Antioxidants

34 pages, 4424 KB

Open AccessArticle

The Flavonoid Extract of Polygonum viviparum L. Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Regulating Intestinal Flora Homeostasis and Uric Acid Levels Through Inhibition of PI3K/AKT/NF-κB/IL-17 Signaling Pathway

by Haoyu Liu, Zhen Yang, Qian Chen, Hongjuan Zhang, Yu Liu, Di Wu, Dan Shao, Shengyi Wang and Baocheng Hao

Antioxidants 2025, 14(10), 1206; https://doi.org/10.3390/antiox14101206 (registering DOI) - 5 Oct 2025

Abstract

Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. [...] Read more.

Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus, Romboutsia, and Enterobacter. Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Antioxidants in Human Health—2nd Edition)

32 pages, 927 KB

Open AccessReview

Environmental Nephrotoxicity Across the Life Course: Oxidative Stress Mechanisms and Opportunities for Early Intervention

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

Antioxidants 2025, 14(10), 1205; https://doi.org/10.3390/antiox14101205 (registering DOI) - 4 Oct 2025

Abstract

Chronic kidney disease (CKD) affects nearly 10% of the global population, ranks among the top ten causes of death, and often progresses silently to end-stage disease without timely intervention. Increasing evidence indicates that many adult-onset cases originate in early life through adverse influences [...] Read more.

Chronic kidney disease (CKD) affects nearly 10% of the global population, ranks among the top ten causes of death, and often progresses silently to end-stage disease without timely intervention. Increasing evidence indicates that many adult-onset cases originate in early life through adverse influences on kidney development, a process termed kidney programming within the Developmental Origins of Health and Disease (DOHaD) framework. Environmental pollutants are now recognized as key drivers of kidney injury across the life course. Heavy metals, air pollutants, plastic contaminants such as bisphenol A, phthalates, and micro/nanoplastics—as well as biocontaminants like mycotoxins and aristolochic acid—and chronic light pollution can accumulate in kidney tissue or act systemically to impair function. These exposures promote oxidative stress, inflammation, and endothelial and circadian disruption, culminating in tubular injury, glomerular damage, and fibrosis. Notably, early-life exposures can induce epigenetic modifications that program lifelong susceptibility to CKD and related complications. Oxidative stress is central to these effects, mediating DNA, lipid, and protein damage while influencing developmental reprogramming during gestation. Preclinical studies demonstrate that antioxidant-based interventions may mitigate these processes, providing both renoprotective and reprogramming benefits. This review explores the mechanistic links between environmental pollutants, oxidative stress, and kidney disease and highlights antioxidant strategies as promising avenues for prevention and intervention in vulnerable populations. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Environmental Toxicity—2nd Edition)

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14 pages, 2098 KB

Open AccessReview

Oxidative Stress in Diabetic Retinopathy: A Comprehensive Review of Mechanisms, Biomarkers, and Therapeutic Perspectives

by Tatsuya Mimura and Hidetaka Noma

Antioxidants 2025, 14(10), 1204; https://doi.org/10.3390/antiox14101204 (registering DOI) - 4 Oct 2025

Abstract

Diabetic retinopathy (DR) is a leading cause of vision loss globally and represents one of the most common microvascular complications of diabetes. In addition to metabolic disturbances associated with hyperglycemia, oxidative stress has emerged as a critical contributor to the onset and progression [...] Read more.

Diabetic retinopathy (DR) is a leading cause of vision loss globally and represents one of the most common microvascular complications of diabetes. In addition to metabolic disturbances associated with hyperglycemia, oxidative stress has emerged as a critical contributor to the onset and progression of DR. Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense mechanisms, leads to cellular injury, inflammation, and increased vascular permeability. In the diabetic retina, excessive ROS production promotes endothelial cell apoptosis, breakdown of the blood-retinal barrier (BRB), and induction of angiogenic factors such as vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of the pathophysiology of DR, focusing on the molecular mechanisms of oxidative stress. Relevant studies were identified through a structured search of PubMed, Web of Science, and Scopus (2000–2025) using terms such as ‘diabetic retinopathy’, ‘oxidative stress’, and ‘antioxidants’. We explore current knowledge on oxidative stress-related biomarkers and therapeutic strategies targeting oxidative damage, including antioxidant compounds and mitochondrial protective agents. Recent findings from both experimental and clinical studies are summarized, highlighting the translational potential of oxidative stress modulation in DR management. Finally, future research directions are discussed, including biomarker standardization, personalized medicine approaches, and long-term clinical validation of antioxidant-based therapies. A deeper understanding of oxidative stress may offer valuable insights into novel diagnostic and therapeutic strategies for DR. Full article

(This article belongs to the Special Issue Oxidative Stress and Diabetic Retinopathy)

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19 pages, 2189 KB

Open AccessArticle

Dissecting the Interplay Between NRF2 and BACH1 at CsMBEs

by Maria-Armineh Tossounian, Alexander Zhyvoloup, Rakesh Chatterjee and Jerome Gouge

Antioxidants 2025, 14(10), 1203; https://doi.org/10.3390/antiox14101203 - 3 Oct 2025

Abstract

BACH1 (BTB And CNC Homology 1) and NRF2 (Nuclear Factor Erythroid 2-related Factor 2) are transcription factors that regulate antioxidant and iron metabolism genes by competing for binding to cis-regulatory Maf-binding elements (CsMBEs) as heterodimers with small Maf proteins (sMafs). To dissect the [...] Read more.

BACH1 (BTB And CNC Homology 1) and NRF2 (Nuclear Factor Erythroid 2-related Factor 2) are transcription factors that regulate antioxidant and iron metabolism genes by competing for binding to cis-regulatory Maf-binding elements (CsMBEs) as heterodimers with small Maf proteins (sMafs). To dissect the mechanisms underlying this competition, we developed a chimeric tethering system where the DNA-binding domains of BACH1 or NRF2 were covalently linked to sMafG via a flexible, cleavable linker. This design enables efficient heterodimer formation on DNA and circumvents kinetic barriers to partner exchange in the solution. The site-specific fluorescent labelling of proteins allowed for the tracking of complex compositions by electrophoretic mobility shift assays. Both BACH1/sMafG and NRF2/sMafG heterodimers bind CsMBEs with similar affinities. Notably, DNA binding by BACH1 was impaired in a C574-dependent, redox-sensitive manner and promoted the exchange of heterodimer partners. Competition assays demonstrated that BACH1 and NRF2 can displace each other from preformed DNA-bound complexes, with greater efficiency when presented as preassembled heterodimers with sMafG. These findings reveal a redox-sensitive mechanism for regulating transcriptional switches at CsMBEs and highlight how preformed heterodimers facilitate the rapid displacement at target promoters. Full article

(This article belongs to the Special Issue Antioxidant Systems, Transcription Factors and Non-Coding RNAs)

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15 pages, 993 KB

Open AccessReview

Antioxidants in Cardiovascular Health: Implications for Disease Modeling Using Cardiac Organoids

by Gracious R. Ross and Ivor J. Benjamin

Antioxidants 2025, 14(10), 1202; https://doi.org/10.3390/antiox14101202 - 3 Oct 2025

Abstract

Cardiovascular disease remains the leading cause of mortality worldwide, and at its molecular core lies a silent disruptor: oxidative stress. This imbalance between reactive oxygen species (ROS) and antioxidant defenses not only damages cellular components but also orchestrates a cascade of pathological events [...] Read more.

Cardiovascular disease remains the leading cause of mortality worldwide, and at its molecular core lies a silent disruptor: oxidative stress. This imbalance between reactive oxygen species (ROS) and antioxidant defenses not only damages cellular components but also orchestrates a cascade of pathological events across diverse cardiac cell types. In cardiomyocytes, ROS overload impairs contractility and survival, contributing to heart failure and infarction. Cardiac fibroblasts respond by promoting fibrosis through excessive collagen deposition. Macrophages intensify inflammatory responses, such as atherosclerosis, via ROS-mediated lipid oxidation—acting both as mediators of damage and targets for antioxidant intervention. This review examines how oxidative stress affects cardiac cell types and evaluates antioxidant-based therapeutic strategies. Therapeutic approaches include natural antioxidants (e.g., polyphenols and vitamins) and synthetic agents (e.g., enzyme modulators), which show promise in experimental models by improving myocardial remodeling. However, clinical trials reveal inconsistent outcomes, underscoring translational challenges (e.g., clinical biomarkers). Emerging strategies—such as targeted antioxidant delivery, activation of endogenous pathways, and disease modeling using 3D organoids—aim to enhance efficacy. In conclusion, we spotlight innovative technologies—like lab-grown heart tissue models—that help scientists better understand how oxidative stress affects heart health. These tools are bridging the gap between early-stage research and personalized medicine, opening new possibilities for diagnosing and treating heart disease more effectively. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Advances in Redox-Tools and Therapies in Cardiovascular Disease)

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19 pages, 1147 KB

Open AccessArticle

Exploring the Potential of Low-Temperature Vacuum Drying to Improve the Bioactive Compound Content and Health-Promoting Properties of Chilean Wild Murta

by Antonio Vega-Galvez, Alexis Pasten, Elsa Uribe, Nicol Mejias, Isadora Corco, Jacqueline Poblete, Jaime Ortiz-Viedma, Gabriela Valenzuela-Barra, Javier Acevedo-Hernández and Tamar Toledo

Antioxidants 2025, 14(10), 1201; https://doi.org/10.3390/antiox14101201 - 3 Oct 2025

Abstract

For the first time, the effect of low-temperature vacuum drying (LTVD) on wild murta (Ugni molinae Turcz) was evaluated, in comparison with freeze-drying (FD) and vacuum drying (VD), to assess their capacity to preserve bioactive compounds and associated bioactivities. Murta was dried [...] Read more.

For the first time, the effect of low-temperature vacuum drying (LTVD) on wild murta (Ugni molinae Turcz) was evaluated, in comparison with freeze-drying (FD) and vacuum drying (VD), to assess their capacity to preserve bioactive compounds and associated bioactivities. Murta was dried using LTVD at 20, 30, and 40 °C under a constant vacuum of 10 mbar, where FD and VD at 60 °C (VD 60) were included as comparative methods. The content of fatty acids and tocols, along with the retention of bioactive compounds and their antioxidant, anti-inflammatory, cytotoxic, and α-glucosidase inhibitory activities, were systematically analyzed. LTVD- and VD-dried murta exhibited higher polyunsaturated-to-saturated fatty acid ratios (>9.0) and markedly greater tocol contents, whereas FD maintained a more balanced ratio (<5.0) but with lower tocol levels. While FD was most effective in preserving catechin, higher levels of other phenolic compounds were observed in samples dried by LTVD at 20 and 40 °C, as well as VD 60, possibly due to the release of bound forms during processing. The drying method significantly influenced murta bioactivity. LTVD 30 preserved the highest antioxidant capacity, while topical anti-inflammatory effects on skin lesions varied by pathway, with LTVD 40 being the most effective in the TPA model and FD in the AA model. These effects were evaluated only using a topical inflammation model in BALB/c mice of both sexes; dietary effects were not assessed in this study. Regarding other bioactivities, VD 60 extracts excelled in both cytotoxic and α-glucosidase inhibitory effects, whereas FD extracts were the most effective against AGS cells and LTVD 20 against α-glucosidase. In conclusion, LTVD emerges as a promising alternative to FD and VD, showing potential to preserve bioactive compounds and key bioactivities of wild murta, although further studies are needed to elucidate the underlying mechanisms. Full article

(This article belongs to the Special Issue Antioxidant Research in Chile—2nd Edition)

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3 pages, 149 KB

Open AccessEditorial

Effect of Dietary Antioxidants in Chronic Disease Prevention

by Baojun Xu

Antioxidants 2025, 14(10), 1200; https://doi.org/10.3390/antiox14101200 - 2 Oct 2025

Abstract

Chronic diseases are a major global public health challenge, with increasing incidence and mortality rates [...] Full article

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

30 pages, 2239 KB

Open AccessArticle

Valorization of Hazelnut (Corylus avellana L.) Skin By-Product as a Multifunctional Ingredient for Cosmetic Emulsions

by Teresa Mencherini, Tiziana Esposito, Francesca Sansone, Daniela Eletto, Martina Pannetta, Oihana Gordobil, Anna Lisa Piccinelli, Carlo Ferniani, Giulia Auriemma, Luca Rastrelli and Rita Patrizia Aquino

Antioxidants 2025, 14(10), 1199; https://doi.org/10.3390/antiox14101199 - 2 Oct 2025

Abstract

Roasted hazelnut skins (RHSs), generated as by-products of industrial hazelnut processing, were extracted by pressurized liquid extraction to yield a hydroalcoholic extract (RHS-H). The extract was rich in polyphenols (308.4 ± 4.6 mg GAE/g) and proanthocyanidins (169.3 ± 10 mg CE/g) and showed [...] Read more.

Roasted hazelnut skins (RHSs), generated as by-products of industrial hazelnut processing, were extracted by pressurized liquid extraction to yield a hydroalcoholic extract (RHS-H). The extract was rich in polyphenols (308.4 ± 4.6 mg GAE/g) and proanthocyanidins (169.3 ± 10 mg CE/g) and showed strong antioxidant activity (DPPH EC₅₀ = 5.08 ± 1.08 µg/mL; TEAC = 2.82 ± 0.03 mM Trolox/mg) together with antimicrobial effects against Staphylococcus aureus and Staphylococcus epidermidis. RHS-H also enhanced the UV absorbance of synthetic UV filters. When incorporated into oil-in-water (O/W) cosmetic emulsions at low concentrations (0.2–2% w/w), RHS-H did not affect physicochemical stability: formulations maintained acceptable organoleptic properties, dermocompatible pH (4.7–5.5), electrostatic stability (ζ-potential ranging from –57 to –60 mV), and rheological behavior. Functionally, RHS-H increased the antioxidant activity of emulsions (radical scavenging > 80% vs. 52% in the blank), ensured microbial protection in challenge tests, and enhanced SPF by 9.4% at 0.2% w/w, with further improvements at higher concentrations, reaching broad-spectrum photoprotection (critical wavelength > 370 nm). Overall, RHS-H represents a natural multifunctional ingredient with antioxidant, preservative, and photoprotective properties, providing a sustainable strategy to upcycle hazelnut processing waste and reduce reliance on synthetic additives in cosmetic formulations. Full article

(This article belongs to the Special Issue Natural Antioxidants for Cosmetic Applications)

31 pages, 2721 KB

Open AccessArticle

Phytochemical Composition and Antioxidant Activity of Traditional Plant Extracts with Biocidal Effects and Soil-Enhancing Potential

by Camelia Hodoșan, Cerasela Elena Gîrd, Ștefan-Claudiu Marin, Alexandru Mihalache, Emanuela-Alice Luță, Elena-Iuliana Ioniță, Andrei Biță, Ştefania Gheorghe, Laura Feodorov, Violeta Popovici, Elena Pogurschi, Lucica Nistor, Iulius Sorin Bărbuică and Lăcrămioara Popa

Antioxidants 2025, 14(10), 1198; https://doi.org/10.3390/antiox14101198 - 2 Oct 2025

Abstract

This research provides a comprehensive evaluation of the phytochemical composition, antioxidant potential, and biological properties of four plant species with longstanding use in ethnobotanical traditions: Calendula officinalis, Mentha × piperita, Urtica dioica, and Juglans regia. Plant extracts were obtained [...] Read more.

This research provides a comprehensive evaluation of the phytochemical composition, antioxidant potential, and biological properties of four plant species with longstanding use in ethnobotanical traditions: Calendula officinalis, Mentha × piperita, Urtica dioica, and Juglans regia. Plant extracts were obtained using a range of solvent systems and subsequently analyzed for their content of total polyphenols, flavonoids, and phenolic acids. Ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) enabled the accurate identification and quantification of major polyphenolic constituents. The antioxidant capacity was assessed through a series of in vitro assays, and elemental analysis was conducted to determine microelement content. To evaluate potential ecological implications, acute toxicity was tested using Daphnia magna, while phytotoxic effects were also examined. The results demonstrate pronounced antioxidant activity along with notable biocidal and soil-enhancing properties. These findings underscore the potential of such plant-based formulations as sustainable alternatives to conventional agrochemicals and highlight the relevance of integrating traditional botanical knowledge with modern strategies for enhancing soil quality, crop performance, and environmental sustainability. Full article

(This article belongs to the Special Issue Antioxidant and Protective Effects of Plant Extracts—2nd Edition)

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24 pages, 2672 KB

Open AccessArticle

Reassessing Whether Biodegradable Microplastics Are Environmentally Friendly: Differences in Earthworm Physiological Responses and Soil Carbon Function Impacts

by Yuze Li, Dongxing Zhou, Hongyan Wang, Wenfei Zhu, Rui Wang and Yucui Ning

Antioxidants 2025, 14(10), 1197; https://doi.org/10.3390/antiox14101197 - 1 Oct 2025

Abstract

Biodegradable plastics are not a primary solution to plastic pollution, and empirical evidence on whether they are environmentally friendly remains lacking. In this study, we systematically compared the toxic effects of traditional microplastics (polypropylene, PP; polystyrene, PS) with biodegradable microplastics (polylactic acid, PLA; [...] Read more.

Biodegradable plastics are not a primary solution to plastic pollution, and empirical evidence on whether they are environmentally friendly remains lacking. In this study, we systematically compared the toxic effects of traditional microplastics (polypropylene, PP; polystyrene, PS) with biodegradable microplastics (polylactic acid, PLA; polyhydroxyalkanoates, PHA) on the haplic phaeozem ecosystem. Through mathematical modeling analysis, it was found that earthworms initially rely on antioxidant enzymes to resist stress, mid-term activation of detoxifying enzymes to repair damage, and maintaining physiological balance through metabolic regulation and immune enhancement in later stages. We elucidated their mechanism differences: PLA and PP caused severe damage to the antioxidant system and cell membrane, with PLA mainly relying on POD to clear peroxides and PP relying on GST. In addition, PLA and PS can induce early neurotoxicity (AChE), while PHA induces late neurotoxicity. Furthermore, this study provides direct evidence proving that biodegradable microplastics are not environmentally friendly by breaking through the one-way research framework of “microplastic biotoxicity” and innovatively constructing a path analysis model that links biological physiological responses with soil ecological functions. We also provide a scientific basis to evaluate the ecological risks of microplastic pollution in soil and the whether biodegradable plastics are truly environmentally friendly. Full article

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16 pages, 629 KB

Open AccessReview

Alcohol-Induced Oxidative Stress and Gut–Liver–Brain Crosstalk: Expanding the Paradigm from ALD to MetALD

by Jeong-Yoon Lee, Young-Min Jee, Keungmo Yang and Tom Ryu

Antioxidants 2025, 14(10), 1196; https://doi.org/10.3390/antiox14101196 - 1 Oct 2025

Abstract

Alcohol-associated liver disease (ALD) includes a spectrum from steatosis and steatohepatitis to cirrhosis and hepatocellular carcinoma driven by oxidative stress, immune activation, and systemic inflammation. Ethanol metabolism through alcohol dehydrogenase, aldehyde dehydrogenase, and cytochrome P450 2E1 generates reactive oxygen and nitrogen species, leading [...] Read more.

Alcohol-associated liver disease (ALD) includes a spectrum from steatosis and steatohepatitis to cirrhosis and hepatocellular carcinoma driven by oxidative stress, immune activation, and systemic inflammation. Ethanol metabolism through alcohol dehydrogenase, aldehyde dehydrogenase, and cytochrome P450 2E1 generates reactive oxygen and nitrogen species, leading to mitochondrial dysfunction, hepatocellular injury, and activation of inflammatory and fibrogenic pathways. Beyond hepatic effects, ALD engages the gut–liver–brain axis, where microbial dysbiosis, blood–brain barrier disruption, and neuroinflammation contribute to cognitive impairment and cerebrovascular risk. The emerging concept, metabolic dysfunction-associated steatotic liver disease and increased alcohol intake (MetALD), presents the synergistic impact of alcohol and metabolic comorbidities, enhancing oxidative injury and fibrosis. This review summarizes key mechanisms connecting oxidative stress to multisystem pathology and highlights the need for precision therapies targeting redox imbalance, immune dysregulation, and gut–brain–liver interactions to improve outcomes in ALD and MetALD. Full article

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

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20 pages, 3633 KB

Open AccessArticle

Dietary Soy Isoflavones Ameliorate Muscle Quality in High-Fat Diet-Fed Rice Field Eels (Monopterus albus) by Modulating Myogenesis, Collagen Synthesis, and Antioxidant Capacity

by Kai Xie, Quan Li, Shuang Zheng, Huahong Wei, Tao Zhou, Yi Hu and Junzhi Zhang

Antioxidants 2025, 14(10), 1195; https://doi.org/10.3390/antiox14101195 - 1 Oct 2025

Abstract

High-fat diets are increasingly used to improve feed efficiency in aquaculture but may deteriorate fillet quality and health; soy isoflavones, plant-derived polyphenols, have emerged as promising modulators of muscle growth, antioxidant defense, and lipid metabolism in fish. This study investigated the effects of [...] Read more.

High-fat diets are increasingly used to improve feed efficiency in aquaculture but may deteriorate fillet quality and health; soy isoflavones, plant-derived polyphenols, have emerged as promising modulators of muscle growth, antioxidant defense, and lipid metabolism in fish. This study investigated the effects of dietary soy isoflavone supplementation on myogenesis, collagen synthesis, fatty-acid composition, and antioxidant capacity in muscle of Monopterus albus fed a high-fat diet. Fish were assigned to four diets: control (CON, 6.16% crude fat), high-fat without soy isoflavones (HSIF0, 11.98% crude fat), and high-fat with 50 mg/kg (HSIF50) or 100 mg/kg (HSIF100) soy isoflavones. HSIF0 significantly elevated whole-body/muscle lipids, reduced ΣSFA/ΣMUFA/Σn-3/Σn-6 ratios (p < 0.05), increased Σn-6 (p < 0.05), impaired water-holding capacity/texture (higher losses, lower hardness/cohesiveness/gumminess/chewiness/resilience) (p < 0.05), induced loosely arranged myofibers with enlarged inter-fiber spaces, downregulated myogenesis (upregulated mstn; downregulated myod/tcap/mrf4/mrf5) and collagen genes (ets1/sp1/p4ha1) (p < 0.05), decreased collagen/hydroxyproline (p < 0.05), and weakened antioxidants (higher MDA/H₂O₂; lower T-AOC/GSH; downregulated nrf2/sod/cat/gpx1/gpx8) (p < 0.05). HSIF50 reversed these effects, enhancing ΣPUFA/Σn-3/EPA+DHA (p < 0.05), restoring structure/gene expression (p < 0.05), and boosting antioxidants (p < 0.05). In contrast, HSIF100 partially diminished benefits, indicating dose-dependency. Overall, 50 mg/kg soy isoflavones optimally mitigated high-fat-induced muscle quality decline via lipid remodeling, structural improvement, collagen promotion, and antioxidant enhancement. Full article

(This article belongs to the Special Issue Antioxidants and Aquaculture: A Synergistic Approach for Sustainable Aquatic Production)

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20 pages, 1176 KB

Open AccessArticle

Protective Effects of Microsorum scolopendria (Burm.f.) Copel. Leaf and Rhizome Extracts on Oxidative Stress and Inflammation Induced by Staphylococcus aureus and Staphylococcus epidermidis

by Cristóbal Balada, Valentina Díaz, Mónica Castro, Macarena Echeverría-Bugueño, María José Marchant and Leda Guzmán

Antioxidants 2025, 14(10), 1194; https://doi.org/10.3390/antiox14101194 - 30 Sep 2025

Abstract

Microsorum scolopendria (Burm.f.) Copel. is a traditional medicinal fern with reported antioxidant and anti-inflammatory properties. In this study, we investigated the protective effects of leaf (HH) and rhizome (RH) extracts of MS on oxidative stress and inflammation in human dermal fibroblast (HDFa) cells [...] Read more.

Microsorum scolopendria (Burm.f.) Copel. is a traditional medicinal fern with reported antioxidant and anti-inflammatory properties. In this study, we investigated the protective effects of leaf (HH) and rhizome (RH) extracts of MS on oxidative stress and inflammation in human dermal fibroblast (HDFa) cells infected with Staphylococcus aureus and Staphylococcus epidermidis. Cytotoxicity assays revealed that both extracts were safe up to 100 µg/mL, although RH exhibited a slight reduction in viability (≈20%) at 63 µg/mL. In infection assays, pretreatment with HH and RH extracts (63–100 µg/mL) for 3 h significantly reduced ROS levels by up to 45% compared with infected controls, while LDH release decreased by ~30%, indicating protection against membrane damage. Regarding anti-inflammatory activity, both extracts showed selective inhibition of COX-2 over COX-1, with RH inhibiting COX-2 by 62% and HH by 55% at 100 µg/mL, whereas COX-1 inhibition remained below 20%. These results highlight differential biological performance between leaf and rhizome extracts, with RH showing slightly higher anti-inflammatory activity but also a modest cytotoxic effect at intermediate concentrations. Overall, MS extracts demonstrated protective effects against oxidative and inflammatory damage induced by bacterial infection, supporting their potential as safe natural therapeutic agents for managing infection-associated skin stress and inflammation. Full article

(This article belongs to the Special Issue Antioxidant Research in Chile—2nd Edition)

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38 pages, 3419 KB

Open AccessReview

Thiol Isomerases: Enzymatic Mechanisms, Models of Oxidation, and Antagonism by Galloylated Polyphenols

by Osamede C. Owegie, Quinn P. Kennedy, Pavel Davizon-Castillo and Moua Yang

Antioxidants 2025, 14(10), 1193; https://doi.org/10.3390/antiox14101193 - 30 Sep 2025

Abstract

Thiol isomerases are a family of enzymes that participate in oxidative protein folding. They contain highly reactive vicinal thiols in a CXXC motif within their catalytic domains to mediate thiol-disulfide switching as part of their reductase, oxidase, and isomerase activity. In addition, they [...] Read more.

Thiol isomerases are a family of enzymes that participate in oxidative protein folding. They contain highly reactive vicinal thiols in a CXXC motif within their catalytic domains to mediate thiol-disulfide switching as part of their reductase, oxidase, and isomerase activity. In addition, they participate in chaperone function by binding to partially folded or misfolded proteins and preventing aggregation, thereby facilitating correct protein folding. The CXXC motif is conducive to oxidative influence based on the sulfur nucleophilicity. Redox modification of the CXXC motif may influence the enzymatic function. In this review we briefly discuss the family of thiol isomerases as it relates to thrombotic disorders. We then discuss the chemical mechanisms of making and breaking disulfides by the enzymes. Enzymatic and chemical models of oxidizing the CXXC motif are proposed. Lastly, we highlight evidence that natural galloylated polyphenols can inhibit both the coronavirus main protease Mpro and thiol isomerases, supporting a therapeutic strategy for COVID-19-associated coagulopathy and thrombosis by targeting the CXXC motif with these anti-oxidative compounds. Full article

(This article belongs to the Special Issue Redox Regulation in Inflammation and Disease—3rd Edition)

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27 pages, 3871 KB

Open AccessArticle

A Cascade Approach to Valorizing Camellia oleifera Abel Shell: Ultrasound-Assisted Extraction Coupled with Resin Purification for High-Efficiency Production of Multifunctional Polyphenols

by Jingyi Chen, Wei Li, Tao Liang, Yuting Yang, Rui Zhou, Rui Li, Daiyu Xie, Dayan Xiang, Shiling Feng, Tao Chen, Lijun Zhou and Chunbang Ding

Antioxidants 2025, 14(10), 1192; https://doi.org/10.3390/antiox14101192 - 29 Sep 2025

Abstract

Camellia oleifera Abel shell is an abundant lignocellulosic byproduct of the Chinese woody oil industry, which is currently underutilized. To achieve its high-value utilization, this study developed an innovative cascade process integrating ultrasound-assisted extraction and macroporous resin purification for the efficient preparation of [...] Read more.

Camellia oleifera Abel shell is an abundant lignocellulosic byproduct of the Chinese woody oil industry, which is currently underutilized. To achieve its high-value utilization, this study developed an innovative cascade process integrating ultrasound-assisted extraction and macroporous resin purification for the efficient preparation of purified polyphenols from the shell (P-CPCS). The major constituents were identified by quadrupole/Orbitrap high-resolution mass spectrometry (HPLC-Q-Exactive-MS: Biotech Pack Co., Ltd., Beijing, China) analysis. The optimized process significantly enhanced the polyphenol yield (40.05 ± 0.58 mg GAE/g dw) and purity (57.72%), surpassing conventional methods. P-CPCS exhibited exceptional multifunctional bioactivities, including potent antioxidant capacity (with low IC₅₀ values against DPPH, ABTS⁺·, and ·OH radicals), effective tyrosinase inhibition (whitening effect), and significant bacteriostatic effects against various pathogens. Furthermore, P-CPCS notably suppressed the LPS-induced inflammatory response in RAW264.7 macrophages by reducing NO overproduction. This work highlights a novel and efficient strategy for upcycling agricultural waste into a high-performance natural antioxidant, positioning P-CPCS as a promising ingredient for applications in functional foods, cosmetics, and biomaterial stabilization. Full article

(This article belongs to the Special Issue From Waste to Health: Upcycling Agrifood By-Products into Functional Antioxidant-Rich Ingredients and Products)

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16 pages, 4613 KB

Open AccessArticle

Inhibitory Effect of S0859 on the Antioxidant Master Switch Nuclear Factor Erythroid 2-Related Factor 2 in Lung Cancer Cells

by Eunsun Lee and Jeong Hee Hong

Antioxidants 2025, 14(10), 1191; https://doi.org/10.3390/antiox14101191 - 28 Sep 2025

Abstract

Cancer cells possess endogenous antioxidant systems such as nuclear factor erythroid 2-related factor 2 (NRF2). The electroneutral sodium bicarbonate cotransporter NBCn1, known as a migratory module, is closely associated with cancer metastasis; however, its regulatory signaling in cancer remains unclear. In particular, the [...] Read more.

Cancer cells possess endogenous antioxidant systems such as nuclear factor erythroid 2-related factor 2 (NRF2). The electroneutral sodium bicarbonate cotransporter NBCn1, known as a migratory module, is closely associated with cancer metastasis; however, its regulatory signaling in cancer remains unclear. In particular, the regulation of NBCn1 in response to oxidative stress and its relationship with NRF2 need to be elucidated. In the present study, we found that hydrogen peroxide–induced oxidative stress dysregulated NBCn1 via inhibition of NF-κB, thereby suppressing cellular migration in non-small cell lung cancer A549 cells. Phosphorylation of NF-κB was required for maintaining NBCn1 function in A549 cells. Oxidative stress also induced NRF2 nuclear translocation, reduced NBC activity, and activated oxidative stress–responsive gene expression. Treatment with the NBC inhibitor S0859 impaired ERK activation, NRF2 nuclear translocation, and oxidative stress defense gene expression in A549 cells. Furthermore, oxidative stimulation in the presence of S0859 disrupted the NRF2-mediated oxidative stress defense system and cellular migration in A549 lung cancer cells. Collectively, these findings suggest that S0859, as a potential NRF2 inhibitor, may exert anti-cancer properties. Full article

(This article belongs to the Special Issue Oxidative Stress and NRF2 in Health and Disease—2nd Edition)

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20 pages, 1222 KB

Open AccessReview

Melatonin-Mediated Nrf2 Activation as a Potential Therapeutic Strategy in Mutation-Driven Neurodegenerative Diseases

by Lucía Íñigo-Catalina, María Ortiz-Cabello, Elisa Navarro, Noemí Esteras, Lisa Rancan and Sergio D. Paredes

Antioxidants 2025, 14(10), 1190; https://doi.org/10.3390/antiox14101190 - 28 Sep 2025

Abstract

Neurodegeneration is intrinsically linked to aging through processes such as oxidative stress, mitochondrial dysfunction, and chronic inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) emerges as a central transcription factor regulating these molecular events and promoting cytoprotective responses. In neurodegenerative diseases, notably, frontotemporal [...] Read more.

Neurodegeneration is intrinsically linked to aging through processes such as oxidative stress, mitochondrial dysfunction, and chronic inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) emerges as a central transcription factor regulating these molecular events and promoting cytoprotective responses. In neurodegenerative diseases, notably, frontotemporal dementia (FTD) and Parkinson’s disease (PD), genetic mutations—including MAPT, LRRK2, PINK1, PRKN, and SNCA—have been reported to alter Nrf2 signaling, both in vitro and in vivo. Melatonin, a neurohormone widely known for its strong antioxidant and mitochondria-stabilizing properties, has been shown to activate Nrf2 and restore redox balance in several experimental models of neurodegeneration. Its effects include a reduction in tau hyperphosphorylation, α-synuclein aggregation, and neuroinflammation. While most data are derived from sporadic models of Alzheimer’s disease and PD, emerging evidence supports a role for melatonin in familial forms of FTD and PD as well. Thus, targeting Nrf2 through melatonin may offer a promising approach to mitigating neurodegeneration, especially in the context of mutation-driven pathologies. Further investigation is warranted to explore mutation-specific responses and optimize the therapeutic strategies. Full article

(This article belongs to the Special Issue Oxidative Stress and NRF2 in Health and Disease—2nd Edition)

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Graphical abstract

14 pages, 3871 KB

Open AccessArticle

fliC Mediates Pseudomonas plecoglossicida’s Hijack of Inflammatory Immunity and Glucose Metabolism in the Large Yellow Croaker

by Xizhi Peng, Yujia Sun, Huanjiao Tan, Huanying Pang, Caiyuan Zhao and Qingpi Yan

Antioxidants 2025, 14(10), 1189; https://doi.org/10.3390/antiox14101189 - 28 Sep 2025

Abstract

The bacterial flagellum plays a crucial role in pathogenesis. However, the mechanism by which the flagellum interferes with host energy metabolism remains unclear. In this study, we confirmed that deletion of the fliC gene resulted in a 30% reduction in the virulence of [...] Read more.

The bacterial flagellum plays a crucial role in pathogenesis. However, the mechanism by which the flagellum interferes with host energy metabolism remains unclear. In this study, we confirmed that deletion of the fliC gene resulted in a 30% reduction in the virulence of Pseudomonas plecoglossicida against the large yellow croaker (Larimichthys crocea). Compared to the wild-type strain (WT) infection group, the ΔfliC infection group exhibited a 29.54% decrease in the number of vacuolar degeneration hepatocytes and a 50.83% higher liver glycogen content. Furthermore, infection led to decreased mitochondrial complex V activity, a reduced NAD+/NADH ratio, lower levels of reduced glutathione (GSH), and increased lipid peroxide levels; however, these metabolic perturbations were significantly ameliorated in the ΔfliC group compared to the WT group. Proteomic analysis revealed that the dysregulation of the complement cascade and core carbon metabolic pathways observed in the WT infection group liver was significantly alleviated in the ΔfliC infection group. Additionally, in the ΔfliC infection group, pro-inflammatory genes (such as Tlr5, Tnfα, and Il1β) were downregulated, while lipid metabolism-related genes (such as Acox1, Cpt1a, and Pparα) were upregulated, suggesting the suppression of the Tlr5/NF-κB immune signaling axis and enhanced fatty acid β-oxidation. Collectively, fliC may mediate the disruption of host glucose and lipid metabolism homeostasis through a Tlr5-triggered immunometabolic regulatory axis. In conclusion, this study demonstrates that bacterial flagella modulate host energy metabolism, expanding our understanding of flagellum-mediated pathogenesis. Full article

(This article belongs to the Topic Immunology and Disease Prevention and Control in Aquatic Animals)

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21 pages, 5322 KB

Open AccessArticle

Influence of Cutting Styles on Antioxidant Capabilities of Fresh-Cut Cauliflower by Regulating ROS Metabolism and Antioxidant Enzyme Activity

by Qihan Guo, Bingheng Li, Jiarui Wang, Minke Shi, Jiayu Wang, Yan Chen, Yunjie Zhang, Sarengaowa, Ying Xiao and Ke Feng

Antioxidants 2025, 14(10), 1188; https://doi.org/10.3390/antiox14101188 - 28 Sep 2025

Abstract

The enzymatic browning and oxidative deterioration of cauliflower during mechanical processing are major challenges for the fresh-cut cauliflower industry. The primary objective of this study was to investigate the impact of cutting styles on the antioxidant capacity of fresh-cut cauliflower during storage. One [...] Read more.

The enzymatic browning and oxidative deterioration of cauliflower during mechanical processing are major challenges for the fresh-cut cauliflower industry. The primary objective of this study was to investigate the impact of cutting styles on the antioxidant capacity of fresh-cut cauliflower during storage. One flower (12 × 1.8 cm) of cauliflower was designated as cutting style 1 (CS1). CS1 was cut longitudinally into strips as cutting style 2 (CS2). CS1 was also cut transversely into cubes, as cutting style 3 (CS3), and longitudinally and transversely into small cubes, as cutting style 4 (CS4). Results indicated that at the conclusion of the 72 h storage period, cutting treatments enhanced the total antioxidant capacity of fresh-cut cauliflower in the ABTS assay by 128.1%, 82.9%, 50.1%, and 38.9% for CS1, CS2, CS3, and CS4, respectively. All treatment groups except CS1 exhibited increased total antioxidant capacity in the FRAP assay. Phenolic compound accumulation increased by 106.82%, 105.24%, 270.4%, and 295.3% in CS1, CS2, CS3, and CS4, respectively. In addition, the O₂⁻· scavenging activity was enhanced; the activities of antioxidant-related enzymes, including catalase (CAT) and superoxide dismutase (SOD), were also increased. In conclusion, the extent of the effect on antioxidant capacity was as follows: CS4 > CS3 > CS2 > CS1. This study has elucidated the patterns of influence exerted by cutting methods upon the quality of fresh-cut cauliflower, thereby providing theoretical foundations and empirical data to inform the selection of appropriate cutting techniques for both commercial processing and domestic culinary applications. Full article

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