Antioxidants

24 pages, 6234 KB

Open AccessArticle

Melatonin Ameliorates decaBDE-Induced Autism-Relevant Behaviors Through Promoting SIRT1/SIRT3/FOXO3a-Dependent Mitochondrial Quality Control

by Lu Gao, Jinghua Shen, Jingjing Gao, Tian Li, Dongying Yan, Xinning Zeng, Jia Meng, Hong Li, Dawei Chen and Jie Wu

Antioxidants 2026, 15(3), 405; https://doi.org/10.3390/antiox15030405 - 23 Mar 2026

Viewed by 477

Abstract

The etiology of autism spectrum disorder (ASD) implicates genetic predispositions and environmental chemicals, such as polybrominated diphenyl ethers (PBDEs). We aimed to identify whether mitochondrial quality control (MQC) was involved in ASD-relevant behavioral changes induced by decabromodiphenyl ether (deca-BDE, BDE-209) and the alleviation [...] Read more.

The etiology of autism spectrum disorder (ASD) implicates genetic predispositions and environmental chemicals, such as polybrominated diphenyl ethers (PBDEs). We aimed to identify whether mitochondrial quality control (MQC) was involved in ASD-relevant behavioral changes induced by decabromodiphenyl ether (deca-BDE, BDE-209) and the alleviation by melatonin. Pregnant rats exposed to BDE-209 (50 mg/kg i.g.) were administrated melatonin through drinking water (0.2 mg/mL) during gestation and lactation. Behavioral assessments integrated open-field test, three-chamber social test, and Morris water maze; mitochondrial detections took transmission electron microscopy, immunofluorescence, and homeostasis together; hippocampal molecular network was identified through transcriptomics profiles, combining dendritic morphology analysis after Golgi-Cox staining. Melatonin supplementation attenuated BDE-209-reduced social and cognitive ability, accompanied by improvements in hippocampal synaptic plasticity (dendritic spines, PSD95, SNAP25). Mitochondrial dysfunctions, shown as decreases in complex IV activity, ATP content, and mtDNA copies, plus redox imbalance (ROS/SOD2) and resultant mitochondrial membrane potential disruption and apoptosis, together with fusion/fission dynamic (MFN2/DRP1), biogenesis (SIRT1-PGC1α-TFAM), and mitophagy (SIRT3-FOXO3-PINK1) suppression, were reversed by melatonin partially through SIRT1 (Sirtuin-1)-dependent pathways, as these protections were abolished by inhibitor EX527. This study highlighted the SIRT1–SIRT3 axis in MQC and behavioral effects, providing novel intervention for PBDEs’ neurodevelopmental impairment. Full article

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

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18 pages, 3742 KB

Open AccessArticle

Neuroprotective Effects of Molecular Hydrogen via Oxidative Stress and Neuroinflammation Regulation in a 5xFAD Mouse Model

by Chaodeng Mo, Johny Bajgai, Md. Habibur Rahman, Hui Ma, Thu Thao Pham, Haiyang Zhang, Buchan Cao, Eun-Sook Jeong, Cheol-Su Kim and Kyu-Jae Lee

Antioxidants 2026, 15(3), 404; https://doi.org/10.3390/antiox15030404 - 23 Mar 2026

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Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which amyloid-beta (Aβ) accumulation, oxidative stress (OS), and chronic inflammation drive synaptic dysfunction and cognitive decline. Molecular hydrogen (H₂) has emerged as a candidate neuroprotective gas with selective antioxidant and anti-inflammatory properties, [...] Read more.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which amyloid-beta (Aβ) accumulation, oxidative stress (OS), and chronic inflammation drive synaptic dysfunction and cognitive decline. Molecular hydrogen (H₂) has emerged as a candidate neuroprotective gas with selective antioxidant and anti-inflammatory properties, although its efficacy in amyloid-driven pathology remains incompletely defined. In this study, 5xFAD transgenic mice harboring human amyloid precursor protein (APP) and presenilin-1 (PSEN1) mutations and age-matched C57BL/6 wild-type mice were exposed to 2% H₂ by inhalation for 1 h/day over 4 weeks. H₂ inhalation reduced hippocampal reactive oxygen species (ROS), increased systemic catalase activity, and enhanced hippocampal ATP levels. In serum, H₂ decreased tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β, restored IL-10, and partially normalized IL-13, shifting the peripheral environment toward a less pro-inflammatory profile. In the hippocampus, H₂ upregulated nuclear factor erythroid 2-related factor 2 (NRF2), attenuated nuclear factor kappa B (NF-κB) activation, reduced the BAX/BCL-2 ratio, preserved neuronal nuclei (NEUN) expression, and decreased hippocampal Aβ42 burden. Collectively, these findings indicate that H₂ inhalation confers multi-faceted neuroprotection in 5xFAD mice by restoring redox homeostasis, suppressing inflammation, improving mitochondrial function, and limiting Aβ accumulation. Full article

(This article belongs to the Special Issue Innovative Approaches to Neuroprotective Strategies: Targeting Oxidative Stress in Neurodegenerative Disorders)

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27 pages, 8189 KB

Open AccessArticle

Phenolamide Extract of Apricot Bee Pollen Alleviates DSS-Induced Ulcerative Colitis in Mice by Reducing Oxidative Stress, Modulating Inflammation, and Regulating Gut Microbiota

by Wei Liu, Rui Liu, Yihang Han, Xin Chen and Qun Lu

Antioxidants 2026, 15(3), 403; https://doi.org/10.3390/antiox15030403 - 23 Mar 2026

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Abstract

Phenolamides in bee pollen exhibit notable bioactivities, such as antioxidant, anti-inflammatory, and antimicrobial effects. Ulcerative colitis (UC) is a prevalent intestinal disorder, while the potential effects of phenolamides on UC remain unclear. This study aims to investigate the effects and mechanisms of phenolamide [...] Read more.

Phenolamides in bee pollen exhibit notable bioactivities, such as antioxidant, anti-inflammatory, and antimicrobial effects. Ulcerative colitis (UC) is a prevalent intestinal disorder, while the potential effects of phenolamides on UC remain unclear. This study aims to investigate the effects and mechanisms of phenolamide extract (PAE) from apricot bee pollen on dextran sulfate sodium (DSS)-induced UC in mice. Firstly, we analyzed the main compounds of PAE. Mice were treated with PAE (100, 200, and 400 mg/kg bw) both during the 7 days preceding 2.5% DSS induction and throughout the induction period (7 days). The results show that the primary compounds of PAE were isomers of tri-p-coumaroyl spermidine (97.78 ± 2.76%). A biochemical analysis showed that PAE decreased the levels of pro-inflammatory cytokines and increased the activities of antioxidant enzymes. Regarding the gut microbiota, PAE reduced the Bacillota/Bacteroidota ratio. Additionally, PAE elevated beneficial bacteria, including norank_f_Muribaculaceae, norank_o_Clostridia_UCG-014, and Lachnospiraceae_NK4A136_group, while reducing harmful bacteria, including Escherichia-Shigella, Clostridium, and Romboutsia. A quantitative analysis of short-chain fatty acids (SCFAs) demonstrated that PAE intervention promotes the biosynthesis of SCFAs in UC mice. This study first demonstrates that PAE attenuates DSS-induced colitis by modulating gut microbiota and SCFAs, suggesting its potential as a functional dietary supplement for colitis. Full article

(This article belongs to the Special Issue Antioxidant and Antimicrobial Activity of Honey Bee Products—3rd Edition)

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24 pages, 4177 KB

Open AccessArticle

NMR-Guided Discovery of Luvunga D: A Novel Propellane-Type Limonoid from Luvunga scandens That Functions as a Non-Classical Ferroptosis Inhibitor

by Bien-Thuy Bui Nguyen, Hoang-Minh Bui, Chia-Ching Liaw, Quoc-Dung Tran Huynh, Chih-Hua Chao, Duy-Hien Tran, I-Wen Lo, Thanh-Hoa Vo, Andreas Koeberle, Solveigh C. Koeberle, Mei-Chuan Chen and Yu-Chi Lin

Antioxidants 2026, 15(3), 402; https://doi.org/10.3390/antiox15030402 - 23 Mar 2026

Viewed by 467

Abstract

Recent phytochemical investigations have demonstrated that Luvunga scandens is a rich source of structurally diverse secondary metabolites; however, its potential antioxidant-active constituents and their underlying mechanisms remain largely unexplored. In this study, an NMR-guided fractionation strategy applied to the rhizomes and leaves of [...] Read more.

Recent phytochemical investigations have demonstrated that Luvunga scandens is a rich source of structurally diverse secondary metabolites; however, its potential antioxidant-active constituents and their underlying mechanisms remain largely unexplored. In this study, an NMR-guided fractionation strategy applied to the rhizomes and leaves of L. scandens led to the isolation of ten limonoids, including three new compounds, Luvungas B–D (3, 4, and 8). Their structures and absolute configurations were determined through extensive spectroscopic analysis, X-ray diffraction, and ECD calculations. Based on the isolated analogues, a biosynthetic pathway is proposed, featuring the metabolic bifurcation of a key acyclic intermediate into the isoobacunoic acid and propellane-type lineages. Biological evaluation revealed that 8 inhibits RSL3-induced ferroptosis in HepaRG liver cells with an EC₅₀ of 16.1 µM. Mechanistic studies demonstrated that, unlike classical antioxidants, compound 8 mitigates lipid peroxidation without exhibiting direct radical-scavenging or iron-chelating activities. These findings suggest that 8 suppresses ferroptosis via non-canonical mechanisms. Full article

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19 pages, 2778 KB

Open AccessArticle

Untargeted Metabolomics Reveals Color-Dependent Nutritional Variation in Raisins: Insights into Composition and Antioxidant Capacity

by Chuan Zhang, Shanwu Lyu and Vivek Yadav

Antioxidants 2026, 15(3), 401; https://doi.org/10.3390/antiox15030401 - 23 Mar 2026

Viewed by 530

Abstract

Raisins come from dried Vitis vinifera L. grapes. They are consumed worldwide, and their shape, color, texture, and taste largely determine consumer preference and market success. Consumers often select raisins based on visual appeal—namely color—without insight into how this relates to nutritional quality. [...] Read more.

Raisins come from dried Vitis vinifera L. grapes. They are consumed worldwide, and their shape, color, texture, and taste largely determine consumer preference and market success. Consumers often select raisins based on visual appeal—namely color—without insight into how this relates to nutritional quality. Therefore, this study evaluated raisins of different colors based on non-targeted metabolomics to reveal the nutritional differences among differently colored raisins and to measure the differences in antioxidant capacity. Compared with green raisins (‘Sultanina’), 377–381 differential metabolites were identified in other colored varieties. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these metabolites were enriched in pathways such as ‘biosynthesis of other secondary metabolites’ and ‘amino acid metabolism’. The comparison of the antioxidant capacity of raisins of different colors shows that the darker the color of the raisins, the stronger their antioxidant capacity. Correlation analysis between total antioxidant capacity and 14 differential metabolites showed a significant positive correlation. Notably, syringetin levels in black raisins (‘Blackcurrant’ and ‘Sweet Sapphire’) were substantially higher—148.31 and 515.94 times greater, respectively—than in green raisins (‘Sultanina’). This elevated syringetin content may significantly contribute to the enhanced antioxidant capacity of black raisins. Furthermore, based on the positive ion mode, the relative contents of 24 and 12 differential metabolites were relatively high in green and red raisins, respectively. The negative ion model identified that 19 and 4 differential metabolites had relatively high contents in green and red raisins. These metabolites may be linked to the unique health benefits of red and green raisins. This study provides valuable insights for consumers selecting raisins based on health needs and for companies developing raisin-based health products. Full article

(This article belongs to the Special Issue Antioxidant Activity of Grape and Grape By-Products)

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5 pages, 205 KB

Open AccessEditorial

Oxidative Stress Is a Double-Edged Sword for the Neonate

by Ru-Jeng Teng

Antioxidants 2026, 15(3), 400; https://doi.org/10.3390/antiox15030400 - 23 Mar 2026

Viewed by 417

Abstract

Fetal oxygen tension is low, with an umbilical venous pO₂ of 30–37 mm Hg in the third trimester, while arterial pO₂ is around 20 mm Hg [...] Full article

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

28 pages, 2045 KB

Open AccessReview

Mitochondrial Homeostasis in Diabetic Cardiomyopathy: From Dysfunction to Therapeutic Strategies

by Yafei Huang, Wenyu Zou, Xindi Jiang, Jing Cheng and Jia Zheng

Antioxidants 2026, 15(3), 399; https://doi.org/10.3390/antiox15030399 - 22 Mar 2026

Viewed by 644

Abstract

Diabetic cardiomyopathy is a specific form of heart dysfunction that occurs in diabetic patients independent of other cardiomyopathies such as coronary artery disease. It significantly contributes to heart failure and mortality in this population. The pathogenesis of diabetic cardiomyopathy mainly includes oxidative stress, [...] Read more.

Diabetic cardiomyopathy is a specific form of heart dysfunction that occurs in diabetic patients independent of other cardiomyopathies such as coronary artery disease. It significantly contributes to heart failure and mortality in this population. The pathogenesis of diabetic cardiomyopathy mainly includes oxidative stress, inflammatory response, apoptosis and disrupted mitochondrial homeostasis. Mitochondrial homeostasis, encompassing mitochondrial dynamics, mitochondrial oxidative metabolism and mitophagy, is regulated by a variety of signaling pathways and plays a pivotal role in maintaining the normal function of cardiomyocytes. At present, the exact mechanisms underlying diabetic cardiomyopathy pathogenesis remain unclear, and effective prevention and treatment methods are lacking. This review therefore expounds the pathogenesis of diabetic cardiomyopathy from the perspective of mitochondrial homeostasis, providing new approaches to clinical management. Full article

(This article belongs to the Topic Cell Signaling and Redox Biology: From Molecular Mechanisms to Therapeutic Applications)

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21 pages, 4983 KB

Open AccessArticle

Echinophora tenuifolia L. subsp. sibthorpiana Modulates Stress Response and Mitochondrial Quality Under Glucose Stress in Caenorhabditis elegans

by Monika N. Todorova, Stanislav Dyankov, Martina S. Savova, Velislava Todorova, Milen I. Georgiev and Stanislava Ivanova

Antioxidants 2026, 15(3), 398; https://doi.org/10.3390/antiox15030398 - 21 Mar 2026

Viewed by 457

Abstract

Echinophora tenuifolia L. subsp. sibthorpiana (E. tenuifolia), Apiaceae, is a traditional medicinal and culinary plant, yet its phytochemical composition and biological activity have not been fully investigated. The aim of the present study was to evaluate the chemical profile of [...] Read more.

Echinophora tenuifolia L. subsp. sibthorpiana (E. tenuifolia), Apiaceae, is a traditional medicinal and culinary plant, yet its phytochemical composition and biological activity have not been fully investigated. The aim of the present study was to evaluate the chemical profile of E. tenuifolia aerial parts extract and to assess its effects on healthspan and metabolic regulation in Caenorhabditis elegans (C. elegans). The characterization of the extract by NMR spectroscopy and HPLC-PDA revealed the presence of secondary metabolites, with rutin being the most abundant phenolic compound identified in the extract, alongside the presence of chlorogenic acid, ferulic acid, rosmarinic acid, caffeic acid, p-coumaric acid, and salicylic acid. The extract supplementation enhanced early-life locomotor activity and chemosensory behavior without affecting the lifespan. It also significantly improved thermotolerance and resistance to oxidative stress in C. elegans. Additionally, in a glucose-induced obesity model, the extract reduced lipid accumulation and triglyceride levels and restored glucose-impaired mitochondrial membrane potential. The extract dose-dependently alleviated glucose-induced endoplasmic reticulum and mitochondrial stress by suppressing the expression of both essential chaperones: endoplasmic reticulum chaperone BiP homolog hsp-4 and heat shock protein hsp-6. These findings indicate that E. tenuifolia extract possesses potential beneficial effects on metabolic and mitochondrial health under glucose-induced stress conditions. These observations are likely mediated by the synergistic phenolic composition of the extract, and reveal E. tenuifolia as a promising source of bioactive compounds relevant to aging and preventive strategies for cardiometabolic health. Full article

(This article belongs to the Special Issue Natural Antioxidants in Functional Foods)

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48 pages, 4538 KB

Open AccessReview

Beyond Sensory Properties: Molecular Interactions of Antioxidant Flavour-Active Polyphenols Across the Food-Oral-Gut Axis

by Inês M. Ferreira, Sara A. Martins, Leonor Gonçalves, Mónica Jesus, Elsa Brandão and Susana Soares

Antioxidants 2026, 15(3), 397; https://doi.org/10.3390/antiox15030397 - 21 Mar 2026

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Abstract

Dietary antioxidants are widely valued for their potential health benefits, but incorporating them into functional foods is not straightforward. Polyphenols are among the most abundant and important antioxidants in foods, and this review focuses on them because the same structural features linked to [...] Read more.

Dietary antioxidants are widely valued for their potential health benefits, but incorporating them into functional foods is not straightforward. Polyphenols are among the most abundant and important antioxidants in foods, and this review focuses on them because the same structural features linked to their health-promoting effects can also cause pronounced bitterness and astringency, ultimately limiting consumer acceptance. This review examines how these challenges are interconnected across three levels: food matrix interactions, bioavailability, and consumer psychobiology. We describe how non-covalent interactions between polyphenols, proteins, and polysaccharides can have both positive and negative effects. While these interactions may alter oral lubrication and flavour release, they also protect highly reactive bioactive compounds from gastric degradation. Furthermore, we broaden the concept of bioavailability by exploring the microbiota-mediated “colonic rescue” of polyphenols that are not released during earlier digestion. We also highlight the role of extraoral bitter taste receptors (TAS2Rs) along the gastrointestinal (GI) tract. Activation of these receptors during digestion can trigger relevant metabolic and endocrine responses, indicating that systemic absorption is not the only pathway to bioactivity. Finally, we connect these mechanisms to individual differences in food acceptance, showing that genetic factors (e.g., TAS2R38 and the salivary proteome) and psychological traits (such as neophobia and reward sensitivity) can shape rejection or flavour-nutrient learning. Overall, the successful development of functional foods will require a “sensory-by-design” approach. This strategy utilises matrix interactions strategically to improve both consumer acceptance and physiological efficacy. Full article

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

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22 pages, 5827 KB

Open AccessArticle

Baohuoside I Combated Cryptocaryon irritans via Dual Targeting of Parasite Apoptosis and Host Defense Enhancement

by Yan Lin, Li Huang, Yuan Yuan, Zhenyu Lin, Lei Huang, Tianxing Lin, Anqi Lin, Yuqi Zhu, Shoujie Jiang, Ying Huang, Yuqian Zheng, Rongjing Cai and Chengzhen Gu

Antioxidants 2026, 15(3), 396; https://doi.org/10.3390/antiox15030396 - 21 Mar 2026

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Abstract

Cryptocaryon irritans Brown, 1951, a ciliated protozoan, is the pathogen of cryptocaryoniasis (white spot disease) in marine fish, causing substantial morbidity and mortality, particularly in tropical and subtropical regions. This is the first study to investigate the antiparasitic activity of baohuoside I, a [...] Read more.

Cryptocaryon irritans Brown, 1951, a ciliated protozoan, is the pathogen of cryptocaryoniasis (white spot disease) in marine fish, causing substantial morbidity and mortality, particularly in tropical and subtropical regions. This is the first study to investigate the antiparasitic activity of baohuoside I, a natural flavonoid isolated from Epimedium brevicornu Maxim., against C. irritans. In vitro exposure to baohuoside I suppressed theront viability and tomont hatching in a dose- and time-dependent manner, inducing an apoptosis-like death in both stages, characterized by ciliary detachment, mitochondrial disruption, nuclear condensation, and extensive vacuolization, as evidenced by transmission electron microscopy and Annexin V-FITC/PI staining. Further studies demonstrated that baohuoside I elevated the intracellular Ca²⁺ and reactive oxygen species levels in tomonts, indicating Ca²⁺ overload and oxidative stress. Transcriptomic analysis of infected Larimichthys crocea skin revealed that baohuoside I upregulated immune-related genes while downregulating pro-inflammatory genes, concurrently enhancing host serum acid phosphatase activity and mitigating oxidative stress in enzyme activity assays. In vivo trials showed that oral administration of baohuoside I reduced trophont attachment and improved fish survival. It did not exhibit hemolytic activity at concentrations effective against the parasites. Collectively, these findings elucidate a multi-target mechanism of baohuoside I, highlighting its potential as an eco-friendly therapeutic agent for cryptocaryoniasis control in marine aquaculture. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Sources with Antioxidant and Anti-Inflammatory Potential)

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23 pages, 4543 KB

Open AccessArticle

Microwave-Assisted Propolis Extract Attenuates Oxidative-Stress- and Replicative Senescence via NRF2 and Wnt/β-Catenin–TERT Activation in Human Dermal Fibroblasts

by Seoungwoo Shin, Youngsu Jang, Kyungeun Jeon, Ji Yun Kim, De-Hun Ryu, Eunae Cho, Hyerin Yeo, Nae Gyu Kang, Deokhoon Park and Eunsun Jung

Antioxidants 2026, 15(3), 395; https://doi.org/10.3390/antiox15030395 - 20 Mar 2026

Viewed by 576

Abstract

Skin aging is characterized by fibroblast senescence, extracellular matrix (ECM) degradation, and impaired wound healing, driven by oxidative stress and telomere dysfunction. Here, we investigated the anti-aging effects of a standardized microwave-assisted propolis extract (MAPE) in both H₂O₂-induced and [...] Read more.

Skin aging is characterized by fibroblast senescence, extracellular matrix (ECM) degradation, and impaired wound healing, driven by oxidative stress and telomere dysfunction. Here, we investigated the anti-aging effects of a standardized microwave-assisted propolis extract (MAPE) in both H₂O₂-induced and replicative senescence models of human dermal fibroblasts (HDFs). MAPE significantly reduced reactive oxygen species (ROS) accumulation and enhanced antioxidant gene expression (NQO1, GCLM), indicating activation of NRF2-dependent defense pathways. It suppressed senescence markers (CDKN2A, CDKN1A, IL6), decreased SA-β-gal activity, and attenuated inflammaging. Moreover, MAPE inhibited MMP1 expression, restored COL1A1, and improved fibroblast wound closure, thereby maintaining ECM homeostasis. Importantly, MAPE modulated Wnt/β-catenin signaling by upregulating WNT3A and LEF1 while suppressing DKK1, and increased TERT expression, suggesting involvement of telomerase-related regulatory pathways. These effects resembled those of CHIR99021, a canonical Wnt activator, while providing additional antioxidant protection. Together, our findings suggest that MAPE is a propolis-derived bioactive ingredient that counteracts fibroblast senescence through coordinated modulation of NRF2 and Wnt/β-catenin–TERT signaling pathways, supporting its potential as a cosmeceutical ingredient for mitigating skin aging. Full article

(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)

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23 pages, 4989 KB

Open AccessArticle

Effects of Fermented Longan Peel (Dimocarpus longan) on Growth Performance, Digestive Enzyme Activity, Intestinal Microstructure, Immune Response, and Gene Expression of Nile Tilapia (Oreochromis niloticus) Raised Under Biofloc System

by Supreya Wannavijit, Punika Ninyamasiri, Wanarsa Nonkrathok, Sudaporn Tongsiri, Phisit Seesuriyachan, Yuthana Phimolsiripol, Seyed Hossein Hoseinifar, Hien Van Doan and Marina Paolucci

Antioxidants 2026, 15(3), 394; https://doi.org/10.3390/antiox15030394 - 20 Mar 2026

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Abstract

The valorization of agricultural by-products as functional feed additives represents a promising strategy for sustainable aquaculture. This study evaluated the effects of dietary fermented longan peel (FLP), produced through enzymatic hydrolysis and Lactiplantibacillus plantarum fermentation, on growth performance, digestive physiology, gut morphology, innate [...] Read more.

The valorization of agricultural by-products as functional feed additives represents a promising strategy for sustainable aquaculture. This study evaluated the effects of dietary fermented longan peel (FLP), produced through enzymatic hydrolysis and Lactiplantibacillus plantarum fermentation, on growth performance, digestive physiology, gut morphology, innate immunity, and gene expression in Nile tilapia (Oreochromis niloticus) cultured under a biofloc system. Five experimental diets were formulated with graded FLP levels (0, 5, 10, 20, and 40 g kg⁻¹) and fed to fish for eight weeks. Growth indices, including final weight, weight gain, and specific growth rate, improved significantly in fish receiving 20 g kg⁻¹ FLP, following a strong quadratic response pattern. In vitro digestibility assays showed enhanced carbohydrate and protein digestibility, coinciding with increased intestinal amylase and protease activities. Histological analysis indicated that moderate FLP inclusion (10–20 g kg⁻¹) promoted villus height, crypt depth, and epithelial organization. Innate immune parameters, including lysozyme, peroxidase, and alternative complement activity, were markedly elevated in serum and mucus, particularly at 20–40 g kg⁻¹ after eight weeks. Gene expression profiling revealed significant up-regulation of growth-related (IGF-1, GH, NPY-α, Galanin), immune-related (TLR-7, TNF-α, NFκB), and antioxidant-related (hsp70, Keap-1, nrf-2, GST-α) genes in fish fed higher FLP levels, with responses plateauing beyond 20 g kg⁻¹. Overall, FLP supplementation at 20 g kg⁻¹ optimally enhanced growth, digestive efficiency, intestinal health, and innate immune status. These findings demonstrate the potential of fermented longan peel as a cost-effective, bioactive, and sustainable functional feed ingredient for tilapia and other warm-water aquaculture species. Full article

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

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19 pages, 4183 KB

Open AccessArticle

Quercetin Inhibits AKT Ser473 Phosphorylation and Disrupts AKT–Androgen Receptor Signaling in Castration-Resistant Prostate Cancer Cells

by Félix Duprat, Sebastián Azócar-Plaza, María Paz Castillo-Cáceres, Yerko Rivas, Javiera Sanzana-Rosas, Paolo Pampaloni, Gabriel Olivas-Henríquez, Jorge Toledo, Jhon López Villa, Romina Bertinat, Nery Jara, Alejandro Vallejos-Almirall, Alexis Salas and Iván González-Chavarría

Antioxidants 2026, 15(3), 393; https://doi.org/10.3390/antiox15030393 - 20 Mar 2026

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Abstract

The progression of prostate cancer to castration-resistant disease (CRPC) remains a clinical challenge in which oxidative stress intersects with the PI3K/AKT–androgen receptor (AR) axis. Quercetin (QRC) is a redox-active dietary flavonol, yet its mechanistic impact on CRPC is incompletely defined. Here, we tested [...] Read more.

The progression of prostate cancer to castration-resistant disease (CRPC) remains a clinical challenge in which oxidative stress intersects with the PI3K/AKT–androgen receptor (AR) axis. Quercetin (QRC) is a redox-active dietary flavonol, yet its mechanistic impact on CRPC is incompletely defined. Here, we tested whether QRC suppresses AR output by directly modulating AKT. C4-2B and 22Rv1 CRPC cell lines were treated with increasing QRC concentrations, with or without enzalutamide (Enz). Proliferation and viability were monitored by IncuCyte imaging and SYTOX Green incorporation. AKT phosphorylation (S473), AR phosphorylation (S210/213), AR abundance and localization, and prostate-specific antigen (PSA) secretion were assessed by immunoblotting, immunofluorescence, and dot blot, respectively. Docking and molecular dynamic simulations were performed to identify and evaluate a putative QRC-binding site on AKT. QRC produced a dose-dependent cytostatic effect (IC₅₀ 24.37 μM in C4-2B; 21.54 μM in 22Rv1) without marked cell death, reduced pAKT(S473) by up to 80%, decreased pAR(S210/213), and diminished nuclear AR and PSA secretion. Simulations suggested a putative druggable allosteric pocket in the AKT1 N-lobe, with G159 emerging as a potential anchor residue. Enz cotreatment with QRC did not produce additive effects, consistent with a model in which QRC acts upstream of ligand-driven AR activation and thereby limits the incremental benefit of AR antagonism under these conditions. These data support QRC as an AKT–AR axis modulator in CRPC and provide a target engagement framework beyond simple ROS scavenging. Full article

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

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26 pages, 18198 KB

Open AccessArticle

L-Selenomethionine Alleviates Cryo-Induced Ferroptosis Through the NRF2–SLC7A11–GPX4 Pathway, Improving Post-Thaw In Vitro Quality of Dairy Goat Spermatozoa

by Zi-Tao Jiang, Shun-Kai Yang, Xu-Dong Zhou, Xu Zhang, Zi-Tong Hu, Song-Mao Guo, Guo-Yu Zhang, Shuai-Qi Han, Fei Wen, Xiao-Xu Chen and Jian-Hong Hu

Antioxidants 2026, 15(3), 392; https://doi.org/10.3390/antiox15030392 - 20 Mar 2026

Viewed by 511

Abstract

Background: Cryopreservation induces oxidative stress, membrane disruption, and mitochondrial injury in spermatozoa, leading to impaired motility and fertility. Selenium, as an essential trace element, protects cells from oxidative damage through selenoproteins such as glutathione peroxidase 4 (GPX4), a critical enzyme that detoxifies lipid [...] Read more.

Background: Cryopreservation induces oxidative stress, membrane disruption, and mitochondrial injury in spermatozoa, leading to impaired motility and fertility. Selenium, as an essential trace element, protects cells from oxidative damage through selenoproteins such as glutathione peroxidase 4 (GPX4), a critical enzyme that detoxifies lipid hydroperoxides and inhibits ferroptosis. This study investigated whether supplementation with L-selenomethionine (L-SeMet), an organic selenium source with superior bioavailability and lower toxicity than inorganic forms, could alleviate cryo-induced sperm injury by suppressing ferroptosis. Methods & Results: Dairy goat sperm were cryopreserved with 0, 2, 4, 6, 8, 10 μM L-SeMet. Supplementation with 6 μM L-SeMet significantly improved motility, membrane and acrosome integrity, and mitochondrial membrane potential. Biochemical assays showed reduced iron, ROS, and MDA levels, alongside increased ATP, SOD, and GSH contents. Proteomic analysis identified 148 differentially expressed proteins, including up-regulation of GPX4, FTH1, VDAC2, and VDAC3—core ferroptosis regulators. Metabolomic profiling further revealed enrichment in unsaturated fatty acid biosynthesis, amino acid metabolism, and the TCA cycle, pathways closely linked to ferroptosis regulation. Transmission electron microscopy confirmed that L-SeMet preserved mitochondrial ultrastructure. Mechanistically, L-SeMet mirrored the ferroptosis inhibitor N-acetyl-L-cysteine and reversed RSL3-induced oxidative damage. Western blotting verified activation of the NRF2–SLC7A11–GPX4 antioxidant axis and inhibition of KEAP1 expression. Conclusions: Collectively, these findings demonstrate that L-SeMet protects spermatozoa from cryo-induced injury by stabilizing redox homeostasis, maintaining mitochondrial function, and inhibiting ferroptosis. The results highlight ferroptosis as a critical mechanism of sperm cryodamage and identify L-SeMet as a promising metabolic intervention to enhance post-thaw sperm quality and fertility. Full article

(This article belongs to the Special Issue Antioxidants and Oxidative Stress at the Crossroads of Autophagy and Ferroptosis)

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29 pages, 29045 KB

Open AccessArticle

Liproxstatin-1 Attenuates Retinal Ischemia–Reperfusion Injury by Suppressing EGR1-Mediated Ferroptosis

by Wei Huang, Yue Dong, Xuan Zhou, Huishan Lin, Jingwei Yao, Zhuoyi Wu, Weng Ian Tam, Yuheng Tan, Chengguo Zuo and Mingkai Lin

Antioxidants 2026, 15(3), 391; https://doi.org/10.3390/antiox15030391 - 19 Mar 2026

Viewed by 512

Abstract

Retinal ischemia–reperfusion (I/R) injury results in irreversible vision loss largely through retinal ganglion cell (RGC) death, with ferroptosis being a key mechanism. This study evaluated the therapeutic potential of the ferroptosis inhibitor Liproxstatin-1 (Lip-1) and deciphered its underlying mechanism. Using a mouse retinal [...] Read more.

Retinal ischemia–reperfusion (I/R) injury results in irreversible vision loss largely through retinal ganglion cell (RGC) death, with ferroptosis being a key mechanism. This study evaluated the therapeutic potential of the ferroptosis inhibitor Liproxstatin-1 (Lip-1) and deciphered its underlying mechanism. Using a mouse retinal I/R model and primary RGC cultures subjected to oxygen–glucose deprivation/reoxygenation (OGD/R), we demonstrated that Lip-1 effectively inhibits ferroptosis. Lip-1 treatment preserved retinal architecture (as assessed by H&E staining and SD-OCT) and partially restored visual function (as measured by electroretinography). Integrated molecular analyses—including immunofluorescence, Western blotting, and RNA sequencing—showed that Lip-1 downregulates early growth response 1 (EGR1), thereby inhibiting p53 and consequently restoring solute carrier family 7 member 11 (xCT) expression. Crucially, lentivirus-mediated EGR1 knockdown attenuated OGD/R-induced ferroptosis, confirming its pivotal role. Our work defines a coherent EGR1–p53–xCT signaling axis driving ferroptosis in retinal I/R injury and identifies Lip-1 as a neuroprotective agent targeting this pathway. These findings establish a druggable ferroptotic cascade and provide a mechanistic rationale for targeting EGR1 in the treatment of ischemic retinopathies. Full article

(This article belongs to the Section ROS, RNS and RSS)

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25 pages, 6587 KB

Open AccessArticle

Spirulina Preconditioning Attenuates Ischemia–Reperfusion Injury in a Steatotic Rat Liver Model

by Eya Baily, Kamel Mhalhel, Soumaya Ben Ahmed, Mohamed Amine Zaouali, Giuseppe Montalbano, Ines Naouar, Antonino Germanà and Hassen Ben Abdennebi

Antioxidants 2026, 15(3), 390; https://doi.org/10.3390/antiox15030390 - 19 Mar 2026

Viewed by 579

Abstract

Ischemia and reperfusion (IR) injuries may produce deleterious effects on hepatic tissue after liver surgery and transplantation. The consequences of IR are more evident in pathological steatotic livers. Spirulina (Arthrospira platensis) is known for its potential to modulate inflammatory responses and [...] Read more.

Ischemia and reperfusion (IR) injuries may produce deleterious effects on hepatic tissue after liver surgery and transplantation. The consequences of IR are more evident in pathological steatotic livers. Spirulina (Arthrospira platensis) is known for its potential to modulate inflammatory responses and enhance antioxidant defenses. The current investigation assessed whether spirulina pretreatment mitigates hepatic IR injury exacerbated by steatosis in rats. Thirty male Wistar rats were divided into five groups: sham, IR, HFD, HFD + IR, and SP1000 (HFD + IR + spirulina 1000 mg/kg/day; oral gavage). Liver injury, oxidative stress, inflammatory signaling, and inflammasome/pyroptosis-related markers were assessed using serum transaminases, hematoxylin–eosin staining, immunofluorescence, and qRT-PCR. High-fat diet-fed rats developed steatosis, which significantly worsened IR-induced liver damage, as shown by the respective steatosis histological score, the elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and higher expression of inflammatory markers, including Toll-like receptor (TLR4), nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β) and inflammasome/pyroptosis-related transcripts, namely NOD-like receptor family pyrin domain-containing 3 (NLRP3), interleukin-18 (IL18), and gasdermin D (GSDMD). Oxidative stress was exacerbated, as reflected by higher levels of malondialdehyde (MDA) and reduced antioxidant defenses (superoxide dismutase (SOD) activity, reduced glutathione (GSH) content, glutathione peroxidase (GPx) expression, and heme oxygenase-1 (HO-1) expression). Furthermore, HFD + IR upregulated sterol regulatory element-binding protein-1c (SREBP-1c) expression and downregulated AMP-activated protein kinase (AMPK) expression. Spirulina supplementation significantly attenuated liver injury and transaminase release, reduced MDA, restored antioxidant parameters, downregulated inflammatory and inflammasome-related gene expression, and shifted both SREBP-1c and AMPK expressions toward control levels. Full article

(This article belongs to the Special Issue Novel Strategies for Oxidative Stress Management: Dietary Interventions for Liver and Gut Health)

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31 pages, 3483 KB

Open AccessReview

Reactive Oxygen and Nitrogen Species on Monocyte and Macrophage Biology

by Francisco Rafael Jimenez-Trinidad, Sofia Morini, Armanda Buffon, Andrea de Prisco, Greta Galati, Astrid de Ciutiis, Alessia d’Aiello, Francesc Jiménez-Altayó, Ana Paula Dantas, Giovanna Liuzzo and Anna Severino

Antioxidants 2026, 15(3), 389; https://doi.org/10.3390/antiox15030389 - 19 Mar 2026

Viewed by 676

Abstract

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are central regulators of monocyte and macrophage biology, shaping their survival, differentiation, migration, and effector functions. In monocytes and macrophages, ROS and RNS arise from endogenous sources, such as mitochondria, NADPH oxidases, and myeloperoxidase, [...] Read more.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are central regulators of monocyte and macrophage biology, shaping their survival, differentiation, migration, and effector functions. In monocytes and macrophages, ROS and RNS arise from endogenous sources, such as mitochondria, NADPH oxidases, and myeloperoxidase, and from exogenous stimuli including pathogens, damaged tissues, and environmental oxidants. These reactive intermediates converge on redox-sensitive pathways such as NF-κB, Nrf2/HO-1, mitochondrial ROS signalling, and the NLRP3 inflammasome, thereby integrating metabolic stress with inflammatory activation. Redox balance is a key determinant of macrophage polarization: heightened ROS and RNS production drives pro-inflammatory M1 programs, whereas tightly regulated oxidative signalling supports M2 phenotypes associated with tissue repair and resolution. In chronic inflammatory disorders, notably atherosclerosis, oxidative stress amplifies monocyte recruitment, foam-cell formation, plaque instability, and maladaptive immunometabolic responses. The aim of this review is to recapitulate the major sources and functions of ROS and RNS in monocytes and macrophages and to synthesize current evidence on how these pathways collectively maintain or disrupt immune homeostasis. We further highlight emerging therapeutic strategies, such as NOX inhibitors, mitochondrial-targeted antioxidants, and Nrf2 activators, that seek to restore redox balance and offer promising avenues for the treatment of cardiovascular and immune-mediated diseases. Full article

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

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27 pages, 5831 KB

Open AccessArticle

The Carnosine–HNE Michael Adduct as a Redox-Active Species Associated with Nrf2-Dependent Antioxidant and Anti-Inflammatory Responses

by Alessandra Altomare, Giovanna Baron, Francesca Gado, Larissa Della Vedova, Giulio Ferrario, Lara Davani, Ettore Gilardoni, Rebecca Ferrisi, Clara Mocchetti, Lavpreet Singh, Barbora De Courten, Marina Carini, Rosalba Siracusa, Ramona D’Amico, Rosanna Di Paola, Clelia Dallanoce, Daniela Impellizzeri and Giancarlo Aldini

Antioxidants 2026, 15(3), 388; https://doi.org/10.3390/antiox15030388 - 19 Mar 2026

Viewed by 449

Abstract

Carnosine (CAR), an endogenous histidine-containing dipeptide, exhibits antioxidant and anti-inflammatory activity in various experimental models; however, its molecular mechanism of action remains poorly understood. Here, we demonstrate that the Michael adduct between CAR and 4-hydroxy-2-nonenal (HNE), which has been detected in previous studies [...] Read more.

Carnosine (CAR), an endogenous histidine-containing dipeptide, exhibits antioxidant and anti-inflammatory activity in various experimental models; however, its molecular mechanism of action remains poorly understood. Here, we demonstrate that the Michael adduct between CAR and 4-hydroxy-2-nonenal (HNE), which has been detected in previous studies in both in vitro and in vivo settings, mediates its bioactivity, particularly its antioxidant and anti-inflammatory responses, through Nrf2 activation. The CAR–HNE adduct was synthesized and its physicochemical, metabolic, and biological properties were evaluated. CAR–HNE exhibited high stability in biological matrices and retained the ability to transfer HNE to thiol nucleophiles at a slow rate under physiologically relevant conditions, consistent with electrophile-mediated Nrf2 activation. This kinetic behavior limits the cytotoxicity typically associated with free HNE while preserving the redox signaling capacity. CAR–HNE induced dose-dependent Nrf2 activation and NF-κB inhibition in cell-based assays without the hormetic toxicity observed for free HNE. Mechanistically, CAR–HNE may act as a redox-tunable electrophilic reservoir, restoring nucleophilic tone and modulating redox-sensitive transcription factors. In vivo, CAR–HNE attenuated DSS-induced colitis more effectively than equimolar doses of either carnosine or HNE alone. Proteomic analyses revealed modulation of canonical Nrf2-dependent antioxidant pathways. Our findings suggest a conceptual shift in carnosine biology: rather than acting as a classical antioxidant or carbonyl quencher, carnosine functions as a precursor of redox-active electrophilic adducts that transduce anti-inflammatory and antioxidant responses via controlled RCS signaling. Full article

(This article belongs to the Special Issue Carnosine: A Multifaceted Antioxidant and Anti-Inflammatory Peptide—Molecular Mechanisms and Biological Relevance)

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34 pages, 2679 KB

Open AccessReview

Oxidative Stress in Pathogenesis of Preeclampsia: Mechanistic and Clinical Insights

by Natnipa Parapob, Suchaya Luewan, Threebhorn Kamlungkuea and Theera Tongsong

Antioxidants 2026, 15(3), 387; https://doi.org/10.3390/antiox15030387 - 19 Mar 2026

Viewed by 579

Abstract

Preeclampsia, affecting 3–8% of pregnancies worldwide, remains a leading cause of maternal and perinatal morbidity and mortality. This review synthesizes current molecular, immunological, and hemodynamic evidence to clarify the central role of oxidative stress in the pathogenesis of preeclampsia. Placental oxidative stress, resulting [...] Read more.

Preeclampsia, affecting 3–8% of pregnancies worldwide, remains a leading cause of maternal and perinatal morbidity and mortality. This review synthesizes current molecular, immunological, and hemodynamic evidence to clarify the central role of oxidative stress in the pathogenesis of preeclampsia. Placental oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) generation and antioxidant defenses, secondary to placental hypoxia due to various etiologies especially impaired spiral artery remodeling, drives mitochondrial dysfunction in trophoblasts, ischemia–reperfusion injury, inflammatory pathway activation, and disruption of angiogenic homeostasis, thereby promoting systemic inflammation. Key regulatory pathways, including Nrf2/HO-1, NF-κB, PI3K/Akt, and HIF-1α, together with biomarkers such as malondialdehyde, 8-isoprostane, and the sFlt-1/PlGF ratio, characterize this redox imbalance. Although experimental studies demonstrate promising effects of targeted antioxidants, mitochondria-directed agents, and pathway-specific modulators, clinical translation remains limited, as non-specific antioxidants such as vitamins C and E have failed to prevent preeclampsia. Future advances will likely depend on mechanism-based therapies initiated early in pregnancy and tailored to the disease subtype and biomarker profiles. Collectively, this review provides an integrated mechanistic framework and highlights critical knowledge gaps that must be addressed to enable the development of effective preventive and therapeutic interventions for preeclampsia. Full article

(This article belongs to the Special Issue Oxidative Stress in Pregnant Women and Fetuses)

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16 pages, 2689 KB

Open AccessArticle

Epigenetic Bridge Between Oxidative Balance of Koreans and TCGA Pan-Cancer Risk: Sex-Specific DNA Methylation Signatures

by Sun-Young Kang, Jeong-Soo Gim, Hyunbin Jo and Jeong-An Gim

Antioxidants 2026, 15(3), 386; https://doi.org/10.3390/antiox15030386 - 19 Mar 2026

Viewed by 369

Abstract

Oxidative stress is a hallmark of carcinogenesis, yet the epigenetic mechanisms linking the lifestyle-based Oxidative Balance Score (OBS) to cancer risk remain poorly understood. This study investigated the epigenetic bridge between OBS and pan-cancer susceptibility using a multi-cohort approach integrating population-based and cancer [...] Read more.

Oxidative stress is a hallmark of carcinogenesis, yet the epigenetic mechanisms linking the lifestyle-based Oxidative Balance Score (OBS) to cancer risk remain poorly understood. This study investigated the epigenetic bridge between OBS and pan-cancer susceptibility using a multi-cohort approach integrating population-based and cancer genomic data. We calculated OBS based on 16 dietary and lifestyle factors (including dietary fiber, vitamins, minerals, physical activity, smoking, alcohol, and BMI) for 2749 participants from the Korean Genome and Epidemiology Study (KoGES) and identified OBS-associated CpG sites via epigenome-wide association analysis. These markers were validated against The Cancer Genome Atlas (TCGA) pan-cancer dataset using a novel Hybrid Pi-score (HyPi) to quantify the directional consistency between OBS-driven methylation in healthy individuals and cancer-specific epigenetic alterations across three clinical comparisons: normal vs. tumor, survival outcomes, and tumor stage. We observed profound sex-specific epigenetic signatures, with zero overlap in the top 200 OBS-associated CpG sites between males and females, underscoring fundamental sexual dimorphism in oxidative stress-epigenome interactions. Notably, the top 20 OBS-associated CpGs demonstrated strong directional consistency with multiple cancer types in TCGA, particularly in kidney renal clear cell carcinoma and lung adenocarcinoma, exhibiting methylation patterns inversely correlated with tumorigenesis. Mechanistically, these findings support the role of one-carbon metabolism and vitamin C-dependent DNA demethylation pathways in mediating OBS effects. Our study provides the first evidence of an epigenetic link between lifestyle-based oxidative balance and pan-cancer risk, highlighting the utility of the HyPi score as a novel sex-specific predictive biomarker for cancer prevention. These results suggest that optimizing oxidative balance through precision nutrition may epigenetically modulate cancer susceptibility, opening new avenues for personalized prevention strategies. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer Biology)

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22 pages, 14631 KB

Open AccessArticle

The NLRP3–CASP1 Axis Contributes to Pyroptosis in Bovine Mammary Epithelial Cells During Clinical Mastitis

by Bohao Zhang, Zhen Yang, Yumeng Gao, Na Chen, Weitao Dong, Yong Zhang, Xingxu Zhao and Quanwei Zhang

Antioxidants 2026, 15(3), 385; https://doi.org/10.3390/antiox15030385 - 19 Mar 2026

Viewed by 347

Abstract

Pyroptosis is a pro-inflammatory form of programmed cell death mediated by inflammasomes and caspases and has been implicated in various inflammatory diseases. However, its function and regulatory role in dairy cows with clinical mastitis (CM) remain poorly understood. This study was conducted to [...] Read more.

Pyroptosis is a pro-inflammatory form of programmed cell death mediated by inflammasomes and caspases and has been implicated in various inflammatory diseases. However, its function and regulatory role in dairy cows with clinical mastitis (CM) remain poorly understood. This study was conducted to investigate the differentially expressed proteins (DEPs) involved in biological processes (BPs) and the Kyoto Encyclopedia of Genes and Genomes pathways related to inflammasome-mediated pyroptosis based on proteomic data and to further explore their potential involvement in mastitis using in vivo and in vitro models. Histopathological analysis revealed morphological features consistent with pyroptosis in the mammary glands of CM-affected cows, including mammary epithelial cell (MEC) membrane disruption, increased reactive oxygen species production, elevated TUNEL–gasdermin D (GSDMD)-positive staining, and inflammatory cell infiltration. Proteomic profiling identified 276 DEPs and 17 BPs, among which NOD-like receptor family pyrin domain-containing 3 (NLRP3) was identified as a key candidate associated with cytokine production, immune defense, and inflammatory responses. Pathway enrichment analysis indicated that NLRP3, caspase-1 (CASP1), and GSDMD were enriched in the NOD-like receptor signaling pathway and were closely associated with mastitis. Immunohistochemical and molecular analyses demonstrated cytoplasmic localization and significant upregulation of NLRP3, CASP1, and GSDMD at both the mRNA and protein levels in CM-affected tissues. In both in vitro and in vivo models, a dose-dependent increase in the expression of pyroptosis-related targets and pro-inflammatory cytokines was observed with the progression of inflammation. Moreover, the pharmacological inhibition of CASP1 attenuated pyroptosis-associated changes and inflammatory responses in BMECs. Collectively, these findings suggest that the NLRP3–CASP1 axis is associated with inflammation-related pyroptosis in bovine mastitis and may represent a potential therapeutic target for clinical mastitis. Full article

(This article belongs to the Special Issue Implication of Oxidative Stress in Promoting Cellular Senescence and Associated Pathologies—2nd Edition)

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18 pages, 3528 KB

Open AccessArticle

An Efficient Starch-Based Delivery System Ameliorates Naringin’s Uptake to Mitigate Acrylamide-Induced Oxidative Stress in Mice

by Feng Cao, Chenxing Liu, Meiyu Zheng, Yan Cao, Qile Xia and Shengmin Lu

Antioxidants 2026, 15(3), 384; https://doi.org/10.3390/antiox15030384 - 19 Mar 2026

Viewed by 281

Abstract

Naringin (NAR), a potent antioxidant flavonoid, suffers from low oral bioavailability, limiting its therapeutic application. Here, an efficient octenyl succinic anhydride-modified porous starch (OSAPS) carrier was adopted to enhance NAR’s delivery and efficacy against acrylamide (AA)-induced oxidative stress. In Caco-2 cells, the OSAPS-NAR [...] Read more.

Naringin (NAR), a potent antioxidant flavonoid, suffers from low oral bioavailability, limiting its therapeutic application. Here, an efficient octenyl succinic anhydride-modified porous starch (OSAPS) carrier was adopted to enhance NAR’s delivery and efficacy against acrylamide (AA)-induced oxidative stress. In Caco-2 cells, the OSAPS-NAR complex demonstrated superior cellular uptake and more effectively mitigated AA-induced cytotoxicity compared to free NAR. Causally, this protection was attributed to its enhanced antioxidant capacity to suppress reactive oxygen species generation, maintain mitochondrial membrane potential, and prevent glutathione (GSH) depletion. Critically, these in vitro advantages translated to remarkable in vivo outcomes. The OSAPS-NAR complex led to a striking 7.91-fold increase in peak plasma concentration and an 11.05-fold increase in relative bioavailability in mice. This enhanced pharmacokinetic profile directly translated to superior antioxidant activities in serum and liver tissues by elevating total antioxidant capacity and GSH content, while simultaneously reducing malondialdehyde levels. These effects collectively led to marked amelioration of AA-induced hepatotoxicity, normalization of the liver index, and restoration of hepatic cellular architecture. In conclusion, the complex effectively overcame NAR’s pharmacokinetic limitations, thereby potentiating its ability to modulate cellular redox imbalance and protect against oxidative organ injury. This work provided a robust proof-of-concept for OSAPS-NAR as a promising nutraceutical agent for combating pathologies driven by oxidative stress. Full article

(This article belongs to the Topic Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress)

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14 pages, 682 KB

Open AccessReview

Cytoglobin in Hepatic Stellate Cells Plays Anti-Fibrotic Role in Chronic Liver Injury

by Norifumi Kawada

Antioxidants 2026, 15(3), 383; https://doi.org/10.3390/antiox15030383 - 19 Mar 2026

Viewed by 396

Abstract

Cytoglobin (Cygb) was discovered in 2001 as a cytoplasmic globin predominantly expressed in hepatic stellate cells (HSCs). While its initial physiological role remained elusive, subsequent studies using Cygb-deficient mouse models of liver injury have demonstrated that Cygb exerts protective effects against liver fibrosis [...] Read more.

Cytoglobin (Cygb) was discovered in 2001 as a cytoplasmic globin predominantly expressed in hepatic stellate cells (HSCs). While its initial physiological role remained elusive, subsequent studies using Cygb-deficient mouse models of liver injury have demonstrated that Cygb exerts protective effects against liver fibrosis and inflammation. It achieves this by regulating HSC activation, thereby preserving hepatic homeostasis. Furthermore, accumulating evidence suggests a significant role for Cygb in hepatocarcinogenesis. Analysis of human liver tissues and cell-based models has further confirmed the critical involvement of CYGB in liver pathology. Functionally, Cygb acts as an antioxidant protein that mitigates oxidative stress, a property that appears to modulate transforming growth factor-beta signaling and downstream fibrogenic responses. Based on these findings, therapeutic strategies employing recombinant CYGB for the treatment of human liver cirrhosis are currently being explored, and their potential clinical applications are eagerly anticipated. Full article

(This article belongs to the Special Issue Heme Proteins and Signaling in Redox Biology)

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20 pages, 2168 KB

Open AccessReview

Interaction of Ferroptosis and Immune-Mediated Inflammation in Psoriasis

by Emanuele Giorgio, Cristiana Galeano, Giuseppe Natali, Lavinia Petriaggi, Maria Concetta Faniello, Elzbieta Janda, Francesco Saverio Costanzo, Anna Martina Battaglia and Flavia Biamonte

Antioxidants 2026, 15(3), 382; https://doi.org/10.3390/antiox15030382 - 18 Mar 2026

Viewed by 410

Abstract

Psoriasis is classically defined as an immune-mediated disease. However, many patients do not achieve durable remission after immune-targeted therapies, suggesting that further pathogenic mechanisms may contribute to the persistence of psoriasis. Here, we propose ferroptosis, an iron-dependent regulated cell death driven by lipid [...] Read more.

Psoriasis is classically defined as an immune-mediated disease. However, many patients do not achieve durable remission after immune-targeted therapies, suggesting that further pathogenic mechanisms may contribute to the persistence of psoriasis. Here, we propose ferroptosis, an iron-dependent regulated cell death driven by lipid peroxidation and failure of lipid repair, as a potential link between metabolic stress and immune-mediated inflammation in psoriasis. We summarize experimental evidence showing that membrane lipids remodeling, antioxidant suppression, lipid peroxidation, and dysregulated iron handling together define ferroptosis-permissive niches within psoriatic lesions. We also discuss functional studies demonstrating that ferroptosis modulation can reshape psoriasiform inflammation and explore how ferroptotic stress may amplify inflammatory signaling at the immune-epidermal interface, reinforcing IL-17/TNF/IFN-γ pathways. Finally, we discuss ferroptosis-related transcriptomic signatures as a potential approach to stratify psoriasis, capturing metabolic features that are not reflected by cytokine profiling. The translational opportunities and constraints for ferroptosis-targeted interventions are outlined, highlighting epidermal redox homeostasis as a new therapeutic frontier in psoriasis. Full article

(This article belongs to the Special Issue Antioxidants and Oxidative Stress at the Crossroads of Autophagy and Ferroptosis)

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136 pages, 3093 KB

Open AccessReview

Radiomitigators: Breakthroughs in Post-Radiation Recovery

by Elena Obrador, José M. Estrela, Rafael López-Blanch, Paz Moreno-Murciano, Alegría Montoro and María Oriol-Caballo

Antioxidants 2026, 15(3), 381; https://doi.org/10.3390/antiox15030381 - 18 Mar 2026

Viewed by 1113

Abstract

Ionizing radiation (IR) exposure poses a significant biomedical challenge in clinical, occupational, and emergency contexts, highlighting the urgent need for effective medical countermeasures against acute radiation syndrome (ARS) and delayed effects of radiation exposure (DEARE). Depending on the timing of administration, radiation countermeasures [...] Read more.

Ionizing radiation (IR) exposure poses a significant biomedical challenge in clinical, occupational, and emergency contexts, highlighting the urgent need for effective medical countermeasures against acute radiation syndrome (ARS) and delayed effects of radiation exposure (DEARE). Depending on the timing of administration, radiation countermeasures are classified as radioprotectors, radiomitigators, or therapeutics. Among these, radiomitigators offer a critical advantage by attenuating IR-induced damage when administered after exposure, thereby expanding their applicability in unanticipated radiation incidents. This review provides an overview of the pathophysiological mechanisms underlying IR-induced injury and summarizes the current FDA-approved radiation countermeasures. It then focuses on radiomitigators that have demonstrated efficacy in preclinical animal models, together with available evidence from clinical studies, emphasizing their translational potential for both emergency preparedness and oncological settings. We examine routes of administration and key mechanisms of action, including modulation of oxidative and nitrosative stress, enhancement of DNA damage response pathways, preservation of mitochondrial function, regulation of inflammatory and immune signaling, attenuation of fibrotic remodeling, maintenance of vascular integrity, and promotion of tissue regeneration and repair. Finally, challenges associated with clinical translation and strategies to optimize radiomitigators for the management of radiation-induced injury are discussed. By integrating these insights and consolidating existing knowledge, this review aims to guide basic and clinical research toward more effective radiomitigative strategies and combination therapies to improve survival, limit tissue damage, and preserve long-term quality of life in individuals exposed to IR. Full article

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

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20 pages, 1013 KB

Open AccessArticle

Upcycling Roman Chamomile Hydrolate and Apple Pomace Agri-Wastes into Sustainable Cosmetic Ingredients

by Kamil Szymczak, Agnieszka Krajewska, Małgorzata Grzyb, Iga Jodłowska, Katarzyna Mietlińska and Radosław Bonikowski

Antioxidants 2026, 15(3), 380; https://doi.org/10.3390/antiox15030380 - 18 Mar 2026

Viewed by 320

Abstract

The aim of this study was to evaluate the potential of selected agri-food by-products—apple pomace extract from Malus domestica cv. ‘Grochówka’ and Roman chamomile (Chamaemelum nobile L.) hydrolate—as functional, sustainable ingredients for cosmetic applications. The work focused on their chemical composition, biological [...] Read more.

The aim of this study was to evaluate the potential of selected agri-food by-products—apple pomace extract from Malus domestica cv. ‘Grochówka’ and Roman chamomile (Chamaemelum nobile L.) hydrolate—as functional, sustainable ingredients for cosmetic applications. The work focused on their chemical composition, biological activity, formulation performance, and in vivo effects on skin condition. Volatile compounds, phenolic acids, and triterpenoids were analyzed by GC–MS, while total phenolic content, antioxidant capacity, and enzyme inhibitory activity were evaluated in vitro. An oil-in-water emulsion containing the by-products was formulated and, in a 14-day split-face study, assessed for its effects on skin hydration, elasticity, inflammation, sensitivity, pore visibility, and melanin index. Biochemical analyses have shown that chamomile hydrolate is characterized by very low antioxidant activity (DPPH 5.0 ± 1.25%, FRAP 0%) and weak protease inhibition (9.70 ± 1.84%). In contrast, apple extract contained a significant amount of polyphenols (23.94 ± 0.3 mg GAE/g) and showed strong antioxidant properties (DPPH 79.4 ± 2.12%, FRAP 70.56 ± 2.23%; IC₅₀ = 21.5 ± 0.196 mg/mL), which confirms the dominant role of phenolic compounds in its biological activity. This extract also demonstrated significant protease inhibition (60.88 ± 2.35%; IC₅₀ = 15.02 ± 0.47 mg/mL), while its lipase inhibition activity was moderate (10%), which may be beneficial from a cosmetic perspective. The obtained results indicate that apple extract is a valuable raw material with multifaceted biological potential. Overall, the results demonstrate that apple pomace extract and chamomile hydrolate can be effectively valorized as bioactive cosmetic ingredients, supporting both skin health benefits and circular economy principles in sustainable cosmetic formulation. 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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13 pages, 1120 KB

Open AccessArticle

Effects of Short-Term Broccoli Powder Supplementation on Acute Oxidative Stress and Recovery Following a Metabolically Demanding Exercise Session

by Leonardo Cesanelli, Tomas Venckunas, Petras Minderis, Viktorija Maconyte, Arvydas Stasiulis, Audrius Snieckus, Mantas Mickevicius, Dalia Mickeviciene and Sigitas Kamandulis

Antioxidants 2026, 15(3), 379; https://doi.org/10.3390/antiox15030379 - 18 Mar 2026

Viewed by 645

Abstract

Background/Objectives: This study aimed to evaluate the effects of short-term broccoli powder supplementation on metabolically demanding exercise performance, muscle power, and blood lactate recovery. It also investigated broccoli powder-derived sulforaphane bioavailability and its effects in attenuating exercise-induced oxidative stress. Methods: Seventeen [...] Read more.

Background/Objectives: This study aimed to evaluate the effects of short-term broccoli powder supplementation on metabolically demanding exercise performance, muscle power, and blood lactate recovery. It also investigated broccoli powder-derived sulforaphane bioavailability and its effects in attenuating exercise-induced oxidative stress. Methods: Seventeen healthy males (age 23.8 ± 4.9 years, height 182.3 ± 6.1 cm, weight 80.0 ± 12.8 kg), in a double-blind crossover design, three weeks apart, consumed ten standard doses of either broccoli powder or spinach powder as a placebo over a period of 2 weeks. They then performed a maximal progressive cycling task with concomitant analysis of expired gas composition. Plasma malondialdehyde (MDA) level was measured before and 60 min after the completion of the task, and blood lactate and muscle power (counter-movement vertical jump (CMJ) performance) were measured before and up to 60 min after exercise. Results: The main findings were that despite urine sulforaphane output being markedly higher following broccoli supplementation (p < 0.05), which confirms effective absorption and systemic availability of the compound, this did not influence exercise-induced changes in plasma MDA concentration, blood lactate dynamics, exercise test performance, or functional recovery measured as muscle power via CMJ performance (p > 0.05). Conclusions: In conclusion, broccoli powder supplementation, despite efficient delivery of sulforaphane, does not seem to either acutely affect performance or modify oxidative stress and recovery from metabolically demanding exercise. Full article

(This article belongs to the Special Issue The Role of Antioxidants in Enhancing Training Adaptation, Exercise Performance, and Post-exercise Recovery)

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15 pages, 1350 KB

Open AccessReview

A Review of HIF-1α-Mediated Integration of Metabolic Reprogramming, Mitochondrial Function, and PI3K/Akt–MAPK–Nrf2–NF-κB Signaling

by Asha Ashraf and Erica D. Bruce

Antioxidants 2026, 15(3), 378; https://doi.org/10.3390/antiox15030378 - 18 Mar 2026

Viewed by 670

Abstract

Hypoxia is a common feature of many physiological and pathological conditions, including inflammation, ischemia, and chronic lung disease, where limited oxygen availability disrupts mitochondrial metabolism and promotes excessive reactive oxygen species (ROS) generation. Hypoxia-inducible factor-1α (HIF-1α) is the central transcriptional regulator that enables [...] Read more.

Hypoxia is a common feature of many physiological and pathological conditions, including inflammation, ischemia, and chronic lung disease, where limited oxygen availability disrupts mitochondrial metabolism and promotes excessive reactive oxygen species (ROS) generation. Hypoxia-inducible factor-1α (HIF-1α) is the central transcriptional regulator that enables cellular adaptation to low-oxygen environments by coordinating metabolic reprogramming, mitochondrial remodeling, and redox control. While HIF-1α is widely recognized for its role in promoting glycolysis, evidence indicates that it also suppresses mitochondrial ROS production through coordinated regulation of mitochondrial metabolism, biogenesis, and quality control. This review examines how HIF-1α integrates these mitochondrial and redox-adaptive mechanisms and highlights its bidirectional interactions with key stress-responsive signaling pathways, including PI3K/Akt, MAPK, Nrf2, and NF-κB, that together shape metabolic adaptation, inflammatory responses, and cell survival under hypoxic stress. By integrating these diverse mechanisms, this review provides a comprehensive understanding of the pathophysiology of hypoxia-associated diseases and underscores the therapeutic potential of targeting HIF-1α-regulated metabolic and inflammatory pathways to mitigate oxidative damage induced by hypoxia and environmental stressors. Full article

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

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44 pages, 12324 KB

Open AccessArticle

Antioxidant Capacity and Polyphenolic Profile of Extractable and Non-Extractable Fractions of Traditional Mediterranean Diet Recipes from Different Regions

by Marta Cuenca-Ortola, Mónica Gandía, Salah Chaji, Fatima Zahrae El Mossaid, Said Ennahli, El Amine Ajal, Stefania Filice, Achraf Ammar, Amparo Gamero and Antonio Cilla

Antioxidants 2026, 15(3), 377; https://doi.org/10.3390/antiox15030377 - 18 Mar 2026

Viewed by 527

Abstract

The Mediterranean Diet (MD) is recognized for its nutritional quality, health-promoting properties, and richness in bioactive compounds, yet studies analyzing complete traditional recipes considering both extractable and non-extractable fractions are limited. This study characterized the total antioxidant capacity (TAC) and phenolic profile of [...] Read more.

The Mediterranean Diet (MD) is recognized for its nutritional quality, health-promoting properties, and richness in bioactive compounds, yet studies analyzing complete traditional recipes considering both extractable and non-extractable fractions are limited. This study characterized the total antioxidant capacity (TAC) and phenolic profile of 56 traditional MD recipes from eight countries, grouped into European Mediterranean (France, Italy, and Spain), African Mediterranean (Tunisia, Algeria, and Morocco), and non-Mediterranean European (Luxembourg and Germany) regions. Samples were freeze-dried and subjected to aqueous-organic extraction followed by acid hydrolysis. TAC was measured using TEAC, ORAC, and total phenolics (Folin–Ciocalteu, reflecting reducing capacity), while phenolic profiles were analyzed by HPLC-DAD. Relationships between phenolics and TAC were evaluated using linear and mixed-effects models, accounting for country-level heterogeneity. Mediterranean recipes showed higher TAC and greater phenolic diversity than non-Mediterranean recipes, with a predominance of phenolic acids, secoiridoids, and flavonoids, reflecting characteristic olive oil use. In all regions, the non-extractable fraction contributed >80% to TAC, highlighting underestimation by conventional methods and its dominant contribution to dietary antioxidant intake. TEAC was positively associated with extractable phenolics, whereas ORAC reflected country-specific culinary features independently of total phenolic content. These findings underscore the significant bioactive potential of traditional MD recipes, which can be considered functional foods, and the importance of comprehensive evaluations of both extractable and non-extractable fractions for nutritional research and dietary interventions. Full article

(This article belongs to the Special Issue Antioxidant Compounds and Health Benefits of Mediterranean Functional Food)

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Open AccessArticle

Antioxidant Activity and Resistance Against Oxidation of Peptide Fractions from Common Bean (Phaseolus vulgaris L.) Landraces Assessed by EPR and Chemical Assays

by Katherine Márquez-Calvo, Guillermo Schmeda-Hirschmann, Felipe Leyton, Felipe Ávila, Pablo Salgado, Victoria Melin, David Contreras and Gipsy Tabilo-Munizaga

Antioxidants 2026, 15(3), 376; https://doi.org/10.3390/antiox15030376 - 18 Mar 2026

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Abstract

The objective of this study was to obtain and characterize bioactive peptides derived from common bean (Phaseolus vulgaris) landraces and to evaluate their antioxidant potential using multiple in vitro assays. Protein isolates were obtained by isoelectric precipitation followed by enzymatic hydrolysis [...] Read more.

The objective of this study was to obtain and characterize bioactive peptides derived from common bean (Phaseolus vulgaris) landraces and to evaluate their antioxidant potential using multiple in vitro assays. Protein isolates were obtained by isoelectric precipitation followed by enzymatic hydrolysis using Alcalase. Peptides were separated by ultrafiltration into fractions < 3 kDa and 3–10 kDa, yielding a total of forty samples. Antioxidant activity was evaluated using DPPH, FRAP, and ORAC assays. Antioxidant responses ranged from 13.06 to 50.8% inhibition in DPPH, 52.2 to 1750 µmol TE/100 g in FRAP, and 305 to 5246 µmol TE/100 g in ORAC. Resistance against oxidation ranged from 10.6 to 68.8%. Peptides < 3 kDa generally exhibited higher antioxidant activity in the functional assays, particularly in the Apolo, Magnum, Boloto, and Hallado landraces, although some 3–10 kDa fractions also showed relevant activity. Peptide extraction yields ranged from 3.73 to 10.39% and from 1.33 to 4.74%, while soluble protein contents ranged from 23.1 to 460 and from 9.9 to 288 mg BSA/100 g beans for <3 kDa and 3–10 kDa fractions, respectively. Overall, the results support the potential of common bean-derived peptides as functional food ingredients with antioxidant activity mediated through multiple mechanisms. Full article

(This article belongs to the Special Issue Antioxidant Activity of Natural Bioactive Compounds in Food and Agricultural Byproducts)

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Antioxidants, Volume 15, Issue 3 (March 2026) – 132 articles

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