Antioxidants

22 pages, 2544 KB

Open AccessSystematic Review

Growth Performance and Antioxidant Responses to Dietary Flavonoids in Swine: A Systematic Review and Meta-Analysis with Exploratory Dose–Time Relationships

by Yi Xiao, Qiannan Han, Zhenglin Dong, Xizi Yang, Zhihao Xu, Kaiyu Hu, Zhihao Xuan, Guiping Liang, Weimin Jiang, Yinglin Peng and Yingying Liu

Antioxidants 2026, 15(8), 980; https://doi.org/10.3390/antiox15080980 (registering DOI) - 7 Aug 2026

Abstract

Dietary flavonoids are increasingly investigated in swine nutrition, but how supplementation level, intervention duration, and growth stage are associated with growth and antioxidant responses remains unclear. This PRISMA 2020 systematic review and meta-analysis evaluated dietary flavonoid supplementation in pigs. Twenty-eight randomized controlled trials [...] Read more.

Dietary flavonoids are increasingly investigated in swine nutrition, but how supplementation level, intervention duration, and growth stage are associated with growth and antioxidant responses remains unclear. This PRISMA 2020 systematic review and meta-analysis evaluated dietary flavonoid supplementation in pigs. Twenty-eight randomized controlled trials were synthesized using three-level random-effects models to account for dependent effect sizes. Flavonoid supplementation was associated with increased average daily gain (ADG; SMD = 0.719, 95% CI: 0.428 to 1.009;

I^{2} = 51.85 %

) and a lower feed-to-gain ratio (F/G; SMD = −0.708, 95% CI: −0.929 to −0.487;

I^{2} = 32.25 %

), whereas the association with average daily feed intake (ADFI) was not statistically significant (SMD = 0.217, 95% CI: −0.101 to 0.535;

I^{2} = 59.30 %

). Supplementation was also associated with increased superoxide dismutase (SMD = 0.907) and glutathione peroxidase activities (SMD = 0.666) and reduced malondialdehyde concentrations (SMD = −0.989), although heterogeneity was substantial for these outcomes (

I^{2} = 96.47

–

97.83 %

). The certainty of evidence was assessed as low for ADG and moderate for ADFI, F/G, and antioxidant outcomes under the adapted GRADE framework. Exploratory stage-specific dose–time meta-regression identified potential relationships between supplementation intensity and ADG in weaned pigs (35 effect sizes from 14 studies) and finishing pigs (12 effect sizes from four studies). In finishing pigs, intervention duration was associated with growth responses. However, this subgroup contained few independent studies, and intervention duration covaried with age, physiological stage, flavonoid source, dose, health status, and basal diet. This association therefore does not establish an independent causal effect of intervention duration. Full article

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

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18 pages, 3031 KB

Open AccessArticle

Novel Exploratory Transcriptomic Candidates as Biomarkers and Cancer Hallmark Fingerprints for Ovarian Endometroid and Clear Cell Carcinomas in Women

by Pawel Kordowitzki and Kejun Ying

Antioxidants 2026, 15(8), 979; https://doi.org/10.3390/antiox15080979 - 6 Aug 2026

Abstract

Background: Endometriosis-associated ovarian cancers (EAOCs), encompassing clear cell (CC) and endometrioid carcinomas (EC), constitute distinct biological entities yet lack robust biomarkers for precise classification, prognostication, and therapeutic decision-making in women. Therefore, we aimed to describe novel biomarkers. Methods: In this study, we conducted [...] Read more.

Background: Endometriosis-associated ovarian cancers (EAOCs), encompassing clear cell (CC) and endometrioid carcinomas (EC), constitute distinct biological entities yet lack robust biomarkers for precise classification, prognostication, and therapeutic decision-making in women. Therefore, we aimed to describe novel biomarkers. Methods: In this study, we conducted an integrated transcriptomic analysis, powered by machine learning, to discover novel consensus biomarkers and delineate cancer hallmark signatures specific to EC and CC. Drawing on gene expression profiles from EAOC specimens, we merged differential expression analysis with LASSO regression and Random Forest classification to generate a reliable biomarker panel that effectively distinguishes EC from CC. Kaplan–Meier survival analyses and mutation analyses have been performed for selected biomarker genes. Results: Novel biomarkers, among others, the genes RPS28, EPAS1, ALKBH2, and DCLRE1A, uncover extensive transcriptional alterations tied to hypoxia signaling, oxidative stress, DNA repair, and metabolic reprogramming. Gene Ontology and pathway enrichment analyses revealed synchronized upregulation of epithelial–mesenchymal transition, TNF-α/NF-κB signaling, oxidative stress, hypoxia, and KRAS signaling pathways. Conclusions: Our work establishes novel exploratory transcriptomic candidates for innovative consensus biomarkers, yielding novel diagnostic and prognostic insights into EAOC and supporting further study of subtype-associated expression programs. The current study was designed primarily as an integrative computational investigation aimed at identifying candidate genes and molecular pathways distinguishing CC from EC. Full article

(This article belongs to the Special Issue Metabolic Reprogramming and Epigenetic Crosstalk in the Tumor Microenvironment)

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33 pages, 3310 KB

Open AccessArticle

Molecular Characterization of Melatonin Receptors in Perccottus glenii and Its Potential Roles in Melatonin-Mediated Antioxidant and Anti-Inflammatory Responses During Post-Freezing Recovery

by Jiajun Zhou, Tianmei Liu, Zhaoyang Ning, Xiaoyu Zhao, Ye Huang, Kaitong Zhu, Xiangxin Kong and Weijie Mu

Antioxidants 2026, 15(8), 978; https://doi.org/10.3390/antiox15080978 - 6 Aug 2026

Abstract

In this study, we report for the first time the cloning and identification of three melatonin receptors (PgMtnr1a, PgMtnr1b, and PgMtnr1c) from the freeze-resistant fish Perccottus glenii, all of which encode typical GPCR proteins. These receptors are expressed [...] Read more.

In this study, we report for the first time the cloning and identification of three melatonin receptors (PgMtnr1a, PgMtnr1b, and PgMtnr1c) from the freeze-resistant fish Perccottus glenii, all of which encode typical GPCR proteins. These receptors are expressed widely in high-metabolism tissues such as the liver. During the freezing and recovery process at −2 °C, the expression of liver receptors exhibited dynamic changes: PgMtnr1a and PgMtnr1c were significantly upregulated during the middle of resuscitation, while PgMTNR1A reached its peak expression in the later stages, suggesting its involvement in stress repair. In vitro experiments confirmed that melatonin significantly enhances the activity of liver antioxidant enzymes in a receptor-dependent manner, an effect that can be inhibited by the antagonist luzindole. Anti-inflammatory analyses indicate that melatonin primarily inhibits inflammation-related genes through Mtnr1a and Mtnr1b. Furthermore, the overexpression of PgMTNR1A can synergistically activate ERK in the presence of melatonin, inhibit the JNK/p38 MAPK pathway, and downregulate the expression of NF-κB and COX2. Pathway inhibition experiments further validated that the MAPK/NF-κB axis, including ERK, JNK, and p38 pathways, mediates the anti-inflammatory effects of melatonin. This study systematically elucidates the molecular mechanisms by which the melatonin receptors of P. glenii play crucial antioxidant and anti-inflammatory roles during the later stages of freeze–thaw resuscitation, particularly by regulating the MAPK/NF-κB signaling axis through MTNR1A, thereby providing a novel basis for understanding the adaptation of vertebrates to extreme environments. Full article

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

28 pages, 12609 KB

Open AccessArticle

Sexual Dimorphism in Placental mTORC1 Signaling, Amino Acid Transport, and Mitochondrial Respiration at Term

by Hiroshi Shimada, Toshihide Sakuragi, Vincent Zaegel, Anita Kramer, Kristen E. Boyle, Theresa L. Powell, Thomas Jansson and Fredrick J. Rosario

Antioxidants 2026, 15(8), 977; https://doi.org/10.3390/antiox15080977 - 6 Aug 2026

Abstract

Male fetuses generally grow faster in utero and are heavier at birth than females, whereas the rates of perinatal mortality and morbidity are often higher in boys than in girls. Sexual dimorphism in placental function is believed to contribute to these differences. However, [...] Read more.

Male fetuses generally grow faster in utero and are heavier at birth than females, whereas the rates of perinatal mortality and morbidity are often higher in boys than in girls. Sexual dimorphism in placental function is believed to contribute to these differences. However, evidence for sex-specific differences in placental function remains limited. We hypothesized that placental nutrient-sensing signaling activity, amino acid transport capacity, and mitochondrial respiration are higher in male than female placentas. Placentas were collected from 46 women (BMI 18.5–29.9 kg/m²) with uncomplicated pregnancies delivering appropriate-for-gestational-age infants (n = 23 female; n = 23 male). In homogenates of male placentas, the phosphorylation of S6RP (Ser235/236) was increased and total 4E-BP1 protein expression was reduced compared with female placentas, indicating enhanced mTORC1 signaling. In vitro System A amino acid transport activity was also greater in microvillous plasma membranes isolated from male placentas. Placental mitochondrial respiratory capacity was assessed in villous tissue using high-resolution respirometry with carbohydrate and lipid substrate–uncoupler–inhibitor titration (Carb SUIT and Lipid SUIT) protocols on the Oroboros O2k platform. Male placentas exhibited greater maximal oxidative phosphorylation capacity, enhanced complex II-linked respiration, and higher maximal electron transport system capacity compared with female placentas under both carbohydrate- and lipid-supported respiratory conditions. Although placental weight did not differ between sexes, the birth weight-to-placental weight ratio was significantly higher in male pregnancies, consistent with greater placental functional efficiency. In conclusion, placental mTORC1 signaling activity, System A amino acid transport activity, and mitochondrial respiratory capacity are greater in male than female placentas and are associated with greater placental functional efficiency and fetal growth in male pregnancies. Full article

(This article belongs to the Special Issue Oxidative Stress and Human Reproduction)

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23 pages, 5519 KB

Open AccessArticle

Bypassing Androgens: Retina-Targeted 17β-Estradiol Delivery via DHED Eye Drops Ameliorates Orchiectomy-Induced Shifts in the Male Rat Visual Cortex Proteome

by Khadiza Zaman, Ammar Kapic, Vien Nguyen, Laszlo Prokai and Katalin Prokai-Tatrai

Antioxidants 2026, 15(8), 976; https://doi.org/10.3390/antiox15080976 (registering DOI) - 6 Aug 2026

Abstract

Mass spectrometry-based proteomics has become instrumental for elucidating the molecular mechanisms of neurodegeneration, enabling the identification of disease-associated proteomic alterations and protein-level responses to therapeutic interventions. Building on our previous proteomic characterization of the orchiectomized (ORX) Brown Norway male rat retina as a [...] Read more.

Mass spectrometry-based proteomics has become instrumental for elucidating the molecular mechanisms of neurodegeneration, enabling the identification of disease-associated proteomic alterations and protein-level responses to therapeutic interventions. Building on our previous proteomic characterization of the orchiectomized (ORX) Brown Norway male rat retina as a model of androgen deprivation, we extend this investigation to the visual cortex (VC), a key node in the visual pathway. Here we report the first comprehensive proteomic characterization of ORX-VC employing nanoflow liquid chromatography–tandem mass spectrometry complemented by bioinformatic pathway analyses and quantitative assessment of selected protein markers of ORX-induced changes. Our discovery-driven proteomics approach revealed over 500 differentially expressed proteins following ORX. Principal component analysis showed complete separation between ORX and naïve groups with no overlap, indicating a profound effect of androgen deprivation on the VC proteome. Ingenuity Pathway Analysis^® predicted that the widespread proteome dysregulation included oxidative stress as a primary contributor, alongside estrogen receptor (ESR) predominance over androgen receptor signaling, consistent with our prior findings in the ORX retina. To explore whether this ESR predominance translates to a benefit of E2 supplementation alone, independent of circulating testosterone, we utilized our DHED (10β,17β-dihydroxyestra-1,4-dien-3-one) prodrug as eye drops to target E2 formation into the retina. Quantitative assessment demonstrated that this approach resulted in attenuation of ORX-induced expression changes in a selected panel of key proteins. These findings warrant future studies to determine whether this effect extends across the full spectrum of ORX-induced proteomic shifts and confers a benefit for vision preservation. Full article

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

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15 pages, 2649 KB

Open AccessArticle

The Nephroprotective Efficacy of Omega-3 Fatty Acids Against Streptozotocin-Induced Diabetic Renal Injury: A Biochemical, Histopathological and Ultrastructural Study

by Emrah Zayman, Eda Nur Özsoy, Mehmet Erman Erdemli, Zeynep Erdemli, Nilüfer Bulut, Feyza İnceoğlu and Mehmet Gül

Antioxidants 2026, 15(8), 975; https://doi.org/10.3390/antiox15080975 - 6 Aug 2026

Abstract

The present study was designed to evaluate the structural and biochemical efficacy of Omega-3 fatty acids in preventing renal injury in streptozotocin (STZ)-induced diabetic kidney injury and to correlate systemic oxidative stress parameters with histological and ultrastructural parameters. Twenty-eight male Wistar Albino rats [...] Read more.

The present study was designed to evaluate the structural and biochemical efficacy of Omega-3 fatty acids in preventing renal injury in streptozotocin (STZ)-induced diabetic kidney injury and to correlate systemic oxidative stress parameters with histological and ultrastructural parameters. Twenty-eight male Wistar Albino rats were randomly divided into four groups (n = 7) as follows: Control, Omega-3 (500 mg/kg, orally), Diabetes Mellitus (DM; 50 mg/kg STZ, i.p.), and DM+Omega-3 (STZ, followed by 500 mg/kg Omega-3 for 42 days). Biochemical analysis of renal function (blood urea nitrogen (BUN) and creatinine) and oxidative status (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI)) was measured by ELISA. Histopathological scoring and Caspase-3 staining were performed by Hematoxylin and Eosin (H&E) and immunohistochemically, respectively. Transmission Electron Microscopy (TEM) was used to examine the renal tissues. Our results showed that the DM group presented with severe hyperglycemia, uremia, and a significant oxidative shift, as evidenced by increased MDA/TOS levels and depleted antioxidant defenses. Light microscopy showed extensive glomerular damage, tubular degeneration and inflammatory infiltration in the kidneys of diabetic rats. Immunohistochemical analysis revealed strong Caspase-3 expression in the tubular and glomerular compartments. TEM showed severe podocyte effacement and damage to the glomerular basement membrane (GBM). Notably, Omega-3 supplementation significantly reversed renal dysfunction, restored the pro-oxidant/antioxidant balance and reduced histopathological injury scores. Moreover, Omega-3 treatment efficiently blocked Caspase-3-mediated apoptotic signaling and preserved the ultrastructural integrity of the glomerular filtration barrier (GFB) and tubular mitochondria. Our results demonstrate the potent nephroprotective effects of Omega-3 fatty acids in reducing oxidative stress, preventing programmed cell death and maintaining the stability of the renal parenchyma’s microarchitecture. These findings suggest that Omega-3 fatty acids could be an effective adjuvant therapeutic agent for the management of diabetic nephropathy. Full article

(This article belongs to the Special Issue Antioxidants in Chronic and End-Stage Kidney Disease: Defining Biological and Clinical Plausibility)

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24 pages, 10375 KB

Open AccessArticle

Ethanolic Extract of Sophora moorcroftiana Seeds Attenuates LPS-Induced Inflammation and Oxidative Stress in RAW 264.7 Macrophages via Modulation of the p62/Keap1/Nrf2 Signaling Pathway

by Nianshou Zhao, Hongya Li, Peng Ji, Yanming Wei, Yongli Hua, Yanan Guo and Fanlin Wu

Antioxidants 2026, 15(8), 974; https://doi.org/10.3390/antiox15080974 - 5 Aug 2026

Abstract

Despite the traditional application of Sophora moorcroftiana seeds (SMS) in Tibetan medicine for heat-clearing, damp-drying, anti-inflammatory and detoxifying properties, the anti-inflammatory mechanisms of SMS remain insufficiently understood and warrant systematic investigation. This study evaluated the protective effects of an ethanolic SMS extract against [...] Read more.

Despite the traditional application of Sophora moorcroftiana seeds (SMS) in Tibetan medicine for heat-clearing, damp-drying, anti-inflammatory and detoxifying properties, the anti-inflammatory mechanisms of SMS remain insufficiently understood and warrant systematic investigation. This study evaluated the protective effects of an ethanolic SMS extract against lipopolysaccharide (LPS)-induced oxidative stress and inflammation in RAW 264.7 macrophages, with emphasis on the p62/Keap1/Nrf2 signaling pathway. In vitro, the extract exhibited significant DPPH, ABTS and ·OH radical scavenging activities, as well as ferric-reducing antioxidant power, in a clear concentration dependent manner. An inflammatory model was established by stimulating RAW 264.7 cells with LPS, followed by treatment with graded concentrations of the ethanolic SMS extract. The extract significantly reduced LPS-induced nitric oxide production and decreased the secretion of TNF-α, IL-6 and IL-1β, while suppressing iNOS and COX-2 expression at both mRNA and protein levels. In parallel, the extract alleviated oxidative stress, as evidenced by reduced intracellular reactive oxygen species (ROS) and MDA levels, increased antioxidant defenses including SOD, GSH and CAT, and decreased LDH release. At the protein-expression level, SMS treatment was accompanied by differential changes in p62, Keap1, total Nrf2 and HO-1 expression, suggesting that its effects may involve regulatory processes associated with cellular stress and antioxidant defense. Collectively, the ethanolic extract of SMS attenuated LPS-induced inflammatory and oxidative stress responses in RAW 264.7 macrophages. These effects may be associated with the suppression of inflammatory mediator production, reduction in the cellular oxidative stress burden and modulation of proteins involved in cellular stress responses and antioxidant defense. Full article

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

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Graphical abstract

16 pages, 5501 KB

Open AccessReview

Beyond Food Preservation: Translational Perspectives of Synthetic Antioxidants

by Daniela Vergara, Felipe Lizama, Carlos Arias-Fuentes, Emigdio Chávez-Ángel and Alejandro Castro-Alvarez

Antioxidants 2026, 15(8), 973; https://doi.org/10.3390/antiox15080973 - 5 Aug 2026

Abstract

Synthetic antioxidants are attracting more interest as research moves beyond their traditional use as preservatives in food and materials. Recent studies are exploring how these redox-active molecules might be used in medicine. This review looks at how synthetic antioxidants are made, what is [...] Read more.

Synthetic antioxidants are attracting more interest as research moves beyond their traditional use as preservatives in food and materials. Recent studies are exploring how these redox-active molecules might be used in medicine. This review looks at how synthetic antioxidants are made, what is known about their biological effects, and the challenges of using them for neuroprotection, cancer treatment, organ protection, and regenerative medicine. In this review, synthetic antioxidants are defined as synthetic or semisynthetic small molecules with redox activity. Other antioxidant systems, such as non-phenolic molecules, prodrugs, peptides, metal complexes, nanocarriers, nanozymes, and biomaterials, are mentioned as related but are not considered classic synthetic antioxidants. Some of these compounds and delivery systems have shown promising results in cell, tissue, and animal studies. They have been found to influence neuroinflammation, mitochondrial function, and tumor redox responses, and to protect tissues from ischemic or inflammatory damage. However, most of these candidates are still in preclinical development. Progress is slowed by issues such as inconsistent bioavailability, dose-dependent toxicity, unclear mechanisms of action, a lack of reliable biomarkers, and manufacturing or regulatory challenges, especially for advanced delivery systems. New research highlights the potential of hybrid molecules, organelle-targeted delivery, and systems that respond to specific triggers. Still, there is not enough strong clinical data to support these approaches. Moving forward, the field will need thorough pharmacological studies, careful safety checks, standardized ways to measure effectiveness, and well-designed clinical trials. Full article

(This article belongs to the Special Issue Recent Trends in Nanoantioxidants—2nd Edition)

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25 pages, 9935 KB

Open AccessReview

Oxidative Stress as a Potential Mechanistic Bridge Between Electronic Cigarette Components and Chronic Disease: A Combined Narrative and Bibliometric Analysis

by Rana Abdel Sater, Youssef El Rayess and Sofi G. Julien

Antioxidants 2026, 15(8), 972; https://doi.org/10.3390/antiox15080972 - 5 Aug 2026

Abstract

Despite their introduction two decades ago as cessation tools, vaping devices and electronic cigarettes (ECs) have surged dramatically among adolescents and adults worldwide. The widespread misconception that ECs are harmless has raised substantial concern about their potential contribution to chronic diseases associated with [...] Read more.

Despite their introduction two decades ago as cessation tools, vaping devices and electronic cigarettes (ECs) have surged dramatically among adolescents and adults worldwide. The widespread misconception that ECs are harmless has raised substantial concern about their potential contribution to chronic diseases associated with oxidative stress (OS) pathways. To map this rapidly growing field, we combined a bibliometric analysis of human research on vaping-associated OS over the past decade with a narrative review of EC component toxicology and regulatory updates. The bibliometric analysis of 189 human studies identified four keyword clusters reflecting clinico-epidemiological, biological/mechanistic, methodological, and acute-event research themes. The results of this bibliometric analysis structure the narrative synthesis, which evaluates the chemical constituents of ECs, including e-liquid constituents, device-derived contaminants, and their aerosol by-products, and links them to pathways associated with OS development. Oxidative stress was the most frequent bridging keyword, reflecting predominant academic trends as research shifted from acute-focused investigations toward mechanistic chronic disease research. No prior review has integrated EC component toxicology with bibliometric evidence to map this landscape. This combined approach provides researchers, clinicians, and policymakers with an integrated evidence base and identifies priority areas for future investigation, including long-term exposure thresholds, age- and sex-specific outcomes, and the urgent need for harmonized global regulation. Full article

(This article belongs to the Special Issue Cigarette Smoke and Oxidative Stress)

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20 pages, 3192 KB

Open AccessArticle

Jostaberry (Ribes × nidigrolaria) as a Functional Ingredient for 3D Printed Snacks: Impact of Starch Type and Storage on Antioxidant Profile and Stability

by Ana Mandura Jarić, Anica Bebek Markovinović, Luna Maslov Bandić, Josipa Ljubičić, Ana Valentić, Manuela Zadravec, Ana Vulić, Boris Duralija, Sandra Zavadlav and Danijela Bursać Kovačević

Antioxidants 2026, 15(8), 971; https://doi.org/10.3390/antiox15080971 - 5 Aug 2026

Abstract

The growing demand for functional foods and personalized nutrition has increased interest in three-dimensional printing (3DP) as a technology for developing customized food products. Jostaberry (Ribes × nidigrolaria), a fruit rich in antioxidant compounds, has rarely been explored in 3DP food [...] Read more.

The growing demand for functional foods and personalized nutrition has increased interest in three-dimensional printing (3DP) as a technology for developing customized food products. Jostaberry (Ribes × nidigrolaria), a fruit rich in antioxidant compounds, has rarely been explored in 3DP food applications. This study evaluated the suitability of jostaberry for producing 3DP snacks and investigated the effects of starch type (corn or wheat) and storage (12 days/4 °C) on physicochemical properties, bioactive compounds, antioxidant capacity, and microbiological stability. Both starch type and storage significantly influenced product characteristics, whereas storage was the main factor affecting stability. During storage, moisture loss, changes in total soluble solids, color differences, and reductions in organic acid concentrations were observed. Although condensed tannins and anthocyanins decreased by 27.6% and 37.3%, respectively, total phenolic content remained relatively stable, suggesting compound-specific changes rather than an overall loss of phenolics. Compared with wheat starch, corn starch resulted in higher total flavonoid and hydroxycinnamic acid contents, whereas wheat starch retained higher malic acid concentrations. Antioxidant capacity also gradually decreased during storage. Despite these changes, the 3DP snacks remained microbiologically stable and complied with food safety requirements throughout the storage period. These findings demonstrate that jostaberry is a promising functional ingredient for 3DP snacks, providing high bioactive potential and acceptable refrigerated storage stability. Full article

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19 pages, 12737 KB

Open AccessArticle

Cinnamomum migao Active Extracts Ameliorate Acute Myocardial Ischemia via Modulation of the HIF-1α/Nrf2/NF-κB/MAPK Pathway Downstream of Oxidative Stress

by Xiaofen Li, Yinju Zhang, Wenxia Dai, Ming Xia and Lang Zhou

Antioxidants 2026, 15(8), 970; https://doi.org/10.3390/antiox15080970 - 5 Aug 2026

Abstract

Acute myocardial ischemia (AMI) is a life-threatening cardiovascular disorder characterized by excessive oxidative stress and persistent inflammatory cascades, yet safe multi-target natural therapeutic agents remain scarce. Cinnamomum migao is a well-known Miao ethnic medicine used for cardiovascular conditions, yet its cardioprotective effects and [...] Read more.

Acute myocardial ischemia (AMI) is a life-threatening cardiovascular disorder characterized by excessive oxidative stress and persistent inflammatory cascades, yet safe multi-target natural therapeutic agents remain scarce. Cinnamomum migao is a well-known Miao ethnic medicine used for cardiovascular conditions, yet its cardioprotective effects and mechanisms remain largely unclear. This study investigated the efficacy and underlying mechanism of C. migao ethyl acetate extract (MGE) against AMI. MGE significantly improved the viability of H9c2 cardiomyocytes subjected to OGD/R injured. UPLC-MS/MS and molecular networking identified 30 constituents in MGE, among which sesquiterpenoids predominated. In ISO-induced AMI rats, MGE dose-dependently mitigated myocardial injury, as reflected by reduced ST-segment elevation, serum CK-MB and LDH levels, and alleviated histopathological damage. MGE enhanced SOD and CAT activities, decreased MDA content, and inhibited the secretion of TNF-α, IL-6 and IL-1β. Mechanistically, MGE downregulated the expression of NOX4, HIF-1α, p38 MAPK and NF-κB p65, while activating the Nrf2/HO-1 pathway. Oxyphyllenone A and magnodelavin C were identified as key active sesquiterpenoids that stably bound to IL-17 and TNF. Collectively, MGE alleviates AMI injury via anti-oxidative, anti-hypoxic, and anti-inflammatory effects through modulation of the HIF-1α/Nrf2/NF-κB/MAPK axis downstream of oxidative stress, with sesquiterpenoids serving as its key bioactive components. This work provides robust experimental evidence supporting C. migao as a promising natural antioxidant candidate for the prevention and treatment of AMI. Full article

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

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22 pages, 4040 KB

Open AccessArticle

Physiological Adaptation Strategy of the Pseudo-Metallophyte Lotus corniculatus L. to Long-Term Metal Contamination

by Marzena Sujkowska-Rybkowska, Anna Rusaczonek, Małgorzata Nykiel, Ewelina Hallmann, Maria Duszyn, Sławomir Jaworski and Wojciech Borucki

Antioxidants 2026, 15(8), 969; https://doi.org/10.3390/antiox15080969 - 5 Aug 2026

Abstract

Lotus corniculatus L. can spontaneously colonize metal-contaminated areas like the old Zn-Pb calamine tailings. This study compared two L. corniculatus ecotypes collected from metal-contaminated (HM) and non-contaminated (NM) sites to identify physiological adaptations to long-term metal exposure. The results indicated that HM ecotype [...] Read more.

Lotus corniculatus L. can spontaneously colonize metal-contaminated areas like the old Zn-Pb calamine tailings. This study compared two L. corniculatus ecotypes collected from metal-contaminated (HM) and non-contaminated (NM) sites to identify physiological adaptations to long-term metal exposure. The results indicated that HM ecotype accumulates Zn, Pb, and Cd in shoots without showing any toxic symptoms at the ultrastructural level. The HM ecotype exhibited a different composition of photosynthetic pigments, lower lipid peroxidation, and oxidative stress levels and increased the efficiency of the antioxidant defense system and antioxidant activity compared to the NM ecotype. Leaf antioxidant enzymes such as SOD, CAT, POX, and GPX were more active in the shoots of the HM ecotype, while GR and APX showed lower activity compared to the NM ecotype. In addition, the HM ecotype was characterized by higher glutathione and total phenolics content (mainly catechin, rutin, ferulic, and salicylic acids); however, these non-enzymatic metabolites primarily function in metal chelation alongside their role in oxidative stress mitigation. The results showed that calamine Lotus plants exhibit effective adaptation to long-term metal exposure by keeping metals away from metabolically active compartments and strengthening antioxidant defenses. These coordinated mechanisms reduce oxidative stress and contribute to the enhanced metal tolerance of calamine plants. Full article

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

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30 pages, 12497 KB

Open AccessArticle

Dietary Application of Synergistically Degraded Low-Molecular-Weight Chitosan to Promote Health and Antioxidant Responses in Pacific White Shrimp (Litopenaeus vannamei)

by Thitirat Rattanawongwiboon, Natthapong Paankhao, Wararut Buncharoen, Benchawan Kumwan, Pakapon Meachasompop, Yosapon Adisornprasert, Chonlatat Rajitdumrong, Pimrawee Chaemlek, Prapansak Srisapoome, Kasinee Hemvichian, Passakorn Kingwascharapong and Anurak Uchuwittayakul

Antioxidants 2026, 15(8), 968; https://doi.org/10.3390/antiox15080968 - 4 Aug 2026

Abstract

This study evaluated the potential of synergistically degraded low-molecular-weight chitosan (LMW-CS) as a functional feed additive to promote growth, antioxidant capacity, innate immunity, and disease resistance in Pacific white shrimp (Litopenaeus vannamei). High-molecular-weight chitosan (HMW-CS, approximately 85 kDa) was degraded using [...] Read more.

This study evaluated the potential of synergistically degraded low-molecular-weight chitosan (LMW-CS) as a functional feed additive to promote growth, antioxidant capacity, innate immunity, and disease resistance in Pacific white shrimp (Litopenaeus vannamei). High-molecular-weight chitosan (HMW-CS, approximately 85 kDa) was degraded using γ-irradiation in combination with H₂O₂ to produce LMW-CS with improved functional properties. Shrimp were fed five experimental diets for 4 weeks: a control diet, HMW-CS0.4 (0.4% w/w), LMW-CS0.1 (0.1% w/w), LMW-CS0.2 (0.2% w/w), and LMW-CS0.4 (0.4% w/w). Growth performance, oxidative stress markers, antioxidant enzyme activities, lysozyme activity, immune-related gene expression, bacterial load, and survival after Vibrio parahaemolyticus challenge were evaluated. The results indicate that dietary LMW-CS supplementation improved growth performance and feed utilization, with LMW-CS0.2 showing significantly higher final weight, total weight gain, and average daily gain than the control group (p < 0.05). Antioxidant assays showed that LMW-CS reduced malondialdehyde levels and increased reduced glutathione, nitric oxide, glutathione reductase, catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase activities in both plasma and hepatopancreas (p < 0.05). Lysozyme activity was significantly enhanced, particularly in the LMW-CS0.4 and HMW-CS0.4 groups (p < 0.05). Gene expression analysis revealed upregulation of genes associated with growth regulation, antimicrobial defense, pathogen recognition, and prophenoloxidase activation, including igf2, cstn, lgbp, lyz, and propo2. Gut microbiota profiling showed that chitosan supplementation altered bacterial community composition, reduced the relative abundance of some Vibrio-associated taxa, and descriptively lowered predicted pathogenic and stress-tolerant bacterial phenotypes. Following the Vibrio parahaemolyticus challenge, shrimp fed LMW-CS0.4 showed the lowest bacterial load and highest survival rate, indicating improved disease resistance (p < 0.05). Overall, synergistically degraded LMW-CS enhanced growth, redox balance, innate immune competence, gut microbial structure, and resistance to V. parahaemolyticus, supporting its potential as an antibiotic-free functional feed additive for sustainable shrimp aquaculture. Full article

(This article belongs to the Special Issue Antioxidants and Aquaculture: A Synergistic Approach for Sustainable Aquatic Production—2nd Edition)

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19 pages, 12372 KB

Open AccessArticle

Discovery and Preclinical Characterization of NE-2-6 as a Potent Thyroid Peroxidase Inhibitor with Antithyroid Activity

by Min-Gyu Lee, Suzie Kang, Hyun-Jun Kang and Cheol-Won Yun

Antioxidants 2026, 15(8), 967; https://doi.org/10.3390/antiox15080967 - 4 Aug 2026

Abstract

Graves’ disease is an autoimmune hyperthyroid disorder in which thyroid peroxidase (TPO) plays a central role in excessive thyroid hormone production. However, current TPO-targeting drugs, such as propylthiouracil, have limited selectivity and can cause serious adverse effects. In this study, we established an [...] Read more.

Graves’ disease is an autoimmune hyperthyroid disorder in which thyroid peroxidase (TPO) plays a central role in excessive thyroid hormone production. However, current TPO-targeting drugs, such as propylthiouracil, have limited selectivity and can cause serious adverse effects. In this study, we established an integrated discovery pipeline to identify and optimize novel small-molecule TPO inhibitors. The pipeline began with high-throughput screening of approximately 7000 compounds from the KRICT chemical library for peroxidase inhibition, followed by cytotoxicity filtering and iterative medicinal chemistry to generate NE-2 derivatives. Lead compounds (NE-2-6, NE-2-7, and NE-2-8) were evaluated using enzymatic assays, selectivity profiling against myeloperoxidase (MPO) and lactoperoxidase (LPO), molecular docking, plasma pharmacokinetic profiling, and in vivo antithyroid pharmacodynamic testing in an Ad-TSHR289-induced thyroid hyperfunction model. NE-2-6 exhibited potent TPO inhibitory activity and relative selectivity within the tested peroxidase panel. UV–visible spectral scanning and H₂O₂-dependent inhibition assays suggested that NE-2-6 perturbs the heme-associated catalytic environment of TPO; however, these data do not establish a definitive binding mode or kinetic inhibition mechanism. In the Ad-TSHR289-induced thyroid hyperfunction model, NE-2-6 reduced serum T4 levels, supporting antithyroid pharmacodynamic activity. Because autoimmune endpoints and dose-matched PK–PD relationships were not fully assessed, the findings should be interpreted as preliminary preclinical evidence supporting further evaluation of NE-2-6 as a TPO-targeting antithyroid candidate. Full article

(This article belongs to the Special Issue Advances in Peroxiredoxin Biology)

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14 pages, 930 KB

Open AccessArticle

Keratinocytes with DNA Aberration Induced by UVB Become Susceptible to Ferroptosis

by Yuliya D. Smirnova, Philipp Sabler, Adelheid Weidinger, Johannes Grillari, Peter Dungel and Andrey V. Kozlov

Antioxidants 2026, 15(8), 966; https://doi.org/10.3390/antiox15080966 - 3 Aug 2026

Abstract

Keratinocytes are key epidermal cells that are highly susceptible to ultraviolet (UV)-induced damage, which can lead to DNA mutations and the development of malignancies. In parallel, UV radiation induces lipid peroxidation (LPO), potentially facilitating the activation of ferroptosis, a form of programmed cell [...] Read more.

Keratinocytes are key epidermal cells that are highly susceptible to ultraviolet (UV)-induced damage, which can lead to DNA mutations and the development of malignancies. In parallel, UV radiation induces lipid peroxidation (LPO), potentially facilitating the activation of ferroptosis, a form of programmed cell death. We hypothesized that UV-mediated DNA damage, resulting in the formation of cyclobutane pyrimidine dimers (CPDs), occurs preferentially in cells with elevated LPO levels, and that mild induction of ferroptosis in proliferating keratinocytes selectively eliminates cells with high CPD levels. A human keratinocyte cell line was exposed to UVB radiation and subsequently treated with the ferroptosis inducers RSL3 and erastin. Cell death was assessed using LDH analysis, LPO was measured using the fluorescent probe BODIPY™ 581/591 C11, and CPD formation was quantified by ELISA. Using different doses of UVB, we confirmed UVB irradiation simultaneously increases the cell death rate and LPO and CPDs levels in proliferating keratinocytes. Mild induction of ferroptosis in these cells led to a slight increase in the cell death rate and simultaneously to a drastic reduction in CPD levels, suggesting that there is a specific pool of cells predominantly susceptible to UVB in terms of DNA damage and LPO induction. Our findings support our hypothesis that induction of ferroptosis in proliferating keratinocytes exposed to UVB radiation preferentially eliminates cells with elevated CPD levels and may therefore serve as a protective mechanism against UV-induced carcinogenesis. Full article

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

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28 pages, 6733 KB

Open AccessReview

The Dark Side of Antioxidants: When Scavenging ROS Undermines Plant Stress Acclimation

by Panqi Qiu, Ziwei Chu and Yurong Xie

Antioxidants 2026, 15(8), 965; https://doi.org/10.3390/antiox15080965 - 2 Aug 2026

Abstract

Reactive oxygen species (ROS) exert dual biological functions in plants. Though they form toxic byproducts of aerobic metabolism, ROS also serve as indispensable secondary messengers that orchestrate stress acclimation programs. For decades, plant physiologists operated under a pervasive assumption that constitutive and non-compartmentalized [...] Read more.

Reactive oxygen species (ROS) exert dual biological functions in plants. Though they form toxic byproducts of aerobic metabolism, ROS also serve as indispensable secondary messengers that orchestrate stress acclimation programs. For decades, plant physiologists operated under a pervasive assumption that constitutive and non-compartmentalized upregulation of antioxidant capacity would universally enhance abiotic stress tolerance. This long-standing dogma has now been thoroughly overturned. A growing body of evidence shows that sustained, global high antioxidant activity often impairs adaptation rather than helping it. In this review, we replace the simplistic “more antioxidants equal better tolerance” framework with a dynamic model of cellular redox homeostasis. We dissect three interconnected mechanisms though which unrestrained ROS scavenging generates deleterious phenotypic outcomes. First, indiscriminate clearance blunts transient ROS pulses and propagating ROS waves, the core signaling events acquired to trigger systemic acquired acclimation (SAA). Second, continuous antioxidant biosynthesis drains finite carbon skeletons, NADPH, and ATP pools, exacerbating evolutionary growth-defense resource trade-offs. Third, non-specific bulk ROS scavenging erases compartment-specific organellar retrograde signals, which rely on tightly controlled spatial and temporal ROS fluctuations. We concurrently define physiological boundary conditions where robust antioxidant activity remains vital for plant survival under extreme stress. Rather than advocating for the complete suppression of ROS detoxification, our analysis advocates context-dependent fine-tuning of redox signaling networks. We also summarize emerging precision redox monitoring and genetic engineering tools, and outline translational breeding pipelines to develop climate-resilient crops that balance stress survival and yield stability. This work delivers novel conceptual perspectives to advance fundamental plant redox biology. Full article

(This article belongs to the Special Issue Advances in Plant Redox Biology Research)

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20 pages, 6271 KB

Open AccessReview

Structure-Guided Design of Planarized Catechin Derivatives: Enhancing Antioxidant and Multifaceted Biological Activities for Therapeutic Applications

by Kiyoshi Fukuhara, Ikuo Nakanishi, Hiromu Ito, Wakana Shimizu, Yoshimi Shoji, Kei Ohkubo, Masao Morita, Sakurako Okada and Akiko Ohno

Antioxidants 2026, 15(8), 964; https://doi.org/10.3390/antiox15080964 - 1 Aug 2026

Abstract

Oxidative stress is a major driver of chronic disease, making natural polyphenols attractive scaffolds for modulating inflammation, proteostasis, and cell fate. However, green-tea catechins possess a twisted, conformationally flexible flavan-3-ol framework that limits π-conjugation, phenoxyl-radical stabilization, and productive interactions with biological targets. This [...] Read more.

Oxidative stress is a major driver of chronic disease, making natural polyphenols attractive scaffolds for modulating inflammation, proteostasis, and cell fate. However, green-tea catechins possess a twisted, conformationally flexible flavan-3-ol framework that limits π-conjugation, phenoxyl-radical stabilization, and productive interactions with biological targets. This review presents a structure-based framework in which conformational planarization serves as a strategy for functional amplification. Preorganization of the A/C–B inter-ring bond into a nearly coplanar arrangement reduces the conformational entropy penalty (−TΔS) upon binding or reaction while extending conjugation, strengthening π–π interactions, and facilitating redox reactions. This review highlights planarized catechin (PCat) architectures, including PCat–DTPA (a lesion-activated metal-responsive antioxidant), PCat–TrOH (a self-regenerating antioxidant network), procyanidin B3–PCat hybrids, and a planar silybin analog, illustrating how planarization and multivalent recognition enhance ROS regulation, inhibit amyloid-β aggregation and neurotoxicity, and suppress cancer cell phenotypes. Collectively, these studies establish PCat as a modular platform for the mechanism-informed design of disease-tailored phenolic antioxidants. Full article

(This article belongs to the Special Issue Phenolics as Antioxidant Agents—2nd Edition)

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16 pages, 3153 KB

Open AccessArticle

Protein Disulfide Isomerase A6 (PDIA6) Restrains Heat-Induced Oxidative Damage in Haemocytes of the Pacific Oyster (Crassostrea gigas)

by Pengcheng Sun, Ming Li, Peng Li, Yang Ma, Lei Gao, Xueshu Zhang, Lingling Wang and Linsheng Song

Antioxidants 2026, 15(8), 963; https://doi.org/10.3390/antiox15080963 - 1 Aug 2026

Abstract

Heat stress causes severe oxidative damage and immune cell death in marine bivalves, but its upstream regulators remain unclear. This study identified regulators linking heat stress to oxidative damage in Pacific oyster haemocytes. Under 30 °C exposure, the apoptosis rate of oyster haemocytes [...] Read more.

Heat stress causes severe oxidative damage and immune cell death in marine bivalves, but its upstream regulators remain unclear. This study identified regulators linking heat stress to oxidative damage in Pacific oyster haemocytes. Under 30 °C exposure, the apoptosis rate of oyster haemocytes increased from ~4.54% to 17.40% at 24 h, accompanied by elevated ROS, malondialdehyde, and lipid hydroperoxide and reduced SOD activity. GSEA and protein interaction analysis of the haemocyte transcriptome pinpointed protein disulfide isomerase A6 (CgPDIA6) as the hub gene linking endoplasmic reticulum stress, apoptosis, and oxidative stress. Single-cell in silico knockout placed CgPDIA6 at the head of a coupled SOD–peroxiredoxin relay (CgSOD1, CgSOD2, CgPRDX6) and shifted haemocytes toward a stress-activated state. This prediction was confirmed by RNAi knockdown, in which silencing CgPDIA6 aggravated heat-induced oxidative injury, reduced the expression of antioxidant-related genes (CgSOD1, CgSOD2, and CgPRDX6), and further suppressed SOD activity. Molecular dynamics simulations showed that heat destabilized its catalytic thioredoxin domains, compromising its protective function. These results demonstrate that CgPDIA6 protects haemocytes against heat-induced oxidative damage by sustaining antioxidant enzyme activity, providing insights into redox regulation and heat adaptation in mollusks. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defenses in Aquatic Animals)

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25 pages, 7256 KB

Open AccessArticle

Starvation Exacerbates Cold-Induced Synergistic Hepatic Injury in Pelteobagrus vachelli via Gut–Liver Axis Disruption and Ferroptosis-Related Metabolic Reprogramming

by Amei Liu, Libo Yang, Yuting Hu, Huaxing Zhou, Huan Wang and Guoqing Duan

Antioxidants 2026, 15(8), 962; https://doi.org/10.3390/antiox15080962 - 31 Jul 2026

Abstract

Overwintering represents a critical bottleneck for farmed fish, during which low temperature and starvation stress frequently co-occur, yet their synergistic effects on fish health remain poorly understood. Here, we exposed Pelteobagrus vachelli, a cold-sensitive freshwater species, to four conditions for 10 days: [...] Read more.

Overwintering represents a critical bottleneck for farmed fish, during which low temperature and starvation stress frequently co-occur, yet their synergistic effects on fish health remain poorly understood. Here, we exposed Pelteobagrus vachelli, a cold-sensitive freshwater species, to four conditions for 10 days: control (25 °C, feeding), starvation alone (25 °C, starvation), cold alone (11 °C, feeding), and combined cold–starvation (11 °C, starvation). Hepatic histopathology, antioxidant and liver function indices, gut microbiota (16S rRNA sequencing), and untargeted metabolomics (LC–MS) were integrated to elucidate gut–liver axis mechanisms underlying synergistic injury. Combined stress synergistically aggravated liver injury, as evidenced by hepatocellular vacuolation and necrosis, elevated aspartate aminotransferase (AST), alanine transaminase (ALT), malondialdehyde (MDA), and suppressed total superoxide dismutase (T–SOD), glutathione (GSH), catalase (CAT), and total antioxidant capacity (T–AOC). Two-way ANOVA confirmed significant interactive effects between cold and starvation stress (p < 0.05). Multi-omics revealed that dual stress uniquely activated multiple cell death pathways (FoxO, autophagy, ferroptosis, apoptosis), with marked oxidative phosphorylation (OXPHOS) activation and glutathione depletion—a signature absent under single stressors. Gut microbiota restructuring showed beneficial commensals (Cetobacterium, Prevotella, Lactobacillus) depleted and opportunistic pathogens (Plesiomonas, Pseudomonas, Flavobacterium) enriched, with Plesiomonas identified as the dominant biomarker (LDA score = 5.32). Integrative networks identified these pathogenic genera as hubs linking metabolic dysregulation to liver damage. Collectively, combined cold–starvation induces synergistic liver injury via gut–liver axis disruption, driving metabolic reprogramming and oxidative damage. These findings provide candidate biomarkers for overwintering stress monitoring and inform management strategies to mitigate cold–starvation-induced hepatic injury in aquaculture. Full article

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