Antioxidants

23 pages, 11281 KB

Open AccessReview

Bioactive Compounds in Mandarin (Citrus reticulata): Composition, Analytical Characterization and Therapeutic Potential

by Esra Gölcü and Keziban Yazici

Antioxidants 2026, 15(10), 1220; https://doi.org/10.3390/antiox15101220 - 22 Sep 2026

Abstract

Mandarin is one of the most widely consumed citrus fruits worldwide and is a rich source of phytochemical compounds with important biological activities for human health. This review comprehensively addresses the distribution, chemical properties, and therapeutic significance of the main bioactive compounds found [...] Read more.

Mandarin is one of the most widely consumed citrus fruits worldwide and is a rich source of phytochemical compounds with important biological activities for human health. This review comprehensively addresses the distribution, chemical properties, and therapeutic significance of the main bioactive compounds found in mandarins, particularly flavonoids, phenolic acids, carotenoids, vitamins, and essential oils. Furthermore, it presents up-to-date information on the chromatographic, spectroscopic, and metabolomic analytical approaches used to identify and quantify these compounds. The biological activities of mandarin-derived phytochemicals have been evaluated in terms of their antioxidant, anti-inflammatory, cardiovascular, anticancer, and metabolic regulatory effects. Current studies indicate that hesperidin, narirutin, nobiletin, tangeretin, and various phenolic acids make significant contributions to the positive health effects of mandarins. Furthermore, the distribution of these bioactive compounds in different fruit tissues, their concentration levels, and their interactions have been explained, and current scientific evidence regarding their potential effects on human health has been evaluated. In conclusion, this review brings together the latest information on the chemical characterization, therapeutic potential, and analytical methods of bioactive compounds found in mandarins, providing a scientific basis for future research and the development of functional foods, nutraceuticals, and natural health products. Full article

(This article belongs to the Special Issue Bioactive Compounds: Antioxidant, Antibacterial, and Anti-Inflammatory Modulation—2nd Edition)

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Graphical abstract

27 pages, 3756 KB

Open AccessSystematic Review

Effects of Coenzyme Q10 Supplementation on Muscle Health and Physical Capacity in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Xundian Liu, Jinxuan Bao, Zhuoxuan Yu, Wende Zheng, Yaxuan Huang, Yifan Zhang and Xiuying Jiang

Antioxidants 2026, 15(10), 1219; https://doi.org/10.3390/antiox15101219 - 22 Sep 2026

Abstract

Age-related declines in physical capacity may partly reflect impaired mitochondrial bioenergetics and oxidative stress. This systematic review and meta-analysis evaluated the effects of oral coenzyme Q10 (CoQ10) supplementation on muscle health and physical capacity in adult populations with a study-level mean or median [...] Read more.

Age-related declines in physical capacity may partly reflect impaired mitochondrial bioenergetics and oxidative stress. This systematic review and meta-analysis evaluated the effects of oral coenzyme Q10 (CoQ10) supplementation on muscle health and physical capacity in adult populations with a study-level mean or median age ≥ 40 years. MEDLINE, Embase, Web of Science, Scopus, and CENTRAL were searched through July 2026 for randomized controlled trials lasting ≥2 weeks. Directly usable evidence formed primary random-effects models, whereas assumption-dependent estimates were included only in sensitivity analyses. Effect measures were expressed as mean differences (MDs) or Hedges’ g, as appropriate. Thirty-three trials involving 3317 randomized participants were included, and 21 contributed to meta-analysis. The relative VO₂peak/VO₂max estimate was small and imprecise (5 studies, n = 172; MD 0.73 mL·kg⁻¹·min⁻¹, 95% CI −0.07 to 1.54; I² = 0%; low certainty) and remained compatible with no benefit. Primary estimates were also uncertain for 6-min walking distances, handgrip strength, lower-limb strength, chair-rise performance, exercise duration, and muscle/lean-tissue quantity. Sensitivity analyses did not materially alter the overall interpretation. Evidence certainty was low or very low for all key outcomes. Current evidence does not establish clinically meaningful benefits of CoQ10 supplementation for aerobic capacity, muscle health, or physical function. Full article

(This article belongs to the Special Issue Unveiling the Essential Role of Coenzyme Q in Health)

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25 pages, 2259 KB

Open AccessArticle

Differential ROS Accumulation, Antioxidant Defense, and Physiological Adaptation in Two Rosa rugosa Cultivars Under Sustained Salt Stress

by Sawaira Ashraf, Muhammad Zahid Ashraf, Zhonghua Bian, Humera Ashraf, Waqar Ahmed, Baohe Miao and Xinxin Zhao

Antioxidants 2026, 15(9), 1218; https://doi.org/10.3390/antiox15091218 - 21 Sep 2026

Abstract

Salt stress is a major abiotic constraint that limits plant growth by inducing oxidative stress, disrupting photosynthetic processes, and damaging cellular membranes. Although Rosa rugosa is considered relatively tolerant to adverse environments, differences in antioxidant defense and physiological responses among its cultivars under [...] Read more.

Salt stress is a major abiotic constraint that limits plant growth by inducing oxidative stress, disrupting photosynthetic processes, and damaging cellular membranes. Although Rosa rugosa is considered relatively tolerant to adverse environments, differences in antioxidant defense and physiological responses among its cultivars under sustained salt stress remain insufficiently understood. Comparative evaluation of these responses is important for identifying salt-tolerant germplasm and understanding stress-adaptation mechanisms. In this study, two R. rugosa cultivars, Siji and Fenghua, were subjected to irrigation treatments with solutions containing 0, 50, 100, or 150 mM NaCl for 28 days under controlled conditions. Morphological traits, salt injury, photosynthetic pigments, osmolytes, ROS accumulation, antioxidant enzyme activities, and lipid peroxidation were measured to assess cultivar-specific differences in salt-stress responses. Salt stress caused concentration-dependent growth inhibition, increased salt injury, and reduced chlorophyll content, while oxidative-stress responses differed between the two cultivars, with stronger adverse effects observed in Fenghua. Siji maintained better growth performance, higher fresh and dry mass of sampled leaves, greater chlorophyll retention, better maintenance of several osmolytes, and stronger antioxidant enzyme activities under the higher NaCl treatments. In contrast, Fenghua showed greater ROS accumulation and higher MDA under the higher NaCl treatments, which are consistent with greater oxidative stress and membrane lipid peroxidation. Exploratory correlation and principal component analyses further showed that antioxidant defense, osmotic adjustment, chlorophyll retention, and reduced oxidative damage were closely associated with salt tolerance in Siji. These results indicate that greater antioxidant capacity, osmotic adjustment, and membrane protection were associated with the superior salt-stress performance of ‘Siji’ compared with ‘Fenghua’. The study identifies Siji as a promising R. rugosa candidate for further salt-tolerance evaluation and provides useful physiological and biochemical indicators for salt-tolerance screening in ornamental rose breeding. Full article

(This article belongs to the Collection Feature Papers in ROS, RNS, RSS)

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16 pages, 5269 KB

Open AccessArticle

Repurposing Pimozide as a Geroprotector: Lifespan Extension via SKN-1 Activation and Collagen Remodeling in Caenorhabditis elegans

by Yuhong Huang, Meijing Wang, Yiming Zhou, Jiali Liu, Lili Ni, Ya Tan, Mengting Zhang, Jiangpeng Huang, Guolin Li and Fang Wei

Antioxidants 2026, 15(9), 1217; https://doi.org/10.3390/antiox15091217 - 21 Sep 2026

Abstract

Aging is a major risk factor for chronic diseases, driving an urgent need for effective geroprotectors. Repurposing psychotropic agents offers an efficient strategy to accelerate anti-aging therapeutics development. In this study, we investigated the effects of pimozide (a diphenylbutylpiperidine-class antipsychotic) on aging in [...] Read more.

Aging is a major risk factor for chronic diseases, driving an urgent need for effective geroprotectors. Repurposing psychotropic agents offers an efficient strategy to accelerate anti-aging therapeutics development. In this study, we investigated the effects of pimozide (a diphenylbutylpiperidine-class antipsychotic) on aging in Caenorhabditis elegans and elucidated the underlying mechanisms. The results demonstrated that 0.1 μM pimozide significantly extends nematode lifespan, increasing mean, median, and maximum lifespans by 44.3%, 50.0%, and 39.8%, respectively. Furthermore, pimozide improves healthspan, as evidenced by reduced age-related lipofuscin accumulation, preserved locomotor function, and decreased paralysis incidence. Moreover, pimozide-treated nematodes showed enhanced resistance to heat, ultraviolet and oxidative stress, concomitant with reduced endogenous reactive oxygen species levels. Transcriptomic profiling and biochemical validation reveal that pimozide markedly upregulates collagen gene expression and increases hydroxyproline content, indicating enhanced collagen synthesis. Mechanistically, pimozide promotes the nuclear localization of SKN-1, and its beneficial effects on lifespan extension and collagen synthesis are SKN-1-dependent, as these effects are abolished in skn-1 mutants. Collectively, our findings demonstrate that pimozide promotes longevity and healthspan by activating skn-1, which is accompanied by enhanced collagen synthesis, providing a preclinical proof of concept for its potential repurposing as a geroprotector. Full article

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13 pages, 291 KB

Open AccessArticle

Tiny but Mighty: A Low Dose of Standardized Dry Grape Extract Potentiates Antioxidant Defenses in Broiler Chickens

by Paul Engler, Sekhou Cisse, Arkadiusz Matuszewski, Sławomir Jaworski, Agata Lange, Damian Bień, Patrycja Kostusiak, Anna Zalewska, Jakub Urban, Monika Michalczuk, Marta Mendel, Urszula Latek, Joanna Polak and Mohammed El Amine Benarbia

Antioxidants 2026, 15(9), 1216; https://doi.org/10.3390/antiox15091216 - 21 Sep 2026

Abstract

Oxidative stress can impair poultry health and performance, underscoring the importance of enhancing endogenous antioxidant defenses as a nutritional strategy. Although plant-derived polyphenols have shown antioxidant potential, their efficacy remains inconsistent owing to variability in extract composition and the frequent evaluation of doses [...] Read more.

Oxidative stress can impair poultry health and performance, underscoring the importance of enhancing endogenous antioxidant defenses as a nutritional strategy. Although plant-derived polyphenols have shown antioxidant potential, their efficacy remains inconsistent owing to variability in extract composition and the frequent evaluation of doses exceeding those authorized for commercial use. This study investigated the effects of dietary supplementation with a standardized dry grape extract (SDGE, Nor-Grape^®, Nor-Feed, France) at an authorized inclusion level (30 mg/kg feed) on growth performance and antioxidant status in broiler chickens under commercial production conditions. A total of 756 one-day-old male Ross 308 broilers were randomly allocated to a control diet (CTL, n = 392) or the same diet supplemented with grape extract (NG, n = 364) for 35 days. Growth performance was recorded throughout this study, and blood samples collected on days 11 and 35 were analyzed for total antioxidant capacity (TEAC), lipid peroxidation (TBARS), and the activities of the endogenous antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Compared with controls, NG birds exhibited greater final body weight (+71.9 g; p < 0.001) and improved FCR during the finisher phase (p < 0.05). Supplementation significantly enhanced systemic antioxidant capacity and endogenous antioxidant enzyme activities while reducing lipid peroxidation, indicating improved oxidative status. These findings demonstrate that SDGE supplementation at commercially authorized inclusion levels effectively enhances antioxidant defenses and improves production performance in broiler chickens. Full article

(This article belongs to the Special Issue Natural Antioxidants in Animal Nutrition)

28 pages, 2891 KB

Open AccessArticle

Bioactive Compound Recovery from Apple Pomace by Aqueous Ultrasound-Assisted Extraction: Machine Learning Modelling and Multi-Objective Optimization

by Biljana Lončar, Milena Terzić, Aleksandra Cvetanović Kljakić, Mirjana Petronijević, Sanja Panić, Jelena Arsenijević, Gokhan Zengin and Slavica Ražić

Antioxidants 2026, 15(9), 1215; https://doi.org/10.3390/antiox15091215 - 21 Sep 2026

Abstract

Apple pomace represents a sustainable source of phenolic compounds with significant antioxidant potential. This study investigated the recovery of water-extractable bioactive constituents from apple pomace using aqueous ultrasound-assisted extraction (UAE) combined with biochemical profiling and machine learning-based modelling. Extraction conditions were varied according [...] Read more.

Apple pomace represents a sustainable source of phenolic compounds with significant antioxidant potential. This study investigated the recovery of water-extractable bioactive constituents from apple pomace using aqueous ultrasound-assisted extraction (UAE) combined with biochemical profiling and machine learning-based modelling. Extraction conditions were varied according to time (10–30 min), temperature (25–75 °C), and solvent-to-solid ratio (10–20 mL/g). The obtained extracts were evaluated for total phenolic content (TP), total flavonoid content (TF), antioxidant capacity (DPPH, ABTS, CUPRAC, FRAP, metal chelating, and phosphomolybdenum assays), and enzyme inhibitory activities against acetylcholinesterase, butyrylcholinesterase, tyrosinase, α-amylase, and α-glucosidase. TP and TF ranged from 4.70 to 9.97 mg GAE/g and 0.21–0.79 mg RE/g, respectively, while antioxidant assays demonstrated substantial variation depending on extraction conditions. Strong correlations (r = 0.827–0.945, p < 0.001) were observed between phenolic content and antioxidant activity. Artificial neural networks, random forests, support vector machines, and a hybrid ensemble model were applied to predict extraction outcomes, with predictive performance varying substantially among biochemical responses and modelling approaches. Multi-objective optimization using the NSGA-II formulation identified a representative Pareto compromise at approximately 15.1 min, 25.7 °C, and a solvent-to-solid ratio of 13.7 mL/g, balancing desirable biochemical responses with processing requirements. Full article

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

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24 pages, 10934 KB

Open AccessArticle

Engineering a Redox-Responsive Bimolecular Prodrug for Targeted Gastric Cancer Combination Therapy: Design, Synthesis, and In Vivo Evaluation

by Chao Wang, Yutao Xiu, Yujing Zhang, Jiazhen Xu, Yanhong Wang and Dongming Xing

Antioxidants 2026, 15(9), 1214; https://doi.org/10.3390/antiox15091214 - 21 Sep 2026

Abstract

Combination chemotherapy often suffers from asynchronous pharmacokinetics and off-target toxicity. To address this, we designed a novel, unreported engineered prodrug—a redox-responsive bimolecular prodrug (CA-4-Gefitinib)—by engineering a disulfide bond as a cleavable linker to covalently conjugate the tubulin inhibitor combretastatin A-4 (CA-4) and the [...] Read more.

Combination chemotherapy often suffers from asynchronous pharmacokinetics and off-target toxicity. To address this, we designed a novel, unreported engineered prodrug—a redox-responsive bimolecular prodrug (CA-4-Gefitinib)—by engineering a disulfide bond as a cleavable linker to covalently conjugate the tubulin inhibitor combretastatin A-4 (CA-4) and the EGFR inhibitor Gefitinib. This molecular-level prodrug design enables tumor-selective drug activation in high-glutathione environments. This prodrug exhibited enhanced cellular uptake and potent antiproliferative activity against SGC-7901 gastric cancer cells, with significantly improved selectivity over normal cells (safety index of 98). Mechanistically, this engineered prodrug disrupted microtubule polymerization, induced G2/M arrest, suppressed ERK signaling, and promoted apoptosis. The prodrug’s pharmacokinetic profile showed prolonged circulation and reduced systemic exposure to free CA-4, indicating favorable biodistribution. In a murine xenograft model, this prodrug demonstrated superior antitumor efficacy and markedly reduced systemic toxicity compared to the combination of free drugs. Our work presents a rational prodrug design strategy—a redox-responsive drug–drug conjugate prodrug—that synchronizes drug delivery, enhances tumor targeting, and maximizes synergistic efficacy, offering a promising platform for advanced cancer combination therapy. Full article

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24 pages, 8462 KB

Open AccessArticle

Thermochemical Valorization of Silkworm Feeding Waste: Chemical Characterization and Biological Activities of the Pyrolysis-Derived Liquid Fraction

by Halil Karan, Aybeniz Yıldırım, Fırat Yılmaz, İnanç Özgen, Ercan Aydoğmuş and Abdulkadir Gül

Antioxidants 2026, 15(9), 1213; https://doi.org/10.3390/antiox15091213 - 21 Sep 2026

Abstract

Silkworm-rearing residues are an underused biomass resource that can be converted into value-added products. In this study, a condensable liquid product (SWP-Liq) was produced from these residues by pyrolysis at 325 ± 5 °C and evaluated for its chemical composition and in vitro [...] Read more.

Silkworm-rearing residues are an underused biomass resource that can be converted into value-added products. In this study, a condensable liquid product (SWP-Liq) was produced from these residues by pyrolysis at 325 ± 5 °C and evaluated for its chemical composition and in vitro biological activities. SWP-Liq yielded phenolic-, flavonoid-, and triterpenoid-equivalent values of 218.47 ± 22.40 mg GAE/g, 79.13 ± 3.55 mg QE/g, and 55.54 ± 6.15 mg EE/g, respectively. The ABTS•⁺ assay showed a higher radical-scavenging response than DPPH, while Fe³⁺- and Cu²⁺-reducing activities were also observed. SWP-Liq inhibited 5-LOX with an IC₅₀ of 33.05 ± 1.10 µg/mL, whereas α-glucosidase inhibition was weaker. Antibacterial activity against all four tested bacterial species was observed at 8 mg/mL but not at 4 mg/mL. Targeted LC–MS/MS quantified five phenolic constituents, with p-coumaric acid (1599.71 µg/g), chlorogenic acid (871.43 µg/g), and ferulic acid (285.50 µg/g) being the most abundant. Overall, these findings support the further investigation of silkworm feeding waste as a feedstock for thermochemical valorization into chemically and biologically evaluable bio-based fractions. Full article

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22 pages, 6914 KB

Open AccessArticle

Modulating Ubiquinone Biosynthesis Rescues Mitochondrial Dysfunction by Genetic Interaction in a Phosphatidylethanolamine (PE)-Deficient Disease Model

by Lavanya Vadupu, Vijay Aditya Mavuduru and Writoban Basu Ball

Antioxidants 2026, 15(9), 1212; https://doi.org/10.3390/antiox15091212 - 20 Sep 2026

Abstract

Mitochondrial dysfunctions are often associated with cellular aging as well as metabolic disorders. Therapeutic strategies for rewiring mitochondrial stress signaling in a disease context could be beneficial. New evidence indicates that mitochondrial membrane lipids actively regulate mitochondrial signaling pathways that influence cellular health, [...] Read more.

Mitochondrial dysfunctions are often associated with cellular aging as well as metabolic disorders. Therapeutic strategies for rewiring mitochondrial stress signaling in a disease context could be beneficial. New evidence indicates that mitochondrial membrane lipids actively regulate mitochondrial signaling pathways that influence cellular health, stress responses, and longevity. Phosphatidylethanolamine (PE), the non-bilayer-forming phospholipid, plays major roles in mitochondrial morphology and ETC function. The biosynthesis of PE takes place within the inner mitochondrial membrane and is catalyzed by the enzyme phosphatidylserine decarboxylase-1 (PSD-1), which converts phosphatidylserine (PS) to PE. While the biochemical role of PSD-1 in PE biosynthesis is well established, how its dysfunction translates into mitochondrial pathology remains poorly understood. In this work, we describe the physiological implications of PSD-1 function and validate a novel disease model for human PISD (the ortholog of C. elegans psd-1) by undertaking targeted gene knockdown using RNA interference (RNAi) in Caenorhabditis elegans. We show that psd-1 deficiency causes several physiological defects in C. elegans, demonstrating that PE biosynthesis via PSD-1 is critical for mitochondrial activity and organismal development (mitochondrial PE levels were reduced by 69.51% in psd-1 knockdown worms compared to controls). These findings establish psd-1 knockdown worms as a reliable model for studying human PISD-related disease. Surprisingly, co-knockdown of psd-1 along with the ETC component clk-1 rescued physiological defects such as restoring the lifespan of from 13.48 ± 0.51 days psd-1 RNAi worms to 17.36 ± 0.44 days in psd-1; clk-1 double-knockdown worms and normalizing oxygen consumption rate, suggesting that ETC-mediated retrograde signaling, rather than phospholipid depletion alone, is the primary driver of the observed pathology. Full article

(This article belongs to the Special Issue Role of Mitochondria and ROS in Health and Disease—2nd Edition)

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24 pages, 11052 KB

Open AccessArticle

Nifuroxazide Pretreatment Protects Against Acute CdCl₂ Exposure-Induced Toxicity via Modulating the USP21/AIM2 Inflammasome Axis

by Jing Yu, Feng Xu, Ran Wang, Qiu-Man Li, Xiang Li, Yi-Fang Jiang, Jian-Fei Lu, Chang-Hong Li, Guan-Jun Yang and Jiong Chen

Antioxidants 2026, 15(9), 1211; https://doi.org/10.3390/antiox15091211 - 20 Sep 2026

Abstract

Cadmium (Cd) is a ubiquitous environmental pollutant with an exceptionally long biological half-life (10–30 years) and high multi-organ toxicity. While chronic cadmium exposure has been extensively studied, the pathological mechanisms and prophylactic strategies for acute cadmium poisoning remain poorly defined. Here, we established [...] Read more.

Cadmium (Cd) is a ubiquitous environmental pollutant with an exceptionally long biological half-life (10–30 years) and high multi-organ toxicity. While chronic cadmium exposure has been extensively studied, the pathological mechanisms and prophylactic strategies for acute cadmium poisoning remain poorly defined. Here, we established an acute cadmium intoxication model in C57BL/6 mice via intraperitoneal injection of CdCl₂ (5 mg/kg) and assessed pathological and molecular changes 12 h post-exposure. Histopathological examination revealed overt hepatic damage and mild extrahepatic changes in kidney and spleen. Mechanistically, acute cadmium challenge disrupted systemic redox homeostasis, as evidenced by significant reductions in superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and total antioxidant capacity (T-AOC). Concurrently, cadmium triggered a robust inflammatory response, upregulating pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and lactate dehydrogenase (LDH) release, and activated the pyroptotic pathway, as shown by elevated cleaved caspase-1 and GSDMD-N levels. To identify potential prophylactic agents, we investigated nifuroxazide (NFX), a multifunctional agent with known anti-cancer, antioxidant, and anti-inflammatory properties. Our results indicate that NFX pretreatment protects against cadmium-induced acute liver injury. Mechanistically, these data support the involvement of the USP21–AIM2 axis in this protection. USP21, a deubiquitinase, stabilizes AIM2 by removing its ubiquitin chains. Cadmium exposure increased USP21-mediated AIM2 deubiquitination, decreased AIM2 ubiquitination, and promoted AIM2 protein accumulation, accompanied by AIM2 inflammasome activation and hepatic stellate cell pyroptosis. In contrast, NFX pretreatment was associated with reduced USP21-mediated AIM2 deubiquitination, increased AIM2 ubiquitination and reduced AIM2 protein accumulation, and suppressed hepatic stellate cell pyroptosis. Collectively, these findings indicate that NFX pretreatment protects against acute CdCl₂-induced hepatic injury with mild improvements in extrahepatic tissue histology, and support the involvement of the USP21–AIM2 axis in regulating AIM2 inflammasome protein stability. Full article

(This article belongs to the Special Issue Antioxidant Defenses Against Stress Caused by Physical or Chemical Environmental Changes)

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23 pages, 12534 KB

Open AccessArticle

Enhanced Levels of Combined Waterlogging and Heat Stress Exacerbate Anatomical Damage, Photosynthetic Impairment, and Oxidative Stress in Tomato

by Wen Qin, Yankai Li, Yang Sun, Rosa M. Rivero, Xiaoming Song, Ron Mittler, Fangling Jiang, Zhen Wu, Dong Xiao, Xuedong Yang and Rong Zhou

Antioxidants 2026, 15(9), 1210; https://doi.org/10.3390/antiox15091210 - 20 Sep 2026

Abstract

Global climate change increases concurrent waterlogging and heat waves, threatening crop production. Tomato, a widely cultivated vegetable crop, is susceptible to both stresses, but their combined effects on tomato responses remain poorly understood. This study analyzed the anatomical, physiological, and molecular responses of [...] Read more.

Global climate change increases concurrent waterlogging and heat waves, threatening crop production. Tomato, a widely cultivated vegetable crop, is susceptible to both stresses, but their combined effects on tomato responses remain poorly understood. This study analyzed the anatomical, physiological, and molecular responses of two tomato genotypes, ‘NT212’ and ‘NT606’ (sensitive and tolerant to combined waterlogging and heat stresses), under control (C), waterlogging (W), heat stress (H1, H2, and H3) (34/27 °C, 38/31 °C, 42/35 °C), and combined stress (WH1, WH2, and WH3) for 48 h. ‘NT212’ exhibited only abaxial epidermal peeling under H2, but severe anatomical degradation including abaxial epidermal peeling and sponge parenchyma cell lysis under WH2. The superoxide anion (O₂^•−) production rate and PsbS and HSP70 expression were significantly higher in ‘NT212’ under WH2 than W and H2. Moreover, as the stress intensity increased from WH1 to WH2 and WH3, the O₂^•− production rate and PsbS and HSP70 expression were significantly increased in ‘NT212’. In contrast, ‘NT606’ did not exhibit obvious cell lysis under any stress treatments. The O₂^•− production rate was highest in ‘NT606’ under WH3 among all the treatments. HSP70 expression was significantly upregulated in ‘NT606’ under H3 and WH3 compared with the other treatments. Consequently, ‘NT212’ exhibited severe wilting under the H2, H3, and all combined stresses, while ‘NT606’ showed severe wilting only under WH3. Thus, combined stress caused synergistic damage exceeding individual stress, with injury intensifying as temperature increased. This study provided vital knowledge for breeding climate-resilient tomato cultivars, especially under combined waterlogging and heat stress. Full article

(This article belongs to the Special Issue Physiological, Multi-Omics, and Functional Validation of Abiotic Stress Responses in Horticultural Crops: Focusing on Antioxidant Defense and Redox Regulation)

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29 pages, 5397 KB

Open AccessReview

Betaine in Metabolic Dysfunction-Associated Steatotic Liver Disease: Mechanisms of Action and Therapeutic Potential

by Tatjana Radosavljevic, Jasmina Djuretic, Milica Brankovic, Janko Samardzic, Ivana Curuvija and Danijela Vucevic

Antioxidants 2026, 15(9), 1209; https://doi.org/10.3390/antiox15091209 - 20 Sep 2026

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The disease develops through the interaction of multiple interconnected pathophysiological mechanisms, including insulin resistance, dysregulated lipid metabolism, [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The disease develops through the interaction of multiple interconnected pathophysiological mechanisms, including insulin resistance, dysregulated lipid metabolism, oxidative stress, mitochondrial and endoplasmic reticulum dysfunction, chronic inflammation, gut–liver axis disruption, and progressive fibrogenesis. Betaine, a naturally occurring methyl donor, has been investigated as a potential therapeutic agent because of its diverse metabolic and cytoprotective effects. This review summarizes current knowledge on the mechanisms by which betaine may influence MASLD development and progression. Preclinical studies indicate that betaine improves insulin sensitivity and hepatic lipid homeostasis, reduces oxidative and endoplasmic reticulum stress, preserves mitochondrial function, mitigates inflammatory signaling, and limits hepatic fibrosis. In addition, growing evidence suggests that betaine contributes to the maintenance of gut–liver axis homeostasis, further supporting its beneficial effects on liver function. Although these findings are consistent across preclinical models, clinical evidence remains limited, and the therapeutic efficacy of betaine in patients with MASLD has not yet been established. Further well-designed clinical trials are required to determine its clinical value, optimal therapeutic strategy, and potential role in the management of MASLD. Full article

(This article belongs to the Special Issue Redox Regulation of Immune and Inflammatory Responses)

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30 pages, 2544 KB

Open AccessReview

Platelet-Derived Growth Factor Receptor Alpha in Male Reproductive Health and Oxidative Stress: Stromal Homeostasis, Injury, and Research Perspectives

by Eun-A Ko, Jeong Seok Hwa and Dawon Kang

Antioxidants 2026, 15(9), 1208; https://doi.org/10.3390/antiox15091208 - 20 Sep 2026

Abstract

Oxidative stress is a well-recognized contributor to male reproductive dysfunction, yet discussion of this mechanism has focused almost exclusively on sperm damage. This focus overlooks the somatic and stromal networks that support testicular development, steroidogenesis, tissue architecture, and erectile function. Platelet-derived growth factor [...] Read more.

Oxidative stress is a well-recognized contributor to male reproductive dysfunction, yet discussion of this mechanism has focused almost exclusively on sperm damage. This focus overlooks the somatic and stromal networks that support testicular development, steroidogenesis, tissue architecture, and erectile function. Platelet-derived growth factor receptor alpha (PDGFRα) is expressed in heterogeneous interstitial and progenitor-enriched populations and has established roles in testicular development. This narrative review examines the evidence on PDGFRα in male reproductive tissues and considers the potential relevance of redox mechanisms identified predominantly in other organ systems. Genetic studies show that Pdgfa deficiency impairs the postnatal establishment of the adult Leydig-cell population, whereas Pdgfra deficiency disrupts fetal testis cord organization and Leydig-cell differentiation. Studies of the adult testis document receptor localization and, in cell-based models, downstream signaling capacity. Preclinical work has further identified PDGFRα-positive cavernosal fibroblasts associated with vascular remodeling in erectile dysfunction, although a receptor-specific function for these cells remains unproven. We propose that PDGFR-associated redox signaling may shape stromal responses to injury in the testis and penis; however, direct evidence for this mechanism in male reproductive tissue is currently lacking. Testing this hypothesis will require cell-resolved measurements of receptor phosphorylation and localized reactive oxygen species, together with lineage-restricted, receptor-specific perturbation. Establishing whether such a pathway exists could open a mechanistic link between oxidative stress and stromal, rather than purely germ-cell, contributions to male reproductive dysfunction—with implications for both testicular endocrine failure and vasculogenic erectile dysfunction. Full article

(This article belongs to the Special Issue Oxidative Stress and Male Reproductive Health—2nd Edition)

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28 pages, 15296 KB

Open AccessArticle

Eucommia ulmoides Extract Attenuates Oxidative Stress, Endoplasmic Reticulum Stress and Apoptosis Induced by Acute Hypoxia via the Nrf2/Keap1 Pathway in Largemouth Bass (Micropterus salmoides)

by Kaiwen You, Yixuan Li, Wanqing Zhong, Jie Yu, Yamei Wu, Yuqi Guo, Haoyang Liu, Haiping Xie, Kai Yuan, Yihong Chen and Lei Wang

Antioxidants 2026, 15(9), 1207; https://doi.org/10.3390/antiox15091207 - 20 Sep 2026

Abstract

Due to the hypoxic environment caused by global warming and intensive aquaculture process, fish are susceptible to oxidative damage and death. Eucommia ulmoides extract (EUE) has demonstrated antioxidant and anti-inflammatory properties. However, whether EUE can mitigate hypoxia-induced negative effects remains uninvestigated in fish. [...] Read more.

Due to the hypoxic environment caused by global warming and intensive aquaculture process, fish are susceptible to oxidative damage and death. Eucommia ulmoides extract (EUE) has demonstrated antioxidant and anti-inflammatory properties. However, whether EUE can mitigate hypoxia-induced negative effects remains uninvestigated in fish. This study investigated the effect of 0 and 1.0 g/kg EUE on acute hypoxia-induced damage in largemouth bass and its potential mechanisms. The results showed that EUE alleviated the deterioration of plasma activities (ALT and AST) induced by acute hypoxic stress, decreased the number of macrophages and increased the total number of blood cells. EUE was effective in reducing the level of apoptosis and the content of ROS, Ca²⁺, and NO in blood cells. Additionally, EUE alleviated liver tissue injury caused by acute hypoxic stress, which could be associated with increased total antioxidant capacity and antioxidant enzyme activities (SOD, CAT and GSH-Px). Furthermore, EUE up-regulated the expression levels of Nrf2 and CAT, activated XBP1 and IRE expression and down-regulated GRP78 expression, relieving the endoplasmic reticulum (ER) stress response. The down-regulation of Caspase3 and Caspase9 is evidence that EUE inhibited apoptosis in acute hypoxic stress. In summary, EUE reduced oxidative damage, ER stress, and apoptosis caused by hypoxic stress via the Nrf2/Keap1 signaling pathway in largemouth bass. This study presents a part of the theoretical foundation for the EUE to resist damage caused by hypoxic stress, thereby establishing a basis for sustainable development in aquaculture. Full article

(This article belongs to the Special Issue Natural Antioxidants and Aquatic Animal Health—3rd Edition)

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35 pages, 1245 KB

Open AccessReview

Antioxidants as a Link Between Diabetes and Potential Plant-Based Therapies

by Alina Kuryłowicz, Leszek Dobrowolski, Monika Słupecka-Ziemilska, Zuzanna Kościów and Marta Kuczeriszka

Antioxidants 2026, 15(9), 1206; https://doi.org/10.3390/antiox15091206 - 20 Sep 2026

Abstract

The pathogenesis and advancement of diabetes mellitus and its associated complications are heavily driven by oxidative stress (OS). It happens when the body produces excessive amounts of reactive oxygen and nitrogen species (RONS). This causes cell damage and leads to chronic health issues, prompting [...] Read more.

The pathogenesis and advancement of diabetes mellitus and its associated complications are heavily driven by oxidative stress (OS). It happens when the body produces excessive amounts of reactive oxygen and nitrogen species (RONS). This causes cell damage and leads to chronic health issues, prompting scientific interest in antioxidant-based treatments. In the context of chronic diseases, such as diabetes, the search for new natural bioactive compounds is of particular importance. Within the realm of traditional healthcare, Ayurveda commands significant scientific interest. Botanical materials in the Ayurvedic tradition frequently demonstrate a wide array of physiological benefits, including (among others) hypoglycaemic and antioxidant effects. Because numerous contemporary medications trace their origins back to natural compounds—with metformin serving as a primary example—investigating these traditional botanicals could be instrumental in identifying novel pharmacological treatments. This review focuses on three traditionally used for diabetes: bitter melon (Momordica charantia), gurmar (Gymnema sylvestre), and jambolan (Syzygium cumini). Their therapeutic properties—such as antioxidant, immuno-modulatory, and anti-inflammatory effects—stem from diverse phytochemicals including alkaloids, flavonoids, polypeptides, polysaccharides, saponins and sterols. Together, their overlapping effects create a powerful, unified approach to managing diabetes. Full article

(This article belongs to the Special Issue Antioxidants in Prevention and Treatment of Diabetes)

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19 pages, 22733 KB

Open AccessArticle

Shengmai Yin Attenuates Hypobaric Hypoxia-Induced Erythrocyte Echinocytosis by Restoring Redox Homeostasis and Normalizing Band 3–Syk/SHP2 Interactions

by Jie Ding, Jiali Hua, Lingyi Meng, Chenyan Lu, Jiawei Liu, Zenghua Lin, Guohua Wang and Qianqian Luo

Antioxidants 2026, 15(9), 1205; https://doi.org/10.3390/antiox15091205 - 20 Sep 2026

Abstract

Acute exposure to high-altitude hypobaric hypoxia (HH) disrupts redox homeostasis and impairs erythrocyte morphology and oxygen transport. Shengmai Yin (SMY) is a botanical formulation with reported antioxidant activity, but its effects on HH-induced erythrocyte injury remain unclear. Male C57BL/6J mice received SMY in [...] Read more.

Acute exposure to high-altitude hypobaric hypoxia (HH) disrupts redox homeostasis and impairs erythrocyte morphology and oxygen transport. Shengmai Yin (SMY) is a botanical formulation with reported antioxidant activity, but its effects on HH-induced erythrocyte injury remain unclear. Male C57BL/6J mice received SMY in drinking water for 3 days before 24 h of simulated HH equivalent to 6000 m. Complementary in vivo and in vitro experiments assessed redox indices, lipid peroxidation, hemoglobin redox status, erythrocyte morphology, arterial oxygenation, and Band 3-associated protein interactions. HH increased serum DHE-derived fluorescence, nitric oxide, and malondialdehyde, reduced antioxidant capacity, induced echinocytosis, decreased oxyhemoglobin, and increased methemoglobin. Among the tested redox challenges, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) most closely reproduced the combined morphological and hemoglobin abnormalities. SMY scavenged DPPH, hydroxyl-radical, and superoxide-related signals in cell-free assays; reduced PTIO- and hypoxia-induced erythrocyte damage; and reversed established echinocytosis within 30 min in vitro. In mice, SMY reduced echinocytosis and improved arterial oxygenation without detectable short-term hepatic, renal, or histological toxicity. SMY also normalized HH- and PTIO-induced changes in Band 3 interactions with Syk and SHP2. These findings support SMY as a redox-modulating intervention that preserves erythrocyte structure and function during acute HH. Full article

(This article belongs to the Topic Natural Compounds in Plants, 3rd Edition)

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30 pages, 26885 KB

Open AccessArticle

Monochromatic Blue Light Enhances Antioxidant Status and Remodels the Gut Microbiome in Association with Increased Plasma Melatonin in Broiler Chickens

by Wanqi Tang, Zixu Wang, Yulan Dong, Jing Cao and Yaoxing Chen

Antioxidants 2026, 15(9), 1204; https://doi.org/10.3390/antiox15091204 - 20 Sep 2026

Abstract

The intestinal microbiome of broiler chickens has potential to regulate host health and growth performance. Although previous studies have revealed that the intestinal microbiota composition is affected by different factors including monochromatic light, the underlying mechanisms remain poorly understood, particularly regarding the causal [...] Read more.

The intestinal microbiome of broiler chickens has potential to regulate host health and growth performance. Although previous studies have revealed that the intestinal microbiota composition is affected by different factors including monochromatic light, the underlying mechanisms remain poorly understood, particularly regarding the causal role of light-sensitive hormones such as melatonin. To address this gap, a 2 × 4 factorial design was adopted in the present study, with two surgical treatments (sham-operation or pinealectomy) and four light conditions (white, blue, green, and red light), to investigate whether blue light modulates gut microbiota and antioxidant status through melatonin-dependent pathways. Broilers were reared under different monochromatic light conditions. On day 3 post-hatching, we ablated circulating melatonin production by conducting a pinealectomy or control sham-operation model. Accordingly, the broilers were assigned to eight groups: white light + sham-operation (WL), white light + pinealectomy (WP), blue light + sham-operation (BL), blue light + pinealectomy (BP), green light + sham-operation (GL), green light + pinealectomy (GP), red light + sham-operation (RL), and red light + pinealectomy (RP). On day 35, blue light was found to most effectively elevate plasma melatonin, which activated the Mel 1a/Nrf2/NQO1 pathway to reduce oxidative stress and remodel the jejunal microbiota. Metagenomic analysis identified Akkermansia muciniphila, Bifidobacterium longum and Ligilactobacillus aviarius as key bacteria enriched in blue light. Consequently, classes of microbiota-derived metabolites like stearidonic acid and indole propionic acid triggered the variation of tryptophan, bile acid and lipid metabolism, which contributed to broiler growth promotion. Moreover, pinealectomy accompanied by plasma melatonin deprivation significantly nullified the blue-light-induced effects. These insights confirm blue light is more effective in microbiota modulation by inducing melatonin secretion and providing a new strategy for light management in the broiler industry. Full article

(This article belongs to the Special Issue Antioxidant Strategies in Animal and Microbial Systems)

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15 pages, 2157 KB

Open AccessArticle

Glutathione Redox Changes in Pulmonary Arterial Blood After Remote Ischemic Conditioning in Pulmonary Hypertension: A Single-Arm Pilot Study

by Suqiao Yang, Linji Li, Junwei Zhang, Xinhua Qiao, Weiyan Sun, Wenbo Zhao, Huimin Hu, Qiumeng Xi, Yidan Li, Xiaojuan Guo, Jianfeng Wang, Juanni Gong, Yuanhua Yang, Chang Chen, Xunming Ji, Xu Zhang and Qi Yang

Antioxidants 2026, 15(9), 1203; https://doi.org/10.3390/antiox15091203 - 19 Sep 2026

Abstract

Oxidative stress contributes to pulmonary hypertension (PH), but acute redox responses within the pulmonary circulation remain poorly characterized. In this prospective, open-label, single-arm pilot study, 15 patients with PH underwent one 50 min session of remote ischemic conditioning (RIC) during right heart catheterization. [...] Read more.

Oxidative stress contributes to pulmonary hypertension (PH), but acute redox responses within the pulmonary circulation remain poorly characterized. In this prospective, open-label, single-arm pilot study, 15 patients with PH underwent one 50 min session of remote ischemic conditioning (RIC) during right heart catheterization. Pulmonary arterial (PA) blood was collected immediately before and after RIC. The prespecified primary biomarker family comprised reduced glutathione (GSH) response and the oxidized glutathione-to-GSH (GSSG/GSH) ratio in PA blood-cell and plasma fractions. PA blood-cell GSH response increased (mean paired difference, 118; 95% CI, 83–152; Holm-adjusted p < 0.001), whereas the blood-cell GSSG/GSH ratio decreased (−0.64; 95% CI, −0.81 to −0.46; Holm-adjusted p < 0.001). Plasma glutathione measures were not significant after multiplicity adjustment. PA lactate, the prespecified secondary endpoint, decreased by 0.45 mmol/L (95% CI, 0.20–0.71; p = 0.002). All participants completed RIC without clinically evident acute adverse events. These preliminary findings identify acute PA blood-cell glutathione and metabolic changes associated with RIC; however, the single-arm design precludes causal inference, and confirmation in randomized sham-controlled studies is warranted. Full article

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

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22 pages, 1403 KB

Open AccessReview

Redox-Regulating Propolis- and Honey-Containing Hydrogels in Osteoarthritis

by Jurate Zarauske, Greta Kaspute and Tatjana Ivaskiene

Antioxidants 2026, 15(9), 1202; https://doi.org/10.3390/antiox15091202 - 19 Sep 2026

Abstract

Oxidative stress and persistent inflammation are central mechanisms in osteoarthritis (OA), contributing to chondrocyte dysfunction, mitochondrial impairment, extracellular matrix degradation, pain-related signaling, and progressive joint tissue remodeling. Reactive oxygen species (ROS) act not only as damaging agents but also as regulators of redox-sensitive [...] Read more.

Oxidative stress and persistent inflammation are central mechanisms in osteoarthritis (OA), contributing to chondrocyte dysfunction, mitochondrial impairment, extracellular matrix degradation, pain-related signaling, and progressive joint tissue remodeling. Reactive oxygen species (ROS) act not only as damaging agents but also as regulators of redox-sensitive inflammatory pathways, including NF-κB, MAPK, and Nrf2-related antioxidant responses. Accordingly, localized strategies capable of modulating the oxidative–inflammatory microenvironment may offer therapeutic advantages over non-targeted antioxidant approaches. This review summarizes current evidence on natural hydrogel-based systems containing propolis and honey as potential redox-modulating and anti-inflammatory platforms for OA-related tissue degeneration. Propolis and honey are bee-derived bioactive products rich in polyphenols and other redox-active compounds with antioxidant, anti-inflammatory, antimicrobial, and tissue-protective properties. Their incorporation into hydrogel matrices may support sustained local delivery, improved tissue retention, and stimulus-responsive release within inflamed or oxidatively stressed tissues. Particular attention is given to mechanisms involving ROS regulation, suppression of inflammatory mediators, activation of endogenous antioxidant defenses, and protection of cartilage extracellular matrix. Current formulation evidence is also critically interpreted according to its disease specificity, distinguishing direct OA/cartilage-related evidence from indirect wound healing and tissue repair data. The review also addresses intra-articular biomechanical requirements, enzyme-responsive degradation, immunological safety, formulation standardization, and translational barriers. Full article

(This article belongs to the Special Issue Redox Regulation of Immune and Inflammatory Responses)

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