Antioxidants

31 pages, 2972 KB

Open AccessArticle

Effect of Nano-Selenium on Intestinal Oxidative Stress Induced by H₂O₂ in Mice

by Xiangyu Mao, Wenyuan Li, Yuanyuan Li, Xuemei Jiang, Ruinan Zhang, Lianqiang Che, Yong Zhuo, Mengmeng Sun, Xianxiang Wang, De Wu and Shengyu Xu

Antioxidants 2025, 14(9), 1073; https://doi.org/10.3390/antiox14091073 - 1 Sep 2025

Abstract

Selenium is an important trace element with certain antioxidant effects. Nano-selenium, as a novel selenium source, has the advantages of strong biological activity, high absorption efficiency, and low toxicity. The aim of the present study was to compare the protective effects of sodium [...] Read more.

Selenium is an important trace element with certain antioxidant effects. Nano-selenium, as a novel selenium source, has the advantages of strong biological activity, high absorption efficiency, and low toxicity. The aim of the present study was to compare the protective effects of sodium selenite and nano-selenium on intestinal oxidative stress induced by hydrogen peroxide (H₂O₂) in mice. A total of 60 female mice were randomly divided into 6 groups with 10 replicates per group and 1 mouse per replicate (n = 10). The first three groups were as follows: the Control group (C), fed with basal diet; the sodium selenite group (SS), basal diet + 0.3 mg·kg⁻¹ sodium selenite; and the nano-selenium group (NS), basal diet + 0.3 mg·kg⁻¹ nano-selenium. The latter three groups (CH, SSH, NSH) were fed the same diet as the former three groups, but the last 10 days of the experiment were fed with drinking water containing 0.3% H₂O₂ to induce oxidative stress. The results showed that under normal conditions, the supplementation with sodium selenite or nano-selenium decreased the spleen index of mice; sodium selenate up-regulates GPX3 expression in the ileum, and increases T-SOD in the colon of mice; and nano-selenium up-regulated GPX1 expression but decreased T-AOC in the jejunum. After drinking water treated with H₂O₂, H₂O₂ increased the expression of intestinal inflammatory factors and selenium proteins, such as IL-1β and SOD in jejunum, IL-1β, NF-κB, IL-10, TXNRD1, TXNRD2, GPX1, GPX3, GPX4, and CAT in ileum, and IL-1β and SOD in colon. At the antioxidant level, H₂O₂ decreased T-AOC in the jejunum. In the H₂O₂ treatment, sodium selenite and nano-selenium increased the ratio of VH to CD (VH/CD) in jejunum; sodium selenite up-regulated the expression of TXNRD1 in jejunum, down-regulated the expression of GPX3 in ileum, at the antioxidant level, decreased the T-SOD and T-AOC in colon, and increased the content of MDA in ileum; and nano-selenium down-regulated the expression of TXNRD1 in colon. At the same time, the expression of IL-1β, NF-κB, IL-10, TXNRD1, TXNRD2, GPX1, GPX4, and CAT can be restored to normal levels by selenium supplementation. According to the results, drinking H₂O₂ induced intestinal oxidative stress in mice to a certain extent, and selenium supplementation mitigated the destructive effect of H₂O₂ on the intestinal morphology of mice jejunum and restored the level of related inflammatory factors, and had a positive effect on antioxidants. Full article

(This article belongs to the Special Issue Applications of Antioxidant Nanoparticles, 2nd Edition)

22 pages, 4544 KB

Open AccessArticle

Immune Enhancement Effects and Extraction Optimization of Polysaccharides from Peristrophe roxburghiana

by Yong Chen, Zilong Zhao, Yanyan Xu, Fuyan Li and Qiping Zhan

Antioxidants 2025, 14(9), 1072; https://doi.org/10.3390/antiox14091072 - 1 Sep 2025

Abstract

The present study aims to optimize the extraction process and systematically investigate the bioactivity of polysaccharides derived from Peristrophe roxburghiana (Schult.) Brem. (CPPRs). To this end, the Box–Behnken design–response surface methodology was employed to optimize the extraction parameters of polysaccharides. The optimal extraction [...] Read more.

The present study aims to optimize the extraction process and systematically investigate the bioactivity of polysaccharides derived from Peristrophe roxburghiana (Schult.) Brem. (CPPRs). To this end, the Box–Behnken design–response surface methodology was employed to optimize the extraction parameters of polysaccharides. The optimal extraction conditions were as follows: extraction temperature, 84 °C; extraction duration, 208 min; liquid-to-material ratio, 1:27 g/mL; extraction times, 4 times. The maximum extraction yield reached 17.89%, and the yield under non-optimal extraction conditions is 11–16%. This study systematically investigated the polysaccharides’ physicochemical, structural, and morphological properties using multiple advanced techniques (FTIR, SEM, XRD, HPLC, rheology, and TGA). CPPRs are primarily composed of arabinose, galactose and glucose as the main monosaccharides, amorphous, and capable of low-viscosity gels at low shear rates. Furthermore, CPPRs displayed notable antioxidant activity in vitro, scavenging ABTS^•+ and DPPH^• and reducing Fe³⁺ (with scavenging/reducing rates exceeding 40% at a concentration of 1 mg/mL). Meanwhile, 3 mg/mL CPPRs reduced oxidative damage of red blood cells induced by AAPH, scavenging more than 50% of ROS, and reducing the hemolysis rate by 94.5%. Additionally, CPPRs significantly promoted secretion of cytokines (including TNF-α, IL-6, and IL-10) and NO in RAW264.7 macrophages in vitro compared with the untreated control group. These findings collectively highlight the potential of CPPRs—possessing both antioxidant and immune-enhancing properties—as promising functional ingredients for application in the food and pharmaceutical industries. Full article

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23 pages, 16307 KB

Open AccessArticle

The Mechanism of Ferroptosis Regulating Granulosa Cell Apoptosis and Oxidative Stress Through the NF-κB/PTGS2 Axis in Porcine Atretic Follicles

by Yiting Yang, Yuxu He, Mailin Gan, Xue Zhao, Tianci Liao, Yuhang Lei, Lei Chen, Lili Niu, Ye Zhao, Yan Wang, Linyuan Shen, Yihui Liu and Li Zhu

Antioxidants 2025, 14(9), 1071; https://doi.org/10.3390/antiox14091071 - 1 Sep 2025

Abstract

Ferroptosis is a new mode of cell death, which is characterized by inducing the accumulation of lipid peroxides dependent on iron ions and reactive oxygen species. It has been found that ferroptosis can lead to follicle atresia by promoting granulosa cell death and [...] Read more.

Ferroptosis is a new mode of cell death, which is characterized by inducing the accumulation of lipid peroxides dependent on iron ions and reactive oxygen species. It has been found that ferroptosis can lead to follicle atresia by promoting granulosa cell death and increasing its reactive oxygen species content, but the specific mechanism has not been elucidated. Through transcriptome sequencing, we found that ferroptosis markers and related genes were upregulated in porcine atretic follicles. PTGS2 was found to be differentially expressed between atretic and healthy follicles. By inhibiting NF-κB nuclear translocation, inhibition of the PTGS2 gene expression reduced the degree of ferroptosis in granulosa cells and rescued granulosa cell death and oxidative stress caused by ferroptosis. Therefore, we propose that the NF-κB/PTGS2 axis plays a key role in ferroptosis-induced granulosa cell death, leading to follicular atresia. Melatonin, a neurohormone secreted by the pineal gland of the upper thalamus, is involved in the regulation of various metabolic, immune, reproductive, and other processes. In the ferroptosis treatment group, melatonin treatment alleviated the degree of ferroptosis (downregulation of ferroptosis marker genes and markers) and decreased the expression of PTGS2. In summary, we have demonstrated that melatonin inhibits ferroptosis via the NF-κB/PTGS2 axis in granulosa cells. Full article

(This article belongs to the Special Issue Recent Advances in Applications of Antioxidants in Livestock Health and Reproduction)

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22 pages, 1088 KB

Open AccessReview

Oxidative Stress and Biomarkers in Craniofacial Fractures Healing: From Lipid Peroxidation to Antioxidant Therapies

by Łukasz Woźniak, Żaneta Anna Mierzejewska, Jan Borys, Wioletta Ratajczak-Wrona and Bożena Antonowicz

Antioxidants 2025, 14(9), 1070; https://doi.org/10.3390/antiox14091070 - 31 Aug 2025

Abstract

Facial bone fractures represent a significant clinical challenge due to their impact on function, aesthetics, and quality of life. Despite advances in imaging and surgical techniques, early and accurate assessment of the healing process remains limited. Conventional diagnostic methods often detect complications, such [...] Read more.

Facial bone fractures represent a significant clinical challenge due to their impact on function, aesthetics, and quality of life. Despite advances in imaging and surgical techniques, early and accurate assessment of the healing process remains limited. Conventional diagnostic methods often detect complications, such as delayed union or non-union, too late for optimal intervention. Oxidative stress—an imbalance between reactive oxygen species (ROS) and antioxidant defenses—plays a critical role in bone regeneration. In this review, biomarkers are presented in two main categories: (1) oxidative damage biomarkers (lipid peroxidation products: malondialdehyde, 4-hydroxynonenal, and F2-isoprostanes) and (2) antioxidant biomarkers (glutathione, enzymatic antioxidants: SOD, GPx, CAT). Their potential as non-invasive diagnostic and prognostic tools in craniofacial fracture healing is evaluated, along with emerging therapeutic strategies. Monitoring their levels in blood samples may provide real-time insights into the dynamics of fracture repair, enabling earlier detection of healing disturbances and informing personalized treatment approaches. Full article

(This article belongs to the Special Issue Adaptive Responses to Oxidative Stress: Insights from Molecular, Cellular, and Animal Studies)

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15 pages, 2017 KB

Open AccessArticle

Antioxidant Effects of Carnosine-Enriched Chicken Meat Consumption in Athletes: Modulation of SOD Activity and Superoxide Levels—A Randomized Control Trial

by Nikolina Kolobarić, Leon Perić, Zrinka Mihaljević, Petar Šušnjara, Alina Boris, Ines Drenjančević, Ivana Jukić and Ana Stupin

Antioxidants 2025, 14(9), 1069; https://doi.org/10.3390/antiox14091069 - 30 Aug 2025

Abstract

Dipeptide carnosine has gained attention for its antioxidant and anti-inflammatory effects demonstrated in preclinical studies, but evidence from human trials remains limited. This study investigated whether dietary carnosine delivered through enriched chicken meat can modulate redox status in competitive athletes. This randomized controlled [...] Read more.

Dipeptide carnosine has gained attention for its antioxidant and anti-inflammatory effects demonstrated in preclinical studies, but evidence from human trials remains limited. This study investigated whether dietary carnosine delivered through enriched chicken meat can modulate redox status in competitive athletes. This randomized controlled trial involved 35 male competitive athletes who were assigned to either a control group (N = 16; CTRL) consuming regular chicken meat (410 mg/day) or a carnosine group (N = 19; CAR) receiving carnosine-enriched chicken meat (590 mg/day) for 21 days. Blood sample collection, cells isolation and anthropometric measurements were performed before and after the intervention to assess antioxidant enzyme activity, intracellular reactive oxygen species production, 8-iso Prostaglandin F2α (8-iso PGF 2α) concentration, and cell adhesion molecules serum concentrations. Results were expressed as mean ± standard deviation (SD). Group comparisons were conducted using parametric and non-parametric tests, ANCOVA was applied to assess post-intervention differences adjusted for baseline values, while a two-way ANOVA was performed to determine the significance of interactions between time and treatment for each parameter, significance set at p < 0.05. CAR group showed a significant reduction in serum 8-iso PGF 2α and increased SOD activity compared to baseline and the CTRL group. Intracellular hydrogen peroxide and peroxynitrite production increased, while superoxide anion production decreased in the CAR group. Carnosine-enriched chicken meat consumption significantly reduced lipid peroxidation, increased serum enzyme activity, and decreased superoxide anion production in competitive athletes. While further research is needed to elucidate the mechanisms and key factors behind it, the observed changes indicate that carnosine-enriched chicken meat consumption affects SOD activity consequently producing an antioxidative effect. Full article

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

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15 pages, 14322 KB

Open AccessArticle

Clinical Evaluation of Oxidative Stress Markers in Patients with Long COVID During the Omicron Phase in Japan

by Osamu Mese, Yuki Otsuka, Yasue Sakurada, Kazuki Tokumasu, Yoshiaki Soejima, Satoru Morita, Yasuhiro Nakano, Hiroyuki Honda, Akiko Eguchi, Sanae Fukuda, Junzo Nojima and Fumio Otsuka

Antioxidants 2025, 14(9), 1068; https://doi.org/10.3390/antiox14091068 - 30 Aug 2025

Abstract

To characterize changes in markers of oxidative stress for the clinical evaluation of patients with long COVID, we assessed oxidative stress and antioxidant activity based on serum samples from patients who visited our clinic between May and November 2024. Seventy-seven patients with long [...] Read more.

To characterize changes in markers of oxidative stress for the clinical evaluation of patients with long COVID, we assessed oxidative stress and antioxidant activity based on serum samples from patients who visited our clinic between May and November 2024. Seventy-seven patients with long COVID (41 [53%] females and 36 [47%] males; median age, 44 years) were included. Median [interquartile range] serum levels of diacron-reactive oxygen metabolites (d-ROM; CARR Unit), biological antioxidant potential (BAP; μmol/L), and oxidative stress index (OSI) were 533.8 [454.9–627.6], 2385.8 [2169.2–2558.1] and 2.0 [1.7–2.5], respectively. Levels of d-ROMs (579.8 vs. 462.2) and OSI (2.3 vs. 1.8), but not BAP (2403.4 vs. 2352.6), were significantly higher in females than in males. OSI levels positively correlated with age and body mass index, whereas BAP levels negatively correlated with these parameters. d-ROM and OSI levels were significantly associated with inflammatory markers, including C-reactive protein (CRP) and fibrinogen, whereas BAP levels were inversely correlated with CRP and ferritin levels. Notably, serum free thyroxine levels were negatively correlated with d-ROMs and OSI, whereas cortisol levels were positively correlated with d-ROMs. Among long COVID symptoms, patients reporting brain fog exhibited significantly higher OSI levels (2.2 vs. 1.8), particularly among females (d-ROMs: 625.6 vs. 513.0; OSI: 2.4 vs. 2.0). The optimal OSI cut-off values were determined to be 1.32 for distinguishing long COVID from healthy controls and 1.92 for identifying brain fog among patients with long COVID. These findings suggest that oxidative stress markers may serve as indicators for the presence or prediction of psycho-neurological symptoms associated with long COVID in a gender-dependent manner. Full article

(This article belongs to the Special Issue Exploring Biomarkers of Oxidative Stress in Health and Disease)

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17 pages, 8241 KB

Open AccessArticle

Maize Peroxidase ZmPrx25 Modulates Apoplastic ROS Homeostasis and Promotes Seed Germination and Growth Under Osmotic and Drought Stresses

by Feixue Zhang, Liangjie Niu, Yingxue Li, Xiaoli Zhou, Hui Zhang, Xiaolin Wu, Hui Liu and Wei Wang

Antioxidants 2025, 14(9), 1067; https://doi.org/10.3390/antiox14091067 - 30 Aug 2025

Abstract

Drought is one of the major abiotic stresses threatening maize production globally. Under drought stress, maize plants produce excessive reactive oxygen species (ROS), leading to oxidative damage. The apoplast, as the site of substance and signal exchange between plant cells and the external [...] Read more.

Drought is one of the major abiotic stresses threatening maize production globally. Under drought stress, maize plants produce excessive reactive oxygen species (ROS), leading to oxidative damage. The apoplast, as the site of substance and signal exchange between plant cells and the external environment, is an important location for the production of ROS under drought stress. Elucidating the ROS scavenging mechanisms in the apoplast is crucial for understanding plant stress responses. However, there is still a lack of research on the ROS scavenging enzymes in maize apoplast and their mediated signaling pathways. We verified that maize peroxidase Prx25 (ZmPrx25) is localized in the apoplast, it scan scavenge hydrogen peroxide (H₂O₂), and we systematically investigated the responses of the apoplastic ZmPrx25-ROS system to osmotic stress. ROS accumulate in the apoplast of maize mesocotyl in response to osmotic stress and transmit the external osmotic stress signals from the apoplast to the inner cellular compartments. The expression of ZmPrx25 is highly upregulated in the meristematic regions of maize seedlings under osmotic and oxidative stress. Overexpression of ZmPrx25 in Arabidopsis promoted seed germination and plant growth, significantly enhancing tolerance to osmotic and oxidative stress. This study provides a new perspective on the role of Prx25 in scavenging ROS under drought stress. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defense in Crop Plants, 2nd Edition)

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18 pages, 1215 KB

Open AccessReview

The Dual Role of Nanomaterials in Ovarian Cancer and Female Fertility as Anti- and Prooxidants

by Massimo Aloisi, Gianna Rossi and Sandra Cecconi

Antioxidants 2025, 14(9), 1066; https://doi.org/10.3390/antiox14091066 - 29 Aug 2025

Abstract

Nanomaterials (NMs) are becoming increasingly important in biomedical applications, especially in reproductive biology and oncology. In this review, we examined the “double face” of NMs as prooxidants and antioxidants in relation to ovarian cancer and female fertility. NMs have been shown to reduce [...] Read more.

Nanomaterials (NMs) are becoming increasingly important in biomedical applications, especially in reproductive biology and oncology. In this review, we examined the “double face” of NMs as prooxidants and antioxidants in relation to ovarian cancer and female fertility. NMs have been shown to reduce oxidative stress pathways in tumors, enhancing the effectiveness of chemotherapy and serving as carriers for drugs and compounds. They are also considered for their protective effects on female fertility by improving oocyte quality, maturation, and survival under various healthy and adverse conditions. However, certain NMs can induce oxidative stress, mitochondrial dysfunction, and ovarian tissue apoptosis when present in high concentrations or after prolonged exposure. These “double face” effects highlight the complex nature of NMs’ concentration, shape, and biocompatibility. Although NMs show promise in cancer treatment and fertility preservation, a comprehensive assessment of their prooxidant potential is necessary for successful clinical application. Full article

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

24 pages, 4763 KB

Open AccessArticle

Elucidating Key Components and Mechanisms Underlying the Synergistic Anti-Type 2 Diabetes Effect of Morus alba L. and Siraitia grosvenorii Combination: An Integrated In Vitro Enzymology, Untargeted Metabolomics, and Network Pharmacology Approach

by Fang He, Shenglan Su, Ruihan Song, Yan Li, Luyan Zou, Zongjun Li, Yu Xiao, Aixiang Hou, Ke Li and Yuanxiang Wang

Antioxidants 2025, 14(9), 1065; https://doi.org/10.3390/antiox14091065 - 29 Aug 2025

Abstract

Although mulberry leaf (Morus alba L., ML) and Siraitia grosvenorii (SG) individually demonstrate anti-diabetic properties, their combined efficacy against type 2 diabetes mellitus (T2DM) remains unexplored. This study systematically explored the multi-target mechanisms and synergistic potential of the MLSG combination (MLSG) for [...] Read more.

Although mulberry leaf (Morus alba L., ML) and Siraitia grosvenorii (SG) individually demonstrate anti-diabetic properties, their combined efficacy against type 2 diabetes mellitus (T2DM) remains unexplored. This study systematically explored the multi-target mechanisms and synergistic potential of the MLSG combination (MLSG) for T2DM intervention. We evaluated the in vitro inhibitory activities of MLSG, ML, and SG on α-amylase and α-glucosidase, alongside antioxidant capacity assessments through DPPH/ABTS radical scavenging, reducing power, and FRAP assays. Bioactive metabolites were identified using non-targeted metabolomics, while core targets and pathways were predicted using network pharmacology and validated through molecular docking. The results reveal MLSG’s significantly enhanced inhibition of α-amylase (IC₅₀ = 14.06 mg/mL) and α-glucosidase (IC₅₀ = 0.02 mg/mL) compared to individual extracts, exhibiting 1.3–15.5-fold higher potency with synergistic effects (combination index < 1). MLSG also showed improved antioxidant capacity, outperforming SG in DPPH/ABTS⁺ scavenging and reducing power (p < 0.05), and surpassing ML in ABTS⁺ scavenging, reducing power, and FRAP values (p < 0.05). Metabolomics identified 26 MLSG-derived metabolites with anti-T2DM potential, and network analysis pinpointed 26 active components primarily targeting STAT3, AKT1, PIK3CA, EGFR, and MAPK1 to regulate T2DM pathways. Molecular docking confirmed strong binding affinities between these components and core targets. Collectively, MLSG exerts potent synergistic anti-T2DM effects through dual-enzyme inhibition, elevated antioxidant activity, and multi-target pathway regulation, providing a solid foundation for developing MLSG as functional food ingredients. Full article

(This article belongs to the Special Issue Potential Health Benefits of Dietary Antioxidants)

28 pages, 858 KB

Open AccessReview

Early-Life Hydrogen Sulfide Signaling as a Target for Cardiovascular–Kidney–Metabolic Syndrome Reprogramming

by Chien-Ning Hsu, Ying-Jui Lin, Chih-Yao Hou, Yu-Wei Chen and You-Lin Tain

Antioxidants 2025, 14(9), 1064; https://doi.org/10.3390/antiox14091064 - 29 Aug 2025

Abstract

Hydrogen sulfide (H₂S), once regarded solely as a toxic gas, is now recognized as a vital endogenous signaling molecule with important roles in both health and disease. Growing evidence supports the developmental origins of health and disease (DOHaD) framework, in which [...] Read more.

Hydrogen sulfide (H₂S), once regarded solely as a toxic gas, is now recognized as a vital endogenous signaling molecule with important roles in both health and disease. Growing evidence supports the developmental origins of health and disease (DOHaD) framework, in which early-life disturbances in H₂S signaling may drive the later development of cardiovascular–kidney–metabolic (CKM) syndrome—a condition that encompasses chronic kidney disease, obesity, diabetes, and cardiovascular disease. This review highlights the emerging importance of H₂S in CKM programming and the potential of H₂S-based interventions during gestation and lactation to prevent long-term adverse health outcomes in offspring. Findings from animal studies suggest that maternal supplementation with sulfur-containing amino acids, N-acetylcysteine, H₂S donors, and related sulfur-containing biomolecules can attenuate CKM-related risks in progeny. Despite these advances, several critical areas remain underexplored, including the role of gut microbiota-derived H₂S, the epigenetic mechanisms influenced by H₂S during development, and the clinical translation of preclinical findings. Targeting H₂S signaling offers a promising strategy for early-life prevention of CKM syndrome and may also hold broader potential for preventing other DOHaD-related chronic diseases. Full article

(This article belongs to the Special Issue Hydrogen Sulfide, Reactive Sulfur Species, and Donor Compounds: Natural and Synthetic Tools for Physiology and Disease)

21 pages, 12113 KB

Open AccessArticle

Chelerythrine Protects Against Acetaminophen-Induced Acute Liver Injury: Insights from Gut Microbiota and Multi-Omics Analysis

by Jinlong Liu, Yanfei Zhang, Hao Wu, Pan Yang, Wenlong Wang, Chenliang Li, Hong Cao, Jinying Wu and Xin Sun

Antioxidants 2025, 14(9), 1063; https://doi.org/10.3390/antiox14091063 - 29 Aug 2025

Abstract

Chelerythrine (CHE) is the main active component of Chelidonium majus L., possessing excellent antioxidant and anti-inflammatory properties. However, the protective effects of CHE against liver injury and its underlying mechanisms remain unclear. We aimed to investigate the effects of CHE on acute liver [...] Read more.

Chelerythrine (CHE) is the main active component of Chelidonium majus L., possessing excellent antioxidant and anti-inflammatory properties. However, the protective effects of CHE against liver injury and its underlying mechanisms remain unclear. We aimed to investigate the effects of CHE on acute liver injury (ALI) and explore its underlying mechanisms. Mice were orally administered with or without CHE (15 and 30 mg/kg) treatment for 7 days, followed by a single intraperitoneal injection of acetaminophen (APAP, 350 mg/kg). After 24 h, serum, liver, and fecal samples were collected. Then, 16S rRNA gene sequencing, metabolomics, and transcriptomics approaches were employed to investigate the protective effects of CHE against ALI. Finally, we elucidated the role of CHE in restoring gut microbiota and metabolic disorders in the context of ALI. The results showed that CHE significantly inhibited ALT and AST levels (p < 0.001). Furthermore, CHE counteracted APAP-induced alterations in IL-6, IL-1β, TNF-α, MPO, MDA, H₂O₂, CAT, SOD, and GSH (p < 0.05). These results indicate that CHE possesses antioxidant properties and inhibits inflammatory factors, thereby protecting the organism from APAP-induced ALI. CHE treatment significantly altered gut microbiota composition, particularly increasing levels of the beneficial bacterium Barnesiella intestinihominis (p < 0.05). In addition, CHE reversed metabolic disturbances and inhibited oxidative and inflammatory signaling pathways. These findings suggest that CHE is a natural hepatoprotective agent that prevents ALI by modulating gut microbiota, related metabolites, oxidative stress, and inflammation. This study provides new insights into CHE as a potential therapeutic approach for ALI. Full article

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

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22 pages, 2225 KB

Open AccessArticle

Box–Behnken Design Optimization of Green Extraction from Tomato Aerial Parts and Axillary Shoots for Enhanced Recovery of Rutin and Complementary Bioactive Compounds

by Simona Marcu Spinu, Mihaela Dragoi Cudalbeanu, Nikola Major, Smiljana Goreta Ban, Igor Palčić, Alina Ortan, Petronela Mihaela Rosu and Narcisa Elena Babeanu

Antioxidants 2025, 14(9), 1062; https://doi.org/10.3390/antiox14091062 - 29 Aug 2025

Abstract

Tomato aerial parts and axillary shoots represent underutilized agricultural residues with promising phytochemical potential. Despite the recognized antioxidant capacity of rutin, current literature lacks optimized, comparative studies on its extraction from distinct tomato vegetative components. This study aimed to maximize the recovery of [...] Read more.

Tomato aerial parts and axillary shoots represent underutilized agricultural residues with promising phytochemical potential. Despite the recognized antioxidant capacity of rutin, current literature lacks optimized, comparative studies on its extraction from distinct tomato vegetative components. This study aimed to maximize the recovery of rutin and other bioactive compounds from tomato plant biomass using green extraction techniques—microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE)—optimized through Box–Behnken design (BBD) and Response Surface Methodology (RSM). The extraction process was optimized for three key variables: temperature, solvent concentration, and plant-to-solvent ratio. Four main responses were evaluated: total phenolic content (TPC), total flavonoid content (TFC), antioxidant activity (DPPH), and rutin concentration. The highest rutin content (8614.23 mg/kg) was obtained in extracts from axillary shoots using MAE. Overall, MAE proved more efficient in recovering both primary and secondary metabolites from axillary shoots, while UAE favored the extraction of certain micronutrients and specific amino acids. Cascade extraction further improved the recovery of key compounds such as vitamin E and quinic acid. The comparative profiling of extracts revealed significant phytochemical differences between tomato aerial parts and axillary shoots, addressing a gap in the literature and underscoring the importance of optimized extraction strategies. These findings highlight tomato plant waste as a valuable source of antioxidant compounds and set the stage for future investigations into their biological activities. Full article

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

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2 pages, 1086 KB

Open AccessCorrection

Correction: Aladaileh et al. Formononetin Upregulates Nrf2/HO-1 Signaling and Prevents Oxidative Stress, Inflammation and Kidney Injury in Methotrexate-Induced Rats. Antioxidants 2019, 8, 430

by Saleem H. Aladaileh, Omnia E. Hussein, Mohammad H. Abukhalil, Sultan A. M. Saghir, May Bin-Jumah, Manal A. Alfwuaires, Mousa O. Germoush, Amer A. Almaiman and Ayman M. Mahmoud

Antioxidants 2025, 14(9), 1061; https://doi.org/10.3390/antiox14091061 - 29 Aug 2025

Abstract

In the original publication, there was a mistake in Figure 1 as published [...] Full article

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9 pages, 1910 KB

Open AccessBrief Report

Increased Levels of Oxidative Stress in Human Prostate Intraepithelial Neoplasia and Prostate Cancer: Evidence from 4-Hydroxyneonal Detection and Its Implications

by Geou-Yarh Liou, Woojung Kim and Tamiya M. Hobbs

Antioxidants 2025, 14(9), 1060; https://doi.org/10.3390/antiox14091060 - 28 Aug 2025

Abstract

Prostate cancer is not only the most common type of cancer in elderly American men but also the 2nd leading cause of cancer death in American men. The currently available treatments in clinics target male hormones that are majorly required for maintaining many [...] Read more.

Prostate cancer is not only the most common type of cancer in elderly American men but also the 2nd leading cause of cancer death in American men. The currently available treatments in clinics target male hormones that are majorly required for maintaining many physiological functions, including muscle strength, leading to poor life quality and subsequent patient-opted intermittent treatment. Aging is a key factor in prostate cancer that is associated with increased levels of oxidative stress. Several lines of evidence indicated elevated levels of reactive oxygen species (ROS) in prostate cancer, including its precursor, prostate intraepithelial neoplasia (PIN). In this current study, we utilized 4-hydroxynonenal (4HNE) as a general readout for overall oxidative stress to demonstrate the imbalance between ROS and antioxidants in human prostate cancer and its precursor lesion in both human culture cell lines and tissue samples. Our results showed that the production of 4HNE adducts was increased in human prostate cancer cells and was non-linearly correlated with prostate cancer stage. They also provided insight into prevention and potential therapeutic strategies for prostate cancer. Full article

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

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17 pages, 3785 KB

Open AccessArticle

Peroxisome Proliferator-Activated Receptor Family of Lipid-Activated Nuclear Receptors Alpha Silencing Promotes Oxidative Stress and Hypertrophic Phenotype in Rat Cardiac Cells

by Marzia Bianchi, Nadia Panera, Sara Petrillo, Nicolò Cicolani, Cristiano De Stefanis, Marco Scarsella, Domenico Ciavardelli, Fiorella Piemonte, Anna Alisi and Anna Pastore

Antioxidants 2025, 14(9), 1059; https://doi.org/10.3390/antiox14091059 - 28 Aug 2025

Abstract

The peroxisome proliferator-activated receptor family of lipid-activated nuclear receptors (PPARs) plays a critical role in the regulation of cellular lipid metabolism. In cardiac muscle, PPARα is highly expressed and regulates genes involved in fatty acid oxidation, but its activity is downregulated in hypertrophic [...] Read more.

The peroxisome proliferator-activated receptor family of lipid-activated nuclear receptors (PPARs) plays a critical role in the regulation of cellular lipid metabolism. In cardiac muscle, PPARα is highly expressed and regulates genes involved in fatty acid oxidation, but its activity is downregulated in hypertrophic hearts; however, the consequences of chronic PPARα deficiency on the cardiac contractile apparatus remain unclear. This study aimed to investigate the PPARα role in hypertrophic phenotype and to evaluate the potential effects of the antioxidant Ebselen (Ebs) treatment on changes associated with PPARα depletion. We thus generated an in vitro model of cardiac hypertrophy by stable silencing of the PPARA gene in H9c2 rat cardiomyoblasts. We observed that PPARα silencing induces a hypertrophic phenotype, characterized by increased NPPB and decreased FBXO32 expression, mitochondrial dysregulation, impaired lipid metabolism, oxidative stress, and ferroptosis-related alterations. Epigenetically, H3K27ac levels increased while H3K27me3 decreased. Moreover, miR-34a, miR-132, and miR-331 were downregulated, implicating a miRNA-mediated mechanism in PPARα-linked cardiac hypertrophy. Treatment with Ebs, a redox-active compound with inhibitory effects on ferroptosis and epigenetics, reversed hypertrophic phenotype and restored miRNA levels. In conclusion, we found that PPARα depletion promotes oxidative stress and hypertrophic phenotype and that Ebs may act as a potential therapeutic agent. Full article

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

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17 pages, 3078 KB

Open AccessArticle

Ferrostatin-1 Prevents Salivary Gland Dysfunction in an Ovariectomized Rat Model by Suppressing Mitophagy-Driven Ferroptosis

by Gi Cheol Park, Soo-Young Bang, Ji Min Kim, Sung-Chan Shin, Yong-il Cheon, Hanaro Park, Sunghwan Suh, Jung Hwan Cho, Eui-Suk Sung, Minhyung Lee, Jin-Choon Lee and Byung-Joo Lee

Antioxidants 2025, 14(9), 1058; https://doi.org/10.3390/antiox14091058 - 28 Aug 2025

Abstract

Salivary gland dysfunction is a common but underexplored complication of menopause that contributes to oral dryness, dysphagia, and increased risk of infection. Although ferroptosis, a form of regulated necrotic cell death driven by iron-dependent lipid peroxidation, has recently been implicated in postmenopausal tissue [...] Read more.

Salivary gland dysfunction is a common but underexplored complication of menopause that contributes to oral dryness, dysphagia, and increased risk of infection. Although ferroptosis, a form of regulated necrotic cell death driven by iron-dependent lipid peroxidation, has recently been implicated in postmenopausal tissue degeneration, its regulatory mechanisms in salivary glands remain unclear. In this study, we investigated the roles of mitochondrial dysfunction and mitophagy in driving ferroptosis-induced salivary gland injury in an ovariectomized (OVX) rat model of estrogen deficiency. OVX rats exhibited elevated markers of oxidative stress, lipid accumulation, and iron overload, and suppression of GPX4 activity in the salivary glands, consistent with ferroptotic activation. These changes were accompanied by impaired mitochondrial dynamics (MFN1 and OPA1), decreased expression of mitochondrial antioxidant regulators (PGC-1α, SOD, and catalase), and upregulation of mitophagy-related genes (PINK1, ULK1, Rab9, and LC3B), as well as LAMP, a lysosomal marker involved in autophagosome–lysosome fusion, while ferritinophagy (NCOA4) remained unchanged. Early administration of ferrostatin-1 effectively suppressed these pathological changes, preserving both glandular structure and function, as evidenced by the restored AQP5 and AMY2A expression. Collectively, our findings reveal that ferroptosis in estrogen-deficient salivary glands is regulated by mitochondrial instability and aberrant mitophagy, and ferrostatin-1 mitigates this cascade through multi-level mitochondrial protection. These results highlight ferrostatin-1 as a promising preventive agent against menopause-associated salivary gland dysfunction, with broader implications for organ-specific ferroptosis modulation. Full article

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

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30 pages, 2944 KB

Open AccessArticle

Synthetic Cyclic C₅-Curcuminoids Increase Antioxidant Defense and Reduce Inflammation in 6-OHDA-Induced Retinoic Acid-Differentiated SH-SY5Y Cells

by Edina Pandur, Gergely Gulyás-Fekete, Győző Kulcsár and Imre Huber

Antioxidants 2025, 14(9), 1057; https://doi.org/10.3390/antiox14091057 - 28 Aug 2025

Abstract

Parkinson’s disease (PD) is recognized as one of the most common neurodegenerative disorders globally. The primary factor contributing to this condition is the loss of dopaminergic neurons, which results in both motor and nonmotor symptoms. The etiology of neurodegeneration remains unclear. However, it [...] Read more.

Parkinson’s disease (PD) is recognized as one of the most common neurodegenerative disorders globally. The primary factor contributing to this condition is the loss of dopaminergic neurons, which results in both motor and nonmotor symptoms. The etiology of neurodegeneration remains unclear. However, it is characterized by the elevated production of reactive oxygen species, which subsequently leads to oxidative stress, lipid peroxidation, mitochondrial dysfunction, and inflammation. The investigation of the applicability of natural compounds and their derivatives to various diseases is becoming increasingly important. The possible role of curcumin from Curcuma longa L. and its derivatives in the treatment of PD has been partially investigated, but there are no data on the action of synthetic cyclic C₅-curcuminoids and chalcones tested in a Parkinson’s model. Two chalcones and five synthetic cyclic C₅-curcuminoids with potential antioxidant properties were investigated in an in vitro model of 6-hydroxydopamine (6-OHDA)-induced neurodegeneration in differentiated SH-SY5Y cells. Reactive oxygen species (ROS) production, total antioxidant capacity, antioxidant enzyme activity, thiol and ATP levels, caspase-3 activity, and cytokine release were examined after treatment with the test compounds. Based on these results, one cyclic chalcone (compound 5) and three synthetic cyclic C₅-curcuminoids (compounds 9, 12, and 13) decreased oxidative stress and apoptosis in our in vitro model of neurodegeneration. Compounds 5 and 9 were also successful in decreasing the production of pro-inflammatory cytokines (IL-6, IL-8, and TNF-α), while promoting the release of anti-inflammatory cytokines (IL-4 and IL-10). These findings indicate that these two compounds exhibit potential antioxidant, anti-apoptotic, and anti-inflammatory properties, rendering them promising candidates for drug development. Full article

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

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27 pages, 11269 KB

Open AccessArticle

Integrated Transcriptomic and Metabolomic Analysis Reveals Regulatory Effects of Fermented Chinese Chive on Early Testicular Development in Piglets

by Yupeng Xie, Suthar Teerath Kumar, Hong Zou, Ting-Ting Luo, Yunpeng Zhang, Qi Zhang, Yang Li, Kai-Min Niu, Zhenya Zhai, Chunfeng Wang, Wu-Sheng Sun and Shu-Min Zhang

Antioxidants 2025, 14(9), 1056; https://doi.org/10.3390/antiox14091056 - 28 Aug 2025

Abstract

Early testicular development is vital for adult male fertility but remains highly vulnerable to stress during the suckling stage. Fermented Chinese chive (Allium tuberosum) is known for its antioxidant and immunomodulatory properties, yet its role in testicular development remains unclear. In [...] Read more.

Early testicular development is vital for adult male fertility but remains highly vulnerable to stress during the suckling stage. Fermented Chinese chive (Allium tuberosum) is known for its antioxidant and immunomodulatory properties, yet its role in testicular development remains unclear. In this study, Songliao Black piglets received 3‰ fermented Chinese chive (LK group) mixed with starter feed and compared to a control (OD group). Testicular samples at weaning (28 days) underwent transcriptomic and metabolomic analyses. Although no significant differences were observed in gross testicular morphology, the LK group significantly increased individual (13.85%) and litter (15.11%) weaning weights (p < 0.05), with elevated serum triglycerides, total cholesterol, and a 32.2% rise in IgG levels (p < 0.05). Integrated analysis identified 76 shared pathways, including ferroptosis, insulin resistance, PI3K-Akt, MAPK, and cAMP signaling. Upregulated genes in the LK group were mainly related to energy metabolism, antioxidant defense, immune regulation, steroidogenesis, and neuroendocrine signaling, suggesting improved metabolic activity, reduced oxidative stress, and accelerated reproductive maturation. Molecular docking indicated that kaempferol and isorhamnetin from Chinese chive bind strongly to proteins involved in testicular development. Overall, fermented Chinese chive supplementation enhances early testicular development in suckling piglets via integrated modulation of metabolic, immune, and signaling pathways, providing a nutritional strategy to optimize reproductive potential in breeding boars. Full article

(This article belongs to the Special Issue Oxidative Stress in Animal Reproduction and Nutrition)

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39 pages, 1987 KB

Open AccessReview

Gas Plasma Combination Therapies—Promises from Preclinical Oncology Research

by Lingyun Yu, Julia Berner, Alice Martinet, Eric Freund, Debora Singer, Thomas von Woedtke, Klaus-Dieter Weltmann, Steffen Emmert, Ramona Clemen and Sander Bekeschus

Antioxidants 2025, 14(9), 1055; https://doi.org/10.3390/antiox14091055 - 27 Aug 2025

Abstract

The absent decline in cancer mortality rates is primarily due to moderate therapeutic efficacy and intrinsic or acquired tumor cell resistance toward treatments. Combining different oncology treatments increases therapy success and decreases the chance of refractory tumor cells. Therefore, combination cancer treatments are [...] Read more.

The absent decline in cancer mortality rates is primarily due to moderate therapeutic efficacy and intrinsic or acquired tumor cell resistance toward treatments. Combining different oncology treatments increases therapy success and decreases the chance of refractory tumor cells. Therefore, combination cancer treatments are the principal paradigm of 21st-century oncology. Physical modalities such as radiotherapy have a long-standing tradition in such combination treatments. In the last decade, another physical principle emerged as a promising anticancer agent: cold gas plasma. This partially ionized gas, operated at about body temperature, emits multiple bioactive components, including reactive oxygen and nitrogen species (ROS/RNS). This technology’s multi-ROS/RNS nature cannot be phenocopied by other means, and it capitalizes on the vulnerability of tumor cells within metabolic and redox signaling pathways. Many cancer models exposed to mono or combination gas plasma treatments have shown favorable results, and first cancer patients have benefited from cold gas plasma therapy. The main findings and proposed mechanisms of action are summarized. Considering the specific application modes, this review identifies promising gas plasma combination therapies within guideline-directed treatment schemes for several tumor entities. In conclusion, gas plasmas may become a potential (neo)adjuvant therapy to existing treatment modalities to help improve the efficacy of oncological treatments. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes—Second Edition)

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