxidants 2025, 14(7), 829; https://doi.org/10.3390/antiox14070829 (registering DOI) - 5 Jul 2025

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Abstract

Antioxidant nanomaterials, particularly mesoporous silica nanoparticles (MSNs) functionalized with polyphenols, offer innovative solutions for protecting oxidation-sensitive components and enhancing bioavailability in pharmaceuticals or extending the shelf life of nutraceutical and food products. This study investigates the influence of MSNs functionalized with caffeic acid [...] Read more.

Antioxidant nanomaterials, particularly mesoporous silica nanoparticles (MSNs) functionalized with polyphenols, offer innovative solutions for protecting oxidation-sensitive components and enhancing bioavailability in pharmaceuticals or extending the shelf life of nutraceutical and food products. This study investigates the influence of MSNs functionalized with caffeic acid (MSN-CAF) on powder flow properties and their tableting performance. Aminated MSNs were synthesized via co-condensation and conjugated with caffeic acid using EDC/NHS chemistry. Antioxidant capacity was evaluated using DPPH^●, ABTS^●+, ORAC, and FRAP assays. Powder blends with varying MSN-CAF concentrations (10–70%) were characterized for flow properties (angle of repose, Hausner ratio, Carr’s index), tablets were produced via direct compression, and critical quality attributes (weight uniformity, hardness, friability, disintegration, nanoparticle release) were assessed. MSN-CAF exhibited reduced antioxidant capacity compared with free caffeic acid due to pore entrapment but retained significant activity. Formulation F1 (10% MSN-CAF) showed excellent flowability (angle of repose: 12°, Hausner ratio: 1.16, Carr’s index: 14%), enabling robust tablet production with rapid disintegration, low friability, and complete nanoparticle release in 10 min. Additionally, the antioxidant nanomaterial demonstrated biocompatibility with the HepG2 cell line. MSN-CAF is a versatile nanoexcipient for direct compression tablets, offering potential as an active packaging agent and delivery system in the nutraceutical and food industries. Full article

(This article belongs to the Special Issue Natural Antioxidants from Plant-Based By-Products: Mechanisms and Applications in Food Systems)

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24 pages, 2920 KiB

Open AccessArticle

The MiBlend Randomized Trial: Investigating Genetic Polymorphisms in Personalized Responses to Fruit and Vegetable Interventions for Chronic Disease Prevention

by Julia N. DeBenedictis, Na Xu, Theo M. de Kok and Simone G. van Breda

Antioxidants 2025, 14(7), 828; https://doi.org/10.3390/antiox14070828 - 4 Jul 2025

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Abstract

Background: The MiBlend Study investigated the effect of consuming different combinations of fruits and vegetables (F&Vs) blends on markers of chronic disease risk and gene expression changes in healthy human subjects. Overall, the increase in F&Vs led to reduced susceptibility to the induction [...] Read more.

Background: The MiBlend Study investigated the effect of consuming different combinations of fruits and vegetables (F&Vs) blends on markers of chronic disease risk and gene expression changes in healthy human subjects. Overall, the increase in F&Vs led to reduced susceptibility to the induction of DNA damage ex vivo, higher antioxidant capacity of plasma, and improved microvasculature as reflected by retinal analysis. As with most dietary intervention studies, inter-individual variability was observed in the responses, which might be the consequence of genetic differences. Therefore, this study aims to identify if genetic variants in relevant genes affect outcomes and responses to the dietary interventions. Methods: The literature review identified 15 polymorphic genes related to phytochemical metabolism, oxidative stress, and detoxification, which were tested in 146 participant samples using TaqMan and PCR analysis. The effect of genotypes on study outcomes was determined via analysis of variance. Results: XRCC1 wildtype carriers were more protected from ex vivo-induced DNA damage after consuming flavanol-rich F&Vs than other variants. XRCC1 is involved in DNA repair, particularly oxidative damage, and its wildtype allele enhances repair efficiency. GSTP1 wildtype carriers had a larger improvement in microvasculature after all F&V blends, especially those rich in polyphenols. GSTP1 polymorphisms likely affect microvascular responses to polyphenol-rich F&V intake by modulating detoxification and fiber-derived butyrate that can influence arterial dilation and endothelial function. Conclusions: Stratifying participants by relevant genetic polymorphisms can reveal predisposed responses to nutrients and guide efforts to personalize disease prevention strategies. Full article

(This article belongs to the Special Issue Potential Health Benefits of Dietary Antioxidants)

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24 pages, 2490 KiB

Open AccessArticle

Hydrogen Sulfide (H₂S)-Donating Formyl Peptide Receptor 2 (FPR2) Agonists: Design, Synthesis, and Biological Evaluation in Primary Mouse Microglia Culture

by Leonardo Brunetti, Fabio Francavilla, Mauro Niso, Jakub Kosma Frydrych, Ewa Trojan, Igor A. Schepetkin, Liliya N. Kirpotina, Beata Grygier, Krzysztof Łukowicz, Mark T. Quinn, Agnieszka Basta-Kaim, Enza Lacivita and Marcello Leopoldo

Antioxidants 2025, 14(7), 827; https://doi.org/10.3390/antiox14070827 - 4 Jul 2025

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Abstract

Chronic neuroinflammation and oxidative stress play an important role in the onset and progression of neurodegenerative disorders, including Alzheimer’s disease, which can ultimately lead to neuronal damage and loss. The mechanisms of sustained neuroinflammation and the coordinated chain of events that initiate, modulate, [...] Read more.

Chronic neuroinflammation and oxidative stress play an important role in the onset and progression of neurodegenerative disorders, including Alzheimer’s disease, which can ultimately lead to neuronal damage and loss. The mechanisms of sustained neuroinflammation and the coordinated chain of events that initiate, modulate, and then lead to the resolution of inflammation are increasingly being elucidated, offering alternative approaches for treating pathologies with underlying chronic neuroinflammation. Here, we propose a new multitarget approach to address chronic neuroinflammation and oxidative stress in neurodegenerative disorders by activating the formyl peptide receptor 2 (FPR2) combined with the potentiation of hydrogen sulfide (H₂S) release. FPR2 is a key player in the resolution of inflammation because it mediates the effects of several endogenous pro-resolving mediators. At the same time, H₂S is an endogenous gaseous transmitter with anti-inflammatory and pro-resolving properties, and it can protect against oxidative stress. Starting from potent FPR2 agonists identified in our laboratories, we prepared hybrid compounds by embedding an H₂S-donating moiety within the molecular scaffold of these FPR2 agonists. Following this approach, we identified several compounds that combined potent FPR2 agonism with the ability to release H₂S. The release of H₂S was assessed in buffer and intracellularly. Compounds 7b and 8b combined potent FPR2 agonist activity, selectivity over FPR1, and the ability to release H₂S. Compounds 7b and 8b were next studied in murine primary microglial cells stimulated with lipopolysaccharide (LPS), a widely accepted in vitro model of neuroinflammation. Both compounds were able to counterbalance LPS-induced cytotoxicity and the release of pro-inflammatory (IL-18, IL-6) and anti-inflammatory (IL-10) cytokines induced by LPS stimulation. Full article

(This article belongs to the Special Issue Inhibition of Oxidative Stress and Related Signaling Pathways in Neuroprotection—2nd Edition)

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17 pages, 1910 KiB

Open AccessArticle

Production of Lambic-like Fruit Sour Beer with Lachancea thermotolerans

by Rubén Bartolomé, Elena Alonso, Antonio Morata and Carmen López

Antioxidants 2025, 14(7), 826; https://doi.org/10.3390/antiox14070826 - 4 Jul 2025

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Abstract

Consumer demand for low-alcohol acidic beers is driving the use of non-conventional yeasts in the brewing process. In this study, the addition of mixed berries and fermentation with L. thermotolerans L31 are performed in crafting a low-alcohol acidic beer. Four different beers were [...] Read more.

Consumer demand for low-alcohol acidic beers is driving the use of non-conventional yeasts in the brewing process. In this study, the addition of mixed berries and fermentation with L. thermotolerans L31 are performed in crafting a low-alcohol acidic beer. Four different beers were brewed in the primary stage with either Saccharomyces cerevisiae or L. thermotolerans and with or without added berry mixture. Beer was fermented for 8 days at 20 °C, stored, and bottled. pH, density, alcoholic content, bitterness, and color of final beer were analyzed for all samples using analytical methods. Volatile compounds, anthocyanin content, and antioxidant activity were also evaluated. Sensory analysis was performed and correlated (PCA) with the analytical results. The obtained data indicated that beers brewed with L. thermotolerans were significantly more acidic and less bitter than S. cerevisiae beers. No difference in alcoholic content was found. Fruity aroma-associated compounds were present in L. thermotolerans beers, which correlated with the sensory analysis. Fruit beers were also redder and showed higher anthocyanin content and stronger antioxidant activity due to the presence of anthocyanins such as cyanidin, delphinidin, and malvidin from fruit, and other antioxidant compounds. Full article

(This article belongs to the Special Issue Antioxidant Capacity of Anthocyanins and Other Vegetal Pigments: Properties, Intake and Health Benefits)

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23 pages, 1771 KiB

Open AccessReview

Reactive Nitrogen Species and Fibrinogen: Exploring the Effects of Nitration on Blood Clots

by Francesca Nencini, Serena Borghi, Elvira Giurranna, Ilenia Barbaro, Niccolò Taddei, Claudia Fiorillo and Matteo Becatti

Antioxidants 2025, 14(7), 825; https://doi.org/10.3390/antiox14070825 - 4 Jul 2025

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Abstract

Reactive nitrogen species (RNS), particularly peroxynitrite (ONOO⁻), play a central role in post-translational modifications (PTMs) of proteins, including fibrinogen, a key component of the coagulation cascade. This review explores the structural and functional consequences of fibrinogen nitration, with a focus on [...] Read more.

Reactive nitrogen species (RNS), particularly peroxynitrite (ONOO⁻), play a central role in post-translational modifications (PTMs) of proteins, including fibrinogen, a key component of the coagulation cascade. This review explores the structural and functional consequences of fibrinogen nitration, with a focus on its impact on clot formation, morphology, mechanical stability, and fibrinolysis. Nitration, primarily targeting tyrosine residues within functional domains of the Aα, Bβ, and γ chains, induces conformational changes, dityrosine crosslinking, and aggregation into high molecular weight species. These modifications result in altered fibrin polymerization, the formation of porous and disorganized clot networks, reduced mechanical resilience, and variable susceptibility to fibrinolysis. Moreover, nitrated fibrinogen may affect interactions with platelets and endothelial cells, although current evidence remains limited. Emerging clinical studies support its role as both a prothrombotic mediator and a potential biomarker of oxidative stress in cardiovascular and inflammatory diseases. Finally, we explore both pharmacological interventions, such as NOX inhibitors, and natural antioxidant strategies at counteracting fibrinogen nitration. Overall, fibrinogen nitration emerges as a critical molecular event linking oxidative stress to thrombotic risk. Full article

(This article belongs to the Special Issue Antioxidants in Cardiovascular Medicine: Emerging Trends and Future Perspectives)

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36 pages, 3577 KiB

Open AccessArticle

Screening of a Plant Extract Library from the Greek Flora for Biological Activities Related to Anti-Aging Applications

by Harris Pratsinis, Despoina D. Gianniou, Gabriela Belén Lemus Ringele, Adamantia Agalou, Asimina Fotopoulou, Xanthippi P. Louka, Christos Nastos, Eleftherios Kalpoutzakis, Aikaterini Argyropoulou, Dimitris Michailidis, Antonia Theodoridi, Ioanna Eleftheriadou, Adamantia Papadopoulou, Sentiljana Gumeni, Stavros Beteinakis, Konstantina Karamanou, Eleni Mavrogonatou, Georgios Stavropoulos, Dimitris Beis, Maria Halabalaki, Ioannis P. Trougakos and Dimitris Kletsas Show full author list Hide full author list

Antioxidants 2025, 14(7), 824; https://doi.org/10.3390/antiox14070824 - 4 Jul 2025

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Abstract

Characteristic manifestations of skin aging, due to either intrinsic or extrinsic factors, such as ultraviolet (UV) radiation and oxidative stress, include cell senescence, alterations in collagen and elastin networks, and melanogenesis disorders. Natural products are considered a rich source of anti-aging molecules. Accordingly, [...] Read more.

Characteristic manifestations of skin aging, due to either intrinsic or extrinsic factors, such as ultraviolet (UV) radiation and oxidative stress, include cell senescence, alterations in collagen and elastin networks, and melanogenesis disorders. Natural products are considered a rich source of anti-aging molecules. Accordingly, the screening of a plant extract library from the Greek flora for a panel of biological activities related to skin aging is presented herein. In particular, 52 plant materials extracted using Accelerated Solvent Extraction (ASE) and Supercritical Fluid Extraction (SFE) were assessed for their effects on (1) human skin cell viability, (2) antioxidant activity—using both cell-free and cell-based methods—(3) photoprotective capacity, and (4) interference with collagenase, elastase, and tyrosinase, as well as with proteasomal and lysosomal activities of human skin cells. In vivo phenotypic screens on Danio rerio (zebrafish) embryos were also used for assessing melanogenesis. Many active extracts were identified, some of them for the first time, and others in agreement with previous reports. In general, ASE extracts exhibited higher activities than SFE ones. Seven extracts showed multiple activities, being highly effective in at least four different assays. These data support the potential use of these extracts against skin aging in medicinal and cosmetic applications. Full article

(This article belongs to the Special Issue Natural Products: Biological, Antioxidant Properties and Health Effects—4th Edition)

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29 pages, 2069 KiB

Open AccessArticle

Explorative Analysis of Antioxidant, Anti-Inflammatory, and Intestinal Barrier Protective Effects of In Vitro Digested Chickpea- and Dark Chocolate-Based Snack: Insights from Caco-2 and THP-1 Cell Models

by Gaia de Simone, Laura Bonfili, Anna Maria Eleuteri, Laura Bordoni and Rosita Gabbianelli

Antioxidants 2025, 14(7), 823; https://doi.org/10.3390/antiox14070823 - 4 Jul 2025

Viewed by 19

Abstract

Chickpeas are used as alternative protein sources in healthy snacks due to their bioactive compounds beneficial for gut health. Combining chickpeas with dark chocolate improves palatability and may enhance biological functionality, although mechanistic evidence is still limited. In this explorative research, we evaluate [...] Read more.

Chickpeas are used as alternative protein sources in healthy snacks due to their bioactive compounds beneficial for gut health. Combining chickpeas with dark chocolate improves palatability and may enhance biological functionality, although mechanistic evidence is still limited. In this explorative research, we evaluate the nutrigenomic, antioxidant and anti-inflammatory properties of a chickpea and chocolate snack using in vitro Caco-2 (colon adenocarcinoma cells) and THP-1 (monocyte-derived macrophages) models. The total polyphenol content and antioxidant activity were measured after in vitro digestion (30.30 mg/mL to 1.9 mg/mL). Caco-2 epithelia and THP-1 were pre-treated for 4 days (2 h/day) with high (15.1 mg/mL) or low (3.8 mg/mL) concentrations of digests. Inflammation was induced for 3 h by LPS (Lipopolysaccharides) and IL-1β (Interleukin-1β). Transepithelial electrical resistance (TEER) was measured to assess barrier integrity. Gene expression related to tight junctions and inflammation was analysed using qPCR (quantitative polymerase chain reaction). Chocolate and snack digests showed the highest total polyphenol content and 2,2-diphenyl-1-picrylhydrazyl activity. Barrier integrity improved with all treatments. Chickpea upregulated tight junction gene expression. Chickpea and chocolate reduced IL-1β expression in both cell types. In THP-1, the chocolate and the snack upregulated CD206 (mannose receptor C-type 1) expression. IL-10 increased with all treatments. These results pave the way for future research that may support the potential use of this snack as a functional food with antioxidant, gut-protective and anti-inflammatory effects. Full article

(This article belongs to the Special Issue The Effect of Nutritional Intervention and Diet on Oxidative Stress and Human Diseases)

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22 pages, 3568 KiB

Open AccessArticle

Galangin Regulates Oxidative Stress Levels in Porcine Embryos Through Interaction with the Neh1 Domain of Nrf2

by Zhi-Chao Chi, Shu-Ming Shi, Li-Ying Liu, Lin-Yi Qu, Jing-Hang Li, Guan-Lin Jia, Yu-Yan He, Lin-Xuan Li, Yong-Xun Jin, Ming-Jun Zhang and Xian-Feng Yu

Antioxidants 2025, 14(7), 822; https://doi.org/10.3390/antiox14070822 - 4 Jul 2025

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Abstract

Oxidative stress poses a challenge to in vitro embryo culture. As a flavonoid, galangin (GAL) has been shown to have antioxidant effects, but the effect and antioxidant capacity of GAL in the in vitro development of porcine parthenogenetic embryos are still unknown. In [...] Read more.

Oxidative stress poses a challenge to in vitro embryo culture. As a flavonoid, galangin (GAL) has been shown to have antioxidant effects, but the effect and antioxidant capacity of GAL in the in vitro development of porcine parthenogenetic embryos are still unknown. In this study, we demonstrated that 1 µM GAL significantly increased the blastocyst rate, decreased the accumulation of intracellular reactive oxygen species (ROS), increased the glutathione (GSH) level, and enhanced mitochondrial function in early porcine embryos. Nuclear factor erythroid-2-related factor 2 (Nrf2) was identified as the target gene of GAL via network pharmacology, and the transcript levels of related antioxidant enzymes (HO-1, NQO1, SOD2, and CAT) were found to be increased. Since Nrf2 has seven domains, we constructed Nrf2 mutants lacking different domains in vitro. We found that GAL specifically binds to the Neh1 domain of Nrf2. Subsequent embryonic experiments demonstrated that the antioxidant effect of GAL was abolished after Nrf2 deletion. These results suggest that GAL can directly bind to Nrf2 to regulate the level of oxidative stress and improve mitochondrial function in embryos. Full article

(This article belongs to the Special Issue Redox Regulation in Animal Reproduction)

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14 pages, 2081 KiB

Open AccessArticle

Dual Upcycling of Olive Leaves for the Biocatalytic Synthesis of Antioxidant Cortisone Derivatives

by Filippo Marchetti, Irene Gugel, Stefania Costa, Ilenia Gugel, Anna Baldisserotto, Erika Baldini, Stefano Manfredini and Silvia Vertuani

Antioxidants 2025, 14(7), 821; https://doi.org/10.3390/antiox14070821 - 3 Jul 2025

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Abstract

Bioconversion of cortisone leads to the synthesis of the steroid derivatives 1,9β,17,21-tetrahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11,20-dione (SCA) and 1,9β,17,20β,21-pentahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11-one (SCB), which have been identified as biologically active molecules in affections associated with oxidative stress and inflammation, particularly in the skin and eye. To date, the synthesis of [...] Read more.

Bioconversion of cortisone leads to the synthesis of the steroid derivatives 1,9β,17,21-tetrahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11,20-dione (SCA) and 1,9β,17,20β,21-pentahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11-one (SCB), which have been identified as biologically active molecules in affections associated with oxidative stress and inflammation, particularly in the skin and eye. To date, the synthesis of SCA and SCB can only be achieved through a biocatalytic approach, following a biotransformation process catalyzed by Rhodococcus rhodnii DSM 43960, a synthetic pathway that adheres to the principles of green chemistry. To further enhance the sustainability of this process, this study demonstrated that SCA and SCB can be synthesized by bioconversion in a complex medium derived from a dual upcycling process involving olive leaves (UOLM). By formulating a medium based on olive leaves, a by-product derived from the previously reported biotechnological production of lactic acid, and using a concentration of 10% v/v UOLM and 1 g/L cortisone at pH 7.5, bioconversion yields of 90 ± 4.5% were achieved, with a predominance of SCB. Investigations into the addition of supplements, such as tryptone, peptone, and corn steep liquor (CSL), to assess potential improvements in yield were conducted, but no significant positive variations were observed. For the first time, bioactive steroids were synthesized from a medium obtained through a dual upcycling process of olive leaves, introducing an innovative method that opens new possibilities for the investigation of a second generation of biosteroids synthesized from lignocellulosic feedstocks. Full article

(This article belongs to the Special Issue Valorization of Waste Through Antioxidant Extraction and Utilization)

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16 pages, 1933 KiB

Open AccessArticle

Investigation of the Effects of 2.45 GHz Near-Field EMF on Yeast

by Boyana Angelova, Momchil Paunov, Meglena Kitanova, Gabriela Atanasova and Nikolay Atanasov

Antioxidants 2025, 14(7), 820; https://doi.org/10.3390/antiox14070820 - 3 Jul 2025

Viewed by 8

Abstract

The study of the effects of 2.45 GHz electromagnetic fields on the health and safety of people and organisms as a whole is essential due to their widespread use in everyday life. It is known that they can cause thermal and non-thermal effects—at [...] Read more.

The study of the effects of 2.45 GHz electromagnetic fields on the health and safety of people and organisms as a whole is essential due to their widespread use in everyday life. It is known that they can cause thermal and non-thermal effects—at the molecular, cellular and organismal level. Yeast suspensions were treated with 2.45 GHz microwave radiation in the near-field of antenna at two distances (2 and 4 cm) and two time periods (20 and 60 min)—setups resembling the use of mobile devices. The release of UV-absorbing substances from the cells was studied as an indicator of membrane permeabilization, total intracellular antioxidant activity and reduced glutathione were determined, and a comet assay for damage to the DNA was performed. A correlation between reduced antioxidants and increased membrane permeability during EMF treatment was observed at a distance of 2 cm for 20 min, suggesting the presence of oxidative stress, while a similar effect was not observed with conventional heating. Slightly increased membrane permeability was observed after irradiation for 60 min at a distance of 4 cm, but this was not related to the antioxidant status of the cells. A trend towards increased DNA damage was observed under both conditions. Full article

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36 pages, 3407 KiB

Open AccessReview

Melatonin—A Powerful Oxidant in Neurodegenerative Diseases

by Renata Kołodziejska, Alina Woźniak, Rafał Bilski, Roland Wesołowski, Daria Kupczyk, Marta Porzych, Weronika Wróblewska and Hanna Pawluk

Antioxidants 2025, 14(7), 819; https://doi.org/10.3390/antiox14070819 - 3 Jul 2025

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Abstract

Melatonin (MEL)is an endogenous hormone with antioxidant potential that plays an important role in maintaining redox homeostasis. MEL and its derivatives directly scavenge free oxygen and nitrogen radicals. Melatonin inhibits lipid peroxidation, stimulates antioxidant enzymes, and reduces metal toxicity. It stabilizes mitochondrial activity [...] Read more.

Melatonin (MEL)is an endogenous hormone with antioxidant potential that plays an important role in maintaining redox homeostasis. MEL and its derivatives directly scavenge free oxygen and nitrogen radicals. Melatonin inhibits lipid peroxidation, stimulates antioxidant enzymes, and reduces metal toxicity. It stabilizes mitochondrial activity and suppresses inflammatory signaling. It takes part in neurogenesis, neuroprotection, and modulation of the cardiovascular system. It prevents many diseases of free radical etiology, i.e., neurodegenerative and circulatory system diseases and ischemic stroke. Supplementation with this antioxidant can slow down the aging process and provide protection against diseases of the central nervous system and support the body’s natural antioxidant system. This study uses current reports from the literature and meta-analyses of the antioxidant mechanisms of melatonin and its importance in neurodegenerative diseases. Full article

(This article belongs to the Special Issue Antioxidant Actions of Melatonin)

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65 pages, 1590 KiB

Open AccessReview

Glucosinolate Metabolites and Brain Health: An Updated Review on Their Potential Benefits in Neurodegenerative, Neurodevelopmental, and Psychiatric Disorders

by Claudia Muscarà, Agnese Gugliandolo, Emanuela Mazzon and Gabriella Calì

Antioxidants 2025, 14(7), 818; https://doi.org/10.3390/antiox14070818 - 2 Jul 2025

Viewed by 28

Abstract

Neurodegenerative, neurodevelopmental, and psychiatric disorders, as well as epilepsy, affect millions of people. Due to their impact on patients’ quality of life, they represent a major health issue. Natural compounds are arising as new treatments for these diseases. Particularly, glucosinolates (GLS) are secondary [...] Read more.

Neurodegenerative, neurodevelopmental, and psychiatric disorders, as well as epilepsy, affect millions of people. Due to their impact on patients’ quality of life, they represent a major health issue. Natural compounds are arising as new treatments for these diseases. Particularly, glucosinolates (GLS) are secondary metabolites found in Cruciferae family plants. Their basic structure consists of a glucose unit linked to a thiohydroximate-O-sulfonate group and an aliphatic, aralkyl, or indolyl side chain, depending on their precursor amino acid. Specifically, aliphatic GLS derive from methionine, aromatic ones from phenylalanine, and indolic ones from tryptophan. Myrosinase (thioglucoside glucohydrolase) is the crucial enzyme for GLS degradation, leading to the production of isothiocyanates (ITCs). ITCs attracted considerable scientific interest for their protective effects against various diseases, thanks to their antioxidant, anti-inflammatory, and neuroprotective properties. Here, we collected the latest evidence regarding ITC effects in neurodegenerative, neurodevelopmental, and psychiatric disorders, including preclinical and clinical studies published in the last decade. These studies evidenced ITCs’ neuroprotective effects, exerted mainly through antioxidant and anti-inflammatory mechanisms. Thus, ITCs’ integration, also through the diet, may represent a safe and efficacious strategy to improve health and limit the risk of neurological and psychiatric disorders. However, new large-scale trials are needed to determine their therapeutic potential, particularly for diseases with no clinical evidence. Full article

(This article belongs to the Special Issue Role of Natural Antioxidants on Neuroprotection)

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20 pages, 4345 KiB

Open AccessArticle

Identification of Peroxiredoxin (PRX) Genes from Pepper Fruits: Involvement in Ripening and Modulation by Nitric Oxide (NO)

by Fátima Ramírez-Mellado, Salvador González-Gordo, José M. Palma and Francisco J. Corpas

Antioxidants 2025, 14(7), 817; https://doi.org/10.3390/antiox14070817 - 2 Jul 2025

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Abstract

Peroxiredoxins (Prxs; EC 1.11.1.15) are a group of thiol peroxidases that catalyze the detoxification of H₂O₂ and other organic hydroperoxides. The ripening of pepper (Capsicum annuum L.) fruit involves significant phenotypic, physiological, and biochemical changes. Based on the available [...] Read more.

Peroxiredoxins (Prxs; EC 1.11.1.15) are a group of thiol peroxidases that catalyze the detoxification of H₂O₂ and other organic hydroperoxides. The ripening of pepper (Capsicum annuum L.) fruit involves significant phenotypic, physiological, and biochemical changes. Based on the available pepper plant genome, eight PRX genes were identified and named CaPRX1, CaPRX1-Cys, CaPRX2B, CaPRX2E, CaPRX2F, CaPRX2-CysBAS1, CaPRX2-CysBAS2, and CaPRX Q. Among these, only CaPRX1-Cys was not detected in the transcriptome (RNA-Seq) of sweet pepper fruits reported previously. This study analyzes the modulation of these seven CaPRX genes during ripening and after treating fruits with nitric oxide (NO) gas. A time-course expression analysis of sweet pepper fruit during ripening revealed that two genes were upregulated (CaPRX1 and CaPRX2E), two were downregulated (CaPRX2B and PRX Q), and three were unaffected (CaPRX2F, CaPRX2-CysBAS1, and CaPRX2-CysBAS2). Gene expression was also studied in three hot pepper varieties with varying capsaicin contents (Piquillo < Padrón < Alegría riojana), showing a differential expression pattern during ripening. Furthermore, NO treatment of sweet pepper fruits triggered the upregulation of CaPRX2B and CaPRXQ genes and the downregulation of CaPRX1 and CaPRX2-CysBAS1 genes, while the other three remained unaffected. Among the CaPrx proteins, four (CaPrx2B, CaPrx2-CysBAS1, CaPrx2-CysBAS2, and CaPrx2E) were identified as susceptible to S-nitrosation, as determined by immunoprecipitation assays with an antibody against S-nitrocysteine and further mass spectrometry analyses. These findings indicate the diversification of PRX genes in pepper fruits and how some of them are regulated by NO, either at the level of gene expression or through protein S-nitrosation, a NO-promoting post-translational modification (PTM). Given that Prxs play a crucial role in stress tolerance, these data suggest that Prxs are vital components of the antioxidant system during pepper fruit ripening, an event that is accompanied by physiological nitro-oxidative stress. Full article

(This article belongs to the Special Issue Reactive Oxygen and Nitrogen Species in Plants―2nd Edition)

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31 pages, 500 KiB

Open AccessSystematic Review

Oxidative Stress and Down Syndrome: A Systematic Review

by Goran Slivšek, Sandra Mijač, Ivan Dolanc, Marija Fabijanec, Silvija Petković, Renato Mautner, Karmen Lončarek, Josip Kranjčić, Alenka Boban Blagaić, Marin Marinović, Ksenija Vitale, Donatella Verbanac, Miran Čoklo and Jadranka Vraneković

Antioxidants 2025, 14(7), 816; https://doi.org/10.3390/antiox14070816 - 2 Jul 2025

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Abstract

Down syndrome (DS), the most common human aneuploidy, is associated with oxidative stress, which contributes to morphological abnormalities, immune dysfunction, cognitive impairment and accelerated ageing. This article aims to provide an overview of the studies on oxidative stress in DS, in particular the [...] Read more.

Down syndrome (DS), the most common human aneuploidy, is associated with oxidative stress, which contributes to morphological abnormalities, immune dysfunction, cognitive impairment and accelerated ageing. This article aims to provide an overview of the studies on oxidative stress in DS, in particular the investigation of endogenous and exogenous antioxidants, with a focus on endogenous systems. A literature search in MEDLINE and Scopus based on the PRISMA 2020 criteria revealed 41 relevant studies that mainly analysed blood samples (plasma or serum) and occasionally saliva or urine. The findings suggest that oxidative stress in DS is multifactorial and results from an imbalance of superoxide dismutase activity, overexpression of genes on chromosome 21, mitochondrial dysfunction and inflammation. Despite extensive studies over the decades, new sources and mechanisms for oxidative stress in DS continue to emerge, further highlighting the complexity of DS. The recognition that oxidative stress is a hallmark of DS emphasises the need to develop more sensitive and specific methods to detect it and to investigate the associated metabolic pathways in DS in more detail. The expansion of in vivo studies could facilitate the development of targeted interventions aimed at mitigating oxidative damage and ultimately improving outcomes for individuals with DS. Full article

(This article belongs to the Special Issue Developmental Origins of Health and Disease: Antioxidants as Strategy for Prevention and Treatment)

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21 pages, 557 KiB

Open AccessReview

Antioxidant Defense and Redox Signaling in Elite Soccer Players: Insights into Muscle Function, Recovery, and Training Adaptations

by Qing Meng and Chun-Hsien Su

Antioxidants 2025, 14(7), 815; https://doi.org/10.3390/antiox14070815 - 2 Jul 2025

Viewed by 36

Abstract

Elite soccer places significant neuromuscular and metabolic stress on athletes, leading to elevated production of reactive oxygen and nitrogen species (RONS), particularly in skeletal muscle, where intense contractile activity and increased oxygen flux drive oxidative processes. These reactive species play a dual role [...] Read more.

Elite soccer places significant neuromuscular and metabolic stress on athletes, leading to elevated production of reactive oxygen and nitrogen species (RONS), particularly in skeletal muscle, where intense contractile activity and increased oxygen flux drive oxidative processes. These reactive species play a dual role in skeletal muscle, supporting adaptive signaling at controlled levels while causing oxidative damage when poorly regulated. This paper presents an integrated synthesis of current knowledge on redox biology in elite soccer players, focusing on the origins and regulation of RONS, the functions of enzymatic and non-enzymatic antioxidant systems, and how both RONS and antioxidant responses influence muscle performance, fatigue, recovery, and long-term physiological adaptation. Drawing on studies conducted between 2000 and 2025, the discussion underscores the seasonal fluctuations in oxidative stress, individual variability in redox responses, and the potential adverse effects of unsystematic antioxidant supplementation. The analysis also emphasizes the value of using biomarker-guided, periodized antioxidant interventions tailored to training demands. Future directions include longitudinal tracking and the use of AI-assisted monitoring to enable personalized strategies for maintaining redox balance and optimizing performance in elite sport. Full article

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

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13 pages, 1352 KiB

Open AccessArticle

Time Matters: Methane Inhalation Mitigates Mitochondrial and Organ Dysfunction in Advanced Experimental Sepsis

by Levente Frigyes Gulácsi, Attila Rutai, László Juhász, Bálint László Czakó, Andrea Szabó, Mihály Boros, József Kaszaki, Marietta Zita Poles and Szabolcs Péter Tallósy

Antioxidants 2025, 14(7), 814; https://doi.org/10.3390/antiox14070814 - 1 Jul 2025

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Abstract

This study aimed to characterize the time-dependent effects of methane (CH₄) inhalation, initiated at defined intervals following sepsis onset, on organ function, systemic oxygen utilization, and mitochondrial respiration in a rodent model. Adult rats were subjected to abdominal sepsis or sham [...] Read more.

This study aimed to characterize the time-dependent effects of methane (CH₄) inhalation, initiated at defined intervals following sepsis onset, on organ function, systemic oxygen utilization, and mitochondrial respiration in a rodent model. Adult rats were subjected to abdominal sepsis or sham operation. Septic animals were assigned to groups receiving 2.2% CH₄ in normoxic air at specific post-insult phases (early: 3–6 h; intermediate: 16–19 h; late: 19–22 h), while a control group remained untreated. At 24 h, organ function was evaluated using a Rat-Specific Organ Failure Assessment (ROFA) score, along with measurements of plasma myeloperoxidase (MPO) activity, Complex I–II-linked oxidative phosphorylation in renal and cerebellar tissues, systemic oxygen extraction, and global tissue perfusion (pCO₂-gap). Sepsis induced significant organ dysfunction, impaired hemodynamics, reduced oxygen utilization, and decreased mitochondrial respiration. CH₄ inhalation improved survival when administered early, restored cerebellar mitochondrial respiration during the intermediate phase, and in the late phase reduced ROFA scores and MPO levels, while attenuating mitochondrial dysfunction in renal and cerebellar tissues. All CH₄-treated groups demonstrated improved renal function and enhanced tissue oxygenation. Targeted CH₄ inhalation during sepsis confers protective effects by preserving mitochondrial function, reducing inflammation, and improving oxygen dynamics, suggesting promising therapeutic potential. Full article

(This article belongs to the Special Issue Cellular ROS and Antioxidants: Physiological and Pathological Role—2nd Edition)

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The Naturally Bioactive Vicine Extracted from Faba Beans Is Responsible for the Transformation of Grass Carp (Ctenopharyngodon idella) into Crisp Grass Carp

by Xinyu Zheng, Minyi Luo, Bing Fu, Gen Kaneko, Jingjing Tian, Jun Xie, Jilun Hou and Ermeng Yu

Antioxidants 2025, 14(7), 813; https://doi.org/10.3390/antiox14070813 - 1 Jul 2025

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Abstract

While faba bean feeding improves grass carp muscle texture via reactive oxygen species (ROS), the main bioactive compound was unclear. In this study, vicine—a pro-oxidant glycoside—was isolated from faba beans using cation-exchange column chromatography and supplemented into the feed of grass carp at [...] Read more.

While faba bean feeding improves grass carp muscle texture via reactive oxygen species (ROS), the main bioactive compound was unclear. In this study, vicine—a pro-oxidant glycoside—was isolated from faba beans using cation-exchange column chromatography and supplemented into the feed of grass carp at 0.6%. To assess the impact of vicine on muscle texture, the grass carp were fed for 150 days with three treatments: control group, faba bean group, and vicine group. The results showed that vicine improved muscle texture similarly to faba beans but caused fewer adverse effects on muscle, liver, and intestinal health. Vicine improved grass carp muscle texture in the following ways: (1) induced ROS overproduction, activating the Caspase apoptosis pathway and downregulating Pax-7 to promote satellite cell-mediated myofiber regeneration; (2) vicine-mediated intestinal microbiota alterations increased lipopolysaccharide (LPS) levels, indirectly elevating muscle ROS via the gut–muscle axis to further affect muscle structure. This study demonstrated that vicine improved muscle texture by activating ROS-dependent myofiber regeneration but also induced oxidative stress and gut microbiota perturbation. While vicine mitigated the severe toxicity of faba beans, its application requires careful evaluation of its toxicological properties to balance benefits and risks. This study offers new insights for enhancing the quality of aquatic animals. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Aquaculture)

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Antioxidants, Volume 14, Issue 7 (July 2025) – 86 articles

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