Antioxidants

23 pages, 1358 KiB

Open AccessArticle

The Manifestation of the Dual ROS-Processing and Redox Signaling Roles of Glutathione Peroxidase-like Enzymes in Development of Arabidopsis Seedlings

by Krisztina Bela, Bernát Tompa, Riyazuddin Riyazuddin, Edit Horváth, Krisztián Jász, Ádám Hajnal, Sajid Ali Khan Bangash, Ágnes Gallé and Jolán Csiszár

Antioxidants 2025, 14(5), 518; https://doi.org/10.3390/antiox14050518 - 25 Apr 2025

Abstract

Plant glutathione peroxidase-like (GPXL) enzymes are thiol-based peroxidases that reduce H₂O₂ or hydroperoxides to water or alcohols using electrons principally from thioredoxin. Arabidopsis thaliana possesses eight isoenzymes (AtGPXL1−8) located in different plant organelles and have various roles in redox-dependent processes. [...] Read more.

Plant glutathione peroxidase-like (GPXL) enzymes are thiol-based peroxidases that reduce H₂O₂ or hydroperoxides to water or alcohols using electrons principally from thioredoxin. Arabidopsis thaliana possesses eight isoenzymes (AtGPXL1−8) located in different plant organelles and have various roles in redox-dependent processes. The determination of the redox potential of 6-day-old T-DNA insertional mutants (Atgpxl1–Atgpxl8) using a cytosolic redox-sensitive fluorescent probe (roGFP2) uncovered more oxidized redox status in the shoot and/or root of the untreated mutants, except for Atgpxl5. To investigate the involvement of AtGPXLs in the growth and abiotic stress responses of seedlings, the 4-day-old Atgpxls were exposed to salt and osmotic stresses for two weeks. The evaluation of the reactive oxygen species (ROS) levels of untreated 18-day-old plants using fluorescent microscopy revealed the elevated accumulation of total ROS in the shoots and, in some cases, the roots of the mutants. Regarding the growth of roots, both the length of primary roots and/or the number of lateral roots were affected by the mutation of AtGPXLs. A strong negative correlation was observed between the ROS level of wild type shoots and the development of lateral roots, but it was altered in mutants, while in the case of Atgpxl1, Atgpxl5, and Atgpxl7 seedlings, it disappeared; in other mutants (Atgpxl4, Atgpxl6, and Atgpxl8), the correlation became stronger. Our analysis underpins the discrete role of AtGPXL enzymes in controlling the growth and development of plants by fine tuning the ROS contents and redox status in an organ-specific way. Differences in root phenotype and metabolic activity between Atgpxl mutants and wild type plants highlight the essential role of AtGPXLs in ROS processing to support growth, which is particularly evident when one GPXL isoenzyme is absent or its activity is reduced, both under normal and abiotic stress conditions. Full article

(This article belongs to the Special Issue Oxidative Stress in Various Forms and Efficient Antioxidant Pathways in Prokaryotic and Eukaryotic Cells)

16 pages, 1463 KiB

Open AccessArticle

Trimethylamine N-Oxide (TMAO) Acts as Inhibitor of Endothelial Nitric Oxide Synthase (eNOS) and Hampers NO Production and Acetylcholine-Mediated Vasorelaxation in Rat Aortas

by Alma Martelli, Federico Abate, Michele Roggia, Giada Benedetti, Eugenio Caradonna, Vincenzo Calderone, Gian Carlo Tenore, Sandro Cosconati, Ettore Novellino and Mariano Stornaiuolo

Antioxidants 2025, 14(5), 517; https://doi.org/10.3390/antiox14050517 - 25 Apr 2025

Abstract

Trimethylamine N-oxide (TMAO) is an endogenous osmolyte produced by enzymatic reactions starting in the human gut, where microbiota release trimethylamine (TMA) from foods, and ending in the liver, where TMA is oxidized to TMAO by flavin-containing monooxygenase 3 (FMO3). While physiological concentrations of [...] Read more.

Trimethylamine N-oxide (TMAO) is an endogenous osmolyte produced by enzymatic reactions starting in the human gut, where microbiota release trimethylamine (TMA) from foods, and ending in the liver, where TMA is oxidized to TMAO by flavin-containing monooxygenase 3 (FMO3). While physiological concentrations of TMAO help proteins preserve their folding, high levels of this metabolite are harmful and promote oxidative stress, inflammation, and atherosclerosis. In humans, elevated levels of circulating TMAO predispose individuals to cardiovascular diseases and chronic kidney disease and increase mortality risk, especially in the elderly. How TMAO exerts its negative effects has been only partially elucidated. In hypertensive rats, the eNOS substrate L-arginine and Taurisolo^®, a nutraceutical endowed with TMAO-reducing activity, act synergistically to reduce arterial blood pressure. Here, we investigate the molecular mechanisms underpinning this synergism and prove that TMAO, the target of Taurisolo^®, acts as direct inhibitor of endothelial nitric oxide synthase (eNOS) and competes with L-arginine at its catalytic site, ultimately inhibiting NO production and acetylcholine (Ach)-induced relaxation in murine aortas. Full article

(This article belongs to the Special Issue The Janus Face of Oxidative Stress in Normal and Pathological Conditions)

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12 pages, 251 KiB

Open AccessArticle

The Effect of Chokeberry Juice and Fiber Consumption on the Concentration of Antioxidant Minerals in Serum

by Ewa Olechno, Małgorzata Elżbieta Zujko, Katarzyna Socha and Anna Puścion-Jakubik

Antioxidants 2025, 14(5), 516; https://doi.org/10.3390/antiox14050516 - 25 Apr 2025

Abstract

Aronia is a fruit that has become increasingly popular in recent years. Numerous health-promoting effects resulting from consumption have been indicated, including the possibility of using aronia as a functional food in the prevention and support of therapy for various ailments. For the [...] Read more.

Aronia is a fruit that has become increasingly popular in recent years. Numerous health-promoting effects resulting from consumption have been indicated, including the possibility of using aronia as a functional food in the prevention and support of therapy for various ailments. For the first time, we assessed the effects of the impact of a 90-day nutritional intervention on the level of selected minerals in the serum of women (n = 67) and men (n = 35). The consumption of 100 mL of juice for 60 days resulted in a significant increase in the levels of copper, manganese, and selenium. The addition of 10 g of aronia fiber resulted in a further increase in the concentration of these elements with antioxidant properties. An interesting observation is that the concentration of zinc decreased, which may indicate the operation of compensatory mechanisms. The above results indicate that regular consumption of aronia bio-products may have a beneficial effect on the concentration of microelements in the serum. Full article

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

20 pages, 2143 KiB

Open AccessReview

Argan Oil: A Natural Bioactive Lipid Modulating Oxidative Stress and Inflammation

by Soufiane Rabbaa, Habiba Bouchab, Yassir Laaziouez, Youness Limami, Boubker Nasser, Pierre Andreoletti, Mustapha Cherkaoui-Malki and Riad El Kebbaj

Antioxidants 2025, 14(5), 515; https://doi.org/10.3390/antiox14050515 - 25 Apr 2025

Abstract

Nutrition is a key determinant in modulating disease risk, with numerous studies highlighting the role of antioxidants and lipids, particularly the micronutrient and fatty acid composition of natural oils and their bioactive metabolites. In this context, argan oil—a vegetable oil extracted from the [...] Read more.

Nutrition is a key determinant in modulating disease risk, with numerous studies highlighting the role of antioxidants and lipids, particularly the micronutrient and fatty acid composition of natural oils and their bioactive metabolites. In this context, argan oil—a vegetable oil extracted from the kernels of Argania spinosa—has gained significant attention due to its well-balanced fatty acid profile, rich in oleic and linoleic acids, and its high levels of antioxidant compounds, including tocopherols, polyphenols, and phytosterols, particularly schottenol and spinasterol. Thanks to its unique composition, argan oil exhibits protective properties against harmful biological processes, such as oxidative stress and inflammation, both of which play a significant role in various diseases. Preclinical studies, both in vitro and in vivo, have demonstrated that argan oil reduces oxidative stress by preventing DNA damage, protein carbonylation, and lipid peroxidation, while simultaneously increasing antioxidant defenses. Furthermore, it modulates inflammatory responses by decreasing pro-inflammatory biomarkers, increasing anti-inflammatory markers, and limiting immune cell infiltration across different tissues. These antioxidant and anti-inflammatory effects are thought to be linked to argan oil’s ability to regulate key signaling pathways, such as Nrf-2 and NF-κB. Although direct evidence remains limited, studies suggest that its main bioactive components—fatty acid, γ-tocopherol, ferulic acid, and campesterol—can influence these pathways, either by activating Nrf2 to boost antioxidant defenses or by inhibiting NF-κB to suppress inflammation. This review explores the antioxidant and anti-inflammatory properties of argan oil, drawing insights from a range of scientific studies to better understand its therapeutic potential. Full article

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15 pages, 3532 KiB

Open AccessArticle

Carbon Monoxide Stimulates Chondrocyte Mitochondria and Protects Mitochondria During Cartilage Injury

by Suryamin Liman, Madeline R. Hines, Piedad C. Gómez-Contreras, Emily Witt, Jacob S. Fisher, Kevin J. Lu, Lauren D. McNally, Alicia T. Cotoia, Maxwell Y. Sakyi, Brett A. Wagner, Michael S. Tift, Douglas Fredericks, Jessica E. Goetz, James D. Byrne and Mitchell C. Coleman

Antioxidants 2025, 14(5), 514; https://doi.org/10.3390/antiox14050514 - 25 Apr 2025

Abstract

Objective: Joint injury precipitates post-traumatic osteoarthritis (PTOA) via chondrocyte mitochondrial oxidative damage. Carbon monoxide (CO) is a small molecule with potent antioxidant and mitochondrial benefits in other tissues that have not been explored in healthy chondrocytes. We hypothesized that CO would subvert the [...] Read more.

Objective: Joint injury precipitates post-traumatic osteoarthritis (PTOA) via chondrocyte mitochondrial oxidative damage. Carbon monoxide (CO) is a small molecule with potent antioxidant and mitochondrial benefits in other tissues that have not been explored in healthy chondrocytes. We hypothesized that CO would subvert the mitochondrial effects of articular cartilage injuries upon resident chondrocytes. Design: We evaluated intra-articular delivery of a novel carbon monoxide-containing foam (COF). We used in vitro impact injuries to explore mitochondrial and redox endpoints after CO exposure. We then applied intra-articular injections of COF or control room air foam (RAF) to assess safety, efficacy, and other intra-articular responses. Results: COF increased the expression of HO1 and mitofusin-1 within 1 h and this increase was sustained for 12 h in vitro. COF increased chondrocyte mitochondrial respiration by 40% and increased reduced (not oxidized) thiols by 50% following in vitro injury to osteochondral explants. After cartilage injury, COF prevented the formation of 3-nitrotyrosine and the loss of articular chondrocyte mitochondria. When injected intra-articularly, COF was retained for 24 h post-injection in mouse stifle joints. It increased HO1 in those joints, enhanced reduced thiol levels in rabbit stifle joints, and exhibited no toxicity 1 and 4 weeks after injection. Conclusions: This study supports the hypothesis that CO functions as an antioxidant for articular chondrocytes by supporting mitochondria and intracellular GSH in the presence or absence of cartilage injury. Challenges in delivering exogenous CO have limited its preclinical development, but new CO-releasing materials like COF may enable new examinations of this promising small molecule. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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20 pages, 2179 KiB

Open AccessReview

Ganoderma lucidum—From Ancient Remedies to Modern Applications: Chemistry, Benefits, and Safety

by Mădălina-Paula Plosca, Maria Simona Chiș, Anca Corina Fărcaș and Adriana Păucean

Antioxidants 2025, 14(5), 513; https://doi.org/10.3390/antiox14050513 - 25 Apr 2025

Abstract

Ganoderma lucidum (G. lucidum), commonly known as Reishi or Lingzhi, is a medicinal mushroom with a rich history in traditional Asian medicine. This review examines diverse bioactive components supporting therapeutic properties, including polysaccharides, triterpenoids, phenolic compounds, fatty acids, peptides and proteins, [...] Read more.

Ganoderma lucidum (G. lucidum), commonly known as Reishi or Lingzhi, is a medicinal mushroom with a rich history in traditional Asian medicine. This review examines diverse bioactive components supporting therapeutic properties, including polysaccharides, triterpenoids, phenolic compounds, fatty acids, peptides and proteins, vitamins, minerals, and sterols. The mushroom offers numerous health benefits, including immunomodulation, antioxidant and anti-inflammatory effects, liver protection, and anti-cancer activities. In addition, it shows potential in managing diabetes, cardiovascular disease, and viral infections. Advances in extraction technologies, such as ultrasound and microwave-assisted methods, have improved the bioavailability and efficacy of compounds. While G. lucidum is an excellent functional food and therapeutic agent it remains an unexploited source of nutrients. Further research is needed to optimize the industrial applications and evaluate the safety in specific populations. Full article

(This article belongs to the Special Issue Advances in Analytical Chemistry in Antioxidant-Rich Functional Foods and Food Supplements)

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19 pages, 2722 KiB

Open AccessArticle

Nitazoxanide Modulates Mitochondrial Function and Inflammatory Metabolism in Chondrocytes from Patients with Osteoarthritis via AMPK/mTORC1 Signaling

by Ha Eun Kim, Jong Yeong Lee, Ga-Yeon Son, Jun-Young Park, Ki Bum Kim, Chul-Min Choi, Young Jae Moon and Jin Kyeong Choi

Antioxidants 2025, 14(5), 512; https://doi.org/10.3390/antiox14050512 - 24 Apr 2025

Abstract

Osteoarthritis (OA) is a long-term degenerative condition of the joints, characterized by persistent inflammation, progressive cartilage breakdown, and impaired mitochondrial function. Recent studies have shown that hyperactivation of the mTORC1 pathway and metabolic reprogramming of chondrocytes contribute to disease progression. Nitazoxanide (NTZ), an [...] Read more.

Osteoarthritis (OA) is a long-term degenerative condition of the joints, characterized by persistent inflammation, progressive cartilage breakdown, and impaired mitochondrial function. Recent studies have shown that hyperactivation of the mTORC1 pathway and metabolic reprogramming of chondrocytes contribute to disease progression. Nitazoxanide (NTZ), an oral antiparasitic agent approved by the Food and Drug Administration, has shown anti-inflammatory and mitochondrial protective effects in various disease situations; despite this, its application in osteoarthritis has yet to be fully investigated. Here, we assessed the therapeutic efficacy of NTZ using IL-1β-stimulated primary chondrocytes derived from patients with OA. NTZ substantially reduced the expression of proinflammatory cytokines and matrix metalloproteinases, restored mitochondrial membrane potential, and reduced mitochondrial reactive oxygen species levels. NTZ also effectively reversed IL-1β-induced glycolytic metabolic changes by inhibiting glucose uptake and GLUT1 expression. Mechanistically, NTZ inhibited the activation of the mTORC1 pathway and substantially increased AMPK phosphorylation. The siRNA-mediated AMPK knockdown negated NTZ-induced mitochondrial and metabolic improvements, suggesting that AMPK is a key upstream regulator of the protective actions of NTZ. NTZ can, therefore, effectively inhibit inflammatory metabolic reprogramming and mitochondrial dysfunction in OA chondrocytes through AMPK-dependent mTORC1 signaling inhibition, highlighting its potential as a disease-modifying therapy for OA. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Bone Metabolism and Diseases)

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16 pages, 932 KiB

Open AccessArticle

Elevated Oxidative Stress in Patients with Coexisting Multiple Sclerosis and Migraine: A Cross-Sectional Study

by Iwona Rościszewska-Żukowska, Marek Biesiadecki, Mateusz Mołoń, Aleksandra Rożek, Halina Bartosik-Psujek and Sabina Galiniak

Antioxidants 2025, 14(5), 511; https://doi.org/10.3390/antiox14050511 - 24 Apr 2025

Abstract

One potential association that is gaining increasing attention is the link between multiple sclerosis (MS) and migraine, which are suggested to frequently coexist in young patients. This is the first study to analyze the levels of multiple markers of oxidative stress in sociodemographically [...] Read more.

One potential association that is gaining increasing attention is the link between multiple sclerosis (MS) and migraine, which are suggested to frequently coexist in young patients. This is the first study to analyze the levels of multiple markers of oxidative stress in sociodemographically similar groups of patients with migraine, MS, and both MS and migraine. A single cross-sectional study was conducted at the Department of Neurology, Rzeszów University. The study included 110 participants, comprising 26 healthy controls, 24 subjects with migraines, 30 with MS, and 30 with both MS and migraine. Oxidative stress markers were measured in patients’ serum. Patients with MS and migraines had statistically elevated levels of 3-nitrotyrosine, Amadori products, 4-hydroxy-nonenal, and oxidative damage to amino acids. Moreover, we observed reduced levels of thiol groups and total antioxidant capacity in the serum of patients with MS and migraines compared to healthy controls. The co-occurrence of migraines in MS leads to greater oxidative stress than MS alone. The impact of chronic oxidative stress on both MS and migraines may exacerbate symptoms and deteriorate the quality of life. Full article

(This article belongs to the Special Issue Role of Antioxidants and Oxidative Stress in Neurodegenerative Diseases)

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21 pages, 4917 KiB

Open AccessArticle

Intestinal Microbiota and Gene Expression Alterations in Chinese Mitten Crab (Eriocheir sinensis) Under Deltamethrin Exposure

by Chunyi Zhong, Jinliang Du, Haojun Zhu, Jiancao Gao, Gangchun Xu and Pao Xu

Antioxidants 2025, 14(5), 510; https://doi.org/10.3390/antiox14050510 - 24 Apr 2025

Abstract

The intestine is an important immune organ of aquatic animals and it plays an essential role in maintaining body health and anti-oxidative stress. To investigate the toxic effects of deltamethrin in intestinal tissue of Chinese mitten crabs (Eriocheir sinensis), 120 healthy [...] Read more.

The intestine is an important immune organ of aquatic animals and it plays an essential role in maintaining body health and anti-oxidative stress. To investigate the toxic effects of deltamethrin in intestinal tissue of Chinese mitten crabs (Eriocheir sinensis), 120 healthy crabs were randomly divided into two experimental groups (blank control group and deltamethrin-treated group), with three replicates in each group. After being treated with deltamethrin for 24 h, 48 h, 72 h, and 96 h, intestinal tissues were collected aseptically to assess the effects of deltamethrin on oxidative stress, immunity, apoptosis-related genes, and the structure of microflora in intestinal tissues. Additionally, correlations between gut microbiota composition and intestinal tissue damage-associated genes were analyzed. The results demonstrated that prolonged exposure to deltamethrin induced oxidative stress damage in intestinal tissue. Compared with the blank control group, the expression of autophagy-related genes B-cell lymphoma/Leukemia-2 (bcl-2), c-Jun N-terminal kinase (jnk), Microtuble-associated protein light chain 3 (lc3c), Cysteine-dependent Aspartate-specific Protease 8 (caspase 8), BECN1(beclin1), oxidative stress damage-related genes MAS1 proto-oncogene (mas), Glutathione Peroxidase (gpx), kelch-like ECH-associated protein 1 (keap1), Sequestosome 1 (p62), Interleukin-6 (il-6), and immune-related genes Lipopolysaccharide-induced TNF-alpha Factor (litaf), Heat shock protein 90 (hsp90) and prophenoloxidase (propo) in the deltamethrin treatment group were significantly up-regulated at 96 h (p < 0.05 or p < 0.01). Additionally, 16S rRNA sequencing showed that the diversity of intestinal flora in the deltamethrin-treated group was significantly higher compared with the blank control group (p < 0.01). Analysis of the differences in the composition of intestinal flora at the genus level showed that the relative abundance of Candidatus Bacilloplasma in the deltamethrin treatment group was significantly lower than that in the blank control group (p < 0.01). In contrast, the relative abundances of Flavobacterium, Lachnospiraceae_NK4A136_group, Acinetobacter, Chryseobacterium, Lacihabitans, Taibaiella, Hydrogenophaga, Acidovorax, and Undibacterium were significantly higher than those in the blank control group (p < 0.05 or p < 0.01). Pearson correlation analysis revealed that Malaciobacter, Shewanella, and Prevotella exhibited significant positive correlations with gene indicators (jnk, gpx, lc3c, litaf, hsp90), while Dysgonomonas, Vibrio, and Flavobacterium demonstrated significant negative correlations with multiple gene indicators (caspase 8, p62, il-16, keap1, jnk, etc). These results demonstrate that deltamethrin significantly impacts the gut microbiota, immune function, and antioxidant capacity of E. sinensis. The changes in gut microbiota have correlations with the biomarkers of intestinal tissue injury genes, indicating that gut microbiota plays a crucial role in deltamethrin-induced intestinal tissue damage. These insights contribute to a better understanding of the ecological risks associated with deltamethrin exposure in aquatic organisms. Full article

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16 pages, 3921 KiB

Open AccessArticle

Alleviating Effects of Ethanol Extract from Acremonium terricola Culture on Patulin Toxicity

by Haiyan Lin, Savindi Kaushalya Edirisinghe, Ijeoma Esther Okolo, Zhen Chen, Juan Sun, Wei Hong and Ruiyu Zhu

Antioxidants 2025, 14(5), 509; https://doi.org/10.3390/antiox14050509 - 24 Apr 2025

Abstract

Exposure to patulin (PAT) poses a significant health risk to animals, emphasizing the need for natural, safe substances to mitigate toxicity. Acremonium terricola culture (ATC), a fungal fermentation-derived feed additive, is known for its antioxidant properties, yet its potential to alleviate mycotoxin-induced toxicity [...] Read more.

Exposure to patulin (PAT) poses a significant health risk to animals, emphasizing the need for natural, safe substances to mitigate toxicity. Acremonium terricola culture (ATC), a fungal fermentation-derived feed additive, is known for its antioxidant properties, yet its potential to alleviate mycotoxin-induced toxicity remains largely uninvestigated. In this study, the ethanol extracts from the ATC (EEAT) were prepared with a total phenolic content of 67.9 mg GAE/g and a total flavonoid content of 32.7 mg RE/g. Ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-ESI-MS/MS) analysis was employed to investigate the bioactive components in EEAT. In PAT-exposed Caenorhabditis elegans models, EEAT treatment significantly enhanced locomotory capacity and elevated antioxidant enzyme activities by 63.1% (SOD) and 90.1% (GSH-ST), respectively. Molecular docking analysis revealed that key active compounds in EEAT, such as coumarin, succinic acid, and trigonelline, exhibited effective binding affinities to potential targets SIR-2.1 and DAF-2. Notably, coumarin and trigonelline were most effective in alleviating PAT toxicity, as evidenced by rescued locomotor rates and oxidative impairment in C. elegans. Our findings not only elucidate the molecular basis of EEAT-mediated PAT mitigation but also establish A. terricola culture as a sustainable antioxidant. Full article

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

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23 pages, 346 KiB

Open AccessReview

Oxidative Stress and Dietary Antioxidants in Head and Neck Cancer

by A Jeong You, Jaehyung Park, Jae-Min Shin and Tae Hoon Kim

Antioxidants 2025, 14(5), 508; https://doi.org/10.3390/antiox14050508 - 24 Apr 2025

Abstract

Oxidative stress serves as both a driver and result of redox metabolism across diverse physiological and pathological states, including cancer. Head and neck squamous cell carcinoma (HNSCC), the sixth most prevalent malignancy worldwide, is no exception. HNSCC is strongly linked to modifiable external [...] Read more.

Oxidative stress serves as both a driver and result of redox metabolism across diverse physiological and pathological states, including cancer. Head and neck squamous cell carcinoma (HNSCC), the sixth most prevalent malignancy worldwide, is no exception. HNSCC is strongly linked to modifiable external risk factors such as tobacco smoking, alcohol consumption, and high-risk human papilloma (HR-HPV) infection. These risk factors are associated with elevated oxidative stress, which contributes to carcinogenesis through DNA damage, chronic inflammation, and dysregulation of cell signaling pathways. Current treatment options for HNSCC have limitations and burden of side effects. Studies have been conducted on potent dietary antioxidants for the prevention and adjunctive treatment of HNSCC. This review aims to explore the contribution of oxidative stress to carcinogenesis in general and the three major risk factors for HNSCC. We evaluate latest evidence for nine dietary antioxidants such as vitamin C, vitamin E, carotenoids, epigallocatechin-3-gallate (EGCG), and curcumin, that have shown promise in preclinical and clinical studies. We discuss how these compounds mitigate ROS, influence cancer-related signaling pathways, and modulate tumor microenvironment. Despite encouraging findings, current clinical data remain limited and inconclusive, highlighting the need for further research on possible dietary antioxidants for HNSCC. Full article

(This article belongs to the Special Issue Effect of Dietary Antioxidants in Chronic Disease Prevention)

17 pages, 1262 KiB

Open AccessArticle

Gingival Inflammation Modulates NLRP3 Inflammasome Signalling in Peripheral Blood Mononuclear Cells of PCOS Patients: A Case-Control Study

by Cecilia Fabiana Márquez-Arrico, María Pelechá-Salvador, Meylin Fernández-Reyes, Francisco Javier Silvestre, Laura Perea-Galera, Jonathan Hermenejildo, Zaida Abad-Jiménez, Javier Silvestre-Rangil, Carlos Morillas, Víctor M. Víctor, Sandra López-Domènech and Milagros Rocha

Antioxidants 2025, 14(5), 507; https://doi.org/10.3390/antiox14050507 - 24 Apr 2025

Abstract

Polycystic ovary syndrome (PCOS) is a complex condition associated with chronic inflammation and oxidative stress and is often linked to periodontal diseases. This study aimed to determine whether gingivitis modulates the NLRP3 inflammasome in peripheral blood mononuclear cells (PBMCs) from women with PCOS. [...] Read more.

Polycystic ovary syndrome (PCOS) is a complex condition associated with chronic inflammation and oxidative stress and is often linked to periodontal diseases. This study aimed to determine whether gingivitis modulates the NLRP3 inflammasome in peripheral blood mononuclear cells (PBMCs) from women with PCOS. Following a case-control design, 104 women were divided into three groups: controls (n = 36), PCOS without gingivitis (PCOS, n = 44) and PCOS with gingivitis (PCOS+, n = 24). Periodontal parameters, proinflammatory regulators (NFκB p65, JNK), NLRP3 components (NLRP3, ASC, procaspase-1, caspase-1) and oxidative stress markers (superoxide, NRF2, GCLC and GSR) were determined. The PCOS+ group presented elevated values for bleeding on probing (BOP) and plaque and calculus indices, both of which were associated with increased protein levels of NFκB p65 and JNK, thus indicating NLRP3 inflammasome priming. Higher protein levels of NLRP3, ASC, procaspase-1 and caspase-1 in the PCOS+ group confirmed that priming had occurred, suggesting an engagement in assembly. When potential assembly signals of inflammasome were evaluated, the patients with PCOS generally presented enhanced total superoxide and an impaired antioxidant response (NRF2, GCLC and GSR). Moreover, BOP was independently associated with JNK, ASC and procaspase-1. These findings suggest that gingival inflammation modulates the innate immune response in leukocytes of women with PCOS via the NLRP3 inflammasome pathway, which is regulated by proinflammatory factors and oxidative damage. Full article

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

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27 pages, 2342 KiB

Open AccessReview

Vitamin C in Cardiovascular Disease: From Molecular Mechanisms to Clinical Evidence and Therapeutic Applications

by Yichen Xu, Huabo Zheng, Ioana Slabu, Elisa Anamaria Liehn and Mihaela Rusu

Antioxidants 2025, 14(5), 506; https://doi.org/10.3390/antiox14050506 - 23 Apr 2025

Abstract

Vitamin C, also known as ascorbic acid, is an essential nutrient that humans cannot synthesize, making its intake crucial for health. Discovered nearly a century ago, vitamin C is widely recognized for its ability to prevent scurvy and has become one of the [...] Read more.

Vitamin C, also known as ascorbic acid, is an essential nutrient that humans cannot synthesize, making its intake crucial for health. Discovered nearly a century ago, vitamin C is widely recognized for its ability to prevent scurvy and has become one of the most commonly used supplements. Beyond its antioxidant activity, vitamin C is pivotal in regulating lipid metabolism, promoting angiogenesis, enhancing collagen synthesis, modulating remodeling, and stabilizing the extracellular matrix. While preclinical studies have shown promising results, clinical trials have yielded inconsistent findings, due to suboptimal study design, results misinterpretation, and misleading conclusions. This review provides a holistic overview of existing evidence on the pleiotropic role of vitamin C in cardiovascular diseases, identifying both the strengths and limitations of current research and highlighting gaps in understandings in vitamin C’s underlying mechanisms. By integrating molecular insights with clinical data and evaluating the pleiotropic role of vitamin C in cardiovascular disease management and prevention, this review aims to guide future research toward personalized, evidence-based therapeutic strategies in clinical practice. Full article

(This article belongs to the Special Issue Antioxidant Therapies in Cardiovascular, Cardiorenal and Metabolic Diseases)

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17 pages, 729 KiB

Open AccessArticle

Composition and Antioxidant Status of Vegan Milk—Pilot Study

by Agnieszka Chrustek, Agnieszka Dombrowska-Pali and Dorota Olszewska-Słonina

Antioxidants 2025, 14(5), 505; https://doi.org/10.3390/antiox14050505 - 23 Apr 2025

Abstract

Background: More and more women are following a vegan and vegetarian diet. For some, the use of a vegan diet during lactation is controversial. Purpose: The aim of the study was to comparatively analyze the concentration of selected hormones, micro- and macronutrients, vitamins, [...] Read more.

Background: More and more women are following a vegan and vegetarian diet. For some, the use of a vegan diet during lactation is controversial. Purpose: The aim of the study was to comparatively analyze the concentration of selected hormones, micro- and macronutrients, vitamins, and the basic composition and antioxidant status of the milk of vegan women, compared to the milk of omnivorous women. Methods: The study included 17 breastfeeding vegan women and 27 omnivorous women. The basic composition of human milk was analyzed using the MIRIS HMATM analyzer (Uppsala, Sweden) The levels of hormones and vitamins were determined by the enzyme-linked immunosorbent method. In order to determine the antioxidant activity and micro- and macroelements, spectrophotometric methods were used. Results: The vegan group was characterized by a lower average age, lower BMI, and lower WHR index compared to the control group. The milk of vegan women showed significantly higher cortisol concentrations and lower iron, vitamin B6, and antioxidant status than the milk of omnivorous women. Conclusions: A vegan diet helps maintain a healthy body weight and is more popular among younger women, under 30 years of age. Higher levels of milk cortisol in vegan women may indicate a high level of anxiety and stress experienced by breastfeeding women, which may have negative consequences not only for breastfeeding mothers but also for the development of their children. Lack of appropriate supplementation in women who do not consume meat and animal products may cause a deficiency of micro- and macroelements in breast milk. Full article

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

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19 pages, 5097 KiB

Open AccessArticle

Impact of Melatonin Application in Winemaking on Phenolic Content, Tryptophan Metabolites, and Bioactivity of Red Wine

by Neda Đorđević, Nevena Todorović Vukotić, Ivana Perić, Otilija Keta, Vladana Petković, Snežana B. Pajović and Branislav Nastasijević

Antioxidants 2025, 14(5), 504; https://doi.org/10.3390/antiox14050504 - 23 Apr 2025

Abstract

Global wine consumption drives the interest for high-quality wine with enhanced health benefits. Yeast-produced tryptophan metabolites, including melatonin, a potent antioxidant, emerged as promising agents for enhancing functional properties of food and beverages. This study represents the pioneering work addressing whether melatonin supplementation [...] Read more.

Global wine consumption drives the interest for high-quality wine with enhanced health benefits. Yeast-produced tryptophan metabolites, including melatonin, a potent antioxidant, emerged as promising agents for enhancing functional properties of food and beverages. This study represents the pioneering work addressing whether melatonin supplementation during vinification affects Moldova red wine quality. Total phenolic/flavonoid contents, DPPH, and FRAP assays were measured via spectrophotometry, anthocyanins, and tryptophan metabolites using UPLC-MS/MS and UPLC-FLD, as well as cytotoxicity with the MTT assay. Results showed that addition of melatonin during the winemaking process increased total phenolic/flavonoid content, as well as the antioxidant capacity evidenced by increased anti-DPPH radical activity. These effects might be due to the stimulation of phenolic compound biosynthesis, particularly anthocyanins malvidin-3-O-glucoside, peonidin-3-O-glucoside, and delphinidin 3-O-glucoside, which were found to be increased in the treated wine. Additionally, the study revealed that melatonin-enriched wine exhibited increased cytotoxicity against two cancer cell lines, HCT116 and PANC-1. Finally, melatonin supplementation enhanced the concentration of kynurenic acid, which, due to its cytoprotective and antioxidant properties, could further increase the health benefits of the resulting wine. These findings offer promising avenue for future research of melatonin-driven functional properties of wine and provide step forward to a natural product with added value. Full article

(This article belongs to the Special Issue Free-Radical Scavenging and Antioxidant Properties of Melatonin, 2nd Edition)

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16 pages, 3661 KiB

Open AccessArticle

Mechanism of Astragalus Polysaccharide in Alleviating Bovine Mammary Fibrosis Through ROS/NLRP3 Inhibition and EMT Regulation

by Jiang Zhang, Kejiang Liu, Tingji Yang, Hongwei Duan, Longfei Xiao, Quanwei Zhang, Yong Zhang, Weitao Dong and Xingxu Zhao

Antioxidants 2025, 14(5), 503; https://doi.org/10.3390/antiox14050503 - 23 Apr 2025

Abstract

Mastitis in dairy cows, typically caused by bacterial infection, is a common inflammatory condition of the mammary tissue that leads to fibrosis, adversely affecting cow health, milk production, and dairy product quality. Astragalus polysaccharide (APS) has shown effectiveness in alleviating inflammation and fibrosis [...] Read more.

Mastitis in dairy cows, typically caused by bacterial infection, is a common inflammatory condition of the mammary tissue that leads to fibrosis, adversely affecting cow health, milk production, and dairy product quality. Astragalus polysaccharide (APS) has shown effectiveness in alleviating inflammation and fibrosis in various organs. The study employed lipopolysaccharide (LPS) to induce fibrotic conditions in two experimental systems: MAC-T bovine mammary epithelial cells and Kunming mouse models. Key parameters, including relative gene mRNA expression, protein levels, and reactive oxygen species (ROS) levels, were assessed using RT-qPCR, Western blotting (WB), and 2’,7’-Dichlorofluorescin diacetate (DCFH-DA) techniques, while histological analysis of mammary tissue was performed using H&E and Masson trichrome staining. Measuring malondialdehyde (MDA) levels, assessing the enzyme activities of catalase (CAT), and superoxide dismutase (SOD) were two methods of assessing oxidative stress. These methods were also tested in mouse mammary glands. APS significantly decreased ROS concentrations (p < 0.01), restored oxidative stress balance in mice (p < 0.05), and reduced fibrosis and inflammation, as demonstrated by histological observations and analysis. It also exerted regulatory effects on fibrosis markers (E-cadherin, N-cadherin, α-SMA) and inflammation markers (NLRP3, ASC, Caspase-1, IL-1β), as demonstrated by changes in their mRNA and protein expression. These findings endorse APS’s viability as an alternative therapeutic agent for mammary fibrosis therapy by demonstrating its ability to inhibit epithelial-mesenchymal transition (EMT) in vitro and mammary fibrosis in vivo, while also mitigating ROS production and reducing inflammation. Full article

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16 pages, 1167 KiB

Open AccessArticle

Phenolic Acid Composition of Coffee Cascara in Connection with Antioxidant Capacity: A Geographic Assessment

by Ningjian Liang, David D. Kitts, Xiwen Wang, Ziying Hu and Maidinai Sabier

Antioxidants 2025, 14(5), 502; https://doi.org/10.3390/antiox14050502 (registering DOI) - 22 Apr 2025

Abstract

Coffee cascara is an underutilized byproduct of coffee processing that has the potential for value-added applications due to its rich phytochemical content and antioxidant properties. The aim of this study was to characterize the phytochemical composition and antioxidant activity of coffee cascara sourced [...] Read more.

Coffee cascara is an underutilized byproduct of coffee processing that has the potential for value-added applications due to its rich phytochemical content and antioxidant properties. The aim of this study was to characterize the phytochemical composition and antioxidant activity of coffee cascara sourced from seven geographic regions, and where possible, a variety of farms in different regions. We compared two different extraction methods: hot water/sonication-assisted extraction and methanol–water extraction to generate phytochemical content. The antioxidant capacity of extracts was assessed through different assays. Correlations between phytochemical compounds and different antioxidant activities were analyzed first using Pearson’s correlations and then substantiated further using principal component analysis (PCA). The dominant phytochemicals identified in the extracted coffee cascara included gallic acid, chlorogenic acid isomers, mangiferin, protocatechuic acid and rutin. Among the water-extracted samples, the Brazil sample exhibited the highest oxygen radical absorbance capacity (ORAC) value, whereas the Zambia sample had the highest 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) value and the Laos sample showed the greatest inhibition of 2′,7′-Dichlorofluorescein diacetate (DCFH-DA) fluorescence. For methanol extracts, the highest ORAC and ABTS values were from the Indonesia sample, and the Laos sample showed the strongest inhibition of DCFH-DA fluorescence. The results show the distinct phytochemical composition and antioxidant activity of coffee cascara according to geographical clustering using PCA. Specifically, gallic acid, p-hydroxybenzoic acid and to a lesser extent rutin correlated (p < 0.05) with ABTS and DCFH-DA assays. This study revealed significant variation in the chemical composition and antioxidant properties of coffee cascara across different geographic regions; less so with different farms associated with the location. The findings offer evidence for potential upscaling of coffee cascara waste for use in value-added functional food or nutraceutical applications. Full article

(This article belongs to the Special Issue Antioxidant Activity of Polyphenolic Extracts)

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Graphical abstract

25 pages, 1135 KiB

Open AccessReview

Targeting Redox Signaling Through Exosomal MicroRNA: Insights into Tumor Microenvironment and Precision Oncology

by Moon Nyeo Park, Myoungchan Kim, Soojin Lee, Sojin Kang, Chi-Hoon Ahn, Trina Ekawati Tallei, Woojin Kim and Bonglee Kim

Antioxidants 2025, 14(5), 501; https://doi.org/10.3390/antiox14050501 - 22 Apr 2025

Abstract

Reactive oxygen species (ROS) play a dual role in cancer progression, acting as both signaling molecules and drivers of oxidative damage. Emerging evidence highlights the intricate interplay between ROS, microRNAs (miRNAs), and exosomes within the tumor microenvironment (TME), forming a regulatory axis that [...] Read more.

Reactive oxygen species (ROS) play a dual role in cancer progression, acting as both signaling molecules and drivers of oxidative damage. Emerging evidence highlights the intricate interplay between ROS, microRNAs (miRNAs), and exosomes within the tumor microenvironment (TME), forming a regulatory axis that modulates immune responses, angiogenesis, and therapeutic resistance. In particular, oxidative stress not only stimulates exosome biogenesis but also influences the selective packaging of redox-sensitive miRNAs (miR-21, miR-155, and miR-210) via RNA-binding proteins such as hnRNPA2B1 and SYNCRIP. These miRNAs, delivered through exosomes, alter gene expression in recipient cells and promote tumor-supportive phenotypes such as M2 macrophage polarization, CD8⁺ T-cell suppression, and endothelial remodeling. This review systematically explores how this ROS–miRNA–exosome axis orchestrates communication across immune and stromal cell populations under hypoxic and inflammatory conditions. Particular emphasis is placed on the role of NADPH oxidases, hypoxia-inducible factors, and autophagy-related mechanisms in regulating exosomal output. In addition, we analyze the therapeutic relevance of natural products and herbal compounds—such as curcumin, resveratrol, and ginsenosides—which have demonstrated promising capabilities to modulate ROS levels, miRNA expression, and exosome dynamics. We further discuss the clinical potential of leveraging this axis for cancer therapy, including strategies involving mesenchymal stem cell-derived exosomes, ferroptosis regulation, and miRNA-based immune modulation. Incorporating insights from spatial transcriptomics and single-cell analysis, this review provides a mechanistic foundation for the development of exosome-centered, redox-modulating therapeutics. Ultimately, this work aims to guide future research and drug discovery efforts toward integrating herbal medicine and redox biology in the fight against cancer. Full article

(This article belongs to the Special Issue Role of Reactive Oxygen Species (ROS) in Tumor Microenvironment Modulation)

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19 pages, 6041 KiB

Open AccessArticle

Allantoin Serves as a Novel Risk Factor for the Progression of MASLD

by Weiqiang Lv, Xueqiang Wang, Zhaode Feng, Cunxiao Sun, Hansen Wu, Mengqi Zeng, Tianlin Gao, Ke Cao, Jie Xu, Xuan Zou, Tielin Yang, Hao Li, Lei Chen, Jiankang Liu, Shanshan Dong and Zhihui Feng

Antioxidants 2025, 14(5), 500; https://doi.org/10.3390/antiox14050500 - 22 Apr 2025

Abstract

Uric acid (UA), traditionally recognized as an extracellular antioxidant, exhibits paradoxical associations with metabolic disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD), though its mechanistic contributions remain elusive. Here, we integrate multi-modal evidence to explore the role of UA and its oxidative [...] Read more.

Uric acid (UA), traditionally recognized as an extracellular antioxidant, exhibits paradoxical associations with metabolic disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD), though its mechanistic contributions remain elusive. Here, we integrate multi-modal evidence to explore the role of UA and its oxidative metabolite, allantoin, in MASLD progression. Analysis of UK Biobank data revealed a strong association between elevated UA levels and increased risks of MASLD and type 2 diabetes (T2D). However, Mendelian randomization analysis of over 2 million samples demonstrated causal effects of urate solely on serum triglycerides and T2D risk. Targeted metabolomics in an elderly Chinese cohort identified allantoin, an oxidative by-product of UA, significantly elevated in individuals with dyslipidemia or T2D, with serum allantoin levels positively correlated with fasting glucose, triglycerides, and cholesterol. Animal studies indicated that allantoin exacerbates hepatic lipid accumulation and glucose intolerance in high-fat diet mice, driven by increased hepatic lipid biogenesis and reduced bile acid production. Notably, further research revealed a strong binding affinity of allantoin for PPARα, leading to the suppression of PPARα activity, which promotes the progression of MASLD. These findings underscore the critical role of allantoin, rather than UA, as a critical driver of MASLD development, offering valuable insights for the prediction and management of hepatic metabolic disorders. Full article

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

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