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Antioxidants, Volume 14, Issue 2 (February 2025) – 124 articles

Cover Story (view full-size image): Diabetic patients experience hyperglycemia, which can affect multiple organs, including brain function, leading to disabling neurological complications. Hyperglycemia plays a key role in promoting neuroinflammation, the most common complication in diabetic individuals, through the activation of microglia. Attenuating hyperglycemia-related neuroinflammation in microglia may reduce diabetes-associated neurological comorbidities. Natural remedies containing phenolic compounds have shown efficacy in mitigating microglia-mediated neuroinflammation. This study describes the efficacy of a Melissa officinalis L. phytocomplex, obtained from plant cell cultures and enriched in rosmarinic acid, in attenuating hyperglycemia-induced neuroinflammation in microglia and its potential neuroprotective action. View this paper
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16 pages, 943 KiB  
Article
Is High-Dose Ubiquinone Therapy Before Cardiac Surgery Enough to Reduce the Incidence of Cardiac Surgery-Associated Acute Kidney Injury? A Randomized Controlled Trial
by Hrvoje Vučemilović, Ruben Kovač, Lada Stanišić, Ana Sanader Vučemilović, Dina Mrčela, Benjamin Benzon and Mladen Carev
Antioxidants 2025, 14(2), 243; https://doi.org/10.3390/antiox14020243 - 19 Feb 2025
Abstract
Cardiac surgery-related acute kidney injury (CS-AKI) is a decrease in kidney function after open-heart surgery, affecting up to 50% of patients. The pathophysiology of CS-AKI involves ischemia–reperfusion injury, inflammation, and oxidative stress. Ubiquinone is a potent antioxidant, and we hypothesized that it could [...] Read more.
Cardiac surgery-related acute kidney injury (CS-AKI) is a decrease in kidney function after open-heart surgery, affecting up to 50% of patients. The pathophysiology of CS-AKI involves ischemia–reperfusion injury, inflammation, and oxidative stress. Ubiquinone is a potent antioxidant, and we hypothesized that it could decrease both the incidence and severity of CS-AKI. The intervention group received ubiquinone (8 mg/kg/day) divided into three daily doses, while the control group received a placebo. The primary outcome was the incidence of CS-AKI, which was manifested as an increase in creatinine ≥26.5 µmol/L or a urine output below 0.5 mL/kg/h for 6 h. Out of 73 patients, 39.7% (N = 29) developed CS-AKI, including 35.3% of the ubiquinone group and 43.6% of the placebo group (X2(1,N = 73) = 0.4931, p = 0.4825). The secondary outcomes revealed that the ubiquinone group experienced reduced postoperative bleeding, with a median (IQR) drainage of 320 mL (230–415) compared to the drainage of 420 mL (242.5–747.5) in the placebo group (t(35.84) = 2.055, p = 0.047). The median hs-TnI level in the ubiquinone group was 239.5 ng/mL (113.25–382.75) after surgery compared to a level of 366 (234.5–672.5) ng/mL in the placebo group (p = 0.024). In conclusion, there was no significant difference in the incidence of CS-AKI between groups. Postoperative hs-TnI and bleeding were significantly reduced among patients receiving ubiquinone. Full article
(This article belongs to the Section Antioxidant Enzyme Systems)
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20 pages, 6681 KiB  
Article
Seed Priming with 2,4-Epibrassionolide Enhances Seed Germination and Heat Tolerance in Rice by Regulating the Antioxidant System and Plant Hormone Signaling Pathways
by Jingya Qian, Xu Mo, Yue Wang and Qiang Li
Antioxidants 2025, 14(2), 242; https://doi.org/10.3390/antiox14020242 - 19 Feb 2025
Abstract
With global climate warming, enhancing the heat stress tolerance of rice seeds is critical for ensuring crop yields and maintaining global food security. 2,4-Epibrassionolide (EBR) has been shown to effectively alleviate the adverse effects of heat stress on rice seed germination, but its [...] Read more.
With global climate warming, enhancing the heat stress tolerance of rice seeds is critical for ensuring crop yields and maintaining global food security. 2,4-Epibrassionolide (EBR) has been shown to effectively alleviate the adverse effects of heat stress on rice seed germination, but its mitigation mechanism has not been fully clarified. In this experiment, exogenous EBR was used as a seed priming agent. The activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), malondialdehyde (MDA), soluble protein contents, and plant hormone levels were measured during rice seed germination under heat stress (38 °C). We constructed a cDNA library for transcriptome sequencing analysis. The results showed that exogenous EBR could effectively alleviate the effect of heat stress on rice seeds by enhancing SOD, POD, and CAT enzyme activity; reducing the MDA content; and increasing the soluble protein content. Additionally, exogenous EBR increases the levels of GA and IAA while decreasing the ABA content. According to a transcriptomic analysis, exogenous EBR can induce the expression of key genes involved in GA, IAA, and ABA hormone biosynthesis and metabolism, regulating GA-, IAA-, ABA-, and H2O2-mediated signaling pathways to promote the germination of rice seeds under heat stress. This study provides new insights into the application of rice seed priming techniques. Full article
(This article belongs to the Section Antioxidant Enzyme Systems)
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23 pages, 9143 KiB  
Article
Antioxidant and Photoprotective Activities of 3,4-Dihydroxybenzoic Acid and (+)-Catechin, Identified from Schima argentea Extract, in UVB-Irradiated HaCaT Cells
by Qi He, Yu-Pei Chen, Junhao Li, Hongtan Wu, Fangfang Chen, Mingyu Li and Chun Wu
Antioxidants 2025, 14(2), 241; https://doi.org/10.3390/antiox14020241 - 19 Feb 2025
Abstract
In traditional Chinese medicine, the root bark and leaves of Schima argentea are utilized to treat dysentery, parasitic infections, and digestive disorders. In this study, the n-butanol extract of S. argentea (NBA) exhibited potent antioxidant properties, protecting HaCaT cells from UVB-induced damage, and [...] Read more.
In traditional Chinese medicine, the root bark and leaves of Schima argentea are utilized to treat dysentery, parasitic infections, and digestive disorders. In this study, the n-butanol extract of S. argentea (NBA) exhibited potent antioxidant properties, protecting HaCaT cells from UVB-induced damage, and was abundant in phenolic and flavonoid compounds. Using UPLC-QTOF-MS analysis, several antioxidants within NBA were identified. Among these, 3,4-dihydroxybenzoic acid, (+)-catechin, and procyanidin B2 effectively reduced ROS levels after 1 h post-UVB treatment (225 mJ/cm2). Notably, all three compounds significantly decreased the phosphorylation of p38 and JNK in a dose-dependent manner. Additionally, the cell survival rate of these compounds was assessed after 12 h post-UVB treatment (225 mJ/cm2). Both 3,4-dihydroxybenzoic acid and (+)-catechin significantly prevented UVB-induced apoptosis in HaCaT cells, as evidenced by MTT, Hoechst, Calcein/PI staining, and flow cytometry analyses. Proteomic analysis revealed that 3,4-dihydroxybenzoic acid achieved photoprotection by downregulating c-Fos and Jun and modulating cell cycle proteins, while (+)-catechin promoted cell repair through the PI3K-Akt and Wnt signaling pathways. These results demonstrated that both compounds can directly absorb UVB, scavenge ROS, and provide cell photoprotection by modulating multiple signaling pathways. The n-butanol extract of S. argentea holds promising potential for future medical applications. Full article
(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)
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15 pages, 778 KiB  
Article
Unlocking Fertility: How Nitric Oxide Pathways Connect Obesity and Reproductive Health—The Role of Bariatric Surgery
by Charalampos Voros, Despoina Mavrogianni, Kyriakos Bananis, Antonia Varthaliti, Anthi-Maria Papahliou, Vasileios Topalis, Panagiota Kondili, Menelaos Darlas, Maria Anastasia Daskalaki, Agni Pantou, Diamantis Athanasiou, Dimitris Mathiopoulos, Marianna Theodora, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakis
Antioxidants 2025, 14(2), 240; https://doi.org/10.3390/antiox14020240 - 19 Feb 2025
Abstract
This study examines the relationship between obesity, oxidative stress, and reproductive dysfunction. It focuses on the effects of sleeve gastrectomy on gene expression and hormone profiles in 29 women with severe obesity (BMI ≥ 40 kg/m2). Pre- and post-surgical investigations revealed [...] Read more.
This study examines the relationship between obesity, oxidative stress, and reproductive dysfunction. It focuses on the effects of sleeve gastrectomy on gene expression and hormone profiles in 29 women with severe obesity (BMI ≥ 40 kg/m2). Pre- and post-surgical investigations revealed significant differences in major gene expressions and hormonal markers. CART expression reduced significantly from 0.27 ± 4.43 to −3.42 ± 1.14 (p < 0.001), while leptin expression decreased from −1.87 ± 1.75 to −0.13 ± 1.55 (p < 0.001), indicating better metabolic regulation. In contrast, eNOS expression increased considerably from −4.87 ± 1.70 to 1.18 ± 2.31 (p = 0.003), indicating improved endothelial function and nitric oxide bioavailability, which is critical for vascular health and reproduction. Correlation research before surgery indicated no significant relationships between eNOS, CART, or leptin and clinical indicators, implying that these genes function independently in pre-surgical metabolism. While most associations remained negligible after surgery, a significant negative connection between eNOS expression and SHBG levels appeared (r = −0.365, p = 0.049), indicating potential interactions in hormonal regulation pathways following metabolic improvements. These findings emphasize the importance of bariatric surgery in reducing the negative effects of obesity on reproductive health by altering critical cellular pathways. Significant increases in CART, leptin, and eNOS expression indicate reduced oxidative stress, improved vascular tone, and hormonal balance, all of which contribute to increased reproductive capacity. This study sheds light on the molecular processes that link obesity, metabolic health, and fertility, underlining bariatric surgery’s therapeutic potential for women experiencing obesity-related infertility. Full article
(This article belongs to the Section ROS, RNS and RSS)
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19 pages, 16595 KiB  
Article
Genome-Wide Identification and Drought-Responsive Functional Analysis of the GST Gene Family in Potato (Solanum tuberosum L.)
by Ningfan Shi, Youfang Fan, Wei Zhang, Zhijia Zhang, Zhuanfang Pu, Zhongrun Li, Lijun Hu, Zhenzhen Bi, Panfeng Yao, Yuhui Liu, Zhen Liu, Jiangping Bai and Chao Sun
Antioxidants 2025, 14(2), 239; https://doi.org/10.3390/antiox14020239 - 19 Feb 2025
Abstract
Glutathione S-transferases (GSTs) play crucial roles in crop stress tolerance through protection against oxidative damage. In this study, we conducted genome-wide identification and expression analysis of the GST gene family in the autotetraploid potato cultivar Cooperative-88 (C88) using bioinformatic approaches. We [...] Read more.
Glutathione S-transferases (GSTs) play crucial roles in crop stress tolerance through protection against oxidative damage. In this study, we conducted genome-wide identification and expression analysis of the GST gene family in the autotetraploid potato cultivar Cooperative-88 (C88) using bioinformatic approaches. We identified 366 GST genes in the potato genome, which were classified into 10 subfamilies. Chromosomal mapping revealed that StGSTs were distributed across all 12 chromosomes, with 13 tandem duplication events observed in three subfamilies. Analysis of protein sequences identified 10 conserved motifs, with motif 1 potentially representing the GST domain. Analysis of cis-acting elements in the StGSTs promoter regions suggested their involvement in stress response pathways. RNA-seq analysis revealed that most StGSTs responded to both drought stress and DNA demethylation treatments. Quantitative PCR validation of 16 selected StGSTs identified four members that showed strong responses to both treatments, with distinct expression patterns between drought-tolerant (QS9) and drought-sensitive (ATL) varieties. Transient expression assays in tobacco demonstrated that these four StGSTs enhanced drought tolerance and may be regulated through DNA methylation pathways, though the precise mechanisms require further investigation. These findings provide a theoretical foundation for understanding the response and epigenetic regulation of potato GST genes under drought stress. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defense in Crop Plants)
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16 pages, 736 KiB  
Review
Pharmacological Mechanism and Drug Research Prospects of Ginsenoside Rb1 as an Antidepressant
by Shuhui Zhuang, Fuqiang Shi, Nazzareno Cannella, Massimo Ubaldi, Roberto Ciccocioppo, Hongwu Li and Di Qin
Antioxidants 2025, 14(2), 238; https://doi.org/10.3390/antiox14020238 - 19 Feb 2025
Abstract
This review explores the antidepressant effects of ginsenoside Rb1, a natural compound in traditional Chinese medicine, and its potential for treating major depressive disorder (MDD). The aetiology of depression was reviewed up to 2024, focusing on the pathways and mechanisms through which ginsenoside [...] Read more.
This review explores the antidepressant effects of ginsenoside Rb1, a natural compound in traditional Chinese medicine, and its potential for treating major depressive disorder (MDD). The aetiology of depression was reviewed up to 2024, focusing on the pathways and mechanisms through which ginsenoside Rb1 may exert its effects. Notably, ginsenoside Rb1 regulates oxidative stress and inflammatory processes while enhancing neural plasticity by downregulating miR-134 expression and alleviating depressive symptoms. Unlike traditional antidepressants that act on a single target, ginsenoside Rb1 interacts with multiple pathways, reflecting its potential for broader therapeutic application. To compensate for the current deficiency in animal experiments, clinical data, and research on the side effects of ginsenoside Rb1 in the treatment of depression, we reviewed some clinical data on the use of this component in the treatment of other diseases to explore its relevance to depression. Ginsenoside Rb1 is expected to serve as a novel antidepressant or as a complementary component in combination with other antidepressant compounds. However, further clinical trials and molecular studies are necessary to confirm its efficacy and potential side effects. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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24 pages, 1912 KiB  
Review
A Comprehensive Review of the Antitumor Activity of Olive Compounds: The Case of Olive Oil, Pomace, and Leaf Extracts, Phenolic Alcohols, Secoiridoids, and Triterpenes
by Diana Melo Ferreira, Maria Beatriz P. P. Oliveira and Rita Carneiro Alves
Antioxidants 2025, 14(2), 237; https://doi.org/10.3390/antiox14020237 - 18 Feb 2025
Abstract
Olive oil is widely recognized for its cancer-prevention properties, and its by-products, such as pomace and leaves, offer an opportunity for compound extraction. This study comprehensively reviews the antitumor activities of olive extracts and compounds in both in vitro and in vivo studies. [...] Read more.
Olive oil is widely recognized for its cancer-prevention properties, and its by-products, such as pomace and leaves, offer an opportunity for compound extraction. This study comprehensively reviews the antitumor activities of olive extracts and compounds in both in vitro and in vivo studies. Key compounds, including hydroxytyrosol (HT), oleuropein (OL), oleocanthal (OC), and maslinic acid (MA), demonstrated significant antiproliferative, apoptotic, antimigratory, and anti-invasive effects, along with selective cytotoxicity, particularly against breast and colorectal cancer. HT, OC, and MA showed anti-angiogenic effects, while HT and OC showed antimetastatic effects. Moreover, HT, OL, and OC also presented synergistic effects when combined with anticancer drugs, improving their efficacy. Additionally, HT, OL, and MA exhibited protective effects against several side effects of chemotherapy. These compounds are able to modulate important signaling pathways such as the mammalian target of rapamycin, regulate oxidative stress through reactive oxygen species production, modulate angiogenic factors, and induce autophagy. Interestingly, the synergistic effects of the compounds within olive extracts appear to be stronger than their individual action. There is a need for dose optimization, further mechanistic studies to clarify the precise mechanisms of action, and future studies using olive pomace extracts with animal models. Full article
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14 pages, 17359 KiB  
Article
Naringin Suppresses CoCl2-Induced Ferroptosis in ARPE-19 Cells
by Yuchang Yang, Manting Liu, Xiaoxv Dong, Jie Bai, Wenjuan Shi, Qian Zhu, Juan Liu, Ziheng Wang, Lisa Yi, Xingbin Yin, Jian Ni and Changhai Qu
Antioxidants 2025, 14(2), 236; https://doi.org/10.3390/antiox14020236 - 18 Feb 2025
Abstract
Hypoxic damage to retinal pigment epithelial (RPE) cells and subsequent neovascularization are key factors in the pathogenesis of branch retinal vein occlusion (BRVO). Naringin (NG), a naturally occurring flavanone glycoside, has demonstrated significant antioxidant and anti-neovascular activities. However, the regulatory effects and mechanisms [...] Read more.
Hypoxic damage to retinal pigment epithelial (RPE) cells and subsequent neovascularization are key factors in the pathogenesis of branch retinal vein occlusion (BRVO). Naringin (NG), a naturally occurring flavanone glycoside, has demonstrated significant antioxidant and anti-neovascular activities. However, the regulatory effects and mechanisms of NG on ferroptosis in BRVO are yet to be explored. Our study aimed to investigate the protective effects of NG on RPE cells under hypoxic stress and to elucidate the underlying molecular mechanisms. Our findings revealed that NG significantly reduced cytotoxicity induced by cobaltous chloride (CoCl2) and also inhibited vascular proliferation in the retina, thereby attenuating choroidal neovascularization. NG pretreatment largely countered the overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA) triggered by hypoxic damage, while also restoring levels of the antioxidants glutathione (GSH) and superoxide dismutase (SOD). Furthermore, NG pretreatment significantly activated the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and its downstream heme oxygenase-1 (HO-1) and NADPH dehydrogenase (NQO1). In conclusion, NG not only inhibits neovascularization but also alleviates inflammation in RPE cells by modulating the HO-1/GPX4 pathway to inhibit ferroptosis. These findings highlight the potential of NG as a promising therapeutic agent for the treatment of BRVO. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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42 pages, 5203 KiB  
Article
Origins of Ultrasensitivity and Complex Signaling Dynamics of Cellular Hydrogen Peroxide and Peroxiredoxin
by Shengnan Liu, Jingbo Pi and Qiang Zhang
Antioxidants 2025, 14(2), 235; https://doi.org/10.3390/antiox14020235 - 18 Feb 2025
Abstract
Hydrogen peroxide (H2O2) plays a crucial role in cell signaling in response to physiological and environmental perturbations. H2O2 can oxidize typical 2-Cys peroxiredoxin (PRX) first into a sulfenic acid, which resolves into a disulfide that can [...] Read more.
Hydrogen peroxide (H2O2) plays a crucial role in cell signaling in response to physiological and environmental perturbations. H2O2 can oxidize typical 2-Cys peroxiredoxin (PRX) first into a sulfenic acid, which resolves into a disulfide that can be reduced by thioredoxin (TRX)/TRX reductase (TR). At high levels, H2O2 can also hyperoxidize sulfenylated PRX into a sulfinic acid that can be reduced by sulfiredoxin (SRX). Therefore, PRX, TRX, TR, and SRX (abbreviated as PTRS system here) constitute the coupled sulfenylation and sulfinylation cycle (CSSC), where certain oxidized PRX and TRX forms also function as redox signaling intermediates. Earlier studies have revealed that the PTRS system is capable of rich signaling dynamics, including linearity, ultrasensitivity/switch-like response, nonmonotonicity, circadian oscillation, and possibly, bistability. However, the origins of ultrasensitivity, which is fundamentally required for redox signal amplification, have not been adequately characterized, and their roles in enabling complex nonlinear dynamics of the PTRS system remain to be determined. Through in-depth mathematical modeling analyses, here we revealed multiple sources of ultrasensitivity that are intrinsic to the CSSC, including zero-order kinetic cycles, multistep H2O2 signaling, and a mechanism arising from diminished H2O2 removal at high PRX hyperoxidation state. The CSSC, structurally a positive feedback loop, is capable of bistability under certain parameter conditions, which requires embedding multiple sources of ultrasensitivity identified. Forming a negative feedback loop with cytosolic SRX as previously observed in energetically active cells, the mitochondrial PTRS system (where PRX3 is expressed) can produce sustained circadian oscillations through supercritical Hopf bifurcations. In conclusion, our study provided novel quantitative insights into the dynamical complexity of the PTRS system and improved appreciation of intracellular redox signaling. Full article
(This article belongs to the Section Antioxidant Enzyme Systems)
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18 pages, 4357 KiB  
Article
Deciphering Antioxidant Responses in Tomato Autografts
by Carlos Frey, Andrés Hernández-Barriuso, José Luis Acebes and Antonio Encina
Antioxidants 2025, 14(2), 234; https://doi.org/10.3390/antiox14020234 - 18 Feb 2025
Abstract
Grafting is a horticultural technique that involves a healing process that requires grafted plants to develop physiological responses to overcome oxidative stress. In this study, oxidative damage, total antioxidant capacity and antioxidant enzymatic activities were analysed in functional and non-functional tomato autografts for [...] Read more.
Grafting is a horticultural technique that involves a healing process that requires grafted plants to develop physiological responses to overcome oxidative stress. In this study, oxidative damage, total antioxidant capacity and antioxidant enzymatic activities were analysed in functional and non-functional tomato autografts for eight days after grafting, considering scion and rootstock tissues separately. The results showed that oxidative damage, measured as lipid peroxidation, was controlled, especially in functional grafts. Scion tissues showed significant increases in total antioxidant capacity and activities of key antioxidant enzymes, including superoxide dismutase and catalase. Non-functional grafts showed elevated levels of class III peroxidase, potentially related to defensive suberisation and lignification. Principal component analysis revealed that antioxidant activities correlated dynamically with grafting stages, highlighting their critical role in stress mitigation. These results suggest that an efficient and asymmetric antioxidant response is essential for successful graft healing in tomato plants. Furthermore, different patterns in non-functional grafts underline the importance of redox balance in determining graft success. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defense in Crop Plants)
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12 pages, 476 KiB  
Perspective
The Role of Elderberry Hydrolate as a Therapeutic Agent in Palliative Care
by Sara Gonçalves and Ana Caramelo
Antioxidants 2025, 14(2), 233; https://doi.org/10.3390/antiox14020233 - 18 Feb 2025
Abstract
Elderberry hydrolate, derived from the berries of Sambucus nigra, has gained attention for its therapeutic properties, particularly in skincare. This review explores its potential applications in palliative care, where patients often experience compromised skin health due to illness or treatment. The bioactive [...] Read more.
Elderberry hydrolate, derived from the berries of Sambucus nigra, has gained attention for its therapeutic properties, particularly in skincare. This review explores its potential applications in palliative care, where patients often experience compromised skin health due to illness or treatment. The bioactive compounds in elderberry hydrolate, including phenylacetaldehyde, 2-acetyl-pyrrole, n-hexanal, furfural, and (E)-beta-damascenone, contribute to its anti-inflammatory, antioxidant, antimicrobial, and skin-healing effects. These properties make it a promising option for addressing common dermatological issues in palliative care, such as irritation, dryness, pruritus, and inflammation. For example, phenylacetaldehyde’s antimicrobial and anti-inflammatory actions help soothe irritated skin, while 2-acetyl-pyrrole’s antioxidant effects protect sensitive skin from oxidative stress. Additionally, n-hexanal’s antimicrobial properties reduce infection risks and furfural aids in skin regeneration. (E)-beta-damascenone’s antioxidant effects help maintain skin health and prevent further damage. Despite these promising effects, barriers to the widespread implementation of elderberry hydrolate in palliative care exist, including cost, accessibility, patient sensitivities, and regulatory challenges. Future research focusing on standardized chemical profiling, clinical trials, and addressing these practical concerns will be crucial for integrating elderberry hydrolate into palliative care regimens. This review highlights its potential as a natural, supportive therapy for enhancing patient comfort and quality of life in palliative care settings. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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15 pages, 3318 KiB  
Article
Antioxidant Activity of Bovine Colostrum in the Colon of a Mouse Model of TNBS-Induced Colitis
by Leonardo Leonardi, Shadi Dib, Egidia Costanzi, Gabriele Brecchia and Giovanna Traina
Antioxidants 2025, 14(2), 232; https://doi.org/10.3390/antiox14020232 - 18 Feb 2025
Abstract
(1) Background: Bovine colostrum (BC) is the initial milk produced by cows after giving birth and has revealed significant potential in helping various health conditions, particularly in diseases of the gastrointestinal tract, such as inflammatory bowel disease, including colitis. BC is renowned for [...] Read more.
(1) Background: Bovine colostrum (BC) is the initial milk produced by cows after giving birth and has revealed significant potential in helping various health conditions, particularly in diseases of the gastrointestinal tract, such as inflammatory bowel disease, including colitis. BC is renowned for its rich composition of components that strengthen the immune system. Inflammatory bowel diseases, including colitis, are characterized by elevated oxidative stress, leading to tissue damage and exacerbated symptoms. The aim of this study was to explore the potential antioxidant activity of bovine colostrum in the context of a mouse model of trinitrobenzene sulfonic acid-induced colitis. The effectiveness of BC in mitigating oxidative stress and its effects on colitis was evaluated. (2) Methods: Mice were divided into two groups, one group received BC by gavage for 21 days, the other group received saline solution; after 21 days one half of each of the two groups of mice were treated intrarectally with trinitrobenzene sulfonic acid to induce colitis. Colon samples were processed by immunocytochemical methods. The immunoreactivity of the main antioxidant enzymes, (i) catalase (CAT), (ii) superoxide dismutase 1 (SOD1), (iii) superoxide dismutase 2 (SOD2) and glutathione peroxidase 4 (GPX4), at the colon level was analyzed. (3) Results: The results showed positive immunoreactivity of catalase and SOD2 activities of BC in the colon of animals after induction of inflammation. (4) Conclusions: The findings have the potential to suggest new strategies for the management of gastrointestinal disorders related to oxidative stress. Furthermore, the knowledge gained could contribute to the development of functional foods or supplements specifically designed for the management of colitis. Future studies will be aimed at identifying the bioactive fractions of BC to study the mechanisms underlying its actions, as well as to trace which populations can benefit most from colostrum consumption, in addition to subjects with gastrointestinal disorders. Full article
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20 pages, 2916 KiB  
Review
Oxidative Stress on the Ground and in the Microgravity Environment: Pathophysiological Effects and Treatment
by Xinyuan Zhang, Huaiying Zhu and Jinhua Zhang
Antioxidants 2025, 14(2), 231; https://doi.org/10.3390/antiox14020231 - 18 Feb 2025
Abstract
With the continued exploration of the universe, there is an increasingly urgent need to address the health challenges arising from spaceflight. In space, astronauts are exposed to radiation, confinement and isolation, circadian rhythm dysregulation, and microgravity conditions that are different from those on [...] Read more.
With the continued exploration of the universe, there is an increasingly urgent need to address the health challenges arising from spaceflight. In space, astronauts are exposed to radiation, confinement and isolation, circadian rhythm dysregulation, and microgravity conditions that are different from those on Earth. These risk factors jeopardize astronauts’ health, thus affecting the quality of space missions. Among these factors, gravitational changes influence the balance between oxidation and antioxidants, stimulating the production of reactive oxygen species (ROS), finally leading to oxidative stress (OS). OS leads to oxidative damage of biomolecules such as lipids, proteins, and DNA, which causes the development of various diseases. The occurrence of OS is increased in microgravity and affects multiple systems, including the musculoskeletal, cardiovascular, nervous, and immune systems. In this review, we discuss the mechanisms of OS, the physiological effects on different systems caused by OS in microgravity environment, and potential treatments for OS. Finally, treatment strategies for oxidative stress in microgravity are summarized, providing some promising approaches for protecting the health of astronauts in future space exploration. Full article
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29 pages, 5116 KiB  
Article
Biodegradable Microplastics from Agricultural Mulch Films: Implications for Plant Growth-Promoting Bacteria and Plant’s Oxidative Stress
by Bruno Carneiro, Paula Marques, Tiago Lopes and Etelvina Figueira
Antioxidants 2025, 14(2), 230; https://doi.org/10.3390/antiox14020230 - 18 Feb 2025
Abstract
This study explores the interactions between biodegradable (BIO) microplastics and plant growth-promoting bacteria (PGPB), assessing their effects on soil health and crop productivity. Five bacterial strains, Bacillus, Enterobacter, Kosakonia, Rhizobium, and Pseudomonas, were exposed to BIO microplastics to [...] Read more.
This study explores the interactions between biodegradable (BIO) microplastics and plant growth-promoting bacteria (PGPB), assessing their effects on soil health and crop productivity. Five bacterial strains, Bacillus, Enterobacter, Kosakonia, Rhizobium, and Pseudomonas, were exposed to BIO microplastics to examine strain-specific responses. This study revealed that while most bacteria experienced growth inhibition, Kosakonia sp. O21 was poorly affected by BIO microplastics, indicating a potential for microplastic degradation. This study further investigated the effect of these microplastics on plant growth and biochemistry. Results showed that exposure to BIO microplastics significatively reduced plant growth and caused oxidative stress, affecting membranes and proteins and inducing the activity of glutathione S-transferases (GSTs), catalase (CAT), and superoxide dismutase (SOD) as antioxidant responses. Bacterial inoculation alleviated plant oxidative stress, especially at lower concentrations of microplastics. These findings emphasize the critical role of oxidative stress in mediating the negative effects of BIO microplastics on plants and the relevance of bacterial strains that can tolerate BIO microplastics to protect plants from BIO microplastics’ effects. Results also highlight the importance of extending research to assess the long-term implications of biodegradable microplastics for soil PGPBs and plant health and crop productivity. This study contributes to sustainable agricultural practices by offering insights into mitigating the risks of microplastic pollution through microbial-based interventions. Full article
(This article belongs to the Section Antioxidant Enzyme Systems)
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2 pages, 152 KiB  
Correction
Correction: Aleem et al. Whole-Genome Identification of APX and CAT Gene Families in Cultivated and Wild Soybeans and Their Regulatory Function in Plant Development and Stress Response. Antioxidants 2022, 11, 1626
by Muqadas Aleem, Saba Aleem, Iram Sharif, Maida Aleem, Rahil Shahzad, Muhammad Imran Khan, Amina Batool, Gulam Sarwar, Jehanzeb Farooq, Azeem Iqbal, Basit Latief Jan, Prashant Kaushik, Xianzhong Feng, Javaid Akhter Bhat and Parvaiz Ahmad
Antioxidants 2025, 14(2), 229; https://doi.org/10.3390/antiox14020229 - 18 Feb 2025
Abstract
In the original publication [...] Full article
16 pages, 1474 KiB  
Article
Enhanced Antitumor Activity of Korean Black Soybean Cultivar ‘Soman’ by Targeting STAT-Mediated Aerobic Glycolysis
by Su Hwan Park, Jeong Hyun Seo, Min Young Kim, Hye Jin Yun, Beom Kyu Kang, Jun Hoi Kim, Su Vin Heo, Yeong Hoon Lee, Hye Rang Park, Man Soo Choi and Jong-Ho Lee
Antioxidants 2025, 14(2), 228; https://doi.org/10.3390/antiox14020228 - 18 Feb 2025
Abstract
Black soybeans have numerous health benefits owing to their high polyphenolic content, antioxidant activity, and antitumor effects. We previously reported that the Korean black soybean cultivar ‘Soman’ possesses higher anthocyanin and isoflavone contents and superior antioxidant potential than other Korean black soybean cultivars [...] Read more.
Black soybeans have numerous health benefits owing to their high polyphenolic content, antioxidant activity, and antitumor effects. We previously reported that the Korean black soybean cultivar ‘Soman’ possesses higher anthocyanin and isoflavone contents and superior antioxidant potential than other Korean black soybean cultivars and landraces (Seoritae) do. Here, we investigated and compared the antitumor effects of Soman and Seoritae and aimed to elucidate the possible mechanisms of action. Soman inhibited cancer cell proliferation and was more potent than Seoritae. Mechanistically, Soman inhibited the phosphorylation of the signal transducer and activator of transcription (STAT1, 3, and 5) in a reactive oxygen species (ROS)-independent manner, subsequently decreasing glycolytic enzyme expression and the activities of pyruvate kinase and lactate dehydrogenase. Thus, Soman suppressed glucose uptake, lactate production, and ATP production in cancer cells. Additionally, it inhibited tumor growth in a B16F10 murine melanoma syngeneic model, accompanied by reduced STAT1 phosphorylation and decreased proliferation in Soman-treated mice, more potently than observed in Seoritae-treated mice. These findings showed that Soman exerted superior antitumor activities by suppressing STAT-mediated aerobic glycolysis and proliferation. Overall, our findings demonstrate the potent, tumor-suppressive role of Soman in human cancer and uncover a novel molecular mechanism for its therapeutic effects in cancer treatment. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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22 pages, 4201 KiB  
Article
Trend in Detection of Anthocyanins from Fresh Fruits and the Influence of Some Factors on Their Stability Impacting Human Health: Kinetic Study Assisted by UV–Vis Spectrophotometry
by Cătălina Ionescu, Adriana Samide and Cristian Tigae
Antioxidants 2025, 14(2), 227; https://doi.org/10.3390/antiox14020227 - 17 Feb 2025
Abstract
Anthocyanins (ANTHs) are polyphenolic compounds with health promoting properties, being known for their strong antioxidant effects as well as for their antimicrobial properties, obesity and cardiovascular disease prevention, and anticarcinogenic activity. Being main dietary components, it is important to know the content of [...] Read more.
Anthocyanins (ANTHs) are polyphenolic compounds with health promoting properties, being known for their strong antioxidant effects as well as for their antimicrobial properties, obesity and cardiovascular disease prevention, and anticarcinogenic activity. Being main dietary components, it is important to know the content of anthocyanins in various dietary sources and their stability in time. The total anthocyanin content (TAC) of various fresh fruits has been spectrophotometrically determined using the pH differential method. The results showed that in the analyzed samples, the TAC increased in the order: blackcurrants > blackberries > blueberries > raspberries > strawberries > plums. The degradation degree of anthocyanins extracted from blueberries (BBEs) in an ethanol/water solution in four experimental conditions was studied. Kinetic studies have been approached, fitting the experimental data recorded by UV–Vis spectrophotometric analysis in agreement with some kinetic models verified for the ANTH degradation reaction. Therefore, zero-order kinetics for BBE extract degradation exposed to sunlight were identified, while for the other storage conditions (shadow, dark, cold), the first-order kinetics were respected. The results indicate that the stability decreased as follows: (ANTH stability)sunlight test << (ANTH stability)shadow test ≈ (ANTH stability)dark test < (ANTH stability)cold test. A mechanism for BBE anthocyanin degradation was proposed and the impact on human health of the degradation products is discussed. Full article
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1 pages, 146 KiB  
Correction
Correction: Sharma et al. Phytochemistry, Pharmacology, and Toxicology of Datura Species—A Review. Antioxidants 2021, 10, 1291
by Meenakshi Sharma, Inderpreet Dhaliwal, Kusum Rana, Anil Kumar Delta and Prashant Kaushik
Antioxidants 2025, 14(2), 226; https://doi.org/10.3390/antiox14020226 - 17 Feb 2025
Abstract
In the original publication [...] Full article
13 pages, 1213 KiB  
Review
Redox Regulation and Glucose Metabolism in the Stallion Spermatozoa
by Fernando J. Peña, Francisco E. Martín-Cano, Laura Becerro-Rey, Eva da Silva-Álvarez, Gemma Gaitskell-Phillips, Inés M. Aparicio, María C. Gil and Cristina Ortega-Ferrusola
Antioxidants 2025, 14(2), 225; https://doi.org/10.3390/antiox14020225 - 17 Feb 2025
Abstract
Stallion spermatozoa are cells which exhibit intense metabolic activity, where oxidative phosphorylation in the mitochondria is the primary ATP generator. However, metabolism must be viewed as a highly interconnected network of oxidation–reduction reactions that generate the energy necessary for life. An unavoidable side [...] Read more.
Stallion spermatozoa are cells which exhibit intense metabolic activity, where oxidative phosphorylation in the mitochondria is the primary ATP generator. However, metabolism must be viewed as a highly interconnected network of oxidation–reduction reactions that generate the energy necessary for life. An unavoidable side effect of metabolism is the generation of reactive oxygen species, leading to the evolution of sophisticated mechanisms to maintain redox homeostasis. In this paper, we provide an updated overview of glucose metabolism in stallion spermatozoa, highlighting recent evidence on the role of aerobic glycolysis in these cells, and the existence of an intracellular lactate shuttle that may help to explain the particular metabolism of the stallion spermatozoa in the context of their redox regulation. Full article
(This article belongs to the Special Issue Oxidative Stress and Male Reproductive Health)
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22 pages, 16626 KiB  
Article
Spermidine Supplementation Effectively Improves the Quality of Mouse Oocytes After Vitrification Freezing
by Li Wang, Weijian Li, Yalan Liu, Airixiati Dilixiati, Zhanzhan Chang, Yibai Liang, Yuhan Wang, Xiuling Ma, Ling Tang, Zhi He, Yuan Zhang and Xuguang Wang
Antioxidants 2025, 14(2), 224; https://doi.org/10.3390/antiox14020224 - 16 Feb 2025
Abstract
The cryopreservation of oocytes through vitrification is imperative for the conservation of livestock germplasm resources. However, as oocytes exhibit significant oxidative stress and organelle damage following vitrification freezing, it is crucial to optimise the vitrification conditions to mitigate the deleterious effects of freezing. [...] Read more.
The cryopreservation of oocytes through vitrification is imperative for the conservation of livestock germplasm resources. However, as oocytes exhibit significant oxidative stress and organelle damage following vitrification freezing, it is crucial to optimise the vitrification conditions to mitigate the deleterious effects of freezing. In this study, we demonstrated that spermidine has been showed to enhance oocyte survival after vitrification freezing (92% ± 4% vs. 82% ± 3%, p < 0.01) and blastocyst formation after freezing for in vitro fertilisation (14.86% ± 7% vs. 6% ± 3, p < 0.05). Spermidine supplementation rescued 47.3% of dysregulated pathways, including ovarian steroidogenesis, and restored normal expression levels in 43.3% of aberrantly expressed genes. Subsequent studies elucidated that spermidine effectively rescued mitochondrial dysfunction after vitrification, alleviated oxidative stress damage, and regulated intracellular calcium homeostasis. Consequently, we concluded that the addition of spermidine during vitrification freezing is an effective method to protect oocytes from freezing damage. Full article
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19 pages, 10474 KiB  
Article
The Effects of Acute Temperature Changes on Transcriptomic Responses in the Liver of Leopard Coral Groupers (Plectropomus leopardus)
by Yilan Guo, Chaofan Jin, Cun Wei, Kangning Zhong, Yurui Gao, Peiyu Li, Zhe Qu, Zhenmin Bao, Bo Wang and Jingjie Hu
Antioxidants 2025, 14(2), 223; https://doi.org/10.3390/antiox14020223 - 15 Feb 2025
Abstract
The leopard coral grouper (Plectropomus leopardus) is a commercially significant tropical marine species. With the ongoing effects of global climate change, increasing attention has been focused on leopard coral grouper’s susceptibility to extreme cold weather. This study investigates the effects of [...] Read more.
The leopard coral grouper (Plectropomus leopardus) is a commercially significant tropical marine species. With the ongoing effects of global climate change, increasing attention has been focused on leopard coral grouper’s susceptibility to extreme cold weather. This study investigates the effects of acute cold exposure and temperature recovery on the liver of P. leopardus. Histological observations and enzyme activity assays revealed that temperature fluctuations caused significant disruptions to normal liver physiology, including lipid accumulation and alterations in antioxidant levels. Transcriptomic analysis of liver tissue identified 2744 differentially expressed genes (DEGs) across three experimental groups: 25 °C (control), 13 °C (cold exposure), and rewarming at 25 °C (R-25 °C). Functional enrichment analysis revealed that these DEGs were significantly associated with biological processes such as lipid metabolism and antioxidant defense, as well as pathways related to metabolism, fatty acid biosynthesis, and ferroptosis. Furthermore, dynamic regulation of lipid metabolism, immune responses, and oxidative stress pathways was observed in response to both cold stress and rewarming. Notably, several redox-related DEGs were identified, and their interactions with lipid metabolism were further explored. Additionally, representative DEGs associated with antioxidants and lipid metabolism, such as got1, gpx1a, gpt, and g6pcla.2, were validated by qRT-PCR and fluorescence in situ hybridization (FISH). Taken together, this study provides a systematic analysis of the effects of acute cold exposure and temperature recovery stress on the liver of the leopard coral grouper, laying the groundwork for further research on the temperature stress responses in teleost species. Full article
(This article belongs to the Special Issue The Role of Oxidative Stress in Aquaculture)
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18 pages, 7306 KiB  
Article
The Regulation of γ-Aminobutyric Acid on Antioxidative Defense Response of Pacific Oyster upon High-Temperature Stress
by Ranyang Liu, Lei Gao, Xueshu Zhang, Pingan Ge, Ling Wang, Keli Zhou, Chuanyan Yang, Lingling Wang and Linsheng Song
Antioxidants 2025, 14(2), 222; https://doi.org/10.3390/antiox14020222 - 15 Feb 2025
Abstract
Recent studies have found that high temperatures cause oxidative stress and even mass mortality in Pacific oysters (Crassostrea gigas). The role of γ-aminobutyric acid (GABA) in improving antioxidative defense in aquatic animals is increasingly of interest. In the present study, the [...] Read more.
Recent studies have found that high temperatures cause oxidative stress and even mass mortality in Pacific oysters (Crassostrea gigas). The role of γ-aminobutyric acid (GABA) in improving antioxidative defense in aquatic animals is increasingly of interest. In the present study, the oxidative stress of Pacific oysters to high-temperature stress was examined, and the regulation of GABA on the antioxidative defense was further investigated. Following 6 h of exposure to 28 °C seawater, a significant increase in the mRNA expression levels of nuclear factor-E2-related factor 2 (Nrf2), superoxide dismutase (SOD), and catalase (CAT), as well as the activities of SOD and CAT, was observed in the gill, compared to those at 0 h. An increase of glutamate decarboxylase (GAD), GABA receptor (GABAAR-α and GABABR-B) mRNA levels, and GABA contents were also detected after 28 °C exposure compared to those at 0 h. Furthermore, the activities and mRNA expression levels of SOD and CAT were significantly upregulated after GABA treatment, while decreased after either GAD inhibitor or GABA receptor inhibitor treatment under high-temperature stress. Meanwhile, the enhanced effects of GABA on antioxidant enzyme activities were reduced when Nrf2 was inhibited by ML385, accompanied by an increase in MDA content. After high-temperature stress, compared with the GABA treatment group, the activities and mRNA expression levels of SOD and CAT were significantly upregulated by GSK-3β inhibitor treatment. Meanwhile, the elevation of antioxidant enzyme activities by GABA was attenuated by the AKT inhibitor treatment. Collectively, GABA first activated GABA receptors under high-temperature stress and then increased the activities of SOD and CAT and reduced MDA content by AKT/GSK-3β and Nrf2 pathways to protect the oysters against oxidative damage upon stress. The present results offer new insights for understanding the regulation mechanisms of antioxidative defense by the neuroendocrine system in molluscs. Full article
(This article belongs to the Special Issue The Role of Oxidative Stress in Aquaculture)
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4 pages, 181 KiB  
Editorial
Nanoparticles with Antioxidant Activity
by Regina G. Daré and Sueli O. S. Lautenschlager
Antioxidants 2025, 14(2), 221; https://doi.org/10.3390/antiox14020221 - 15 Feb 2025
Abstract
Oxidative stress is commonly defined as an imbalance between reactive oxygen species (ROS) production and an organism’s ability to neutralize them via antioxidant defense mechanisms, leading to damage to biomolecules, including lipids, proteins, and DNA [...] Full article
(This article belongs to the Special Issue Nanoparticles with Antioxidant Activity)
4 pages, 151 KiB  
Editorial
Multi-Target Profiling of Antioxidant Compounds, Including Repurposing and Combination Strategies
by Roberta Rocca
Antioxidants 2025, 14(2), 220; https://doi.org/10.3390/antiox14020220 - 15 Feb 2025
Abstract
Multifactorial diseases, such as cancer, neurodegenerative disorders, and stroke, present significant challenges in modern medicine due to their complex origins and the absence of definitive treatments [...] Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
18 pages, 2337 KiB  
Article
Unveiling the Potential of Three Endemic Gypsophila L. (Caryophyllaceae) Taxa as Promising Carbonic Anhydrase Inhibitors—Bio-Metabolic Profiles and In Vitro Evaluation of Enzyme Inhibition and Antioxidant Capacity
by Eda Büker, Ayşenur Kayabaş Avşar, Ertan Yildirim, Dorina Casoni, Simona Codruța Aurora Cobzac and Claudia Cimpoiu
Antioxidants 2025, 14(2), 219; https://doi.org/10.3390/antiox14020219 - 14 Feb 2025
Abstract
The Caryophyllaceae family, commonly utilized in traditional medicine, exhibits various effects revealed by ethnopharmacological studies. Thus, the diuretic effect of the leaf and stem of three Gypsophila taxa endemic to Türkiye was evaluated for the first time by comparing their bio-metabolic profiles, antioxidant [...] Read more.
The Caryophyllaceae family, commonly utilized in traditional medicine, exhibits various effects revealed by ethnopharmacological studies. Thus, the diuretic effect of the leaf and stem of three Gypsophila taxa endemic to Türkiye was evaluated for the first time by comparing their bio-metabolic profiles, antioxidant capacities, carbonic anhydrase inhibition, and infrared spectra. The leaf and stem of Gypsophila taxa were macerated in 50% ethanol and 50% water, bio-metabolic profiles were performed by a new validated ultra-performance liquid chromatographic (UPLC) method and spectrophotometric methods, the antioxidant capacity was determined by DPPH and ABTS assays, and the in vitro diuretic activity was evaluated by carbonic anhydrase inhibition. The results show that the G. simonii leaf exhibited the highest quantity of rutin and total polyphenols content (TPC). On the other hand, the G. germanicopolitana leaf showed the highest quantity of rosmarinic acid, and the G. eriocalyx leaf contained the maximum total flavonoids content (TFC). The antioxidant results indicated that G. eriocalyx has the highest capacity. The G. germanicopolitana leaf strongly inhibited the enzyme activity. The ATR-FTIR spectra showed that the general chemical composition in the leaf and stem parts was preserved after the extraction process. Band intensity changes may be due to the extraction process and the amount of substances. In conclusion, the species of Gypsophila taxa show considerable potential for utilization in the pharmaceutical area. Full article
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17 pages, 4190 KiB  
Article
miR-205-5p Modulates High Glucose-Induced VEGFA Levels in Diabetic Mice and ARPE-19 Cells
by María Ybarra, Miriam Martínez-Santos, Maria Oltra, María Muriach, Maria E. Pires, Chiara Ceresoni, Javier Sancho-Pelluz and Jorge M. Barcia
Antioxidants 2025, 14(2), 218; https://doi.org/10.3390/antiox14020218 - 14 Feb 2025
Abstract
High glucose levels may cause vascular alterations in patients with diabetes, which can lead to complications such as diabetic retinopathy—an abnormal growth of retinal blood vessels. The micro-RNA miR-205-5p is known to regulate angiogenesis by modulating the expression of the vascular endothelial growth [...] Read more.
High glucose levels may cause vascular alterations in patients with diabetes, which can lead to complications such as diabetic retinopathy—an abnormal growth of retinal blood vessels. The micro-RNA miR-205-5p is known to regulate angiogenesis by modulating the expression of the vascular endothelial growth factor (VEGFA) in different systems. This study investigates the role of miR-205-5p in controlling VEGFA expression both in vitro and in the eye under hyperglycemic conditions. An alloxan-induced diabetic mouse model and retinal pigment epithelium human cell line (ARPE-19) were exposed to high glucose and treated with an ectopic miR-205-5p mimic. VEGFA mRNA and protein levels were assessed using qRT-PCR, Western blot, and immunocytochemistry. Additionally, human umbilical vein endothelial cells (HUVECs) were employed to evaluate angiogenesis. Our results show that high glucose significantly reduced miR-205-5p levels while upregulating VEGFA expression in both ARPE-19 cells and diabetic mice. The ectopic administration of miR-205-5p (via transfection or intravitreal injection) restored VEGFA levels and inhibited angiogenesis in HUVEC cultures. Based on these preliminary data, we suggest a potential therapeutic strategy against VEGFA involving miR-205-5p in proliferative eye-related vascular disorders. Full article
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22 pages, 5902 KiB  
Article
Molecular Response and Metabolic Reprogramming of the Spleen Coping with Cold Stress in the Chinese Soft-Shelled Turtle (Pelodiscus sinensis)
by Liqin Ji, Qing Shi, Yisen Shangguan, Chen Chen, Junxian Zhu, Zhen Dong, Xiaoyou Hong, Xiaoli Liu, Chengqing Wei, Xinping Zhu and Wei Li
Antioxidants 2025, 14(2), 217; https://doi.org/10.3390/antiox14020217 - 14 Feb 2025
Abstract
The Chinese soft-shelled turtle (Pelodiscus sinensis), as a type of warm-water reptile, could be induced to massive death by sharp temperature decline. Hence, the mechanism of spleen tissue responding to cold stress in the P. sinensis was investigated. The present results [...] Read more.
The Chinese soft-shelled turtle (Pelodiscus sinensis), as a type of warm-water reptile, could be induced to massive death by sharp temperature decline. Hence, the mechanism of spleen tissue responding to cold stress in the P. sinensis was investigated. The present results showed that the superoxide dismutase (SOD) activity declined from 4 to 16 days post-cold-stress (dps), while the catalase (CAT) and glutathione peroxidase (GSH-Px) activities increased, from 4 to 8 dps in the 14 °C (T14) and 7 °C (T7) stress groups. The spleen transcriptome in the T7 group and the control group (CG) at 4 dps obtained 2625 differentially expressed genes (DEGs), including 1462 upregulated and 1663 downregulated genes. The DEGs were enriched mainly in the pathways “intestinal immune network for IgA production” (Pigr, Il15ra, Tnfrsf17, Aicda, and Cd28), “toll-like receptor signaling pathway” (Mapk10, Tlr2, Tlr5, Tlr7, and Tlr8), and “cytokine–cytokine receptor interaction” (Cx3cl1, Cx3cr1, Cxcl14, Cxcr3, and Cxcr4). The metabolomic data showed that esculentic acid, tyrosol, diosgenin, heptadecanoic acid, and 7-ketodeoxycholic acid were obviously increased, while baccatin III, taurohyocholate, parthenolide, enterolactone, and tricin were decreased, in the CG vs. T7 comparison. Integrated analysis of the two omics revealed that “glycine, serine and threonine metabolism”, “FoxO signaling pathway”, and “neuroactive ligand–receptor interaction” were the main pathways responding to the cold stress. Overall, this work found that low temperature remarkably influenced the antioxidant enzyme activities, gene expression pattern, and metabolite profile in the spleen, indicating that immunity might be weakened by cold stress in P. sinensis. Full article
(This article belongs to the Special Issue The Role of Oxidative Stress in Aquaculture)
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16 pages, 2501 KiB  
Article
Protective Effect of Methyl Sulfonyl Methane on the Progression of Age-Induced Bone Loss by Regulating Oxidative Stress-Mediated Bone Resorption
by Duo Zhang, Leilei Wang, Lu Tang, Yeting Zhang, Huaiyong Zhang and Lin Zou
Antioxidants 2025, 14(2), 216; https://doi.org/10.3390/antiox14020216 - 13 Feb 2025
Abstract
Aging is associated with detrimental bone loss, often leading to fragility fractures, which may be driven by oxidative stress. In this study, the outcomes of comparing the differences among young, adult and aged C57BL/6J mice found that the trabecular bone volume was significantly [...] Read more.
Aging is associated with detrimental bone loss, often leading to fragility fractures, which may be driven by oxidative stress. In this study, the outcomes of comparing the differences among young, adult and aged C57BL/6J mice found that the trabecular bone volume was significantly lower in the aged mice compared to young mice, and the bone characteristics were significantly correlated with the oxidative status. To counteract the adverse effects of aging, methyl sulfonyl methane (MSM), a stable metabolite of dimethyl sulfoxide, was used to supplement the drinking water (400 mg/kg/day) of the aged mice (73 weeks old) for 8 weeks. The MSM supplementation improved the maximum load, bone microarchitecture, and mRNA levels of osteocyte-specific genes in the tibia. Furthermore, MSM reduced the serum level of the C-terminal telopeptide of type I collagen, a marker of bone resorption, and downregulated the mRNA levels of genes related to osteoclast proliferation and activity. MSM also decreased the levels of pro-inflammatory cytokines in both the serum and bone marrow. Importantly, the MSM-treated mice exhibited an enhanced antioxidant status, characterized by increased glutathione peroxidase (GPx) activity and glutathione concentration in plasma, erythrocytes and bone marrow. These improvements were linked to the activation of the nuclear factor E2 related factor 2 (Nrf2) pathway and its downstream antioxidant gene expression, including that of superoxide dismutase and GPx. These findings suggested that age-related bone loss is closely tied to oxidative stress, and MSM supplementation effectively reverses bone loss by mitigating oxidative stress-mediated bone resorption. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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37 pages, 12809 KiB  
Article
Polydatin and Nicotinamide Prevent Iron Accumulation and Lipid Peroxidation in Cellular Models of Mitochondrial Diseases
by Paula Cilleros-Holgado, David Gómez-Fernández, Rocío Piñero-Pérez, José Manuel Romero-Domínguez, Diana Reche-López, Mónica Álvarez-Córdoba, Ana Romero-González, Alejandra López-Cabrera, Marta Castro De Oliveira, Andrés Rodríguez-Sacristán, Susana González-Granero, José Manuel García-Verdugo and José Antonio Sánchez-Alcázar
Antioxidants 2025, 14(2), 215; https://doi.org/10.3390/antiox14020215 - 13 Feb 2025
Abstract
Ferroptosis, an iron-dependent form of non-apoptotic cell death, is regulated by a complex network involving lipid metabolism, iron homeostasis, and the oxidative-reductive system, with iron accumulation and lipid peroxidation as key drivers. Mitochondrial dysfunction and ROS overproduction often underlie the pathogenesis of mitochondrial [...] Read more.
Ferroptosis, an iron-dependent form of non-apoptotic cell death, is regulated by a complex network involving lipid metabolism, iron homeostasis, and the oxidative-reductive system, with iron accumulation and lipid peroxidation as key drivers. Mitochondrial dysfunction and ROS overproduction often underlie the pathogenesis of mitochondrial diseases, for which treatment options are limited, emphasizing the need for novel therapies. In this study, we investigated whether polydatin and nicotinamide could reverse ferroptosis-related pathological features in cellular models derived from patients with pathogenic GFM1 variants. Mutant fibroblasts showed increased iron and lipofuscin accumulation, altered expression of iron metabolism-related proteins, elevated lipid peroxidation, and heightened susceptibility to erastin-induced ferroptosis. Treatment with polydatin and nicotinamide effectively corrected these alterations and reduced iron accumulation and lipid peroxidation in induced neurons. Furthermore, chloramphenicol treatment in control cells mimicked the mutant phenotype, suggesting that these pathological changes are linked to the mitochondrial protein synthesis defect characteristic of pathogenic GFM1 variants. Notably, adding vitamin E to the polydatin and nicotinamide co-treatment resulted in a reduction in the minimum effective concentration, suggesting potential benefits of its inclusion. In conclusion, the combination of polydatin, nicotinamide, and vitamin E could represent a promising therapeutic option for patients with mitochondrial disorders caused by pathogenic GFM1 variants. Full article
(This article belongs to the Section Antioxidant Enzyme Systems)
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32 pages, 9628 KiB  
Article
Chronic Wound Initiation: Single-Cell RNAseq of Cutaneous Wound Tissue and Contributions of Oxidative Stress to Initiation of Chronicity
by Parnian Jabbari, Jane H. Kim, Brandon H. Le, Wei Zhang, Huimin Zhang and Manuela Martins-Green
Antioxidants 2025, 14(2), 214; https://doi.org/10.3390/antiox14020214 - 13 Feb 2025
Abstract
Chronic wounds (CWs) in humans affect millions of people in the US alone, cost billions of dollars, cause much suffering, and still there are no effective treatments. Patients seek medical care when wound chronicity is already established, making it impossible to investigate factors [...] Read more.
Chronic wounds (CWs) in humans affect millions of people in the US alone, cost billions of dollars, cause much suffering, and still there are no effective treatments. Patients seek medical care when wound chronicity is already established, making it impossible to investigate factors that initiate chronicity. In this study, we used a diabetic mouse model of CWs that mimics many aspects of chronicity in humans. We performed scRNAseq to compare the cell composition and function during the first 72 h post-injury and profiled 102,737 cells into clusters of all major cell types involved in healing. We found two types of fibroblasts. Fib 1 (pro-healing) was enriched in non-CWs (NCWs) whereas Fib 2 (non-healing) was in CWs. Both showed disrupted proliferation and migration, and extracellular matrix (ECM) deposition in CWs. We identified several subtypes of keratinocytes, all of which were more abundant in NCWs, except for Channel-related keratinocytes, and showed altered migration, apoptosis, and response to oxidative stress (OS) in CWs. Vascular and lymphatic endothelial cells were both less abundant in CWs and both had impaired migration affecting the development of endothelial and lymphatic microvessels. Study of immune cells showed that neutrophils and mast cells are less abundant in CWs and that NCWs contained more proinflammatory macrophages (M1) whereas CWs were enriched in anti-inflammatory macrophages (M2). Also, several genes involved in mitochondrial function were abnormally expressed in CWs, suggesting impaired mitochondrial function and/or higher OS. Heat shock proteins needed for response to OS were downregulated in CWs, potentially leading to higher cellular damage. In conclusion, the initiation of chronicity is multifactorial and involves various cell types and cellular functions, indicating that one type of treatment will not fix all problems, unless the root cause is fundamental to the cell and molecular mechanisms of healing. We propose that such a fundamental process is high OS and its association with wound infection/biofilm. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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