Antioxidants

21 pages, 1877 KiB

Open AccessReview

Puerarin as a Phytochemical Modulator of Gastrointestinal Homeostasis in Livestock: Molecular Mechanisms and Translational Applications

by Jiehong Zhou, Jianyu Lv, Xin Chen, Tian Li, Jianzhong Shen, Zhanhui Wang, Chongshan Dai and Zhihui Hao

Antioxidants 2025, 14(6), 756; https://doi.org/10.3390/antiox14060756 - 19 Jun 2025

Abstract

The gut serves as the main site for nutrient digestion and absorption. Simultaneously, it functions as the body’s largest immune organ, playing a dual role in sustaining physiological equilibrium and offering immunological defense against intestinal ailments. Maintaining the structural and functional integrity of [...] Read more.

The gut serves as the main site for nutrient digestion and absorption. Simultaneously, it functions as the body’s largest immune organ, playing a dual role in sustaining physiological equilibrium and offering immunological defense against intestinal ailments. Maintaining the structural and functional integrity of the intestine is paramount for ensuring animal health and productivity. Puerarin, a naturally derived isoflavonoid from the Pueraria species, exhibits multifaceted bioactivities, such as antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Emerging evidence highlights puerarin’s capacity to enhance gut health in farm animals through four pivotal mechanisms: (1) optimization of intestinal morphology via crypt-villus architecture remodeling, (2) augmentation of systemic and mucosal antioxidant defenses through Nrf2/ARE pathway activation, and (3) reinforcement of intestinal barrier function by regulating tight junction proteins (e.g., ZO-1, occludin), mucin secretion, intestinal mucosal immune barrier, the composition of microbiota, and the derived beneficial metabolites; (4) regulating the function of the intestinal nervous system via reshaping the distribution of intestinal neurons and neurotransmitter secretion function. This review synthesizes current knowledge on puerarin’s protective effects on intestinal physiology in farm animals, systematically elucidates its underlying molecular targets (including TLR4/NF-κB, MAPK, and PI3K/Akt signaling pathways), and critically evaluates its translational potential in mitigating enteric disorders such as post-weaning diarrhea and inflammatory bowel disease in agricultural practices. Full article

(This article belongs to the Topic Recent Advances in Veterinary Pharmacology and Toxicology)

► Show Figures

Figure 1

3 pages, 155 KiB

Open AccessEditorial

Redox Metabolism in Ecophysiology and Evolution, 2nd Edition

by Marko D. Prokić, Marcelo Hermes-Lima and Daniel C. Moreira

Antioxidants 2025, 14(6), 755; https://doi.org/10.3390/antiox14060755 - 19 Jun 2025

Abstract

The ability of organisms to regulate the production of reactive oxygen and nitrogen species (RONS), manage pro-oxidant activity, and make use of redox pathways has significantly influenced their evolution [...] Full article

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

35 pages, 5123 KiB

Open AccessReview

Prebiotic Oligosaccharides in Skin Health: Benefits, Mechanisms, and Cosmetic Applications

by Meijun Zeng, Yang Li, Jie Cheng, Jingyu Wang and Qiyu Liu

Antioxidants 2025, 14(6), 754; https://doi.org/10.3390/antiox14060754 - 18 Jun 2025

Abstract

Prebiotic oligosaccharides have attracted significant interest in dermatology and skin health due to their ability to modulate the skin microbiome and microbiota–host interactions. This review offers a novel dual perspective, systematically examining the benefits of both oral intake and topical application of prebiotic [...] Read more.

Prebiotic oligosaccharides have attracted significant interest in dermatology and skin health due to their ability to modulate the skin microbiome and microbiota–host interactions. This review offers a novel dual perspective, systematically examining the benefits of both oral intake and topical application of prebiotic oligosaccharides, including well-established prebiotics (e.g., human milk oligosaccharides, galacto- and fructo-oligosaccharides) and emerging prebiotic candidates (e.g., gluco-oligosaccharides, chitosan-oligosaccharides, agaro-oligosaccharides). First, cutting-edge synthetic processes for producing diverse oligosaccharides and their structural chemistry are introduced. Then, we discuss in vitro studies demonstrating their efficacy in promoting skin commensals, inhibiting pathogens, and conferring protective effects, such as antioxidant, anti-inflammatory, anti-melanogenic, and wound-healing properties. Furthermore, we emphasize in vivo animal studies and clinical trials revealing that prebiotic oligosaccharides, administered orally or topically, alleviate atopic dermatitis, enhance skin hydration, attenuate acne, and protect against photo-aging by modulating skin–gut microbiota and immune responses. Mechanistically, we integrate genetic and molecular insights to elucidate how oligosaccharides mediate these benefits, including gut–skin axis crosstalk, immune regulation, and microbial metabolite signaling. Finally, we highlight current commercial applications of oligosaccharides in cosmetic formulations while addressing scientific and practical challenges, such as structure–function relationships, clinical scalability, and regulatory considerations. This review bridges mechanistic understanding with practical applications, offering a comprehensive resource for advancing prebiotic oligosaccharides-based skincare therapies. Full article

(This article belongs to the Special Issue Exploring Plant-Derived Bioactive Compounds: The Role of Peptides, Polysaccharides, and Antioxidants in Nutriceutical Development and Health Promotion)

► Show Figures

Figure 1

23 pages, 2102 KiB

Open AccessArticle

Impact of a Formulation Containing Chaga Extract, Coenzyme Q10, and Alpha-Lipoic Acid on Mitochondrial Dysfunction and Oxidative Stress: NMR Metabolomic Insights into Cellular Energy

by Maria D’Elia, Carmen Marino, Rita Celano, Enza Napolitano, Chiara Colarusso, Rosalinda Sorrentino, Anna Maria D’Ursi and Luca Rastrelli

Antioxidants 2025, 14(6), 753; https://doi.org/10.3390/antiox14060753 - 18 Jun 2025

Abstract

Objectives: The aim of this study was to evaluate the impact of a novel antioxidant formulation (RE:PAIR, RP-25) containing CoQ10, alpha-lipoic acid, and Chaga extract on mitochondrial dysfunction and oxidative stress. To explore the activity of the formulation on neuronal cells, we explored [...] Read more.

Objectives: The aim of this study was to evaluate the impact of a novel antioxidant formulation (RE:PAIR, RP-25) containing CoQ10, alpha-lipoic acid, and Chaga extract on mitochondrial dysfunction and oxidative stress. To explore the activity of the formulation on neuronal cells, we explored cell metabolism and its activity as an antioxidant, using a combination of NMR-based metabolomics and UHPLC-HRMS analytical techniques. Methods: SH-SY5Y neuroblastoma cells were treated with RP-25, and cell viability was assessed via CCK-8 assay. Metabolomic profiles of the treated and untreated cells were analyzed by 1D-NMR, providing insights into both intracellular metabolites (endometabolome) and excreted metabolites (exometabolome). Additionally, a UHPLC-HRMS method was developed for quality control and analysis of the RP-25 formulation. Multivariate statistical approaches, including PLS-DA and volcano plot analyses, were used to identify key metabolic changes. Changes in mitochondrial membrane potential were assessed by means of TMRE assay, while radical oxygen species (ROS) were measured by means of the DCHF assay. Results: RP-25 treatment did not affect cell viability but significantly increased metabolic pathways, including amino acid biosynthesis, oxidative phosphorylation, and glycolysis. Higher levels of ATP, glutamate, tyrosine, and proline were observed in treated cells than in control cells, indicating enhanced cellular energy production, as also proved by the increased stability of the mitochondrial membrane after RP-25 treatment, an index of preserved mitochondrial functions. In support, the formulation RP-25 showed antioxidant activity when cells underwent peroxide oxygen stimulation. This effect was mainly due to the combination of Chaga, CoQ10, and ALA, main components of the RP25 formulation. Moreover, the analysis of enriched pathways highlighted that RP formulation influenced mitochondrial energy and oxidative stress response. Conclusions: RP-25 demonstrated biological activity in that it mitigated mitochondrial dysfunction and oxidative stress in neuronal cells, with potential implications in neuronal diseases associated with dysfunctional mitochondria. Full article

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

► Show Figures

Figure 1

27 pages, 921 KiB

Open AccessArticle

Influence of Kombucha Fermentation on Antioxidant and Antimicrobial Activity of Monofloral Rapeseed Bee-Collected Pollen

by Aleksandar Ž. Kostić, Aleksandra Sknepnek, Danijel D. Milinčić, Uroš Gašić, Sofija Kilibarda and Mirjana B. Pešić

Antioxidants 2025, 14(6), 752; https://doi.org/10.3390/antiox14060752 - 18 Jun 2025

Abstract

Bee-collected pollen (BCP) can serve as an excellent enhancer of functional food bioactivity, particularly when it is fermented. The aim of this study was to prepare a novel kombucha-based beverage (KPE) enriched with fermented monofloral rapeseed (Brassica napus L.) BCP. To characterize [...] Read more.

Bee-collected pollen (BCP) can serve as an excellent enhancer of functional food bioactivity, particularly when it is fermented. The aim of this study was to prepare a novel kombucha-based beverage (KPE) enriched with fermented monofloral rapeseed (Brassica napus L.) BCP. To characterize the obtained samples, a proximate phytochemical composition analysis (including total phenolic and flavonoid content) was performed, as well as a detailed untargeted UHPLC-Q-ToF-MS profiling of phenolics and phenylamides. To biologically characterize KPE, antioxidant and antimicrobial activities were monitored. The total phenolic and flavonoid content, enhanced by the addition of BCP to the kombucha green tea beverage, was dose-dependent. The control sample showed a strong predominance of flavan-3-ols, distinguishing it from the KPE samples, where flavonol predominance and an increased content of phenolic acids were observed. Notably, the most significant markers of BCP were phenylamides, which were completely absent in the control. Although antioxidant activity was proximately highest in the control sample, KPE samples exhibited significantly improved antimicrobial activity. Full article

(This article belongs to the Special Issue Antioxidant and Antimicrobial Activity of Honey Bee Products—2nd Edition)

► Show Figures

Figure 1

14 pages, 781 KiB

Open AccessArticle

Chemical Composition and Antioxidant Activity of Prokupac Grape Pomace Extract: Implications for Redox Modulation in Honey Bee Cells

by Uroš Glavinić, Đura Nakarada, Jevrosima Stevanović, Uroš Gašić, Marko Ristanić, Miloš Mojović and Zoran Stanimirović

Antioxidants 2025, 14(6), 751; https://doi.org/10.3390/antiox14060751 - 18 Jun 2025

Abstract

There is a growing interest in using agri-food by-products and a demand for natural substances that might help maintain healthy honey bee colonies. We investigated a by-product of the wine industry, a grape pomace (GP) of the autochthonous Prokupac grape cultivar from Serbia. [...] Read more.

There is a growing interest in using agri-food by-products and a demand for natural substances that might help maintain healthy honey bee colonies. We investigated a by-product of the wine industry, a grape pomace (GP) of the autochthonous Prokupac grape cultivar from Serbia. A hydroethanolic extract (50% (w/v) ethanol) of GP (Prokupac GP extract) obtained by the pressurized liquid extraction (PLE) method was subjected to qualitative profiling of phenolic composition by liquid chromatography with OrbiTrap Exploris 120 mass spectrometer. Then, the extracts’ antioxidant and redox-modulatory activities were evaluated through Electron Paramagnetic Resonance (EPR) spectroscopy. Finally, the extract’s potential to modulate cellular redox status was evaluated using cultured AmE-711 honey bee cells. The results show that the Prokupac GP extract contains a wide array of flavonoids, anthocyanins, stilbenes, and their various conjugated derivatives and that anthocyanins, particularly malvidin-based compounds, dominate. EPR measurements showed strong scavenging activity against superoxide anion (O₂^•−) and hydroxyl radicals (^•OH), with inhibition efficiencies of 84.37% and 81.81%, respectively, while activity against the DPPH radical was lower (17.75%). In the cell-based assay, the Prokupac GP extract consistently provided strong antioxidant protection and modulated the cellular response to oxidative stress by over 14%. In conclusion, while the Prokupac GP extract demonstrated antioxidant properties and the ability to modulate cellular responses to oxidative stress, in vivo studies on honey bees are required to confirm its efficacy and safety for potential use in beekeeping practice. Full article

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

► Show Figures

Figure 1

17 pages, 3214 KiB

Open AccessArticle

SENP1 Senses Oxidative Stress to Regulate the SUMOylation Modification of ZIP8 and Maintain Zinc Transport Functions

by Tao Liu, Chang-Chun Song, Fu-Xuan Duan, Chong-Chao Zhong, Sheng-Zan Liu, Jia-Cheng Guo, An-Gen Yu and Zhi Luo

Antioxidants 2025, 14(6), 750; https://doi.org/10.3390/antiox14060750 - 18 Jun 2025

Abstract

Zinc (Zn) is a crucial trace element in vertebrates, fulfilling a range of physiological functions, whose metabolism and homeostasis are manipulated by Zn transporter proteins. SUMOylation, a reversible post-translational modification (PTM), extensively participates in various biological processes in the body, yet its underlying [...] Read more.

Zinc (Zn) is a crucial trace element in vertebrates, fulfilling a range of physiological functions, whose metabolism and homeostasis are manipulated by Zn transporter proteins. SUMOylation, a reversible post-translational modification (PTM), extensively participates in various biological processes in the body, yet its underlying mechanism in regulating Zn transporters remains unexplored. Our findings indicate that high dietary Zn substantially elevated intestinal Zn content and modulated the expression profiles of Zn transporter-related genes and proteins, including ZIP8 transporter. In addition, high Zn diet tended to inhibit the SUMOylation modification and upregulate deSUMOylation modification in the intestine and intestinal epithelial cells. Furthermore, we found that the ZIP8 protein undergoes SUMOylation modification; UBC9 upregulated but SENP1 and Zn downregulated the SUMOylation level of ZIP8, and the K24 and K222 positions are the primary SUMOylation modification sites of ZIP8 protein in yellow catfish. Mechanistically, SENP1 modulates the deSUMOylation modification of ZIP8 by sensing Zn-induced oxidative stress. In summary, for the first time, we have uncovered a unique regulatory mechanism of ZIP8 mediated by SUMOylation modification in vertebrates and demonstrate that SENP1 is capable of sensing oxidative stress to reduce the SUMOylation modification of ZIP8 at K24 and K222 sites. Full article

► Show Figures

Figure 1

24 pages, 4782 KiB

Open AccessArticle

Ferroptosis and Sterol Biosynthesis Dysregulation in Granulosa Cells of Patients with Diminished Ovarian Reserve

by Yang Yu, Yali Shan, Jiani Lu, Yexing Xian, Zhengshan Tang, Xinyu Guo, Yan Huang and Xin Ni

Antioxidants 2025, 14(6), 749; https://doi.org/10.3390/antiox14060749 - 17 Jun 2025

Viewed by 12

Abstract

Granulosa cell (GC) dysfunction contributes to diminished ovarian reserve (DOR). We collected GC and follicular fluid samples from the patients of normal ovarian reserve (NOR) and DOR. RNA-seq of GCs showed that cholesterol/sterol metabolism and biosynthesis and extracellular matrix organization were enriched in [...] Read more.

Granulosa cell (GC) dysfunction contributes to diminished ovarian reserve (DOR). We collected GC and follicular fluid samples from the patients of normal ovarian reserve (NOR) and DOR. RNA-seq of GCs showed that cholesterol/sterol metabolism and biosynthesis and extracellular matrix organization were enriched in the DOR group. Metabolomics of follicular fluid revealed enrichment in steroid hormone biosynthesis, tryptophan metabolism, and fatty acid β-oxidation in DOR. The apoptosis rate was increased, whereas the proliferative rate was decreased in GCs of DOR. The Prussian blue staining rate was increased whilst GPX4 and SLC7A11 expression were downregulated in GCs of DOR. Mitochondrial morphology displayed the features of ferroptosis in GCs of DOR. FSHR, CYP19A1, NR5A1, and phosphorylated CREB levels were substantially downregulated in GCs, accompanied by increased androgen levels in follicular fluids in DOR. The key factors linked to the mevalonate pathway, HMGCR, SQLE, and SREBF2, were robustly increased in DOR. FSHR and NR5A1 levels were correlated with CYP19A1 levels, whilst CYP19A1 levels were positively correlated with GPX4 and SLC7A11 levels. Our findings indicate ferroptosis and dysregulation of cholesterol/sterol metabolism and biosynthesis occurrence in GCs of DOR, which might be associated with reduced FSHR signaling and decreased conversion of androgen to estrogen. Full article

18 pages, 2824 KiB

Open AccessArticle

Aerobic Exercise Alleviates Cardiac Dysfunction Correlated with Lipidomics and Mitochondrial Quality Control

by Kunzhe Li, Sujuan Li, Hao Jia, Yinping Song, Zhixin Chen and Youhua Wang

Antioxidants 2025, 14(6), 748; https://doi.org/10.3390/antiox14060748 - 17 Jun 2025

Viewed by 10

Abstract

Cardiac adaptations induced by aerobic exercise have been shown to reduce the risk of cardiovascular disease, and the autonomic nervous system is closely associated with the development of cardiovascular disease. Aerobic exercise intervention has been shown to enhance cardiac function and mitigate myocardial [...] Read more.

Cardiac adaptations induced by aerobic exercise have been shown to reduce the risk of cardiovascular disease, and the autonomic nervous system is closely associated with the development of cardiovascular disease. Aerobic exercise intervention has been shown to enhance cardiac function and mitigate myocardial fibrosis and hypertrophy in heart failure mice. Further insights reveal that cardiomyocytes experiencing chronic heart failure undergo modifications in their lipidomic profile, including remodeling of multiple myocardial membrane phospholipids. Notably, there is a decrease in the total content of cardiolipin, as well as in the levels of total lysolipid CL and the CL (22:6). These alterations disrupt mitochondrial quality control processes, leading to abnormal expressions of proteins such as Drp1, MFN2, OPA1, and BNIP3, thereby resulting in a disrupted mitochondrial dynamic network. Whereas aerobic exercise ameliorated mitochondrial damage to a large extent by activating parasympathetic nerves, this beneficial effect was accomplished by modulating myocardial membrane phospholipid remodeling and restoring the mitochondrial dynamic network. In conclusion, aerobic exercise activated the parasympathetic state in mice and attenuated lipid peroxidation and oxidative stress injury, thereby maintaining mitochondrial dynamic homeostasis and improving cardiac function. Full article

(This article belongs to the Special Issue Innovative Therapeutic Approaches for Hypertension and Cardiovascular Diseases: Targeting Oxidative Stress Pathways)

► Show Figures

Figure 1

24 pages, 11046 KiB

Open AccessArticle

A Theoretical Analysis of the Effects That the Glycocalyx and the Internal Elastic Lamina Have on Nitric Oxide Concentration Gradients in the Arterial Wall

by Yaroslav R. Nartsissov and Irena P. Seraya

Antioxidants 2025, 14(6), 747; https://doi.org/10.3390/antiox14060747 - 17 Jun 2025

Viewed by 6

Abstract

Nitric oxide (NO) is a well-known member of the reactive oxygen species (ROS) family. The extent of its concentration influences whether it produces beneficial physiological effects or harmful toxic reactions. In a blood system, NO is generally produced by nitric oxide synthase (NOS) [...] Read more.

Nitric oxide (NO) is a well-known member of the reactive oxygen species (ROS) family. The extent of its concentration influences whether it produces beneficial physiological effects or harmful toxic reactions. In a blood system, NO is generally produced by nitric oxide synthase (NOS) in the endothelium. Then, it diffuses into the smooth muscle wall causing a vasodilatation, and it can also be diluted in a lumen blood stream. In the present study, we analyzed a convectional reaction–diffusion of NO in a 3D digital phantom of a short segment of small arteries. NO concentrations were analyzed by applying numerical solutions to the boundary problems, which included the Navier–Stokes equation, Darcy’s law, varying consumption of NO, and the dependence of NOS activity on shear stress. All the boundary problems were evaluated using COMSOL Multiphysics software ver. 5.5. The role of two diffusive barriers surrounding the endothelium producing NO was theoretically proven. When the eNOS rate remains unchanged, an increase in the fenestration of the internal elastic lamina (IEL) and a decrease in the diffusive permeability of a thin layer of endothelial surface glycocalyx (ESG) lead to a notable rise in the NO concentration in the vascular wall. The alterations in pore count in IEL and the viscosity of ESG are considered to be involved in the physiological and pathological regulation of NO concentrations. Full article

(This article belongs to the Special Issue Nitric Oxide and Redox Mechanisms)

► Show Figures

Figure 1

27 pages, 6312 KiB

Open AccessArticle

Transcriptomic Redox Dysregulation in a Rat Model of Metabolic Syndrome-Associated Kidney Injury

by Chien-Lin Lu, Yi-Yun Wang, Yih-Jeng Tsai, Hsuan-Ting Chen, Ming-Chieh Ma and Wen-Bin Wu

Antioxidants 2025, 14(6), 746; https://doi.org/10.3390/antiox14060746 - 17 Jun 2025

Viewed by 7

Abstract

Metabolic syndrome (MetS), characterized by obesity, insulin resistance, and dyslipidemia, is a major risk factor for renal injury. Oxidative stress (OxS) plays a pivotal role in its progression; however, the underlying molecular mechanisms are not fully understood. In this study, we established a [...] Read more.

Metabolic syndrome (MetS), characterized by obesity, insulin resistance, and dyslipidemia, is a major risk factor for renal injury. Oxidative stress (OxS) plays a pivotal role in its progression; however, the underlying molecular mechanisms are not fully understood. In this study, we established a rat model of MetS using a high-fat diet combined with a single-dose streptozotocin injection in male Wistar rats. MetS rats exhibited systemic OxS, evidenced by elevated circulating levels of free oxygen radicals and decreased antioxidant defense capacity, as well as hypertension, renal lipid peroxidation, glomerular hyperfiltration, and renal tubular injury. Transcriptomic profiling of renal tissue revealed significant downregulation of six OxS-related genes: C-C motif chemokine ligand 5 (CCL5), glutamate-cysteine ligase catalytic subunit, glutathione peroxidase 6, recombination activating gene 2, NAD(P)H: quinone oxidoreductase 1, and selenoprotein P-1. Among these downregulated genes, CCL5 was further confirmed to be repressed at both mRNA and protein levels across intrarenal and systemic compartments. Given its documented functions in immune signaling and redox homeostasis, CCL5 downregulation may contribute to enhanced oxidative damage in MetS-associated renal injury. These findings highlight the role of redox gene dysregulation in the pathogenesis of MetS-related kidney disease and support the potential of CCL5 as a biomarker for oxidative renal injury. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic Syndrome and Cardiovascular Diseases)

► Show Figures

Figure 1

19 pages, 545 KiB

Open AccessArticle

Blood Orange (Citrus sinensis L. Osbeck) Juice By-Product Extract as a Functional Feed Additive: Effects on Growth Performance, Digestive Enzyme Activity, Antioxidant Status, Immune Parameters, and Disease Resistance Against Vibrio harveyi in Juvenile Black Rockfish (Sebastes schlegelii)

by Ahyeong Yun, Hwa Yong Oh, Tae Hoon Lee, Da Ye Kang, Ki-Tae Kim, Hyun-Soo Kim and Hee Sung Kim

Antioxidants 2025, 14(6), 745; https://doi.org/10.3390/antiox14060745 - 17 Jun 2025

Viewed by 7

Abstract

This study evaluated the antibacterial activity and residual functional compounds of blood orange (Citrus sinensis L. Osbeck) juice by-product extract (BJBE). The effects of dietary BJBE on growth performance, digestive enzyme activity, antioxidant status, immune parameters, and disease resistance against Vibrio harveyi [...] Read more.

This study evaluated the antibacterial activity and residual functional compounds of blood orange (Citrus sinensis L. Osbeck) juice by-product extract (BJBE). The effects of dietary BJBE on growth performance, digestive enzyme activity, antioxidant status, immune parameters, and disease resistance against Vibrio harveyi were examined in juvenile black rockfish (Sebastes schlegelii). In total, 630 juvenile rockfish were randomly assigned to 21 rectangular tanks (50 L) for a feeding trial, with 30 fish per tank in triplicate. Seven isonitrogenous and isolipidic experimental diets were formulated with BJBE at 0 (control, BJBE0), 0.1 (BJBE0.1), 0.2 (BJBE0.2), 0.3 (BJBE0.3), 0.5 (BJBE0.5), 0.7 (BJBE0.7), and 1.0 (BJBE1) g kg⁻¹. A disk diffusion assay confirmed BJBE’s strong antibacterial efficacy against V. harveyi. After an 8-week feeding trial, fish fed BJBE0.7 and BJBE1 exhibited significantly a greater final weight, weight gain, and specific growth rate compared with those fed BJBE0. Feed efficiency was significantly higher in fish fed BJBE0.7 than in those fed BJBE0. The protein efficiency ratio was significantly higher in fish fed BJBE0.3, BJBE0.5, BJBE0.7, and BJBE1 relative to those fed BJBE0. Intestinal amylase activity was significantly higher in fish fed BJBE0.7 and BJBE1 compared with those fed BJBE0, and trypsin activity was significantly higher in BJBE0.7-fed fish than in BJBE0-fed fish. In comparison to the BJBE0 diet, the plasma superoxide dismutase, catalase, and glutathione levels of fish fed BJBE0.7 and BJBE1 diets were significantly higher. Lysozyme activity and immunoglobulin M level in fish fed BJBE0.7 and BJBE1 were significantly higher than that in fish fed BJBE0. After a challenge with V. harveyi, disease resistance was significantly higher in fish fed BJBE0.5, BJBE0.7, and BJBE1 compared with those fed BJBE0. Overall, 0.7–1.0 g kg⁻¹ is proposed as the optimal dietary BJBE inclusion level for enhancing growth performance, digestive enzyme activity, antioxidant status, immune parameters, and disease resistance against V. harveyi infection in juvenile black rockfish. Full article

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

► Show Figures

Figure 1

22 pages, 3518 KiB

Open AccessArticle

Cannabinol’s Modulation of Genes Involved in Oxidative Stress Response and Neuronal Plasticity: A Transcriptomic Analysis

by Serena Silvestro, Marco Calabrò, Alessandra Trainito, Stefano Salamone, Federica Pollastro, Emanuela Mazzon and Aurelio Minuti

Antioxidants 2025, 14(6), 744; https://doi.org/10.3390/antiox14060744 - 17 Jun 2025

Viewed by 5

Abstract

Cannabis sativa is a remarkable source of bioactive compounds, with over 150 distinct phytocannabinoids identified to date. Among these, cannabinoids are gaining attention as potential therapeutic agents for neurodegenerative diseases. Previous research showed that cannabinol (CBN), a minor cannabinoid derived from Δ⁹ [...] Read more.

Cannabis sativa is a remarkable source of bioactive compounds, with over 150 distinct phytocannabinoids identified to date. Among these, cannabinoids are gaining attention as potential therapeutic agents for neurodegenerative diseases. Previous research showed that cannabinol (CBN), a minor cannabinoid derived from Δ⁹-tetrahydrocannabinol, exhibits antioxidant, anti-inflammatory, analgesic, and anti-bacterial effects. The objective of this study was to assess the protective potential of 24 h CBN pre-treatment, applied at different concentrations (5 µM, 10 µM, 20 µM, 50 µM, and 100 µM), in differentiated neuroblastoma × spinal cord (NSC-34) cells. Transcriptomic analysis was performed using next-generation sequencing techniques. Our results reveal that CBN had no negative impact on cell viability at the tested concentrations. Instead, it showed a significant effect on stress response and neuroplasticity-related processes. Specifically, based on the Reactome database, the biological pathways mainly perturbed by CBN pre-treatment were investigated. This analysis highlighted a significant enrichment in the Reactome pathway’s cellular response to stress, cellular response to stimuli, and axon guidance. Overall, our results suggest that CBN holds promise as an adjuvant agent for neurodegenerative diseases by modulating genes involved in neuronal cell survival and axon guidance. Full article

(This article belongs to the Special Issue Oxidative Stress and Its Mitigation in Neurodegenerative Disorders)

► Show Figures

Figure 1

52 pages, 1239 KiB

Open AccessReview

Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia—Focus on the NO System

by Olena Popazova, Igor Belenichev, Nina Bukhtiyarova, Victor Ryzhenko, Nadia Gorchakova, Valentyn Oksenych and Oleksandr Kamyshnyi

Antioxidants 2025, 14(6), 743; https://doi.org/10.3390/antiox14060743 - 16 Jun 2025

Viewed by 73

Abstract

Prenatal hypoxia (PH) adversely affects the development of the fetal heart, contributing to persistent cardiovascular impairments in postnatal life. A key component in regulating cardiac physiology is the nitric oxide (NO) system, which influences vascular tone, myocardial contractility, and endothelial integrity during development. [...] Read more.

Prenatal hypoxia (PH) adversely affects the development of the fetal heart, contributing to persistent cardiovascular impairments in postnatal life. A key component in regulating cardiac physiology is the nitric oxide (NO) system, which influences vascular tone, myocardial contractility, and endothelial integrity during development. Exposure to PH disrupts NO-related signaling pathways, leading to endothelial dysfunction, mitochondrial damage, and an escalation of oxidative stress—all of which exacerbate cardiac injury and trigger cardiomyocyte apoptosis. The excessive generation of reactive nitrogen species drives nitrosative stress, thereby intensifying inflammatory processes and cellular injury. In addition, the interplay between NO and hypoxia-inducible factor (HIF) shapes adaptive responses to PH. NO also modulates the synthesis of heat shock protein 70 (HSP70), a critical factor in cellular defense against stress. This review emphasizes the involvement of NO in cardiovascular injury caused by PH and examines the cardioprotective potential of NO modulators—Angiolin, Thiotriazoline, Mildronate, and L-arginine—as prospective therapeutic agents. These agents reduce oxidative stress, enhance endothelial performance, and alleviate the detrimental effects of PH on the heart, offering potential new strategies to prevent cardiovascular disorders in offspring subjected to prenatal hypoxia. Full article

(This article belongs to the Special Issue Nitric Oxide and Redox Mechanisms)

► Show Figures

Figure 1

15 pages, 2012 KiB

Open AccessArticle

Food Grade Synthesis of Hetero-Coupled Biflavones and 3D-Quantitative Structure–Activity Relationship (QSAR) Modeling of Antioxidant Activity

by Hongling Zheng, Xin Yang, Qiuyu Zhang, Joanne Yi Hui Toy and Dejian Huang

Antioxidants 2025, 14(6), 742; https://doi.org/10.3390/antiox14060742 - 16 Jun 2025

Viewed by 79

Abstract

Biflavonoids are a unique subclass of dietary polyphenolic compounds known for their diverse bioactivities. Despite these benefits, these biflavonoids remain largely underexplored due to their limited natural availability and harsh conditions required for their synthesis, which restricts broader research and application in functional [...] Read more.

Biflavonoids are a unique subclass of dietary polyphenolic compounds known for their diverse bioactivities. Despite these benefits, these biflavonoids remain largely underexplored due to their limited natural availability and harsh conditions required for their synthesis, which restricts broader research and application in functional foods and nutraceuticals. To address this gap, we synthesized a library of rare biflavonoids using a radical–nucleophile coupling reaction previously reported by our group. The food grade coupling reaction under weakly alkaline water at room temperature led to isolation of 28 heterocoupled biflavones from 11 monomers, namely 3′,4′-dihydroxyflavone, 5,3′,4′-trihydroxyflavone, 6,3′,4′-trihydroxyflavone, 7,3′,4′-trihydroxyflavone, diosmetin, chrysin, acacetin, genistein, biochanin A, and wogonin. The structures of the dimers are characterized by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectroscopy (HRMS). In addition, we evaluated the antioxidant potential of these biflavones using a DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay and the DPPH value ranges between 0.75 to 1.82 mM of Trolox/mM of sample across the 28 synthesized dimers. Additionally, a three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis was conducted to identify structural features associated with enhanced antioxidant activity. The partial least squares (PLS) regression QSAR model showed acceptable r² = 0.936 and q² = 0.869. Additionally, the average local ionization energy (ALIE), electrostatic potential (ESP), Fukui index (F-), and electron density (ED) were determined to identify the key structural moiety that was capable of donating electrons to neutralize reactive oxygen species. Full article

► Show Figures

Figure 1

42 pages, 18742 KiB

Open AccessArticle

Mitochondrial Unfolded Protein Response (mtUPR) Activation Improves Pathological Alterations in Cellular Models of Ethylmalonic Encephalopathy

by José Manuel Romero-Domínguez, Paula Cilleros-Holgado, David Gómez-Fernández, Rocío Piñero-Pérez, Diana Reche-López, Ana Romero-González, Mónica Álvarez-Córdoba, Alejandra López-Cabrera, Marta Castro De Oliveira, Andrés Rodríguez-Sacristán, Susana González-Granero, José Manuel García-Verdugo, Angeles Aroca and José A. Sánchez-Alcázar

Antioxidants 2025, 14(6), 741; https://doi.org/10.3390/antiox14060741 - 16 Jun 2025

Viewed by 70

Abstract

Ethylmalonic encephalopathy (EE) is a serious metabolic disorder that usually appears in early childhood development and the effects are seen primarily in the brain, gastrointestinal tract, and peripheral vessels. EE is caused by pathogenic variants in the gene that encodes the ETHE1 protein, [...] Read more.

Ethylmalonic encephalopathy (EE) is a serious metabolic disorder that usually appears in early childhood development and the effects are seen primarily in the brain, gastrointestinal tract, and peripheral vessels. EE is caused by pathogenic variants in the gene that encodes the ETHE1 protein, and its main features are high levels of acidic compounds in body fluids and decreased activity of the mitochondrial complex IV, which limits energy production in tissues that require a large supply of energy. ETHE1 is a mitochondrial sulfur dioxygenase that plays the role of hydrogen sulfide (H₂S) detoxification, and, when altered, it leads to the accumulation of this gaseous molecule due to its deficient elimination. In this article, we characterised the pathophysiology of ETHE1 deficiency in cellular models, fibroblasts, and induced neurons, derived from a patient with a homozygous pathogenic variant in ETHE1. Furthermore, we evaluated the effect of the activation of the mitochondrial unfolded protein response (mtUPR) on the mutant phenotype. Our results suggest that mutant fibroblasts have alterations in ETHE1 protein expression levels, associated with elevated levels of H₂S and protein persulfidation, mitochondrial dysfunction, iron/lipofuscin accumulation, and oxidative stress. We also identified a cocktail of compounds consisting of pterostilbene, nicotinamide, riboflavin, thiamine, biotin, lipoic acid, and L-carnitine that improved the cellular and metabolic alterations. The positive effect of the cocktail was dependent on sirtuin 3 activation (SIRT3) and was also confirmed in induced neurons obtained by direct reprogramming. In conclusion, personalised precision medicine in EE using patient-derived cellular models can be an interesting approach for the screening and evaluation of potential therapies. In addition, the activation of the SIRT3 axe of mtUPR is a promising therapeutic strategy for rescuing ETHE1 pathogenic variants. Full article

(This article belongs to the Special Issue Inhibition of Oxidative Stress and Related Signaling Pathways in Neuroprotection—2nd Edition)

► Show Figures

Graphical abstract

26 pages, 2049 KiB

Open AccessSystematic Review

Unlocking the Power of Magnesium: A Systematic Review and Meta-Analysis Regarding Its Role in Oxidative Stress and Inflammation

by Violeta Cepeda, Marina Ródenas-Munar, Silvia García, Cristina Bouzas and Josep A. Tur

Antioxidants 2025, 14(6), 740; https://doi.org/10.3390/antiox14060740 - 16 Jun 2025

Viewed by 97

Abstract

Magnesium plays a crucial role in over 300 enzymatic reactions related to energy production, muscle contraction, and nerve function. Given its essential biological functions and increasing prevalence of suboptimal intake, magnesium supplementation has gained attention for its potential health benefits, particularly in mitigating [...] Read more.

Magnesium plays a crucial role in over 300 enzymatic reactions related to energy production, muscle contraction, and nerve function. Given its essential biological functions and increasing prevalence of suboptimal intake, magnesium supplementation has gained attention for its potential health benefits, particularly in mitigating oxidative stress and inflammation. This systematic review and meta-analysis aimed to evaluate the antioxidant effects of dietary and supplemental magnesium on several biomarkers related to oxidative stress and inflammation. A systematic search of studies published from 2000 to 2025 identified 28 relevant articles, including both animal and human studies. The meta-analysis assessed the effects of magnesium supplementation on oxidative stress biomarkers such as nitric oxide (NO), total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), and C-reactive protein (CRP). While results showed a statistically significant reduction in CRP levels, suggesting an anti-inflammatory effect, no conclusive impact on oxidative stress biomarkers was observed. The findings highlight magnesium’s potential role in inflammation regulation, though its direct antioxidant effects remain uncertain. Further high-quality clinical trials are needed to clarify the impact of magnesium supplementation on oxidative stress and to explore its broader health implications. Full article

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

► Show Figures

Graphical abstract

14 pages, 1282 KiB

Open AccessArticle

Serum 3-Nitrotyrosine in the Cardiovascular Disease of Patients with Systemic Lupus Erythematosus

by Juan C. Quevedo-Abeledo, Marta Hernández-Díaz, María García-González, Fuensanta Gómez-Bernal, Cristina Almeida-Santiago, Elena Heras-Recuero, Antonia de Vera-González, Alejandra González-Delgado, Pedro Abreu-González, Beatriz Tejera-Segura, Candelaria Martín-González, Miguel Á. González-Gay and Iván Ferraz-Amaro

Antioxidants 2025, 14(6), 739; https://doi.org/10.3390/antiox14060739 - 16 Jun 2025

Viewed by 74

Abstract

3-Nitrotyrosine (3-NT) is a product of tyrosine nitration mediated by reactive nitrogen species such as peroxynitrite anion and nitrogen dioxide. It serves as an indicator of inflammation, cell damage, and nitric oxide production. Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by [...] Read more.

3-Nitrotyrosine (3-NT) is a product of tyrosine nitration mediated by reactive nitrogen species such as peroxynitrite anion and nitrogen dioxide. It serves as an indicator of inflammation, cell damage, and nitric oxide production. Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by multisystem involvement and increased oxidative stress. Notably, cardiovascular (CV) disease has emerged as the leading cause of mortality among SLE patients. Our objective was to investigate the association between serum 3-NT levels and a wide range of disease characteristics in patients with SLE, with a particular emphasis on CV comorbidity. A total of 214 patients with SLE were enrolled. The serum levels of 3-NT as well as the activity (SLEDAI) and damage index (SLICC-SDI) scores, full lipid profile, insulin resistance indices, and carotid subclinical atherosclerosis were assessed. Multivariable linear regression analysis was carried out to study the relationship between 3-NT and clinical and laboratory disease characteristics, especially focusing on CV comorbidities. Except for body mass index, which showed a significant positive correlation, the demographic data and traditional CV risk factors did not correlate with 3-NT. After multivariable adjustments, several disease characteristics, including the disease duration, activity and damage indices, and autoantibody profile, showed significant positive associations with 3-NT. Regarding CV characteristics, several lipid profile molecules showed significant relationships with 3-NT. This was not the case for insulin resistance and subclinical atherosclerosis. Remarkably, patients with a high CV risk by SCORE2 showed higher 3-NT values compared to those with a low risk, although after the multivariable adjustment, this relationship was attenuated (but still showed a trend). In conclusion, serum 3-NT levels demonstrated significant positive correlations with multiple disease characteristics, including the disease activity and damage and the autoantibody profile. The lipid pattern in the SLE subjects also significantly and independently correlated with the 3-NT values. Our findings highlight the pathophysiological role of 3-NT specifically, and peroxidation in general, in patients with SLE. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Diseases (CVDs))

► Show Figures

Figure 1

18 pages, 3304 KiB

Open AccessArticle

Enhancement of Hypoxia Tolerance of Gibel Carp (Carassius auratus gibelio) via a Ferroporphyrin-Rich Diet

by Hualiang Liang, Haifeng Mi, Kai Wang, Mingchun Ren, Lu Zhang, Dongyu Huang and Jiaze Gu

Antioxidants 2025, 14(6), 738; https://doi.org/10.3390/antiox14060738 - 16 Jun 2025

Viewed by 66

Abstract

Gibel carp (Carassius auratus gibelio) were hypoxia stressed for 12 h after an 8-week FPR nutrient-enriched feeding experiment, which was to evaluate the role of FPR in hypoxic stress in gibel carp (Carassius auratus gibelio). The dissolved oxygen was [...] Read more.

Gibel carp (Carassius auratus gibelio) were hypoxia stressed for 12 h after an 8-week FPR nutrient-enriched feeding experiment, which was to evaluate the role of FPR in hypoxic stress in gibel carp (Carassius auratus gibelio). The dissolved oxygen was reduced to a range of 0.6 ± 0.2 mg/L. Results showed that FPR supplementation could maintain the osmotic pressure equilibrium by improving the ion concentrations of plasma including Na⁺, Ca⁺ and K⁺, and Na⁺/K⁺-ATPase activity of liver. FPR supplementation could effectively enhance the antioxidant capacity by improving the levels of GPX, SOD, CAT, and GSH, and reduce the level of MDA. FPR supplementation could improve the core gene expressions of Nrf2 signalling pathway including nrf2, sod, ho-1, gpx, and cat. The high levels of FPR supplementation (0.04%) might had a negative effect on immunity. FPR supplementation could improve the expression levels of HIF-1 signalling pathway-related genes to adapt to hypoxia condition including hif-1α, epo, angpt1, vegf, et1, and tfr-1. These results also were supported by higher SR and number of gill mitochondria in FPR supplementation. In general, the appropriate FPR supplementation was 0.01% based on the results of this study and economic cost, which could heighten hypoxic adaptation and SR. Full article

(This article belongs to the Special Issue Antioxidants Benefits in Aquaculture—3rd Edition)

► Show Figures

Figure 1

23 pages, 5946 KiB

Open AccessArticle

Inactivated Cells and Metabolites of Saccharomyces boulardii Alleviate Inflammation Damage in Caco-2 Monolayer Cells and Mice with Ulcerative Colitis

by Yuxin Jin, Zehui Niu, Menglin Feng, Huilian Che and Zhihong Liang

Antioxidants 2025, 14(6), 737; https://doi.org/10.3390/antiox14060737 - 16 Jun 2025

Viewed by 102

Abstract

Saccharomyces boulardii (S. boulardii) has attracted widespread attention due to its antimicrobial and anti-inflammatory properties. In this study, we prepared postbiotics from the heat-inactivated cells (HIC) and cell-free supernatant (CFS) of S. boulardii, with the important component L-arginine (Arg) from [...] Read more.

Saccharomyces boulardii (S. boulardii) has attracted widespread attention due to its antimicrobial and anti-inflammatory properties. In this study, we prepared postbiotics from the heat-inactivated cells (HIC) and cell-free supernatant (CFS) of S. boulardii, with the important component L-arginine (Arg) from the metabolic products included as one of the experimental groups. The results showed that in LPS-stimulated Caco-2 cells, HIC, CFS, and Arg protect intestinal epithelial barrier integrity by inhibiting the expression of TNF-α, IL-1β, and IL-6 while enhancing the expression of occludin and ZO-1 proteins. In dextran sulfate sodium (DSS)-induced colitis mice, HIC, CFS, and Arg alleviate symptoms such as weight loss and colonic damage while suppressing the upregulation of pro-inflammatory factors and the downregulation of tight junction proteins. Moreover, these postbiotics help restore the gut microbiota composition and functionality in colitis mice, with potentially superior regulatory effects compared to sulfasalazine (SASP). Overall, HIC and CFS protect the intestinal barrier function and improve DSS-induced colitis, supporting the development of functional food supplements. Full article

(This article belongs to the Topic Functional Food and Anti-Inflammatory Function)

► Show Figures

Figure 1

16 pages, 3742 KiB

Open AccessArticle

Redox Imbalance Is Associated with Neuronal Apoptosis in the Cortex of Neonates Gestated Under Chronic Hypoxia

by Esteban G. Figueroa, Rodrigo L. Castillo, Adolfo A. Paz, Matías Monsalves-Alvarez, Francisca Salas-Pérez, Ximena Calle, Tamara A. Jiménez, Emilio A. Herrera and Alejandro Gonzaléz-Candia

Antioxidants 2025, 14(6), 736; https://doi.org/10.3390/antiox14060736 - 15 Jun 2025

Viewed by 220

Abstract

Gestational chronic hypoxia impacts prenatal development, leading to fetal growth restriction (FGR), defined as the fetus’s failure to reach its genetic growth potential. Postnatal hypoxia in the cerebral tissue can induce a redox imbalance and mitochondrial dysfunction, consequently increasing neuronal death. However, these [...] Read more.

Gestational chronic hypoxia impacts prenatal development, leading to fetal growth restriction (FGR), defined as the fetus’s failure to reach its genetic growth potential. Postnatal hypoxia in the cerebral tissue can induce a redox imbalance and mitochondrial dysfunction, consequently increasing neuronal death. However, these data cannot necessarily be extrapolated to prenatal hypoxia. In this regard, this study aims to describe the effect of gestational hypoxia on redox balance and apoptosis cell death mechanisms in the prefrontal cortex of guinea pigs. Ten Guinea pig (Cavia porcellus) pregnant dams were utilized in this study; five gestated in normoxia (Nx; three newborn males, and two females) and five gestated under chronic hypobaric hypoxia (Hx; two newborn males, and three females). We monitored the pregnancies by ultrasound examinations from gestational days 20 to 65 (term ~ 70). At birth, pups were euthanized, and the fetal brain was collected for cellular redox measurement, mitochondrial enzyme expression, and apoptosis assay. Gestation under hypoxia induced an imbalance in the expression of anti- and pro-oxidant enzymes, resulting in increased oxidative stress. Additionally, a decrease in cytochrome I and III expression and neuronal density in the neonatal prefrontal cortex was observed. Finally, DNA fragmentation was increased by the TUNEL assay in the brain tissue of newborns gestated under chronic hypoxia. Our findings demonstrate the association of gestational hypoxia with oxidative stress and neuronal death in newborns, which may predispose to neuronal dysfunction in adulthood. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Hypoxia and Human Pathophysiology Settings, 2nd Edition)

► Show Figures

Graphical abstract

53 pages, 1497 KiB

Open AccessReview

Oxidative Stress and Inflammation: Drivers of Tumorigenesis and Therapeutic Opportunities

by Meimei Wang, Yaping Xiao, Jie Miao, Xin Zhang, Meng Liu, Longchao Zhu, Hongxin Liu, Xiaoyan Shen, Jihui Wang, Biao Xie and Di Wang

Antioxidants 2025, 14(6), 735; https://doi.org/10.3390/antiox14060735 - 15 Jun 2025

Viewed by 159

Abstract

As two pivotal regulatory factors in cancer biology, oxidative stress and inflammation interact dynamically through complex network mechanisms to influence tumor initiation, progression, and treatment resistance. Oxidative stress induces genomic instability, oncogenic signaling activation, and tumor microenvironment (TME) remodeling via the abnormal accumulation [...] Read more.

As two pivotal regulatory factors in cancer biology, oxidative stress and inflammation interact dynamically through complex network mechanisms to influence tumor initiation, progression, and treatment resistance. Oxidative stress induces genomic instability, oncogenic signaling activation, and tumor microenvironment (TME) remodeling via the abnormal accumulation of reactive oxygen species (ROS) or reactive nitrogen species (RNS). Conversely, inflammation sustains malignant phenotypes by releasing pro-inflammatory cytokines and chemokines and promoting immune cell infiltration. These processes create a vicious cycle via positive feedback loops whereby oxidative stress initiates inflammatory signaling, while the inflammatory milieu further amplifies ROS/RNS production, collectively promoting proliferation, migration, angiogenesis, drug resistance, and immune evasion in tumor cells. Moreover, their crosstalk modulates DNA damage repair, metabolic reprogramming, and drug efflux pump activity, significantly impacting the sensitivity of cancer cells to chemotherapy, radiotherapy, and targeted therapies. This review systematically discusses these advances and the molecular mechanisms underlying the interplay between oxidative stress and inflammation in cancer biology. It also explores their potential as diagnostic biomarkers and prognostic indicators and highlights novel therapeutic strategies targeting the oxidative stress–inflammation axis. The goal is to provide a theoretical framework and translational roadmap for developing synergistic anti-tumor therapies. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer Biology)

► Show Figures

Figure 1

27 pages, 2952 KiB

Open AccessArticle

Promising Dietary Supplements with Potential Senotherapeutic Effects: Aqueous Extracts from Enzymatically Hydrolysed Hemp Seed Cake Flour and Hemp Seed Protein Concentrate

by Anthea Miller, Inga Kwiecień, Marek Bednarski, Małgorzata Zygmunt, Jacek Sapa, Mateusz Sablik, Giorgia Pia Lombardo, Concetta Condurso, Maria Merlino and Magdalena Kotańska

Antioxidants 2025, 14(6), 734; https://doi.org/10.3390/antiox14060734 - 15 Jun 2025

Viewed by 195

Abstract

In the present study, the primary by-products of the hemp-seed oil process—hemp seed cake flour and hemp seed protein concentrate—underwent enzymatic hydrolysis using proteases and carbohydrases, either individually or in combination. The effectiveness of these enzymatic treatments in releasing bioactive compounds was evaluated [...] Read more.

In the present study, the primary by-products of the hemp-seed oil process—hemp seed cake flour and hemp seed protein concentrate—underwent enzymatic hydrolysis using proteases and carbohydrases, either individually or in combination. The effectiveness of these enzymatic treatments in releasing bioactive compounds was evaluated by assessing the antioxidant and anti-inflammatory properties of the aqueous extracts of both hydrolysed and untreated hemp by-products. The aim was to explore their potential senotherapeutic properties and promote their application as dietary supplements. Secondary metabolites such as flavonoids, phenolic acids, and catechins were analysed using high-performance liquid chromatography. Total phenolic, flavonoid, and protein contents were determined using spectrophotometric methods. Scavenging activity (2,2-Diphenyl-1-picrylhydrazyl scavenging assay (DPPH assay)), antioxidant power (Ferric reducing antioxidant power assay (FRAP assay)), and lipid peroxidation-reducing activity (thiobarbituric acid-reactive substance analysis) were assessed through in vitro assays. Possible anti-inflammatory effects were evaluated by assessing haemolysis inhibition. The impact of extracts on albumin glycation induced by exposure to fructose was also determined. To assess the toxicity of extracts, a zebrafish larvae model was employed. All extracts contained significant amounts of phenolic compounds, flavonoids, and proteins, and they exhibited notable activities in reducing lipid peroxidation and stabilising erythrocyte cell membranes. However, they did not significantly influence protein glycation (the glycation inhibition was only in the range of 15–40%). Our research demonstrates the substantial health-promoting potential, including senescence delay, of aqueous extracts from by-products of the hemp-seed oil process, which are available in large quantities and can serve as valuable supplements to support the health of animals, including humans, rather than being discarded as waste from oil production. Full article

(This article belongs to the Special Issue Natural Antioxidants and Their Oxidized Derivatives in Processed Food)

► Show Figures

Figure 1

17 pages, 675 KiB

Open AccessArticle

Evaluation of Bioactive Properties of Ultrasound-Assisted Extracts from Prokupac Grape Skins for Functional Foods

by Edina Avdović, Dušan Dimić, Đura Nakarada, Dušica Simijonović, Sandra Jovičić Milić, Katarina Marković, Mirjana Grujović, Marko Antonijević, Andrija Ćirić, Dejan Milenković and Zoran Marković

Antioxidants 2025, 14(6), 733; https://doi.org/10.3390/antiox14060733 - 15 Jun 2025

Viewed by 162

Abstract

The phenolic compounds present in wine industry by-products are a valuable source of biologically active ingredients that could be used in the development of functional foods. This manuscript investigates the potential of ultrasound-assisted extracts from Prokupac grape skins—a wine industry by-product—as functional food [...] Read more.

The phenolic compounds present in wine industry by-products are a valuable source of biologically active ingredients that could be used in the development of functional foods. This manuscript investigates the potential of ultrasound-assisted extracts from Prokupac grape skins—a wine industry by-product—as functional food ingredients. Four extracts were prepared using different solvents and evaluated for their antioxidant, anti-inflammatory, and antimicrobial properties. Antioxidant activity was assessed through DPPH, ABTS, and FRAP assays, as well as EPR spectroscopy. Phenolic composition was determined via HPLC analysis, and anti-inflammatory potential was evaluated using a lipoxygenase inhibition assay. Results indicated that the extracts PSE3 (ethyl acetate) and PSE0 (direct extraction with 50% ethanol) exhibited superior antioxidant and anti-inflammatory activities, which can be attributed to their high polyphenolic content. Additionally, the extracts demonstrated antimicrobial effects against the tested microorganisms. These findings suggest that Prokupac grape skin extracts, particularly PSE3 and PSE0, could be valuable additions to functional foods, offering health benefits through their bioactive properties. Full article

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

► Show Figures

Figure 1

18 pages, 4187 KiB

Open AccessArticle

Lactobacillus fermentum ZC529 Protects Intestinal Epithelial Barrier Integrity by Activating the Keap1-Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway

by Zian Yuan, Lang Huang, Zhenguo Hu, Junhao Deng, Yehui Duan, Qian Jiang, Bi’e Tan, Xiaokang Ma, Chen Zhang and Xiongzhuo Tang

Antioxidants 2025, 14(6), 732; https://doi.org/10.3390/antiox14060732 - 14 Jun 2025

Viewed by 167

Abstract

The probiotic bacteria Lactobacillus fermentum ZC529 (L.f ZC529) has been identified from the colon of the Diannan small-ear (DSE) pig, but its intestinal protective function still lacks investigation. Here, we established a dextran sodium sulfate (DSS)-induced intestinal oxidative stress model in both [...] Read more.

The probiotic bacteria Lactobacillus fermentum ZC529 (L.f ZC529) has been identified from the colon of the Diannan small-ear (DSE) pig, but its intestinal protective function still lacks investigation. Here, we established a dextran sodium sulfate (DSS)-induced intestinal oxidative stress model in both Drosophila and porcine small intestinal epithelial (IPEC-J2) cell lines to explore the anti-oxidative and anti-inflammatory effects of L.f ZC529. The data showed that the intestinal colonization of L.f ZC529 counteracted DSS-induced intestinal oxidative stress and excessive reactive oxygen species (ROS) generation by activation of the CncC pathway, a homology of the nuclear factor erythroid 2-related factor 2 (Nrf2) in mammalian systems. Moreover, L.f ZC529 supplementation prevented flies from DSS-induced intestinal barrier damage, inflammation, abnormal excretory function, and shortened lifespan. Finally, L.f ZC529 also attenuated DSS-induced intestinal injury in the IPEC-J2 cell line by activating the Keap1-Nrf2 signaling and inhibiting the NF-κB signaling pathways. Together, this study unraveled the profound intestinal protective function of L.f ZC529 and provides its potential application as a new antioxidant in improving animal intestinal health as well as in developing a new probiotic in the food industry. Full article

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

► Show Figures

Figure 1

29 pages, 1416 KiB

Open AccessReview

Restoring Glutathione Homeostasis in Glycation-Related Eye Diseases: Mechanistic Insights and Therapeutic Interventions Beyond VEGF Inhibition

by Yong Chool Boo

Antioxidants 2025, 14(6), 731; https://doi.org/10.3390/antiox14060731 - 14 Jun 2025

Viewed by 246

Abstract

Advanced glycation end-products (AGEs) and oxidative stress are recognized as central contributors to the pathogenesis of age-related or diabetic cataracts, diabetic retinopathy (DR), and age-related macular degeneration (AMD). These glycation-related diseases are characterized by impaired redox balance and decreased glutathione (GSH) levels. This [...] Read more.

Advanced glycation end-products (AGEs) and oxidative stress are recognized as central contributors to the pathogenesis of age-related or diabetic cataracts, diabetic retinopathy (DR), and age-related macular degeneration (AMD). These glycation-related diseases are characterized by impaired redox balance and decreased glutathione (GSH) levels. This review aims to examine the mechanistic links between AGEs and GSH depletion across ocular tissues by integrating in vitro, ex vivo, in vivo, and clinical studies relevant to this topic. The multiple levels of evidence highlight GSH homeostasis as both a biomarker and therapeutic target in glycation-related ocular disorders. Therapeutic strategies aimed at restoring GSH homeostasis under glycation stress are categorized into four mechanistic domains: (I) promoting GSH supply and synthesis, (II) enhancing GSH recycling, (III) mitigating glycation stress, and (IV) reducing oxidative and nitrosative stress. Most of these strategies have been explored via different approaches, and experimental findings with various interventions have shown promise in restoring GSH balance and mitigating AGE-induced damage. A pathological link between GSH depletion and vascular endothelial growth factor (VEGF) overexpression is observed in DR and wet AMD. GSH-centered interventions act upstream to modulate redox homeostasis while anti-VEGF therapies target downstream angiogenesis. This study supports the rationale for a dual-targeting strategy that combines redox-based interventions with VEGF inhibition in glycation-related ocular diseases. Full article

(This article belongs to the Special Issue Oxidative Stress in Eye Diseases)

► Show Figures

Figure 1

35 pages, 776 KiB

Open AccessReview

Pathways to the Brain: Impact of Fine Particulate Matter Components on the Central Nervous System

by Yasuhiro Ishihara, Miki Tanaka, Naoyuki Nezu, Nami Ishihara, Ami Oguro and Christoph F. A. Vogel

Antioxidants 2025, 14(6), 730; https://doi.org/10.3390/antiox14060730 - 14 Jun 2025

Viewed by 158

Abstract

Fine particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM_2.5) has been extensively studied due to its adverse health effects. Most research has focused on its impact on the respiratory system; however, increasing attention is being directed toward its effects [...] Read more.

Fine particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM_2.5) has been extensively studied due to its adverse health effects. Most research has focused on its impact on the respiratory system; however, increasing attention is being directed toward its effects on the brain. Associations between air pollution and neurological disorders—such as Alzheimer’s disease, cerebral infarction, and autism spectrum disorder—have been reported, with mechanism-based studies in animal models providing further insights. PM_2.5 comprises a complex mixture of thousands of chemical constituents. To elucidate its neurotoxicity mechanisms, it is essential to investigate both its transport pathways to the brain and the specific actions of its individual components. This review highlights key PM_2.5 components—water-soluble ions, metals, carbonaceous particles, polycyclic aromatic hydrocarbons, quinones, plastics, and bioaerosols—and outlines their potential routes of entry into the central nervous system, along with their associated mechanisms of action. By integrating these findings, this review contributes to a deeper understanding of the neurological effects mediated by PM_2.5, which represent one of the most critical aspects of its health impact. Full article

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

► Show Figures

Figure 1

24 pages, 2342 KiB

Open AccessArticle

Topically Applied Molecular Hydrogen Normalizes Skin Parameters Associated with Oxidative Stress: A Pilot Study

by Natalia Debkowska, Marek Niczyporuk, Arkadiusz Surazynski and Katarzyna Wolosik

Antioxidants 2025, 14(6), 729; https://doi.org/10.3390/antiox14060729 - 14 Jun 2025

Viewed by 289

Abstract

Topical application of molecular hydrogen (H₂) has recently emerged as a promising strategy to counteract oxidative stress-related skin damage. This pilot clinical study aimed to assess the efficacy of hydrogen-rich water treatments in improving objective skin parameters in healthy adults. The [...] Read more.

Topical application of molecular hydrogen (H₂) has recently emerged as a promising strategy to counteract oxidative stress-related skin damage. This pilot clinical study aimed to assess the efficacy of hydrogen-rich water treatments in improving objective skin parameters in healthy adults. The hypothesis was that H₂, through its selective antioxidant and anti-inflammatory properties, would reduce oxidative stress, modulate inflammatory pathways, and enhance skin barrier integrity, leading to measurable improvements in skin appearance. Fifteen participants received topical treatments with hydrogen-rich water for four weeks. Skin parameters, including porphyrin levels, pigmentation irregularities, pore size, wrinkle severity, and biological skin age, were quantitatively assessed before and one week post-treatment. A statistically significant reduction in pore visibility was observed, particularly in younger participants. Although porphyrin levels showed a trend toward reduction, this change was not statistically significant. Improvements were also noted in pigmentation, wrinkle severity, and estimated biological skin age. The treatment was well tolerated, with no adverse effects reported. Despite promising outcomes, this study was limited by the absence of a control group and a relatively short follow-up period. Further controlled studies with larger sample sizes and molecular biomarker analyses are needed to confirm these effects and elucidate the underlying mechanisms. This study addresses a gap in the literature regarding standardized, clinical evaluation of topical H₂ application and highlights its potential for utilization in cosmetic and preventive dermatology. Full article

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

► Show Figures

Figure 1

11 pages, 689 KiB

Open AccessArticle

Critical Evaluation and Validation of a High-Throughput Microplate-Based Cupric Reducing Antioxidant Capacity Method for the Analysis of Fish Feed Ingredients

by Aleksander Arnø, Viviana Sarmiento, Odd Elvebø and Pedro Araujo

Antioxidants 2025, 14(6), 728; https://doi.org/10.3390/antiox14060728 - 14 Jun 2025

Viewed by 213

Abstract

The cupric ion reducing antioxidant capacity (CUPRAC) assay, originally developed to measure the antioxidant capacity of nutritional products spectrophotometrically, utilized water as the solvent for Trolox. Due to the limited solubility of Trolox in aqueous solutions, the optimization of the solvent system was [...] Read more.

The cupric ion reducing antioxidant capacity (CUPRAC) assay, originally developed to measure the antioxidant capacity of nutritional products spectrophotometrically, utilized water as the solvent for Trolox. Due to the limited solubility of Trolox in aqueous solutions, the optimization of the solvent system was investigated to enhance analytical performance. Solvent combinations consisting of methanol, ethanol, and water were evaluated to identify the mixture that ensures complete dissolution and maximum absorbance signal, using a ternary plot diagram and mathematical modeling. A methanol/water ratio of 0.64:0.36 was identified as the optimal solvent composition. Under these conditions, the CUPRAC assay demonstrated a linear range of 0–50 μM, a limit of detection of 0.91 μM, and a limit of quantification of 2.75 μM. Precision, expressed as the coefficient of variation, was below 5%, and accuracy—defined as the deviation between nominal and back-calculated concentrations—remained within ±7.0%, in accordance with the variation range recommended by the International Committee on Harmonization. The estimated molar absorption coefficient at the optimized solvent ratio (ε_Trolox = 2.62 × 10⁴ L mol⁻¹ cm⁻¹) was applied to determine the antioxidant capacity of fish commercial feed ingredients containing a mixture of rosemary and olive extracts. Full article

► Show Figures

Figure 1

43 pages, 4992 KiB

Open AccessArticle

Restorative Effects of Synbiotics on Colonic Ultrastructure and Oxidative Stress in Dogs with Chronic Enteropathy

by Dipak Kumar Sahoo, Tracey Stewart, Emily M. Lindgreen, Bhakti Patel, Ashish Patel, Jigneshkumar N. Trivedi, Valerie Parker, Adam J. Rudinsky, Jenessa A. Winston, Agnes Bourgois-Mochel, Jonathan P. Mochel, Karin Allenspach, Romy M. Heilmann and Albert E. Jergens

Antioxidants 2025, 14(6), 727; https://doi.org/10.3390/antiox14060727 - 13 Jun 2025

Viewed by 358

Abstract

Synbiotics can be used to reduce intestinal inflammation and mitigate dysbiosis in dogs with chronic inflammatory enteropathy (CIE). Prior research has not assessed the colonic mucosal ultrastructure of dogs with active CIE treated with synbiotics, nor has it determined a possible association between [...] Read more.

Synbiotics can be used to reduce intestinal inflammation and mitigate dysbiosis in dogs with chronic inflammatory enteropathy (CIE). Prior research has not assessed the colonic mucosal ultrastructure of dogs with active CIE treated with synbiotics, nor has it determined a possible association between morphologic injury and signaling pathways. Twenty client-owned dogs diagnosed with CIE were randomized to receive either a hydrolyzed diet (placebo; PL) or a hydrolyzed diet supplemented with synbiotic-IgY (SYN) for 6 weeks. Endoscopic biopsies of the colon were obtained for histopathologic, ultrastructural, and molecular analyses and were compared before and after treatment. Using transmission electron microscopy (TEM), an analysis of the ultrastructural alterations in microvilli length (MVL), mitochondria (MITO), and rough endoplasmic reticulum (ER) was compared between treatment groups. To explore potential signaling pathways that might modulate MITO and ER stress, a transcriptomic analysis was also performed. The degree of mucosal ultrastructural pathology differed among individual dogs before and after treatment. Morphologic alterations in enterocytes, MVL, MITO, and ER were detected without significant differences between PL and SYN dogs prior to treatment. Notable changes in ultrastructural alterations were identified post-treatment, with SYN-treated dogs exhibiting significant improvement in MVL, MITO, and ER injury scores compared to PL-treated dogs. Transcriptomic profiling showed many pathways and key genes to be associated with MITO and ER injury. Multiple signaling pathways and their associated genes with protective effects, including fibroblast growth factor 2 (FGF2), fibroblast growth factor 7 (FGF7), fibroblast growth factor 10 (FGF10), synaptic Ras GTPase activating protein 1 (SynGAP1), RAS guanyl releasing protein 2 (RASGRP2), RAS guanyl releasing protein 3 (RASGRP3), thrombospondin 1 (THBS1), colony stimulating factor 1 (CSF1), colony stimulating factor 3 (CSF3), interleukin 21 receptor (IL21R), collagen type VI alpha 6 chain (COL6A6), ectodysplasin A receptor (EDAR), forkhead box P3 (FoxP3), follistatin (FST), gremlin 1 (GREM1), myocyte enhancer factor 2B (MEF2B), neuregulin 1 (NRG1), collagen type I alpha 1 chain (COL1A1), hepatocyte growth factor (HGF), 5-hydroxytryptamine receptor 7 (HTR7), and platelet derived growth factor receptor beta (PDGFR-β), were upregulated with SYN treatment. Differential gene expression was associated with improved MITO and ER ultrastructural integrity and a reduction in oxidative stress. Conversely, other genes, such as protein kinase cAMP-activated catalytic subunit beta (PRKACB), phospholipase A2 group XIIB (PLA2G12B), calmodulin 1 (CALM1), calmodulin 2 (CALM2), and interleukin-18 (IL18), which have harmful effects, were downregulated following SYN treatment. In dogs treated with PL, genes including PRKACB and CALM2 were upregulated, while other genes, such as FGF2, FGF10, SynGAP1, RASGRP2, RASGRP3, and IL21R, were downregulated. Dogs with CIE have colonic ultrastructural pathology at diagnosis, which improves following synbiotic treatment. Ultrastructural improvement is associated with an upregulation of protective genes and a downregulation of harmful genes that mediate their effects through multiple signaling pathways. Full article

► Show Figures

Figure 1

Journal Menu

Journal Browser

Antioxidants, Volume 14, Issue 6 (June 2025) – 140 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI