Antioxidants

27 pages, 12816 KiB

Open AccessArticle

Differential Cell Death Pathways Induced by Oxidative Stress in Multi-Organs of Amur Grayling (Thymallus grubii) Under Gradient Ammonia Stress

by Cunhua Zhai, Yutao Li, Ruoyu Wang, Ying Zhang and Bo Ma

Antioxidants 2025, 14(4), 499; https://doi.org/10.3390/antiox14040499 - 21 Apr 2025

Abstract

Ammonia nitrogen is a common contaminant in aquatic environments, and its potential toxicity to organisms has attracted extensive attention. However, few studies have comprehensively evaluated the negative impacts of ammonia stress on cold-water fish. In this study, liver, gill, and intestine specimens of [...] Read more.

Ammonia nitrogen is a common contaminant in aquatic environments, and its potential toxicity to organisms has attracted extensive attention. However, few studies have comprehensively evaluated the negative impacts of ammonia stress on cold-water fish. In this study, liver, gill, and intestine specimens of Amur grayling (Thymallus grubii) from three treatment groups (control (0 mg/L), low ammonia (43.683 mg/L), and high ammonia (436.8 mg/L)), were collected for histological observation, biochemical examination, and transcriptomic, metabolomic, and intestinal microbiome analysis. Our results showed that excessive ammonia nitrogen blocked the normal immune function and compromised the integrity of liver and gill tissues through oxidative stress-mediated differential cell death pathways. Meanwhile, the multi-omics analysis revealed that ammonia exposure predominantly altered the carbohydrate, lipid, and amino acid metabolism modes. In addition, it was also demonstrated that ammonia nitrogen stress affected the composition of intestinal microbiota taxa. This study provides insights into the potential risks and hazards of ammonia stress on cold fish in natural waters and provides a reference for the environment control of the water quality in aquaculture. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Aquaculture)

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35 pages, 1430 KiB

Open AccessReview

Synthetic and Natural Agents Targeting Advanced Glycation End-Products for Skin Anti-Aging: A Comprehensive Review of Experimental and Clinical Studies

by Joon Yong Choi, Nam Gyoung Ha, Weon Ju Lee and Yong Chool Boo

Antioxidants 2025, 14(4), 498; https://doi.org/10.3390/antiox14040498 - 20 Apr 2025

Abstract

Advanced glycation end-products (AGEs) cause blood vessel damage and induce diabetic complications in various organs, such as the eyes, kidneys, nerves, and skin. As glycation stress causes aesthetic, physical, and functional changes in the skin, glycation-targeting skin anti-aging strategies are attracting attention in [...] Read more.

Advanced glycation end-products (AGEs) cause blood vessel damage and induce diabetic complications in various organs, such as the eyes, kidneys, nerves, and skin. As glycation stress causes aesthetic, physical, and functional changes in the skin, glycation-targeting skin anti-aging strategies are attracting attention in cosmetology and dermatology. The primary goal of this review is to understand the significance of glycation-induced skin aging and to examine the therapeutic potential of glycation-targeting strategies. This study covers experimental and clinical studies exploring various interventions to attenuate glycation-induced skin aging. Glycation stress decreases the viability of cells in culture media, the cell-mediated contraction of collagen lattices in reconstructed skin models, and the expression of fibrillin-1 at the dermo-epidermal junction in the skin explants. It also increases cross-links in tail tendon collagen in animals, prolonging its breakdown time. However, these changes are attenuated by several synthetic and natural agents. Animal and clinical studies have shown that dietary or topical administration of agents with antiglycation or antioxidant activity can attenuate changes in AGE levels (measured by skin autofluorescence) and skin aging parameters (e.g., skin color, wrinkles, elasticity, hydration, dermal density) induced by chronological aging, diabetes, high-carbohydrate diets, ultraviolet radiation, or oxidative stress. Therefore, the accumulating experimental and clinical evidence supports that dietary supplements or topical formulations containing one or more synthetic and natural antiglycation agents may help mitigate skin aging induced by AGEs. Full article

(This article belongs to the Special Issue Antioxidants for Skin Health)

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13 pages, 2887 KiB

Open AccessArticle

Role of Reactive Oxygen Species in Collagen-Induced Platelet Activation and the Protective Effects of Antioxidants

by Jin-Yi Han, Hideo Utsumi and Han-Young Chung

Antioxidants 2025, 14(4), 497; https://doi.org/10.3390/antiox14040497 - 20 Apr 2025

Abstract

Collagen plays a crucial role in platelet activation and thrombosis, yet the underlying mechanisms involving reactive oxygen species (ROS) remain incompletely understood. This study investigated how collagen modulates ROS generation and platelet aggregation both in vitro and in vivo, as well as evaluating [...] Read more.

Collagen plays a crucial role in platelet activation and thrombosis, yet the underlying mechanisms involving reactive oxygen species (ROS) remain incompletely understood. This study investigated how collagen modulates ROS generation and platelet aggregation both in vitro and in vivo, as well as evaluating the protective effects of antioxidants. In vitro, collagen induced dose-dependent platelet aggregation and increased ROS generation, evidenced by the enhanced EMPO adduct formation detected via electron spin resonance (ESR). In vivo experiments demonstrated that collagen administration significantly accelerated CAT-1 decay, indicating elevated oxidative stress with a transient peak around 1 minute post-treatment. Furthermore, escalating collagen doses correlated with increased ROS generation and reduced survival rates in mice, underscoring collagen’s impact on oxidative stress and thrombosis severity. Importantly, treatment with enzymatic antioxidants (superoxide dismutase, catalase) and non-enzymatic antioxidants (DMTU, Tiron, mannitol) significantly attenuated collagen-induced oxidative stress and improved animal survival. Collectively, these findings elucidate the pivotal role of ROS in collagen-induced platelet activation and thrombosis and highlight antioxidants as promising therapeutic candidates for preventing thrombotic disorders and managing cardiovascular risk. Full article

(This article belongs to the Special Issue Blood Cells and Redox Homeostasis in Health and Disease, 2nd Edition)

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22 pages, 7200 KiB

Open AccessArticle

Genome-Wide Identification of the Sulfate Transporter Gene Family Reveals That BolSULTR2;1 Regulates Plant Resistance to Alternaria brassicicola Through the Modulation of Glutathione Biosynthesis in Broccoli

by Guize Wu, Yunhua Ding, Ning Li, Hongji Zhang and Ning Liu

Antioxidants 2025, 14(4), 496; https://doi.org/10.3390/antiox14040496 - 20 Apr 2025

Abstract

Sulfate transporters (SULTRs) are key players that regulate sulfur acquisition and distribution within plants, thereby influencing cellular redox hemostasis under pathogen attacks, such as Alternaria brassicicola (Ab). In this study, a total of 23 BolSULTR (Brassica oleracea SULTR) genes were [...] Read more.

Sulfate transporters (SULTRs) are key players that regulate sulfur acquisition and distribution within plants, thereby influencing cellular redox hemostasis under pathogen attacks, such as Alternaria brassicicola (Ab). In this study, a total of 23 BolSULTR (Brassica oleracea SULTR) genes were identified from the Brassica genome. These BolSULTRs are distributed across nine chromosomes, with all collinear BolSULTR gene pairs undergoing purifying selections. Phylogenetic analysis reveals that the SULTR family is evolutionarily conserved among plant kingdoms. qRT-PCR analysis demonstrated that the expression of BolSULTRs varies across different plant organs and is modulated by hormonal signals. Furthermore, transcriptome analysis identified several BolSULTRs whose expression levels were depressed in Ab-challenged leaves in broccoli. Among them, the BolSULTR2;1 gene emerged as a key player in the plant’s response to Ab. Virus-induced gene silencing (VIGS) of BolSULTR2;1s resulted in elevated glutathione (GSH) levels and enhanced tolerance to Ab. Taken together, these findings underscore the role of BolSULTR2;1 in maintaining redox homeostasis and enhancing plant disease resistance, suggesting its potential as a target for genome editing to develop broccoli varieties with improved pathogen tolerance. Full article

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

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24 pages, 22656 KiB

Open AccessArticle

Influence of High Temperature and Ammonia and Nitrite Accumulation on the Physiological, Structural, and Genetic Aspects of the Biology of Largemouth Bass (Micropterus salmoides)

by Yuexing Zhang, Hui Qiao, Leyang Peng, Yujie Meng, Guili Song, Cheng Luo and Yong Long

Antioxidants 2025, 14(4), 495; https://doi.org/10.3390/antiox14040495 - 20 Apr 2025

Abstract

Hyperthermia and nitrogenous pollutants like ammonia and nitrite are common risk factors that adversely affect fish health and pose significant threats to the aquaculture industry. However, the impacts of high temperatures on the accumulation of nitrogenous pollutants in the water of the aquaculture [...] Read more.

Hyperthermia and nitrogenous pollutants like ammonia and nitrite are common risk factors that adversely affect fish health and pose significant threats to the aquaculture industry. However, the impacts of high temperatures on the accumulation of nitrogenous pollutants in the water of the aquaculture systems and their toxicity to farmed fish are not well understood. In this study, juvenile largemouth bass (Micropterus salmoides, LMB) were kept at 28 °C and 34 °C in a closed aquatic system to investigate the effects of higher temperatures on ammonia and nitrite accumulation. The fish were fed 2% of their body weight daily for a 14-day experiment. Ammonia levels gradually increased, peaking on day 7 at 34 °C and on day 9 at 28 °C, then decreased to near zero. Nitrite levels remained low initially and increased rapidly along with the reduction in ammonia levels at both temperatures. The 34 °C high temperature accelerated the accumulation of ammonia and its transformation into nitrite compared to 28 °C. Fish were sampled on day 1 (low ammonia and low nitrite, LALN), day 8 (high ammonia and low nitrite, HALN), and day 14 (low ammonia and high nitrite, LAHN) to explore toxic effects. Successive exposure to high levels of ammonia and nitrite caused oxidative stress in the liver and significant pathogenic changes in the liver and spleen, with more pronounced impacts observed at 34 °C. Significant changes in gene expression were detected in the liver and spleen of fish sampled at HALN and LAHN, compared to those at LALN, with upregulated genes primarily associated with extracellular matrix (ECM) and cytoskeleton organization. A second experiment was conducted at the same temperatures but without ammonia/nitrite accumulation. The results of this experiment confirmed the combined effects of hyperthermia and ammonia/nitrite toxicity on the expression of genes involved in ECM–receptor interaction and TGF-beta signaling. These findings are valuable for optimizing cultivation environments and promoting the health of farmed LMB. Full article

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18 pages, 6741 KiB

Open AccessArticle

Competitive Ligand-Induced Recruitment of Coactivators to Specific PPARα/δ/γ Ligand-Binding Domains Revealed by Dual-Emission FRET and X-Ray Diffraction of Cocrystals

by Shotaro Kamata, Akihiro Honda, Sayaka Yashiro, Chihiro Kaneko, Yuna Komori, Ayumi Shimamura, Risa Masuda, Takuji Oyama and Isao Ishii

Antioxidants 2025, 14(4), 494; https://doi.org/10.3390/antiox14040494 - 20 Apr 2025

Viewed by 62

Abstract

Peroxisome proliferator-activated receptors (PPARs), composed of the α/δ/γ subtypes, are ligand-activated nuclear receptors/transcription factors that sense endogenous fatty acids or therapeutic drugs to regulate lipid/glucose metabolism and oxidative stress. PPAR forms a multiprotein complex with a retinoid X receptor and corepressor complex in [...] Read more.

Peroxisome proliferator-activated receptors (PPARs), composed of the α/δ/γ subtypes, are ligand-activated nuclear receptors/transcription factors that sense endogenous fatty acids or therapeutic drugs to regulate lipid/glucose metabolism and oxidative stress. PPAR forms a multiprotein complex with a retinoid X receptor and corepressor complex in an unliganded/inactive state, and ligand binding induces the replacement of the corepressor complex with the coactivator complex to initiate the transcription of various genes, including the metabolic and antioxidant ones. We investigated the processes by which the corepressor is replaced with the coactivator or in which two coactivators compete for the PPARα/δ/γ-ligand-binding domains (LBDs) using single- and dual-emission fluorescence resonance energy transfer (FRET) assays. Single-FRET revealed that the respective PPARα/δ/γ-selective agonists (pemafibrate, seladelpar, and pioglitazone) induced the dissociation of the two corepressor peptides, NCoR1 and NCoR2, from the PPARα/δ/γ-LBDs and the recruitment of the two coactivator peptides, CBP and TRAP220. Meanwhile, dual-FRET demonstrated that these processes are simultaneous and that the four coactivator peptides, CBP, TRAP220, PGC1α, and SRC1, were competitively recruited to the PPARα/δ/γ-LBDs with different preferences upon ligand activation. Furthermore, the five newly obtained cocrystal structures using X-ray diffraction, PPARα-LBDs–NCoR2/CBP/TRAP220/PGC1α and PPARγ-LBD–NCoR2, were co-analyzed with those from our previous studies. This illustrates that these coactivators bound to the same PPARα-LBD loci via their consensus LXXLL motifs in the liganded state; that NCoR1/NCoR2 corepressors bound to the same loci via the IXXXL sequences within their consensus LXXXIXXXL motifs in the unliganded state; and that ligand activation induced AF-2 helix 12 formation that interfered with corepressor binding and created a binding space for the coactivator. These PPARα/γ-related biochemical and physicochemical findings highlight the coregulator dynamics on limited PPARα/δ/γ-LBDs loci. Full article

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23 pages, 4552 KiB

Open AccessArticle

Cell-Permeable Microprotein from Panax Ginseng Protects Against Doxorubicin-Induced Oxidative Stress and Cardiotoxicity

by Bamaprasad Dutta, Shining Loo, Antony Kam, Xiaoliang Wang, Na Wei, Kathy Qian Luo, Chuan-Fa Liu and James P. Tam

Antioxidants 2025, 14(4), 493; https://doi.org/10.3390/antiox14040493 - 19 Apr 2025

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Abstract

(1) Background: Doxorubicin (DOX) is a frontline chemotherapeutic, but its side-effects from oxidative stress, leading to cardiotoxicity, pose significant challenges to its clinical use. We recently discovered a novel family of proteolysis-resistant, cystine-dense, and cell-penetrating microproteins from Panax ginseng that we term ginsentides. [...] Read more.

(1) Background: Doxorubicin (DOX) is a frontline chemotherapeutic, but its side-effects from oxidative stress, leading to cardiotoxicity, pose significant challenges to its clinical use. We recently discovered a novel family of proteolysis-resistant, cystine-dense, and cell-penetrating microproteins from Panax ginseng that we term ginsentides. Ginsentides, such as the 31-residue TP1, coordinate multiple biological systems to prevent vascular dysfunction and endoplasmic reticulum stress induced by internal and external stressors. (2) Methods: We assessed the protective effects of ginsentide TP1 on DOX-induced cardiotoxicity using both in vitro functional studies on H9c2 cardiomyocytes and in vivo animal models by zebrafish and ICR mouse models. In these models, we examined oxidative stress, apoptosis, intracellular calcium levels, mitochondrial function, inflammatory responses, and cardiac function. (3) Results: We show that ginsentide TP1 protects against DOX-induced cytotoxicity in the mitochondria-rich H9c2 cardiomyocytes and reduces myocardial injury in zebrafish and mice by mitigating oxidative stress, inflammation, calcium, and mitochondrial dysfunction, as well as apoptosis-mediated cell death. Importantly, TP1 preserves cellular homeostasis without compromising the anticancer potency of DOX in breast cancer cells. (4) Conclusions: our findings highlight a specific antioxidative function of ginsentide TP1 in managing DOX-induced cardiotoxicity during cancer treatment and provide a promising lead for developing cardioprotective peptides and microproteins against oxidative stress. Full article

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

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44 pages, 6718 KiB

Open AccessReview

Advanced Glycation End Products in Disease Development and Potential Interventions

by Yihan Zhang, Zhen Zhang, Chuyue Tu, Xu Chen and Ruikun He

Antioxidants 2025, 14(4), 492; https://doi.org/10.3390/antiox14040492 - 18 Apr 2025

Viewed by 114

Abstract

Advanced glycation end products (AGEs) are a group of compounds formed through non-enzymatic reactions between reducing sugars and proteins, lipids, or nucleic acids. AGEs can be generated in the body or introduced through dietary sources and smoking. Recent clinical and animal studies have [...] Read more.

Advanced glycation end products (AGEs) are a group of compounds formed through non-enzymatic reactions between reducing sugars and proteins, lipids, or nucleic acids. AGEs can be generated in the body or introduced through dietary sources and smoking. Recent clinical and animal studies have highlighted the significant role of AGEs in various health conditions. These compounds accumulate in nearly all mammalian tissues and are associated with a range of diseases, including diabetes and its complications, cardiovascular disease, and neurodegeneration. This review summarizes the major diseases linked to AGE accumulation, presenting both clinical and experimental evidence. The pathologies induced by AGEs share common mechanisms across different organs, primarily involving oxidative stress, chronic inflammation, and direct protein cross-linking. Interventions targeting AGE-related diseases focus on inhibiting AGE formation using synthetic or natural antioxidants, as well as reducing dietary AGE intake through lifestyle modifications. AGEs are recognized as significant risk factors that impact health and accelerate aging, particularly in individuals with hyperglycemia. Monitoring AGE level and implementing nutritional interventions can help maintain overall health and reduce the risk of AGE-related complications. Full article

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

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20 pages, 17279 KiB

Open AccessArticle

In Vitro Structural Characteristics and Antioxidant and Expectorant Activities of Polysaccharides from Citri grandis fructus immaturus

by Jingwen Li, Suifen Mo, Yingshan Feng, Yan Xiang, Chen Ni, Qing Luo, Jing Zhou, Yujia Wang, Ruoting Zhan and Ping Yan

Antioxidants 2025, 14(4), 491; https://doi.org/10.3390/antiox14040491 - 18 Apr 2025

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Abstract

The aim of this study was to investigate the structural characteristics of four polysaccharides derived from Citri grandis fructus immaturus and their antioxidant and expectorant activities. ECP1 fraction passing through a 500 kDa dialysis bag (ECP1A) and ECP2 fraction retained in a 300 [...] Read more.

The aim of this study was to investigate the structural characteristics of four polysaccharides derived from Citri grandis fructus immaturus and their antioxidant and expectorant activities. ECP1 fraction passing through a 500 kDa dialysis bag (ECP1A) and ECP2 fraction retained in a 300 kDa dialysis bag (ECP2B) had molecular weights of 340 and 1217 kDa, respectively. All four polysaccharides were composed of six monosaccharides, including l-rhamnose, d-arabinose, d-xylose, d-mannose, d-glucose, and d-galactose, with molar ratios of 1.99:52.38:6.99:2.64:5.15:31.15 for ECP1A and 1.54:65.13:6.34:2.51:3.58:22.07 for ECP2B. ECP1A had an α/β-glucopyranose ring, and the glycosyl groups were linked mainly by 1→4, 1→2, or 1→6 glycosidic bonds. It likely adopted a single-stranded helical conformation. ECP2B had a β-glucopyranose ring, and the glycosyl groups were linked mainly by 1→4, 1→2, or 1→6 glycosidic bonds. Furthermore, in vitro experiments showed that ECP1A displayed excellent antioxidant activity (IC₅₀ = 0.4614 mg/mL). ECP2B significantly inhibited MUC5AC mucin content expression in the mucus hypersecretion model of BEAS-2B cells, thus exerting an expectorant effect. A significant negative correlation was observed between the molecular weight of Citri grandis fructus immaturus polysaccharides and their antioxidant activity, and the uronic acid and d-arabinose contents of these polysaccharides exhibited strong negative trends with both antioxidant and expectorant activities. This study shows the potential for developing and utilizing polysaccharides from Citri grandis fructus immaturus as an antioxidant and expectorant agent. Full article

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23 pages, 10645 KiB

Open AccessArticle

Cyanidin-3-O-Glucoside Mitigates Amyloid-Beta (1–42)-Induced Apoptosis in SH-SY5Y Cells by Regulating Ca²⁺ Homeostasis and Inhibiting Mitochondrial Dysfunction

by Chao Ma, Yu Nie, Donglei Zhang, Lulu Ran, Su Xu, Xun Ran, Junya Huang and Lingshuai Meng

Antioxidants 2025, 14(4), 490; https://doi.org/10.3390/antiox14040490 - 18 Apr 2025

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Abstract

Background: Blueberry anthocyanin such as Cyanidin-3-O-glucoside may help prevent Alzheimer’s disease. We aimed to investigate the preventive and therapeutic effects of Cyanidin-3-O-glucoside against Aβ_1–42-induced apoptosis of SH-SY5Y cells as well as the underlying mechanisms. Methods: Cell viability [...] Read more.

Background: Blueberry anthocyanin such as Cyanidin-3-O-glucoside may help prevent Alzheimer’s disease. We aimed to investigate the preventive and therapeutic effects of Cyanidin-3-O-glucoside against Aβ_1–42-induced apoptosis of SH-SY5Y cells as well as the underlying mechanisms. Methods: Cell viability and intracellular and mitochondrial reactive oxygen species were detected by MTT, a reactive oxygen species detection kit, and a MitoSOX red mitochondrial superoxide indicator. The mitochondrial membrane potential, intracellular calcium ion content, and adenotriphophate (ATP) were identified via a mitochondrial membrane potential detection kit, calcium ion detection kit, and ATP detection kit, and apoptosis was detected via flow cytometry. Transcription of apoptosis-related genes was detected using real-time fluorescence quantitative polymerase chain reaction, and expression of apoptosis-related proteins was identified using Western blot. Results: We found that Cyanidin-3-O-glucoside could downregulate the expression of cytochrome c, caspase 9, caspase 3, and other genes and proteins, which consequently reduced the rate of apoptosis. Additionally, it could upregulate Bcl-2 gene and protein expression, downregulate Bax gene and protein expression, regulate mitochondrial membrane permeability and calcium-release channels, reduce calcium influx into mitochondria, maintain intracellular calcium ion levels, reduce intracellular levels of reactive oxygen species and increase ATP levels, maintain the mitochondrial membrane potential at a normal level, maintain normal mitochondrial functioning, and prevent apoptosis. Discussion: Taken together, Cyanidin-3-O-glucoside showed dose-dependent preventive and therapeutic effects against Aβ_1–42-induced apoptosis of SH-SY5Y cells. Conclusions: Cyanidin 3-O-glucoside showed a better preventive effect than therapeutic effect against Aβ_1–42-induced apoptosis in SH-SY5Y cells. Full article

(This article belongs to the Special Issue Antioxidant Activities of Phytochemicals in Fruits and Vegetables)

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23 pages, 995 KiB

Open AccessReview

Exploring Oxidative Stress Mechanisms of Nanoparticles Using Zebrafish (Danio rerio): Toxicological and Pharmaceutical Insights

by Denisa Batir-Marin, Monica Boev, Oana Cioanca, Ionut-Iulian Lungu, George-Alexandru Marin, Ana Flavia Burlec, Andreea-Maria Mitran, Cornelia Mircea and Monica Hancianu

Antioxidants 2025, 14(4), 489; https://doi.org/10.3390/antiox14040489 - 18 Apr 2025

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Abstract

Nanoparticles (NPs) have revolutionized biomedical and pharmaceutical applications due to their unique physicochemical properties. However, their widespread use has raised concerns regarding their potential toxicity, particularly mediated by oxidative stress mechanisms. This redox imbalance, primarily driven by the overproduction of reactive oxygen species [...] Read more.

Nanoparticles (NPs) have revolutionized biomedical and pharmaceutical applications due to their unique physicochemical properties. However, their widespread use has raised concerns regarding their potential toxicity, particularly mediated by oxidative stress mechanisms. This redox imbalance, primarily driven by the overproduction of reactive oxygen species (ROS), plays a central role in NP-induced toxicity, leading to cellular dysfunction, inflammation, apoptosis, and genotoxicity. Zebrafish (Danio rerio) have emerged as a powerful in vivo model for nanotoxicology, offering advantages such as genetic similarity to humans, rapid development, and optical transparency, allowing real-time monitoring of oxidative damage. This review synthesizes current findings on NP-induced oxidative stress in zebrafish, highlighting key toxicity mechanisms and case studies involving metallic (gold, silver, copper), metal oxide (zinc oxide, titanium dioxide, iron oxide), polymeric, and lipid-based NPs. The influence of NP physicochemical properties, such as size, surface charge, and functionalization, on oxidative stress responses is explored. Additionally, experimental approaches used to assess ROS generation, antioxidant enzyme activity, and oxidative damage biomarkers in zebrafish models are examined. In addition to toxicity concerns, pharmaceutical applications of antioxidant-modified NPs are evaluated, particularly their potential in drug delivery, neuroprotection, and disease therapeutics. Notably, studies show that curcumin- and quercetin-loaded nanoparticles enhance antioxidant defense and reduce neurotoxicity in zebrafish models, demonstrating their promise in neuroprotective therapies. Furthermore, cerium oxide nanoparticles, which mimic catalase and SOD enzymatic activity, have shown significant efficacy in reducing ROS and protecting against oxidative damage. Challenges in zebrafish-based nanotoxicology, the need for standardized methodologies, and future directions for optimizing NP design to minimize oxidative stress-related risks are also discussed. By integrating insights from toxicity mechanisms, case studies, and pharmaceutical strategies, this review supports the development of safer and more effective nanoparticle-based therapies while addressing the challenges of oxidative stress-related toxicity. Full article

(This article belongs to the Special Issue Natural Antioxidants in Pharmaceuticals and Dermatocosmetology)

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13 pages, 426 KiB

Open AccessArticle

The Effect of Antioxidant Administration on Semen Quality in Men with Infertility: A Randomized Placebo-Controlled Clinical Trial

by Pinelopi Ioannidou, Theodosia Zeginiadou, Christos Venetis, Dimitrios Papanikolaou, Leonidas Zepiridis, Despoina Savvaidou, Katerina Chatzimeletiou, Alexandros Lambropoulos, Dimitrios G. Goulis, Grigoris Grimbizis and Efstratios M. Kolibianakis

Antioxidants 2025, 14(4), 488; https://doi.org/10.3390/antiox14040488 - 18 Apr 2025

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Abstract

A randomized, placebo-controlled, quadruple-blind trial was performed to evaluate the effect of oral administration of the antioxidant combination Spermotrend^® for three months on semen quality in infertile men with at least one abnormal variable in semen analysis. Eighty men were randomized between [...] Read more.

A randomized, placebo-controlled, quadruple-blind trial was performed to evaluate the effect of oral administration of the antioxidant combination Spermotrend^® for three months on semen quality in infertile men with at least one abnormal variable in semen analysis. Eighty men were randomized between 2019 and 2022, receiving either the antioxidant combination Spermotrend^® (n = 40, spermotrend-group) or placebo (n = 40, placebo-group). Although a total of 80 patients were enrolled in the study, the final data is only from 70 patients. The primary outcome measure was sperm motility (rapid progressive, progressive, and total motility). The values of primary and secondary outcomes between treatment initiation and treatment completion were compared within groups. Moreover, their changes between treatment initiation and treatment completion were compared between the placebo- and the spermotrend-groups. Sperm rapid progressive motility significantly increased in infertile men treated for three months with antioxidant combination Spermotrend^® (+1.0%, 95% CI: 0.0 to +2.0, p = 0.04), while this increase was not observed in the placebo-group. Sperm progressive motility significantly increased in infertile men treated for three months with antioxidant combination Spermotrend^® (+3.0%, 95% CI: 0.0 to +15.1, p = 0.02), while this increase was not observed in the placebo-group. Similarly, DFI was significantly decreased in infertile men treated for three months by antioxidant combination Spermotrend^® (−3.2%, 95% CI: −5.8 to −0.5, p = 0.02). However, no statistically significant differences were observed in the changes of pre- and post-treatment values between the spermotrend- and the placebo-group regarding sperm progressive motility, concentration, normal morphology, DFI, and formation of 8-OH-dG. The antioxidant combination Spermotrend^® appears to exert limited benefit on sperm motility and DFI in infertile men with at least one abnormal variable in semen analysis. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Male Infertility)

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17 pages, 4696 KiB

Open AccessArticle

Potentillae argenteae herba—Antioxidant and DNA-Protective Activities, and Microscopic Characters

by Tsvetelina Andonova, Yordan Muhovski, Samir Naimov, Elena Apostolova, Silviya Mladenova, Ivayla Dincheva, Vasil Georgiev, Atanas Pavlov, Rumen Mladenov and Ivanka Dimitrova-Dyulgerova

Antioxidants 2025, 14(4), 487; https://doi.org/10.3390/antiox14040487 - 18 Apr 2025

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Abstract

Antioxidants from natural sources are essential for the development of new therapeutics to improve human health. The objects of study are the aerial flowering parts of Potentilla argentea, a plant species known in traditional medicine for the astringent, hemostatic, wound-healing, and anti-inflammatory [...] Read more.

Antioxidants from natural sources are essential for the development of new therapeutics to improve human health. The objects of study are the aerial flowering parts of Potentilla argentea, a plant species known in traditional medicine for the astringent, hemostatic, wound-healing, and anti-inflammatory effects of its rhizomes. A Potentillae argenteae herba ethanol dry tincture was chromatographically analyzed (GC/MS, HPLC) and its antioxidant (ABTS, DPPH, CUPRAC, FRAP assays) and DNA nicking protection potentials were evaluated. The eighteen volatiles were identified by GC/MS, where the predominant components were n-nonacosane (39.38 mg/g dt), squalene (28.88 mg/g dt), n-tricosane (18.36 mg/g dt), ethyl oleate (15.24 mg/g dt), and n-pentacosane (10.60 mg/g dt). A high content of total polyphenols was obtained (440.78 mg GAE/g dt), and HPLC analysis identified two flavonoids and three phenolic acids, of which rosmarinic acid and rutin were above 10 mg/g dt. The tincture exhibited strong antioxidant activity by all four methods, especially CUPRAC assay (8617.54 μM TE/g). DNA protective activity against oxidative damage and microscopic identification of P. argenteae herba powder were established for the first time. Therefore, the tincture could be incorporated into phytopreparations for the treatment of human diseases caused by reactive oxygen species. Full article

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

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19 pages, 2232 KiB

Open AccessArticle

Redox Mechanisms Driving Skin Fibroblast-to-Myofibroblast Differentiation

by Marzieh Aminzadehanboohi, Manousos Makridakis, Delphine Rasti, Yves Cambet, Karl-Heinz Krause, Antonia Vlahou and Vincent Jaquet

Antioxidants 2025, 14(4), 486; https://doi.org/10.3390/antiox14040486 - 18 Apr 2025

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Abstract

Transforming Growth Factor-Beta 1 (TGF-β1) plays a pivotal role in the differentiation of fibroblasts into myofibroblasts, which is a critical process in tissue repair, fibrosis, and wound healing. Upon exposure to TGF-β1, fibroblasts acquire a contractile phenotype and secrete collagen and extracellular matrix [...] Read more.

Transforming Growth Factor-Beta 1 (TGF-β1) plays a pivotal role in the differentiation of fibroblasts into myofibroblasts, which is a critical process in tissue repair, fibrosis, and wound healing. Upon exposure to TGF-β1, fibroblasts acquire a contractile phenotype and secrete collagen and extracellular matrix components. Numerous studies have identified hydrogen peroxide (H₂O₂) as a key downstream effector of TGF-β1 in this pathway. H₂O₂ functions as a signalling molecule, regulating various cellular processes mostly through post-translational redox modifications of cysteine thiol groups of specific proteins. In this study, we used primary human skin fibroblast cultures to investigate the oxidative mechanisms triggered by TGF-β1. We analyzed the expression of redox-related genes, evaluated the effects of the genetic and pharmacological inhibition of H₂O₂-producing enzymes, and employed an unbiased redox proteomics approach (OxICAT) to identify proteins undergoing reversible cysteine oxidation. Our findings revealed that TGF-β1 treatment upregulated the expression of oxidant-generating genes while downregulating antioxidant genes. Low concentrations of diphenyleneiodonium mitigated myofibroblast differentiation and mitochondrial oxygen consumption, suggesting the involvement of a flavoenzyme in this process. Furthermore, we identified the increased oxidation of highly conserved cysteine residues in key proteins such as the epidermal growth factor receptor, filamin A, fibulin-2, and endosialin during the differentiation process. Collectively, this study provides insights into the sources of H₂O₂ in fibroblasts and highlights the novel redox mechanisms underpinning fibroblast-to-myofibroblast differentiation. Full article

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

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19 pages, 1849 KiB

Open AccessArticle

Trace Element Concentrations in Degenerative Lumbar Spine Tissues: Insights into Oxidative Stress

by Mikołaj Dąbrowski, Wojciech Łabędź, Łukasz Kubaszewski, Marta K. Walczak, Anetta Zioła-Frankowska and Marcin Frankowski

Antioxidants 2025, 14(4), 485; https://doi.org/10.3390/antiox14040485 - 17 Apr 2025

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Abstract

Degenerative changes are characterized by the formation of vertebral osteophytes, the hypertrophy of facet joints, and narrowing of the intervertebral space. This study aimed to investigate the concentrations of trace elements (Al, As, Se, Zn, Fe, Mo, Cu) in spinal tissues (intervertebral discs, [...] Read more.

Degenerative changes are characterized by the formation of vertebral osteophytes, the hypertrophy of facet joints, and narrowing of the intervertebral space. This study aimed to investigate the concentrations of trace elements (Al, As, Se, Zn, Fe, Mo, Cu) in spinal tissues (intervertebral discs, muscle, and bone) of patients with degenerative lumbar spine disease (DLSD) and their potential associations with the disease. The research involved 13 patients undergoing surgery for symptomatic degenerative spine disease. The trace element concentrations were analyzed using chemical and radiographic assessments, with a statistical analysis performed through a Mann–Whitney U-test, Spearman’s rank correlation test, principal component analysis (PCA), and canonical discriminant analysis (CDA). The results showed significant variations and correlations among the trace elements across different spinal tissues, suggesting their roles in metabolic and oxidative processes and the pathology of spinal degeneration. Full article

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

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42 pages, 2001 KiB

Open AccessSystematic Review

Natural Products from the Mediterranean Area as Wound Healing Agents—In Vitro Studies: A Systematic Review

by Eleftheria Chorti-Tripsa, Vasilis-Zois Galanis, Theodoros C. Constantinides and Christos Kontogiorgis

Antioxidants 2025, 14(4), 484; https://doi.org/10.3390/antiox14040484 - 17 Apr 2025

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Abstract

Wound healing is a process that happens when lost tissue replenishes. For this process, both protective elements and wound healing accelerating factors are required. In recent years, the search for natural products that promote faster healing and prevent adverse effects has gained momentum. [...] Read more.

Wound healing is a process that happens when lost tissue replenishes. For this process, both protective elements and wound healing accelerating factors are required. In recent years, the search for natural products that promote faster healing and prevent adverse effects has gained momentum. This is a systematic review, adhering to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) criteria, of the wound healing effects of natural products, with a focus on natural products from the Mediterranean region. This study sourced the PubMed and Scopus databases for eligible articles and publications over the last six years. Due to the information volume, only the in vitro studies were included in this review. The criteria set concluded in the 28 studies included. These studies showed that many natural products found in the Mediterranean have been studied for the treatment of wounds. The wound healing effect seems to be related to dose, type of wounded tissue, and application time. Moreover, half of the studies were additionally tested and shown antioxidant activity through DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and FRAP (Ferric Reducing Antioxidant Power) assays. Full article

(This article belongs to the Special Issue From Natural to Synthetic Small-Molecule Antioxidants: New Candidates in Drug Discovery—Second Edition)

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20 pages, 3431 KiB

Open AccessReview

Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases

by Massimo Bortolotti, Letizia Polito, Maria Giulia Battelli and Andrea Bolognesi

Antioxidants 2025, 14(4), 483; https://doi.org/10.3390/antiox14040483 - 17 Apr 2025

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Abstract

Non-communicable neurological disorders are the second leading cause of death, and their burden continues to increase as the world population grows and ages. Oxidative stress and inflammation are crucially implicated in the triggering and progression of multiple sclerosis, Alzheimer’s disease, amyotrophic lateral sclerosis, [...] Read more.

Non-communicable neurological disorders are the second leading cause of death, and their burden continues to increase as the world population grows and ages. Oxidative stress and inflammation are crucially implicated in the triggering and progression of multiple sclerosis, Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, Parkinson’s disease, and even stroke. In this narrative review, we examine the role of xanthine oxidoreductase (XOR) activities and products in all the above-cited neurological diseases. The redox imbalance responsible for oxidative stress could arise from excess reactive oxygen and nitrogen species resulting from the activities of XOR, as well as from the deficiency of its main product, uric acid (UA), which is the pivotal antioxidant system in the blood. In fact, with the exception of stroke, serum UA levels are inversely related to the onset and progression of these neurological disorders. The inverse correlation observed between the level of uricemia and the presence of neurological diseases suggests a neuroprotective role for UA. Oxidative stress and inflammation are also caused by ischemia and reperfusion, a condition in which XOR action has been recognized as a contributing factor to tissue damage. The findings reported in this review could be useful for addressing clinical decision-making and treatment optimization. Full article

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

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22 pages, 5990 KiB

Open AccessArticle

Involvement of Nuclear Receptors PPAR-α, PPAR-γ, and the Transcription Factor Nrf2 in Cellular Protection Against Oxidative Stress Regulated by H₂S and Induced by Hypoxia–Reoxygenation and High Glucose in Primary Cardiomyocyte Cultures

by Luz Ibarra-Lara, Araceli Sánchez-López, Leonardo del Valle-Mondragon, Elizabeth Soria-Castro, Gabriela Zarco-Olvera, Mariana Patlán, Verónica Guarner-Lans, Juan Carlos Torres-Narváez, Angélica Ruiz-Ramírez, Fernando Díaz de León-Sánchez, Víctor Hugo Oidor-Chan and Vicente Castrejón-Téllez

Antioxidants 2025, 14(4), 482; https://doi.org/10.3390/antiox14040482 - 17 Apr 2025

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Abstract

Myocardial oxidative stress increases under conditions of hyperglycemia and ischemia/reperfusion (I/R) injury, leading to cellular damage. Inhibition of oxidative stress is involved in the cardioprotective effects of hydrogen sulfide (H₂S) during I/R and diabetes, and H₂S has the potential [...] Read more.

Myocardial oxidative stress increases under conditions of hyperglycemia and ischemia/reperfusion (I/R) injury, leading to cellular damage. Inhibition of oxidative stress is involved in the cardioprotective effects of hydrogen sulfide (H₂S) during I/R and diabetes, and H₂S has the potential to protect the heart. However, the mechanism by which H₂S regulates the level of cardiac reactive oxygen species (ROS) during I/R and hyperglycemic conditions remains unclear. Therefore, the objective of this study was to evaluate the cytoprotective effect of H₂S in primary cardiomyocyte cultures subjected to hyperglycemia, hypoxia–reoxygenation (HR), or both conditions, by assessing the PPAR-α/Keap1/Nrf2/p47phox/NOX4/p-eNOS/CAT/SOD and the PPAR-γ/PGC-1α/AMPK/GLUT4 signaling pathways. Treatment with NaHS (100 μM) as an H₂S donor in cardiomyocytes subjected to hyperglycemia, HR, or a combination of both increased cell viability, total antioxidant capacity, and tetrahydrobiopterin (BH₄) concentrations, while reducing ROS production, malondialdehyde concentrations, 8-hydroxy-2′-deoxyguanosine, and dihydrobiopterin (BH₂) concentrations. Additionally, the H₂S donor treatment increased the expression and activity of PPAR-α, reversed the reduction in the expression of PPAR-γ, PGC-1α, AMPK, GLUT4, Nrf2, p-eNOS, SOD, and CAT, and decreased the expression of Keap1, p47phox and NOX4. Therefore, the treatment with the H₂S donor protects cardiomyocytes from damage caused by hyperglycemia, HR, or both conditions by reducing oxidative stress markers and improving antioxidant mechanisms, thereby increasing cell viability and “cardiomyocyte ultrastructure”. Full article

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

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2 pages, 435 KiB

Open AccessCorrection

Correction: Peritore et al. PEA/Polydatin: Anti-Inflammatory and Antioxidant Approach to Counteract DNBS-Induced Colitis. Antioxidants 2021, 10, 464

by Alessio Filippo Peritore, Ramona D’Amico, Marika Cordaro, Rosalba Siracusa, Roberta Fusco, Enrico Gugliandolo, Tiziana Genovese, Rosalia Crupi, Rosanna Di Paola, Salvatore Cuzzocrea and Daniela Impellizzeri

Antioxidants 2025, 14(4), 481; https://doi.org/10.3390/antiox14040481 - 17 Apr 2025

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Abstract

In the original publication [...] Full article

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

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9 pages, 1353 KiB

Open AccessOpinion

ROS Signaling and NADPH Oxidase in Red Algae

by Gwang-Hoon Kim, Eunyoung Shim and Giuseppe C. Zuccarello

Antioxidants 2025, 14(4), 480; https://doi.org/10.3390/antiox14040480 - 16 Apr 2025

Viewed by 154

Abstract

We explore the diverse roles of reactive oxygen species (ROS) and NADPH oxidases in red algae, focusing on their involvement in fertilization, wound repair, stress adaptation, and development. Once considered mere metabolic byproducts, ROS are now recognized as pivotal signaling molecules in red [...] Read more.

We explore the diverse roles of reactive oxygen species (ROS) and NADPH oxidases in red algae, focusing on their involvement in fertilization, wound repair, stress adaptation, and development. Once considered mere metabolic byproducts, ROS are now recognized as pivotal signaling molecules in red algae. ROS are actively produced and regulated by NADPH oxidase homologs in red algae. During fertilization, ROS facilitate gamete recognition and post-fertilization cell wall development. NADPH oxidase-produced ROS also play essential roles in wound repair, aiding cellular migration and cytoskeletal reorganization at injury sites. A survey of NADPH oxidase homologs in transcriptomic and genomic datasets shows that NADPH oxidase homologs have a long evolutionary history in red algae, with some orthologs duplicating before the split of the Bangiophyceae–Flordeophyceae, approximately 1.1 billion years ago. Additionally, we discuss modifications in red algal NADPH oxidase genes related to calcium binding compared to plants and hypothesize that independent calcium signaling pathways are involved. These insights reveal the significance of NADPH oxidase at a molecular level in supporting red algae’s physiological processes and adaptive strategies. Full article

(This article belongs to the Special Issue Redox Metabolism in Ecophysiology and Evolution, 2nd Edition)

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31 pages, 8706 KiB

Open AccessArticle

Gross Antioxidant Capacity and Anti-Inflammatory Potential of Flavonol Oxidation Products: A Combined Experimental and Theoretical Study

by Karen Acosta-Quiroga, Esteban Rocha-Valderrama, Matías Zúñiga-Bustos, Raúl Mera-Adasme, Gustavo Cabrera-Barjas, Claudio Olea-Azar and Mauricio Moncada-Basualto

Antioxidants 2025, 14(4), 479; https://doi.org/10.3390/antiox14040479 - 16 Apr 2025

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Abstract

This study evaluated the antioxidant capacity of the oxidation products of three flavonols using oxygen radical absorbance capacity—fluorescein assay (ORAC-FL), oxygen radical absorbance capacity—pyrogallol red assay (ORAC-PGR), and the cellular antioxidant activity (CAA) assay in human dermal fibroblast (HFF) cells, with 2,2’-azobis(2-amidinopropane) dihydrochloride [...] Read more.

This study evaluated the antioxidant capacity of the oxidation products of three flavonols using oxygen radical absorbance capacity—fluorescein assay (ORAC-FL), oxygen radical absorbance capacity—pyrogallol red assay (ORAC-PGR), and the cellular antioxidant activity (CAA) assay in human dermal fibroblast (HFF) cells, with 2,2’-azobis(2-amidinopropane) dihydrochloride (AAPH) as a free radical generator under controlled pH and solvent conditions. At pH 2 in a polar aprotic solvent, BZF-OH (benzofuranone-OH) compounds were formed, while methoxylated analogs were obtained at pH 7 in a polar protic solvent. The products generated at pH 2 exhibited significantly higher antioxidant capacities, demonstrating the influence of the reaction environment on modulating antioxidant properties. The antioxidant activity was observed to reflect the combined action of the flavonol precursor and its oxidation products. This led to the proposal of the Gross Antioxidant Capacity (GAC) concept to integrate the contribution of all generated species. Since chemical assays such as ORAC do not fully capture the complexity of biological systems, they should be complemented with cellular approaches for a more accurate evaluation. Additionally, BZF-OH compounds were analyzed as potential cyclooxygenase-2 (COX-2) inhibitors through docking and molecular dynamics simulations, where BZF-Quer-OH showed binding affinities comparable to celecoxib, a selective COX-2 inhibitor. These findings were complemented by an analysis of COX-2 expression in RAW 264.7 cells treated with lipopolysaccharide (LPS), where treatment with the antioxidants significantly inhibited COX-2 expression. In the case of the oxidation products, only the oxidation product of rhamnetin showed a reduction in COX-2 expression compared to the LPS-treated control. Together, these results highlight that flavonol-derived oxidation products not only retain significant antioxidant capacity but may also possess anti-inflammatory properties, opening new perspectives for the development of innovative therapies targeting oxidative stress and chronic inflammation. Full article

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

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13 pages, 5589 KiB

Open AccessArticle

Iturin A Potentiates Differentiation of Intestinal Epithelial Defense Cells by Modulating Keap1/Nrf2 Signaling to Mitigate Oxidative Damage Induced by Heat-Stable Enterotoxin B

by Geng-Xiu Zan, Hao-Zhan Qu, Xin-Yang Li, Qi-Liang Peng, Xiao-Fan Wang, Run-Sheng Li, Yu-Guang Zhao, Hui-Chao Yan, Jia-Yi Zhou and Xiu-Qi Wang

Antioxidants 2025, 14(4), 478; https://doi.org/10.3390/antiox14040478 - 16 Apr 2025

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Abstract

Intestinal stem cells (ISCs) maintain epithelial renewal through their proliferation and differentiation capabilities, responding to various intestinal insults. However, the impact of iturin A, a natural antimicrobial peptide, on ISC viability and its potential to mitigate heat-stable enterotoxin b (STb)-induced intestinal damage remains [...] Read more.

Intestinal stem cells (ISCs) maintain epithelial renewal through their proliferation and differentiation capabilities, responding to various intestinal insults. However, the impact of iturin A, a natural antimicrobial peptide, on ISC viability and its potential to mitigate heat-stable enterotoxin b (STb)-induced intestinal damage remains unclear. Our recent study demonstrated that oral administration of iturin A enhances tight junction protein expression, accelerates crypt-villus regeneration, and restores epithelial barrier integrity in STb-exposed mice. Furthermore, iturin A promotes ISC proliferation and differentiation, significantly increasing the numbers of goblet and Paneth cells in the jejunum following STb exposure. Notably, iturin A regulates intestinal homeostasis by scavenging reactive oxygen species (ROS), while elevating total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) levels in both serum and jejunal mucosa. Mechanistically, iturin A facilitates nuclear factor-erythroid 2- related factor 2 (Nrf2) release by disrupting Kelch-like ECH-associated protein 1 (Keap1), leading to the upregulation of the antioxidant enzyme glutathione peroxidase 4 (GPX4). In conclusion, our findings indicate that iturin A alleviates oxidative stress induced by STb through modulation of the Keap1/Nrf2 pathway and promotes ISC differentiation into goblet and Paneth cells, thereby enhancing resistance to STb-induced damage. Full article

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21 pages, 6706 KiB

Open AccessArticle

Evaluation of Efficacy of Water-Soluble Fraction of Rhus semialata Gall Extract and Penta-O-Galloyl-β-D-Glucose on Mitigation of Hair Loss: An In Vitro and Randomized Double-Blind Placebo-Controlled Clinical Study

by Hee-Sung Lee, Jae Sang Han, Ji-Hyun Park, Min-Hyeok Lee, Yu-Jin Seo, Se Yeong Jeon, Hye Ryeong Hong, Miran Kim, Seon Gil Do, Bang Yeon Hwang and Chan-Su Park

Antioxidants 2025, 14(4), 477; https://doi.org/10.3390/antiox14040477 - 16 Apr 2025

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Abstract

Hair loss, a prevalent condition affecting individuals across various demographics, is associated with hormonal imbalances, oxidative stress, inflammation, and environmental factors. This study evaluated the anti-hair loss potential of the water-soluble fraction of Rhus semialata gall extract (WRGE) and its primary component, Penta-O-Galloyl-β-D-Glucose [...] Read more.

Hair loss, a prevalent condition affecting individuals across various demographics, is associated with hormonal imbalances, oxidative stress, inflammation, and environmental factors. This study evaluated the anti-hair loss potential of the water-soluble fraction of Rhus semialata gall extract (WRGE) and its primary component, Penta-O-Galloyl-β-D-Glucose (PGG), through both in vitro and clinical studies. WRGE was obtained using a standardized extraction process, and PGG was identified via HPLC-DAD and HRESIMS/MS techniques. Human dermal papilla cells (HDPCs) are specialized fibroblasts that can regulate the hair growth cycle and hair follicle growth. HDPCs are widely used in research focused on anti-hair loss. In this study, the anti-hair loss effects of WRGE and PGG on HDPCs were confirmed. WRGE and PGG enhance cell proliferation in HDPCs. These results are associated with the activation of the Wnt/β-catenin signaling pathway and the upregulation of hair growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and fibroblast growth factor (FGF). Furthermore, WRGE and PGG significantly inhibited dihydrotestosterone (DHT)-mediated DKK-1 secretion and H₂O₂-medicated cytotoxicity. Clinical trials further validated these results, demonstrating significant improvements in hair density and visual hair appearance scores in participants treated with WRGE compared to a placebo group. These results collectively suggest that WRGE and PGG may serve as promising natural agents for the prevention and treatment of hair loss by targeting multiple biological pathways, including the regulation of hair growth factors, oxidative stress, and hormonal imbalances. Full article

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27 pages, 3178 KiB

Open AccessReview

Synthesis and Health Effects of Phenolic Compounds: A Focus on Tyrosol, Hydroxytyrosol, and 3,4-Dihydroxyacetophenone

by Wenyu Wang, Lixin Du, Qidong Wei, Mengyao Lu, Dehong Xu and Ya Li

Antioxidants 2025, 14(4), 476; https://doi.org/10.3390/antiox14040476 - 16 Apr 2025

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Abstract

Tyrosol (Tyr), hydroxytyrosol (TH), and 3,4-Dihydroxyacetophenone (3,4-DHAP) are three phenolic compounds naturally present in plants that have attracted considerable research attention due to their potent antioxidant, anti-inflammatory, anticancer, and cardiovascular protective properties. In recent years, mounting evidence has indicated that these phenolic compounds [...] Read more.

Tyrosol (Tyr), hydroxytyrosol (TH), and 3,4-Dihydroxyacetophenone (3,4-DHAP) are three phenolic compounds naturally present in plants that have attracted considerable research attention due to their potent antioxidant, anti-inflammatory, anticancer, and cardiovascular protective properties. In recent years, mounting evidence has indicated that these phenolic compounds hold broad potential in both disease prevention and treatment. This paper reviews the chemical structures and synthetic methods of Tyr, HT, and 3,4-DHAP, as well as their multifaceted effects on human health, particularly their roles and mechanisms in antioxidation, anti-inflammation, cardiovascular protection, neuroprotection, and anticancer activity. In addition, this paper explores the future prospects of these compounds and the current challenges associated with their application—such as low bioavailability and long-term safety concerns—and proposes directions for further investigation. Full article

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19 pages, 1497 KiB

Open AccessArticle

Valorization of Artichoke Bracts in Pasta Enrichment: Impact on Nutritional, Technological, Antioxidant, and Sensorial Properties

by Anna Rita Bavaro, Palmira De Bellis, Vito Linsalata, Serena Rucci, Stefano Predieri, Marta Cianciabella, Rachele Tamburino and Angela Cardinali

Antioxidants 2025, 14(4), 475; https://doi.org/10.3390/antiox14040475 - 16 Apr 2025

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Abstract

The incorporation of artichoke bracts, a by-product of artichoke processing, into pasta formulations represents an innovative approach to enhancing the nutritional and functional properties of this staple food while promoting environmental sustainability. This study aimed to evaluate the impact of artichoke powder (AP) [...] Read more.

The incorporation of artichoke bracts, a by-product of artichoke processing, into pasta formulations represents an innovative approach to enhancing the nutritional and functional properties of this staple food while promoting environmental sustainability. This study aimed to evaluate the impact of artichoke powder (AP) enrichment (10% w/w replacement of semolina) on the technological, nutritional, antioxidant, and sensory properties of pasta. The enriched pasta (P-AP) was compared to control pasta (P-CTR) through comprehensive physicochemical analyses, including cooking performance, polyphenol characterization, and in vitro digestion. Polyphenol analysis revealed that chlorogenic acid, dicaffeoylquinic acids, and flavonoids accounted for 87% of total identified phenolic compounds in P-AP. Despite a 42% reduction in free polyphenols due to cooking, in vitro digestion revealed a 47% increase in total identified polyphenols, attributed to the release of bound polyphenols. Antioxidant assays (DPPH, ABTS, and FRAP) confirmed a significantly higher antioxidant capacity in P-AP compared to P-CTR. Additionally, P-AP exhibited a lower predicted glycemic index (pGI = 56.67) than the control (pGI = 58.41), a beneficial feature for blood glucose regulation. Sensory analysis highlighted distinct differences between samples, with P-AP showing stronger vegetal, artichoke, and legume-like notes, as well as higher intensity in bitterness and astringency. While panelists rated P-CTR higher in overall liking, enriched pasta maintained acceptable sensory characteristics. These findings support the valorization of artichoke by-products in pasta production, demonstrating their potential to enhance nutritional quality and functional properties while contributing to a circular economy. Full article

(This article belongs to the Special Issue Antioxidant Properties and Applications of Food By-Products)

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15 pages, 4783 KiB

Open AccessArticle

Sucralose Promotes Benzo(a)Pyrene-Induced Renal Toxicity in Mice by Regulating P-glycoprotein

by Jun Hu, Ji Feng, Yan Bai, Zhi-Sheng Yao, Xiao-Yu Wu, Xin-Yu Hong, Guo-Dong Lu and Kun Xue

Antioxidants 2025, 14(4), 474; https://doi.org/10.3390/antiox14040474 - 16 Apr 2025

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Abstract

Background: Sucralose and benzo(a)pyrene (B[a]P) are widespread foodborne substances known to harm human health. However, the effects of their combined exposure on kidney function remain unclear. This study aimed to investigate the mechanisms by which sucralose and B[a]P induce [...] Read more.

Background: Sucralose and benzo(a)pyrene (B[a]P) are widespread foodborne substances known to harm human health. However, the effects of their combined exposure on kidney function remain unclear. This study aimed to investigate the mechanisms by which sucralose and B[a]P induce kidney injury through P-glycoprotein (PGP/ABCB1), a crucial protein involved in cellular detoxification. Methods: C57BL/6N mice were co-treated with sucralose and B[a]P for 90 days to evaluate their impact on kidney histopathology and function. In vitro experiments assessed cell viability, reactive oxygen species (ROS) levels, and B[a]P accumulation by flow cytometry. Molecular docking and cellular thermal shift assay (CETSA) were used to determine the binding affinity of sucralose to PGP. Furthermore, PCR, Western blotting, and immunohistochemistry were performed to analyze the expression of PGP and its upstream transcription factors. Results: Ninety days of co-exposure to sucralose and B[a]P significantly exacerbated renal dysfunction in mice, as evidenced by the elevated level of serum creatinine and urea nitrogen, which could be reverted by ROS scavenger N-acetyl cysteine (NAC). In vitro, sucralose promoted cellular accumulation of B[a]P, consequently enhancing B[a]P-induced cell growth inhibition and ROS production. Consistently, B[a]P accumulation was enhanced by PGP knockdown in both HK2 and HEK-293 cells. Mechanistically, sucralose can directly bind to PGP, competitively inhibiting its efflux capacity and increasing intracellular B[a]P retention. Prolonged co-exposure further downregulated PGP expression, possibly through the reductions of its transcriptional regulators (PXR, NRF2, and NF-κB). Conclusions: Co-exposure to sucralose and B[a]P exacerbates renal injury by impairing PGP function. Mechanistically, sucralose inhibits PGP activity, resulting in the accumulation of B[a]P within renal cells. This accumulation triggers oxidative stress and inhibits cell growth, which demonstrates that sucralose potentiates B[a]P-induced nephrotoxicity by directly inhibiting PGP-mediated detoxification pathways, thus underscoring the critical need to evaluate toxicity risks associated with combined exposure to these compounds. Full article

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

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22 pages, 2019 KiB

Open AccessArticle

A Diet Fortified with Anthocyanin-Rich Extract (RED) Reduces Ileal Inflammation in a Senescence-Prone Mice Model of Crohn’s-Disease-like Ileitis

by Giulio Verna, Vicky Caponigro, Stefania De Santis, Emanuela Salviati, Fabrizio Merciai, Fabiano De Almeida Celio, Pietro Campiglia, Katia Petroni, Chiara Tonelli, Aurelia Scarano, Angelo Santino, Manuela Giovanna Basilicata, Marcello Chieppa and Fabio Cominelli

Antioxidants 2025, 14(4), 473; https://doi.org/10.3390/antiox14040473 - 15 Apr 2025

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Abstract

SAMP mice develop progressive Crohn’s disease (CD)-like ileitis without spontaneous colitis that worsens over time without chemical, genetic, or immunological manipulation. Even growing in an identical vivarium and fed with the same diet, SAMP mice reveal a distinct fecal microbiome, metabolome, and lipidome [...] Read more.

SAMP mice develop progressive Crohn’s disease (CD)-like ileitis without spontaneous colitis that worsens over time without chemical, genetic, or immunological manipulation. Even growing in an identical vivarium and fed with the same diet, SAMP mice reveal a distinct fecal microbiome, metabolome, and lipidome profile compared to AKR mice, their non-inflamed parental control strain. Differences are already present in 5-week-old mice, with a tendency to increase in 15-week-old mice. SAMP and AKR mice metabolome and lipidome profiles were substantially different, belonging to two clusters in line with the progression of intestinal disease. Similarly, the 16S analysis confirmed differences between 15-week-old AKR and SAMP mice. The protective role of dietary polyphenols has been documented in inflammatory bowel diseases (IBD); thus, we supplemented the chow diet with an anthocyanin-rich extract (RED) to evaluate disease reduction in SAMP mice and changes in fecal microbiota/metabolome. Our data reveal that 10-week supplementation with anthocyanin-rich extract ameliorated disease severity in SAMP mice despite limited fecal microbiota/metabolome differences. Full article

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

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27 pages, 18741 KiB

Open AccessArticle

Phytochemical Screening, Pharmacognostic Characterization, Antioxidant Activity, and Hepatoprotective Effects of Abroma augustum (L.) L.f. on Human Hepatocellular Carcinoma (HepG2) Cells and Goat Liver Homogenate

by Sandipan Das, Tanushree Deb, Filomena Mottola, Nithar Ranjan Madhu, Yogisharadhya Revanaiah, Israel Maldonado Rosas, Sarbani Dey Ray and Shubhadeep Roychoudhury

Antioxidants 2025, 14(4), 472; https://doi.org/10.3390/antiox14040472 - 15 Apr 2025

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Abstract

Abroma augustum (L.) L. f. is characterized by its fibrous structure, spiny trichomes, and distinctive leaf formations, which collectively contribute to its unique morphology and potential medicinal applications. This study aims to investigate the phytochemical constituents and elucidate the pharmacognostic and physicochemical characteristics [...] Read more.

Abroma augustum (L.) L. f. is characterized by its fibrous structure, spiny trichomes, and distinctive leaf formations, which collectively contribute to its unique morphology and potential medicinal applications. This study aims to investigate the phytochemical constituents and elucidate the pharmacognostic and physicochemical characteristics of the stem bark powder, including evaluation of its antioxidant capacity and hepatoprotective effects against carbon tetrachloride (CCl₄)-induced hepatotoxicity in both in vitro and ex vivo experimental models. Comprehensive phytochemical screening identified 50 distinct phytochemicals, including a range of alkaloids, flavonoids, terpenes, phenolics, and coumarins, among others. The extract displayed substantial solubility, with total phenolic and flavonoid content quantified as 12.32 ± 0.01 mg/g and 42.14 ± 3.5 mg/g, respectively. The antioxidant activity revealed IC₅₀ values obtained from 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), measured at 214.007 µg/mL, 132.307 µg/mL, and 45.455 µg/mL, respectively. Additionally, the methanolic extract exhibited significant hepatoprotective properties, with observable reductions in lipid peroxidation and decreased concentrations of liver damage biomarkers (ALT, AST, and LDH) in both HepG2 cells and goat liver homogenate. Future investigations are warranted to elucidate the underlying mechanisms of these effects, including histopathological examinations and biochemical assays, followed by the administration of plant methanolic extracts. Full article

(This article belongs to the Special Issue Antioxidant and Protective Effects of Plant Extracts—2nd Edition)

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51 pages, 7131 KiB

Open AccessReview

Major Oxidative and Antioxidant Mechanisms During Heat Stress-Induced Oxidative Stress in Chickens

by Bikash Aryal, Josephine Kwakye, Oluwatomide W. Ariyo, Ahmed F. A. Ghareeb, Marie C. Milfort, Alberta L. Fuller, Saroj Khatiwada, Romdhane Rekaya and Samuel E. Aggrey

Antioxidants 2025, 14(4), 471; https://doi.org/10.3390/antiox14040471 - 15 Apr 2025

Viewed by 415

Abstract

Heat stress (HS) is one of the most important stressors in chickens, and its adverse effects are primarily caused by disturbing the redox homeostasis. An increase in electron leakage from the mitochondrial electron transport chain is the major source of free radical production [...] Read more.

Heat stress (HS) is one of the most important stressors in chickens, and its adverse effects are primarily caused by disturbing the redox homeostasis. An increase in electron leakage from the mitochondrial electron transport chain is the major source of free radical production under HS, which triggers other enzymatic systems to generate more radicals. As a defense mechanism, cells have enzymatic and non-enzymatic antioxidant systems that work cooperatively against free radicals. The generation of free radicals, particularly the reactive oxygen species (ROS) and reactive nitrogen species (RNS), under HS condition outweighs the cellular antioxidant capacity, resulting in oxidative damage to macromolecules, including lipids, carbohydrates, proteins, and DNA. Understanding these detrimental oxidative processes and protective defense mechanisms is important in developing mitigation strategies against HS. This review summarizes the current understanding of major oxidative and antioxidant systems and their molecular mechanisms in generating or neutralizing the ROS/RNS. Importantly, this review explores the potential mechanisms that lead to the development of oxidative stress in heat-stressed chickens, highlighting their unique behavioral and physiological responses against thermal stress. Further, we summarize the major findings associated with these oxidative and antioxidant mechanisms in chickens. Full article

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19 pages, 2923 KiB

Open AccessArticle

Rubicon, a Key Molecule for Oxidative Stress-Mediated DNA Damage, in Ovarian Granulosa Cells

by Kiyotaka Yamada, Masami Ito, Haruka Nunomura, Takashi Nishigori, Atsushi Furuta, Mihoko Yoshida, Akemi Yamaki, Tomoko Nakamura, Akira Iwase, Tomoko Shima and Akitoshi Nakashima

Antioxidants 2025, 14(4), 470; https://doi.org/10.3390/antiox14040470 - 15 Apr 2025

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Abstract

Aging drives excessive ovarian oxidative stress (OS), impairing fertility and affecting granulosa cells (GCs), which are involved in folliculogenesis. This study aims to clarify the relationship between OS and autophagy in GCs and to identify compounds that enhance OS resistance. We identified Rubicon, [...] Read more.

Aging drives excessive ovarian oxidative stress (OS), impairing fertility and affecting granulosa cells (GCs), which are involved in folliculogenesis. This study aims to clarify the relationship between OS and autophagy in GCs and to identify compounds that enhance OS resistance. We identified Rubicon, an autophagy suppressor, as a key mediator of DNA damage in GCs under OS. Hydrogen peroxide (H₂O₂) compromised cell viability via DNA damage in the human GC cell line, HGrC1, without affecting autophagic activity. However, autophagy activation increased OS resistance in HGrC1 cells, and vice versa. Among clinically safe materials, trehalose, a disaccharide, protected cells as an autophagy activator against H₂O₂-induced cytotoxicity. Trehalose significantly increased autophagic activity, accompanied by reduced Rubicon expression, compared to other carbohydrates. It also reduced the expression of DNA damage-responsive proteins and the production of reactive oxygen species. Rubicon knockdown mitigated OS-induced DNA damage, while Rubicon overexpression enhanced DNA damage and decreased HGrC1 cell viability. Trehalose enhanced OS resistance by activating autophagy and suppressing Rubicon in a bidirectional manner. As Rubicon expression increases in aged human ovaries, trehalose may improve ovarian function in patients with infertility and other OS-related diseases. Full article

(This article belongs to the Special Issue Antioxidant Systems, Transcription Factors and Non-Coding RNAs)

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Antioxidants, Volume 14, Issue 4 (April 2025) – 129 articles

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