Antioxidants

24 pages, 5319 KB

Open AccessArticle

Deciphering the Class III Peroxidase Gene Family and Verifying Their Expression in Modulating Seed Germination in Tomato

by Jingbo Sun, Feng Zhang, Zhichao Zhao, Mengxia Zhang and Chunjuan Dong

Antioxidants 2025, 14(11), 1310; https://doi.org/10.3390/antiox14111310 (registering DOI) - 30 Oct 2025

Abstract

Seed germination is crucial for seedling establishment and is regulated by precise reactive oxygen species (ROS) signaling. Class III peroxidases (PRXs), which are plant-specific enzymes, play crucial roles in plant growth, development, and responses to abiotic stress by maintaining ROS homeostasis. However, members [...] Read more.

Seed germination is crucial for seedling establishment and is regulated by precise reactive oxygen species (ROS) signaling. Class III peroxidases (PRXs), which are plant-specific enzymes, play crucial roles in plant growth, development, and responses to abiotic stress by maintaining ROS homeostasis. However, members of the PRX gene family in tomato, particularly their functions in modulating seed germination, remain poorly understood. In this study, 102 tomato PRXs (SlPRXs) were identified, and they were classified into five groups based on phylogenic analysis. Chromosomal localization revealed that these SlPRX genes are unevenly distributed across 12 tomato chromosomes, with chromosome 02 harboring the highest densities. Gene structure analysis revealed that SlPRXs contain 1 to 10 exons, and SlPRX4 possesses the most exons. All SlPRX proteins possess the characteristic peroxidase domain and share conserved structural motifs. Collinearity analysis suggested that segmental duplications might be the main contributor to the expansion of the SlPRX family. Promoter analysis revealed numerous cis-acting elements related to abiotic/biotic stress responses, phytohormones, and growth and development. Notably, seed germination-related elements such as CARE and RY element were identified in some SlPRXs. Enzymatic and electrophoresis assays indicated that PRX activity increased with seed germination. Moreover, SHAM, the inhibitor of PRX, exerted an inhibitory effect on tomato seed germination. Transcriptome data revealed stage-specific induction of SlPRXs during germination, with distinct expression peaks between 0 and 96 h post imbibition. These findings were further validated by qRT-PCR of the selected SlPRX genes. Overall, the findings enhance our understanding of SlPRX family members in tomato and highlight their potential for improving seed germination. This study also provides valuable genetic resources and potential molecular markers for breeding tomato varieties with improved germination vigor and stress resilience. Full article

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

27 pages, 6344 KB

Open AccessArticle

Effects of Black Soldier Fly (Hermetia illucens) Larvae Meal Replacement for Fish Meal on Growth Performance, Muscle Quality, Antioxidant Status, Immune Function, and Gut Microbiota in Juvenile Southern Catfish (Silurus meridionalis)

by Huiying Wang, Gao Gao, Jialong Chen, Dan Jia, Qing Hu, Hanqi Duan, Bin Zhang, Run Bi, Qingquan Hu and Baoliang Bi

Antioxidants 2025, 14(11), 1309; https://doi.org/10.3390/antiox14111309 (registering DOI) - 30 Oct 2025

Abstract

This study evaluated the effects of feeding juvenile southern catfish (Silurus meridionalis) with one of six isonitrogenous and isoenergetic diets where fish meal (FM) was replaced by black soldier fly larval meal (BSFLM) at 0%, 10%, 20%, 30%, 40%, and 50% [...] Read more.

This study evaluated the effects of feeding juvenile southern catfish (Silurus meridionalis) with one of six isonitrogenous and isoenergetic diets where fish meal (FM) was replaced by black soldier fly larval meal (BSFLM) at 0%, 10%, 20%, 30%, 40%, and 50% levels on growth, muscle quality, antioxidant capacity, immune response, and gut microbiota of juvenile southern catfish (Silurus meridionalis). A total of 1620 fish (9.20 ± 0.15 g) were fed one of six experimental diets for 8 weeks. Results demonstrated that a 50% replacement (H50 group) significantly improved weight gain rate, specific growth rate, and protein efficiency ratio (p < 0.001). Antioxidant capacity (T-AOC) was enhanced in groups H30 and H50, while immune markers lysozyme (LZM) and alkaline phosphatase (AKP) showed mixed responses. Muscle texture properties such as chewiness and adhesiveness were significantly altered across treatments. Gut villi remained structurally intact in all groups, and liver histology appeared normal. No significant differences were found in muscle amino acid or fatty acid profiles. Gut microbiota analysis revealed shifts in microbial composition, with increased abundance of Clostridia and Escherichia and functional enrichment in metabolic pathways at higher substitution levels. Interspecies network analysis indicated potential cooperation among beneficial microbes through metabolite exchange. It is concluded that 50% BSFLM substitution optimizes growth performance, muscle quality, and antioxidant capacity, while modulating gut microbiota, indicating its promise as a sustainable FM alternative and functional ingredient in aquafeeds. Full article

(This article belongs to the Special Issue Antioxidant Properties in Novel Feed Ingredients for Fish)

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19 pages, 1189 KB

Open AccessArticle

Genus Veronica—Antioxidant, Cytotoxic and Antibacterial Activity of Phenolic Compounds from Wild and Cultivated Species

by Ivana Vrca, Antonija Mikrut, Željana Fredotović, Karla Akrap, Dario Kremer, Stjepan Orhanović, Katarina Bačić, Valerija Dunkić and Marija Nazlić

Antioxidants 2025, 14(11), 1308; https://doi.org/10.3390/antiox14111308 (registering DOI) - 30 Oct 2025

Abstract

(1) Background: The conservation of plant resources is important because many wild plant populations are threatened by various influences. Growing plants from seeds is one way to ensure their survival. Comparing the biological potential of extracts between plants cultivated from seeds and wild [...] Read more.

(1) Background: The conservation of plant resources is important because many wild plant populations are threatened by various influences. Growing plants from seeds is one way to ensure their survival. Comparing the biological potential of extracts between plants cultivated from seeds and wild plants provides information about their specialized metabolites. For this reason, this study compared the biological potential of phenolic extracts from four wild-collected species of the genus Veronica and the same four cultivated species. The studied species of the genus Veronica are V. anagallis-aquatica L., V. persica Poir., V. polita Fr. and V. hederifolia L. (2) Methods: The phenolic composition was investigated with LC-QTOF (Liquid Chromatography-Quadrupole Time-of-Flight). The main methods for biological activities were as follows: ORAC (Oxygen Radical Absorbance Capacity) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical for antioxidant activity, the disk diffusion test for antibacterial activity and the MTS test of cytotoxic activity. (3) Results: The major compound in all extracts was apigenin. Cultivated species showed higher antioxidative activity. Phenolic compounds isolated from the V. anagallis-aquatica species showed the highest cytotoxic effect on all tested lines. The extracts showed antibacterial activity on three bacterial strains: Streptococcus pyogenes, Listeria monocytogenes and L. innocua. Extracts of V. anagallis-aquatica showed the highest antibacterial activity, both from the natural habitat and cultivated habitat. (4) Conclusions: A comparison of the different activities tested for phenolic extracts between wild and cultivated species of the genus Veronica showed that cultivated species also have significant biological activity and are suitable for further research and applications. Full article

(This article belongs to the Special Issue Phytochemical Profiling, Antioxidant Activity and Therapeutic Properties of Medicinal Plants)

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21 pages, 2976 KB

Open AccessArticle

In Vivo Studies on the Interaction Between Orally Administered Nitrite and Omeprazole: Beyond Proton-Catalyzed S-Nitrosation

by Macario A. Rebelo, Alessandra Cássia-Barros, Sandra O. Conde-Tella, Sabrina F. Frugeri, Paula P. Ovidio, Alceu A. Jordão Junior, Cezar Kayzuka, Riccardo Lacchini, Alessandra O. Silva, Carlos R. Tirapellli, Martin Feelisch and Jose E. Tanus-Santos

Antioxidants 2025, 14(11), 1307; https://doi.org/10.3390/antiox14111307 (registering DOI) - 30 Oct 2025

Abstract

Inorganic nitrite contributes to the nitrosation of biomolecules and exerts antioxidant effects. The proton pump inhibitor omeprazole has pro-oxidant effects, inhibits the formation of nitroso species in the stomach, and abrogates the blood pressure-lowering effects of orally administered nitrite. Here, we examine whether [...] Read more.

Inorganic nitrite contributes to the nitrosation of biomolecules and exerts antioxidant effects. The proton pump inhibitor omeprazole has pro-oxidant effects, inhibits the formation of nitroso species in the stomach, and abrogates the blood pressure-lowering effects of orally administered nitrite. Here, we examine whether a two-week treatment with nitrite leads to tissue nitrosation that scales with local thiol concentrations and whether oral nitrite treatment can prevent the pro-oxidant effects of omeprazole. Male Sprague–Dawley rats received daily doses of omeprazole 10 mg/kg i.p. (or vehicle) and sodium nitrite 15 mg/kg by gavage (or water) for 14 days. Animals were euthanized 6 h after the last nitrite dose, and blood and tissues (brain, heart, and liver) were collected for biochemical analyses. We found that nitrite treatment increased liver nitrite and total nitroso species (RxNO) concentrations approximately eight-fold (with minor increases in other organs), and omeprazole treatment attenuated these effects. Nitrite treatment selectively elevated non-protein thiol concentrations in the liver, but not in animals also receiving omeprazole. Tissue thiol elevation was associated with increased nitrosation of hepatic proteins, which was prevented by omeprazole. Nitrite upregulated mRNA expression of microsomal glutathione S-transferase-1 (Mgst1) and decreased superoxide and hydrogen peroxide production, especially in rats co-treated with omeprazole. While omeprazole increased liver xanthine oxidoreductase (XOR), nitrite treatment attenuated this effect. These results demonstrate that oral nitrite treatment robustly elevates nitrite and RxNO concentrations in the liver, and these effects are associated with increased hepatic glutathione production and an upregulation of Mgst1 expression, counteracting the pro-oxidant effects induced by omeprazole. Full article

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

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17 pages, 2299 KB

Open AccessArticle

Reactive Oxygen Species (ROS) Drive Osteocyte Dysfunction in Diabetic Osteoporosis by Impairing Autophagy and Triggering Apoptosis

by Mengqi Han, Minyue Zhao, Furong Bai, Mengying Wang, Bo Zhang, Jianfeng Shi and Zhongbo Liu

Antioxidants 2025, 14(11), 1306; https://doi.org/10.3390/antiox14111306 (registering DOI) - 30 Oct 2025

Abstract

This study investigates the mechanisms underlying osteocyte injury in a high glucose (HG) environment and explores potential therapeutic targets and diagnostic markers for diabetic osteoporosis, a common complication of type 2 diabetes mellitus (T2DM). Hyperglycemia induces oxidative stress through the reactive oxygen species [...] Read more.

This study investigates the mechanisms underlying osteocyte injury in a high glucose (HG) environment and explores potential therapeutic targets and diagnostic markers for diabetic osteoporosis, a common complication of type 2 diabetes mellitus (T2DM). Hyperglycemia induces oxidative stress through the reactive oxygen species (ROS) production, which impair osteocytes and accelerate bone loss. To examine these effects, MLO-Y4 cells and primary mouse osteocytes were cultured under normal glucose and HG conditions, with additional treatments using N-acetylcysteine (NAC, ROS scavenger) and rapamycin (autophagy promoter and mTOR inhibitor). Cell viability, ROS levels, and the autophagy and apoptosis markers expression (Beclin1, LC3, p62, Bax, Bcl2, cytochrome C, and caspase3) were assessed using CCK8/ATP level assay, flow cytometry, Western blot, qRT-PCR, immunofluorescence, and TUNEL staining. The results showed that HG inhibits cell proliferation, induces insulin resistance, generates ROS, alters antioxidant enzymes, and promotes oxidative stress, leading to mTOR activation, subsequent autophagy inhibition, and osteocyte apoptosis. NAC mitigated these effects, while rapamycin prevented HG-induced apoptosis by inhibiting mTOR activation and promoting autophagy. This suggests that ROS-induced mTOR activation impairs autophagy and hinders the clearance of damaged osteocytes, triggering apoptosis. This research provides foundational evidence and novel insights into diabetic osteoporosis pathogenesis and potential therapies. Full article

(This article belongs to the Special Issue In Honor of Jiankang Liu for His Contributions and Impact on Redox and Mitochondrial Biology and Medicine)

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14 pages, 1101 KB

Open AccessArticle

Determinants of Outcome Variability in Ischemic Stroke: A Focus on Routinely Collected Biomarkers

by Alexandru Gerdanovics, Sorana D. Bolboacă, Ioana Cristina Stănescu, Camelia Manuela Mîrza, Gabriela Bombonica Dogaru, Cristina Ariadna Nicula, Paul Mihai Boarescu, Cezara-Andreea Gerdanovics and Adriana-Elena Bulboacă

Antioxidants 2025, 14(11), 1305; https://doi.org/10.3390/antiox14111305 (registering DOI) - 30 Oct 2025

Abstract

Ischemic stroke remains a leading cause of mortality and disability, with proinflammatory, metabolic, and oxidative stress-related factors contributing to outcome variability. We conducted a retrospective cross-sectional study of 124 consecutive patients (53 women, 71 men; median age 71 [62–76]) discharged with ICD-10 code [...] Read more.

Ischemic stroke remains a leading cause of mortality and disability, with proinflammatory, metabolic, and oxidative stress-related factors contributing to outcome variability. We conducted a retrospective cross-sectional study of 124 consecutive patients (53 women, 71 men; median age 71 [62–76]) discharged with ICD-10 code I69.3 from the Neurology Department of the Clinical Rehabilitation Hospital in Cluj-Napoca (January 2023–September 2024). Men were younger (median age of 69 vs. 73 years, p-value = 0.010), more frequently smokers (42% vs. 9%, p < 0.001), and alcohol consumers (21% vs. 4%, p-value = 0.007) than women. In contrast, women were more frequently sedentary (68% vs. 49%, p-value = 0.038) and had higher LDL cholesterol (89 vs. 74 mg/dL, p = 0.026) than men. Patients with at least moderate disability (n = 84) presented higher levels of C-Reactive Protein (CRP), 1.4 vs. 1.1 mg/L, p-value = 0.027) and more frequently low HDL cholesterol serum levels (29.8% vs. 7.5%, p-value = 0.006) compared to those with minor disability. In multivariable regression, low HDL was the sole independent predictor of disability severity (OR = 4.58, 95% CI 1.21–17.41; AUC = 0.78, sensitivity = 88%, specificity = 42%), while CRP and age did not retain the significance obtained in univariable regression. Our findings highlight sex-specific risk profiles and underline the contribution of proinflammatory, metabolic, and oxidative pathways to ischemic stroke severity, underscoring the need for prospective validation in larger cohorts. Full article

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

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16 pages, 4013 KB

Open AccessArticle

Alpha-Tocopherol Protects Porcine Oocytes from Acetamiprid-Induced Meiotic Defects by Alleviating Oxidative Stress-Mediated Ferroptosis

by Yanhong Liu, Yijing He, Miaoyu Chen, Qinfeng Sun, Biao Zhang, Genkui Zhang, Aiqiao Cao, Qiao Li, Weihan Wang and Shiqiang Ju

Antioxidants 2025, 14(11), 1304; https://doi.org/10.3390/antiox14111304 (registering DOI) - 30 Oct 2025

Abstract

Acetamiprid (ACE), a widely used neonicotinoid insecticide, has raised concerns due to its potential reproductive toxicity. While its adverse effects on animal reproductive systems have been documented, the impact of ACE on mammalian oocytes remains poorly understood. This study aimed to investigate the [...] Read more.

Acetamiprid (ACE), a widely used neonicotinoid insecticide, has raised concerns due to its potential reproductive toxicity. While its adverse effects on animal reproductive systems have been documented, the impact of ACE on mammalian oocytes remains poorly understood. This study aimed to investigate the potential effects of ACE exposure on porcine oocytes and evaluate whether alpha-tocopherol (α-TOC), a fat-soluble antioxidant, could alleviate ACE-induced oocyte damage. Porcine cumulus oocyte complexes (COCs) were exposed to ACE alone or co-treated with α-TOC for 44 h during in vitro maturation. ACE exposure significantly reduced the first polar body (PB1) excretion rate, arrested meiotic progression, and disrupted spindle assembly in porcine oocytes. Furthermore, ACE impaired mitochondrial function, evidenced by decreased mitochondrial membrane potential (MMP), while increasing intracellular reactive oxygen species (ROS) accumulation and lipid peroxidation (LPO). Additionally, ACE exposure induced intracellular iron overload and dysregulated ferroptosis-related genes, downregulating solute carrier family 7 member 11 (SLC7a11) and glutathione peroxidase 4 (GPX4) while upregulating transferrin receptor 1 (TfRC) and acyl-CoA synthetase long-chain family member 4 (ACSL4), contributing to the occurrence of oocyte ferroptosis. Notably, α-TOC co-treatment effectively alleviate oxidative stress and lipid peroxidation, thereby protecting oocytes from ACE-induced ferroptosis. Collectively, these findings indicate that oxidative stress-mediated ferroptosis may be a major contributing pathway through which ACE impairs oocyte maturation and suggest that α-tocopherol may serve as a protective agent against ACE-induced oocyte damage. Full article

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

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15 pages, 1401 KB

Open AccessArticle

Genomic Analysis of Carotenoid and Vitamin E Biosynthetic Pathways in the Extremophilic Red Alga Cyanidioschyzon merolae

by Yuanyuan Hui, Dexin Lyu, Na Huang, Shan Luo, Libao Zheng, Linyuan Zheng, Chuanming Hu, Li-En Yang, Pengfu Li, Shan Lu and Yinyin Deng

Antioxidants 2025, 14(11), 1303; https://doi.org/10.3390/antiox14111303 - 30 Oct 2025

Abstract

Cyanidioschyzon merolae, an extremophilic unicellular red alga thriving in acidic hot springs at temperatures of 40–56 °C and pH 0.5–4.0, faces extreme oxidative stress conditions. This study presents a comprehensive genomic analysis of the carotenoid and vitamin E biosynthetic pathways, which are [...] Read more.

Cyanidioschyzon merolae, an extremophilic unicellular red alga thriving in acidic hot springs at temperatures of 40–56 °C and pH 0.5–4.0, faces extreme oxidative stress conditions. This study presents a comprehensive genomic analysis of the carotenoid and vitamin E biosynthetic pathways, which are essential for antioxidant defense in this organism. Through comparative genomics using Arabidopsis thaliana sequences as queries, we identified and characterized genes encoding key enzymes involved in their metabolism. Our analysis reveals that C. merolae exclusively utilizes the methylerythritol-4-phosphate (MEP) pathway for isoprenoid biosynthesis and lacks a complete mevalonate (MVA) pathway. We identified eleven genes involved in terpenoid metabolism and seven genes specifically for carotenoid biosynthesis. Pigment analysis confirmed a streamlined carotenoid profile consisting solely of β-carotene, β-cryptoxanthin, and zeaxanthin, lacking the entire β,ε-branch and part of the β,β-branch. The complete tocopherol biosynthetic pathway produces exclusively α-tocopherol. The absence of the β,ε-carotenoid branch and the exclusive production of α-tocopherol demonstrate metabolic streamlining while maintaining antioxidant efficacy. These findings provide molecular blueprints for biotechnological applications, enabling targeted strategies to enhance antioxidant production through pathway optimization and metabolic engineering, while offering insights into developing stress-tolerant organisms and enhancing nutritional content in crops. Full article

(This article belongs to the Special Issue Algal Antioxidants: Physiology, Metabolism, and Evolution)

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23 pages, 3244 KB

Open AccessArticle

Influence of Blueberry Mosaic Disease on Polyphenolic Profile and Antioxidant Capacity of Highbush Blueberry ‘Duke’ Fruits

by Nemanja Miletić, Danijel D. Milinčić, Mirjana B. Pešić, Biljana Lončar, Marko Petković, Bojana Vasilijević and Darko Jevremović

Antioxidants 2025, 14(11), 1302; https://doi.org/10.3390/antiox14111302 (registering DOI) - 29 Oct 2025

Abstract

Blueberry mosaic virus (BlMaV) is a persistent pathogen that alters host physiology; however, its impact on secondary metabolism in blueberry fruits remains poorly characterized. In this study, the phenolic profile of the cultivar ‘Duke’ was systematically examined in healthy and BlMaV-infected plants over [...] Read more.

Blueberry mosaic virus (BlMaV) is a persistent pathogen that alters host physiology; however, its impact on secondary metabolism in blueberry fruits remains poorly characterized. In this study, the phenolic profile of the cultivar ‘Duke’ was systematically examined in healthy and BlMaV-infected plants over two successive years. Using UHPLC Q-ToF MS, a total of 46 phenolic compounds were detected, spanning flavonols, phenolic acids, and anthocyanins. Comparative analyses revealed consistent shifts in metabolite abundance between healthy and infected samples. Several flavonol aglycones and phenolic acid derivatives accumulated in infected fruits, whereas multiple anthocyanins and glycosides were reduced. To further explore metabolic relationships, color correlation analysis highlighted distinct co-variation patterns among compound classes. Principal component analysis clearly separated infected and healthy fruits, confirming that viral infection was the dominant source of variation, surpassing the influence of harvest year or environmental factors. Nevertheless, the antioxidant capacity remained unchanged, regardless of the presence of the virus or the variation in environmental conditions. These results provide novel biochemical evidence that BlMaV infection reshapes the phenolic composition of blueberries and lays the groundwork for future studies on the metabolic consequences of viral stress in fruit crops. Full article

(This article belongs to the Special Issue Bioactive Compounds and Antioxidants in Fruits and Vegetables—2nd Edition)

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20 pages, 2638 KB

Open AccessArticle

Shikonin-Loaded Nanoparticles Attenuate Particulate Matter-Induced Skin Injury by Inhibiting Oxidative Stress and Inflammation

by Feifei Huang, Qinghua Tang, Ke Wang, Lingmei Zhou, Ruiwei Liao, Zhuoya Wang, Yan Li, Lin Zhou and Ming Li

Antioxidants 2025, 14(11), 1301; https://doi.org/10.3390/antiox14111301 - 29 Oct 2025

Abstract

Exposure to fine particulate matter (PM2.5) poses a major threat to skin health, yet effective prevention strategies remain limited. Shikonin, a naphthoquinone derived from Lithospermum erythrorhizon, exhibits potent antioxidant and anti-inflammatory activities. However, its therapeutic application is limited by low bioavailability. To address [...] Read more.

Exposure to fine particulate matter (PM2.5) poses a major threat to skin health, yet effective prevention strategies remain limited. Shikonin, a naphthoquinone derived from Lithospermum erythrorhizon, exhibits potent antioxidant and anti-inflammatory activities. However, its therapeutic application is limited by low bioavailability. To address this limitation, we developed shikonin-loaded nanoparticles (SH-NPs) using an emulsion solvent evaporation method and characterized their physicochemical properties. The protective effects of SH-NPs against PM2.5-induced skin damage were evaluated in a mouse model. The SH-NPs exhibited favorable characteristics, including a mean particle size of 209.03 ± 2.45 nm, a PDI of 0.064 ± 0.03, and a zeta potential of –17.69 ± 2.06 mV. The encapsulation efficiency is 88% and the drug loading capacity is 5.5%, respectively. In vitro, SH-NPs significantly enhanced cellular uptake in HaCaT cells. In vivo, treatment with SH-NPs significantly improved skin structural disorders, epidermal thickening, and collagen fiber reduction, while downregulating the expression of MMP-2 and MMP-9. Furthermore, SH-NPs increased the expression of SOD1 and SOD2, reduced MDA levels, and decreased the expression of TNF-α, IL-1β, and NO. In conclusion, SH-NPs attenuated PM2.5-induced skin toxicity via enhanced antioxidant, anti-inflammatory, and anti-degradation mechanisms, offering a novel strategy to boost shikonin bioavailability and prevent PM2.5-related skin damage. Full article

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

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19 pages, 5744 KB

Open AccessArticle

Resveratrol Alleviates Effects of LPS on Estrogen Synthesis, Oxidative Stress, Inflammation, and Pyroptosis of Goat Granulosa Cells by Activating the PPARG/NRF2/HO-1 Signaling Pathway

by Jie Zhao, Xianyi Zhou, Zhen Cang, Xin Liu, Muhammad Tariq and Dagan Mao

Antioxidants 2025, 14(11), 1300; https://doi.org/10.3390/antiox14111300 - 29 Oct 2025

Abstract

This study aims to investigate the effect and mechanism of resveratrol (RES) on lipopolysaccharide (LPS)-induced injury in goat granulosa cells (GCs). First, the appropriate time and concentration were screened for LPS (4 μg/mL, 12 h), RES (1 μM, 6 h), and GW9662 (an [...] Read more.

This study aims to investigate the effect and mechanism of resveratrol (RES) on lipopolysaccharide (LPS)-induced injury in goat granulosa cells (GCs). First, the appropriate time and concentration were screened for LPS (4 μg/mL, 12 h), RES (1 μM, 6 h), and GW9662 (an antagonist of PPARG, 1 μM, 12 h) through CCK8 and RT-qPCR. Then, cells were treated with LPS, RES, or/and GW9662, to examine steroidogenesis, inflammation, oxidative stress, and pyroptosis by RIA, RT-qPCR, WB, flow cytometry, and IF, respectively. Results showed that RES inhibited LPS-induced increases in MDA content, ROS production, gene expressions of IL-1β, NLRP3, Caspase1, and GSDMD, as well as protein levels of IL-1β, and GSDMD, accompanied by decreases in SOD activity, T-AOC and E2 content, gene expressions of SOD, CYP19A1, and HSD3B, and protein levels of SOD and HSD3B. Furthermore, RES inhibited LPS-induced decreases in PPARG, NRF2, and HO-1 gene expressions and protein levels. However, GW9662 could block all the alleviating effects of RES on LPS. In conclusion, RES regulates the effects of LPS on hormone secretion, inflammation, oxidative stress, and pyroptosis by modulating the PPARG/NRF2/HO-1 pathway, providing a new theoretical basis for improving goat reproduction. Full article

(This article belongs to the Special Issue Antioxidant Effects of Natural Compounds on Cell Metabolism)

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31 pages, 1123 KB

Open AccessReview

Selenium: A Key Element in Inflammatory Bowel Disease

by Francesca Gorini and Alessandro Tonacci

Antioxidants 2025, 14(11), 1299; https://doi.org/10.3390/antiox14111299 - 29 Oct 2025

Abstract

Inflammatory bowel disease (IBD) is a multifactorial and complex condition of the gastrointestinal tract shaped by host genetics, immune dysregulation, gut microbiota and environmental determinants, with a steadily rising global prevalence. Although the etiology of IBD remains incompletely understood, chronic inflammation accompanied by [...] Read more.

Inflammatory bowel disease (IBD) is a multifactorial and complex condition of the gastrointestinal tract shaped by host genetics, immune dysregulation, gut microbiota and environmental determinants, with a steadily rising global prevalence. Although the etiology of IBD remains incompletely understood, chronic inflammation accompanied by oxidative stress, immune dysregulation, and gut dysbiosis is widely recognized as a hallmark of the condition. Given the frequent occurrence of undernutrition in IBD patients, the role of vitamins and micronutrients in modulating disease activity has been recently explored. Selenium (Se) is universally recognized as an essential trace element due to its diverse physiological functions, including potent antioxidant activity, anti-inflammatory effects, immunomodulatory properties, and the ability to influence gut microbial composition and diversity. This comprehensive review examines current evidence on the relationship between Se status and IBD, integrating epidemiological and experimental findings, elucidating the underlying biological mechanisms, and introducing Se nanoparticles, a viable therapeutic option using Se in IBD management. Full article

(This article belongs to the Special Issue Antioxidants as Adjuvants for Inflammatory Bowel Disease Treatment)

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23 pages, 1026 KB

Open AccessArticle

Dimerocostus strobilaceus (Caña Agria) as an Emerging Reservoir of Bioactive Metabolites with Potential Antioxidant, Antimicrobial, Anticancer and Anti-Inflammatory Health Benefits

by Elena Coyago-Cruz, Rebeca Gonzalez-Pastor, Gabriela Méndez, Jeico Usinia-Carranza, Juan A. Puente-Pineda, Johana Zúñiga-Miranda, Marco Cerna and Jorge Heredia-Moya

Antioxidants 2025, 14(11), 1298; https://doi.org/10.3390/antiox14111298 - 29 Oct 2025

Abstract

The Amazon region is home to a wide variety of plant species that are of interest for their medicinal and nutritional properties. This study aimed to evaluate the physicochemical properties, bioactive compound profile, and antioxidant, antimicrobial, anticancer and anti-inflammatory activity of Dimerocostus strobilaceus [...] Read more.

The Amazon region is home to a wide variety of plant species that are of interest for their medicinal and nutritional properties. This study aimed to evaluate the physicochemical properties, bioactive compound profile, and antioxidant, antimicrobial, anticancer and anti-inflammatory activity of Dimerocostus strobilaceus leaves, stems, and seeds. Vitamin C, organic acids, carotenoids, and phenolic compounds were quantified using RPLC. Antioxidant activity was determined using ABTS and DPPH, while antimicrobial activity was assessed against pathogenic and multidrug-resistant bacteria. Anticancer activity was evaluated in tumour cell lines (HeLa, HCT116, HepG2, and THJ29T), and anti-inflammatory activity was examined in RAW 264.7 macrophages. The seeds stood out for their content of ferulic, caffeic and chlorogenic acids, while kaempferol and quercetin predominated in the leaves. The leaves exhibited greater antimicrobial efficacy and antiproliferative activity (IC₅₀ < 0.2 mg/mL), albeit with limited selectivity. These findings suggest that ‘caña agria’ is a promising source of bioactive metabolites with biotechnological and therapeutic applications. Full article

(This article belongs to the Special Issue Bioactive Compounds: Antioxidant, Antibacterial, Anti-inflammatory Modulation)

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21 pages, 7106 KB

Open AccessArticle

Investigation into Bioactive Selenium Species and the Mechanism of Action Behind Selenium-Enriched Rapeseed Flowering Stalks Alleviating Cadmium-Induced Toxicity in Mouse Sertoli Cells

by Huatao Che, Yiqing Lu, Tong Li, Xiaoli Fang, Xinfa Wang, Hanzhong Wang, Xiaoling Dun and Zhenna Chen

Antioxidants 2025, 14(11), 1297; https://doi.org/10.3390/antiox14111297 (registering DOI) - 28 Oct 2025

Abstract

Cadmium (Cd) is a recognized environmental contaminant, present in soil, water, and food, which has been reported to cause male reproductive damage in vivo and vitro. Selenium-enriched rapeseed flowering stalks exhibit protective effects against Cd-induced reproductive damage, yet the bioactive components and underlying [...] Read more.

Cadmium (Cd) is a recognized environmental contaminant, present in soil, water, and food, which has been reported to cause male reproductive damage in vivo and vitro. Selenium-enriched rapeseed flowering stalks exhibit protective effects against Cd-induced reproductive damage, yet the bioactive components and underlying mechanisms remain unclear. We optimized the process of obtaining the crude extract (CE) via single-factor experiments. Subsequent bioassay-guided fractionation identified the water extract (WE) as significantly more effective in alleviating Cd-induced cytotoxicity compared to the petroleum ether extract, ethyl acetate extract, and n-butanol extract. High-performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC-ICP-MS) analysis revealed that WE contained the highest contents of methylselenocysteine (MeSeCys) and selenocystine (SeCys₂) among four fractions. Both MeSeCys and SeCys₂ exhibited protective effects against Cd-induced cytotoxicity. To further elucidate the underlying mechanisms, network pharmacology, RNA-Seq, qPCR, and Western blotting analysis were employed. The results revealed that WE exhibited good free radical scavenging capabilities, and the protective mechanisms of WE, MeSeCys, and SeCys₂ against Cd-induced cytotoxicity were related to a reduction in oxidative damage, the inhibition of the ERK/p38 MAPK signaling pathway, and the suppression of cell cycle arrest, inflammation, and apoptosis triggered by Cd exposure. Collectively, these findings suggest that selenium-enriched rapeseed flowering stalks may serve as a promising dietary supplement in the prevention of Cd-induced reproductive toxicity. Full article

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

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20 pages, 6283 KB

Open AccessArticle

Scorpion Venom Heat-Resistant Synthetic Peptide Alleviates DSS-Induced Colitis via α7nAChR-Mediated Modulation of the JAK2/STAT3 Pathway

by Kang Cheng, Guangbo He, Xiaxia Li, Yuqian Li, Xiaolin Cui, Xuefei Wu, Jau-Shyong Hong, Jie Zhao, Sheng Li and Yanjie Guo

Antioxidants 2025, 14(11), 1296; https://doi.org/10.3390/antiox14111296 - 28 Oct 2025

Abstract

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with limited treatment options. Emerging evidence reveals bidirectional crosstalk between gut and brain through inflammatory signaling, leading us to hypothesize that anti-neuroinflammatory agents may concurrently ameliorate intestinal inflammation. The scorpion venom-derived heat-resistant [...] Read more.

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with limited treatment options. Emerging evidence reveals bidirectional crosstalk between gut and brain through inflammatory signaling, leading us to hypothesize that anti-neuroinflammatory agents may concurrently ameliorate intestinal inflammation. The scorpion venom-derived heat-resistant synthetic peptide (SVHRSP), a bioactive peptide initially identified in scorpion venom and subsequently synthesized by our laboratory, possesses neuroprotective, anti-inflammatory, and antioxidative activities. Its properties make SVHRSP a promising candidate for investigating the therapeutic potential of anti-neuroinflammatory strategies in mitigating intestinal inflammation. Methods: Using a chronic dextran sodium sulfate (DSS)-induced colitis model in wild-type and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice, along with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, we assessed SVHRSP’s effects on inflammation, histopathology, gut permeability, oxidative stress markers, and α7nAChR-Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. Results: SVHRSP treatment significantly ameliorated colitis symptoms in wild-type mice by reducing inflammation, repairing histological damage, restoring gut barrier function, and attenuating oxidative stress, with these effects abolished in α7nAChR knockout mice. Mechanistically, SVHRSP activated JAK2/STAT3 signaling through α7nAChR engagement, suppressing proinflammatory cytokine production in macrophages. Conclusion: These results demonstrated that SVHRSP alleviated intestinal inflammation via α7nAChR-dependent JAK2/STAT3 activation. Combined with its known neuroprotective properties, our findings support the repurposing of this neuroactive peptide, SVHRSP, for treating intestinal inflammatory disorders. Full article

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

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34 pages, 976 KB

Open AccessReview

Lung Ischemia–Reperfusion Injury in Lung Transplant Surgery: Where Do We Stand?

by Lawek Berzenji, Jeroen M. H. Hendriks, Stijn E. Verleden, Suresh Krishan Yogeswaran, Wen Wen, Patrick Lauwers, Geert Verleden, Rudi De Paep, Pieter Mertens, Inez Rodrigus, Dirk Adriaensen and Paul Van Schil

Antioxidants 2025, 14(11), 1295; https://doi.org/10.3390/antiox14111295 - 28 Oct 2025

Abstract

Lung ischemia–reperfusion injury (LIRI) remains a major contributor to perioperative morbidity and mortality in thoracic surgery, especially for lung transplantations, where it is one of the principal drivers of primary graft dysfunction (PGD). Although substantial advances have been made in surgical technique, donor [...] Read more.

Lung ischemia–reperfusion injury (LIRI) remains a major contributor to perioperative morbidity and mortality in thoracic surgery, especially for lung transplantations, where it is one of the principal drivers of primary graft dysfunction (PGD). Although substantial advances have been made in surgical technique, donor management, and perioperative care, LIRI continues to pose a significant clinical challenge. Mechanistically, LIRI reflects a combined pathology of oxidative stress, endothelial and glycocalyx disruption, innate immune activation, mitochondrial dysfunction, and regulated cell death, resulting in loss of alveolar–capillary barrier integrity and gas exchange failure. Current management is phase-specific and multimodal, spanning donor care and preservation, controlled reperfusion and lung-protective ventilation, and pharmacological treatments. Treatment candidates that target oxidative stress and inflammatory cascades (e.g., antioxidants, complement and adenosine pathways, mesenchymal stromal cell products, and dipeptidyl-peptidase-4 inhibition) show promise, yet translation into a clinical scenario remains difficult. Increasing evidence supports endothelial-preserving and mitochondria-sparing strategies, rigorous perioperative bundles, and biomarker-guided trials to move from pathophysiology to practice. Ultimately, addressing LIRI requires an integrated, multidisciplinary approach that spans surgical, anesthetic, and pharmacologic domains, with the goal of improving both early outcomes and long-term graft survival in lung transplant patients. Full article

(This article belongs to the Special Issue New Strategies in Preventing Inflammatory and/or Oxidative Stress-Induced Damages in Ischemia-Reperfusion Injury, 2nd Edition)

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20 pages, 19960 KB

Open AccessArticle

Protective Role of Spermidine Against Diabetes-Induced Ovarian and Endometrial Injury via LC3 and Beclin-1 Modulation

by Bakiye Akbaş, Gülseren Dinç, Ahmet Akbaş, Nadir Adnan Hacım, Gülçin Ercan, Hatice Aygün and Oytun Erbaş

Antioxidants 2025, 14(11), 1294; https://doi.org/10.3390/antiox14111294 - 28 Oct 2025

Abstract

Background: Diabetes mellitus adversely affects female reproductive health by inducing oxidative stress, impairing autophagy, and promoting fibrotic remodeling in ovarian and uterine tissues. Spermidine, a natural polyamine, has gained attention as an antioxidant and autophagy enhancer. This study aimed to investigate the potential [...] Read more.

Background: Diabetes mellitus adversely affects female reproductive health by inducing oxidative stress, impairing autophagy, and promoting fibrotic remodeling in ovarian and uterine tissues. Spermidine, a natural polyamine, has gained attention as an antioxidant and autophagy enhancer. This study aimed to investigate the potential protective role of spermidine against diabetes-induced reproductive injury in rats. Methods: Thirty adult female Wistar rats were randomly divided into three groups (n = 10 each): Control, Diabetes, and Diabetes + Spermidine. Diabetes was induced with streptozotocin (60 mg/kg, i.p.). After confirmation of hyperglycemia (≥250 mg/dL), rats received either saline or spermidine (40 mg/kg/day, oral gavage) for four weeks. At sacrifice, plasma anti-Müllerian hormone (AMH) levels were determined, and ovarian and uterine tissues were assessed histologically and biochemically for oxidative stress markers (GSH, MDA, Nrf2), autophagy proteins (LC3, Beclin-1), and fibrosis indicators (TGF-β, histological scoring). Results: Diabetic rats exhibited severe hyperglycemia, pronounced follicular and endometrial degeneration, increased fibrosis, reduced plasma AMH, depleted GSH, SOD, CAT, GPx and Nrf2, and elevated MDA (p < 0.001). Spermidine treatment significantly mitigated these alterations, lowering glucose levels, alleviating histopathological injury, elevating the antioxidant defense (GSH, SOD, CAT, GPx) and the Nrf2 and decreasing MDA and TGF-β concentrations (p < 0.05 vs. Diabetes). Moreover, spermidine supplementation enhanced LC3 and Beclin-1 expression, suggesting improved autophagic activity. Conclusions: Spermidine counteracts diabetes-induced ovarian and uterine damage by reinforcing antioxidant defense, stimulating autophagy, and limiting fibrosis. These findings highlight spermidine as a promising adjunctive agent to support female reproductive health under diabetic conditions. Full article

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

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24 pages, 4484 KB

Open AccessArticle

Optimization of Polyphenol-Rich Extracts from Defatted Avocado Peel and Seed Residues Using Ultrasound-Assisted RSM: Antioxidant Potential and Valorization Prospects

by Argyro Petrantonaki, Vasiliki-Ioanna Theodoropoulou, Martha Mantiniotou, Vassilis Athanasiadis, Eleni Bozinou and Stavros I. Lalas

Antioxidants 2025, 14(11), 1293; https://doi.org/10.3390/antiox14111293 - 28 Oct 2025

Abstract

It is well known that a significant amount of processed avocado fruit, specifically peel and seed, is treated as waste. During this study, these by-products were valorized through a two-step approach combining lipid profiling and optimized antioxidant extraction. Initially, oil was extracted and [...] Read more.

It is well known that a significant amount of processed avocado fruit, specifically peel and seed, is treated as waste. During this study, these by-products were valorized through a two-step approach combining lipid profiling and optimized antioxidant extraction. Initially, oil was extracted and analyzed via GC-FID, revealing distinct fatty acid compositions: peel oil was rich in oleic (32.0%), linoleic (21.9%), and α-linolenic acids (9.7%), while seed oil was dominated by oleic (48.0%) and palmitic acids (20.7%), with moderate linoleic content (24.0%). Following defatting, the dried residues were subjected to ultrasound-assisted extraction, which was optimized by response surface methodology (RSM) to maximize the recovery of antioxidant-rich fractions. Peel extracts exhibited the highest total polyphenolic content (105.98 mg GAE/g), FRAP (673.89 μmol AAE/g), and ascorbic acid (17.9 mg/g), while seed extracts showed superior DPPH activity (1071.31 μmol AAE/g). Regression modeling identified optimal conditions for each antioxidant metric, highlighting matrix-specific bioactivity. The combined analysis of lipid and polar fractions underscores the multifunctional potential of avocado residues as sustainable sources of natural antioxidants. These findings support their application in food, cosmetic, and nutraceutical formulations, contributing to circular bioeconomy strategies. Full article

(This article belongs to the Special Issue Bioactive Antioxidants from Agri-Food Wastes)

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17 pages, 6051 KB

Open AccessArticle

Differential Expression of Antioxidant and Oxidant Pathways in Chronic Rhinosinusitis Without Nasal Polyps

by Yih-Jeng Tsai, Jiunn-Min Shieh, Ming-Chieh Ma and Wen-Bin Wu

Antioxidants 2025, 14(11), 1292; https://doi.org/10.3390/antiox14111292 - 28 Oct 2025

Abstract

Chronic rhinosinusitis without nasal polyps (CRSsNP) is a chronic inflammatory disease that lacks a clear pathogenesis/pathophysiology. While large studies focused on elucidating the pathophysiology of CRS with NPs (CRSwNP), this study aimed to use a systemic evaluation approach to identify the redox gene [...] Read more.

Chronic rhinosinusitis without nasal polyps (CRSsNP) is a chronic inflammatory disease that lacks a clear pathogenesis/pathophysiology. While large studies focused on elucidating the pathophysiology of CRS with NPs (CRSwNP), this study aimed to use a systemic evaluation approach to identify the redox gene expression profile, its association with oxidative damage in CRSsNP, and the differences between CRSsNP and -wNP. The expression of 84 redox genes was analyzed using real-time PCR array in control and CRSsNP nasal mucosae. Changes in the mRNA and protein levels of these redox differentially expressed genes (DEGs) were verified using a customized real-time PCR array, RT-PCR, and Western blotting in an additional 18 patients. 4-Hydroxynonenal (lipid peroxidation) and 3-nitrotyrosine (protein nitrosylation) expression, representing oxidative stress (OxS) and nitrosative stress (NsS) status, were examined using immunohistochemistry. We found 27 DEGs (24 upregulated and 3 downregulated) in CRSsNP. AKR1C2, GCLM, GPX2, NOS2, and NQO1 were upregulated and LPO was downregulated more than 4-fold. These changes led to a substantial increase in OxS in CRSsNP nasal mucosa. In a comparison of the currently identified 27 DEGs with the 23 previously reported CRSwNP genes, there were 16 unique redox DEGs expressed between CRSsNP and -wNP. A String protein interaction network analysis revealed that CRSsNP possessed “an adaptive antioxidant defense signature”, while CRSwNP showed “a pro-inflammatory and -oxidant pathway”. Collectively, we systemically performed transcriptomic analysis to profile OxS-related genes in CRSsNP and highlighted the unique redox gene sets and pathway differences between CRSsNP and -wNP. Full article

(This article belongs to the Special Issue Antioxidants and Antioxidant Mechanisms in the Prevention and Treatment of Infectious Diseases)

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