Antioxidants

22 pages, 925 KiB

Open AccessArticle

Improvement of the Structure and Antioxidant Activity of Protein–Polyphenol Complexes in Barley Malts Using Roasting Methods

by Guozhi Wu, Huiting Lin and Yongsheng Chen

Antioxidants 2025, 14(5), 538; https://doi.org/10.3390/antiox14050538 (registering DOI) - 29 Apr 2025

Abstract

Proteins and polyphenols are important components in barley malt. During the roasting process of barley malt, proteins and polyphenols interact and influence each other, ultimately altering the nutritional profile and functional properties of barley malt. In this research, polyphenol-free proteins and protein–polyphenol complexes [...] Read more.

Proteins and polyphenols are important components in barley malt. During the roasting process of barley malt, proteins and polyphenols interact and influence each other, ultimately altering the nutritional profile and functional properties of barley malt. In this research, polyphenol-free proteins and protein–polyphenol complexes were extracted from barley malt subjected to varying degrees of roasting. The antioxidant activity of protein–polyphenol complexes was assessed by ABTS, FRAP, and ORAC assays. The structural characteristics of the proteins were examined through UV, FL, CD, FTIR, and SEM. We found that roasting enhances the solubility of globulin, prolamin, and glutenin and facilitates the binding of these proteins with polyphenols. Conversely, the impact of roasting on albumin exhibits a trend opposite to that observed in the other three proteins. The antioxidant activity of protein–polyphenol complexes was significantly higher than that of polyphenol-free proteins. Additionally, the microenvironment of the amino acid residues of the four proteins exhibited increased polarity following the roasting process, and the structural conformation of albumin, globulin, and glutelin transitioned from an ordered to a disordered state. Our results indicate that roasting enhances the antioxidant activity of protein–polyphenol complexes by altering the secondary and tertiary structures of these proteins, thereby exposing more hydrophobic side-chain groups inside the proteins and offering more binding sites for polyphenols. Full article

12 pages, 490 KiB

Open AccessCommunication

A Highly Potent Apomorphine Derivative Enhancing Neurite Outgrowth via Nrf2 Activation

by Tamaki Ishima, Hitoshi Osaka, Ryozo Nagai and Kenichi Aizawa

Antioxidants 2025, 14(5), 537; https://doi.org/10.3390/antiox14050537 (registering DOI) - 29 Apr 2025

Abstract

Apomorphine (APO), a dopamine agonist, activates nuclear factor erythroid 2-related factor 2 (Nrf2) and exerts antioxidant effects, making it a promising candidate for neuroprotection against oxidative stress. This study evaluated neuroplasticity-enhancing properties of newly synthesized APO derivatives, focusing on their ability to promote [...] Read more.

Apomorphine (APO), a dopamine agonist, activates nuclear factor erythroid 2-related factor 2 (Nrf2) and exerts antioxidant effects, making it a promising candidate for neuroprotection against oxidative stress. This study evaluated neuroplasticity-enhancing properties of newly synthesized APO derivatives, focusing on their ability to promote neurite outgrowth in PC12 cells under nerve growth factor (NGF) stimulation. D55, an APO derivative, retains the hydroxyl group at APO’s 11th position while substituting the 10th with an ethoxy group. D55 exhibited the highest potency (EC₅₀ = 0.5661 nM), significantly enhancing neurite outgrowth. APO demonstrated the highest efficacy (Emax ~10-fold increase), while edaravone (Eda) required higher concentrations (EC₅₀ = 22.5 nM) for moderate effects (Emax ~4-fold increase). D30, in which the 11th hydroxyl was replaced with a methoxy group, had no effect. Neurite outgrowth-promoting effects of APO, D55, and Eda were significantly attenuated by Nrf2 siRNA knockdown, confirming that their neuroplasticity effects are Nrf2-mediated. These findings confirm that D55 is a highly potent Nrf2-activating compound with strong neuroprotective potential, providing new insights into its therapeutic applications for neurodegenerative diseases associated with oxidative stress. Full article

(This article belongs to the Special Issue Role of Nrf2 in Neurodegenerative Diseases)

17 pages, 1797 KiB

Open AccessArticle

Time Course of Plasma Proteomic and Oxylipin Changes Induced by LPS Challenge and Modulated by Antioxidant Supplementation in a Randomized Controlled Trial

by Gerhard Hagn, Andrea Bileck, Thomas Mohr, Doreen Schmidl, David M. Baron, Bernd Jilma, Leopold Schmetterer, Gerhard Garhöfer and Christopher Gerner

Antioxidants 2025, 14(5), 536; https://doi.org/10.3390/antiox14050536 (registering DOI) - 29 Apr 2025

Abstract

Systemic molecular responses to pathogen-associated molecular patterns and their modulation by antioxidants are poorly understood in humans. Here, we present a two-stage clinical interventional study in healthy humans challenged with lipopolysaccharide. In the first step, the kinetics of inflammatory modulators within 8 h [...] Read more.

Systemic molecular responses to pathogen-associated molecular patterns and their modulation by antioxidants are poorly understood in humans. Here, we present a two-stage clinical interventional study in healthy humans challenged with lipopolysaccharide. In the first step, the kinetics of inflammatory modulators within 8 h were investigated by plasma proteomics and lipidomics. In a second step, the effects of a placebo-controlled antioxidant intervention on the individual responses prior to another lipopolysaccharide challenge were determined. Plasma proteomics revealed an early involvement of the endothelium and platelets, followed by the induction of liver-derived acute phase proteins and an innate immune cell response. Untargeted lipidomics revealed an early release of fatty acids and taurocholic acid, followed by complex regulatory events exerted by oxylipins. The consistent lipopolysaccharide-induced downregulation of lysophospholipids suggested the involvement of the Lands cycle, and the downregulation of deoxycholic acid reinforced emerging links between the inflammasome and bile acids. Groups of molecules with similar kinetics to lipopolysaccharide challenge were observed to share precursors, synthesizing enzymes or cellular origin. Dietary antioxidant supplementation prior to lipopolysaccharide challenge had no detectable effect on protein kinetics but significantly downregulated pro-inflammatory sphingosine-1-phosphate and increased levels of oxylipins, 20-HEPE, and 22-HDoHE, which have been described to facilitate the resolution of inflammation. The present study identified a complex network of lipid mediators deregulated in plasma upon lipopolysaccharide challenge and highlighted the role of platelets, endothelial cells, and erythrocytes as potential inflammatory modulators. While dietary antioxidant supplementation hardly affected the initiation of inflammation, it may exert its effects supporting the resolution of inflammation. Full article

(This article belongs to the Special Issue Oxidative Stress in Hemoglobin and Red Blood Cells)

25 pages, 6284 KiB

Open AccessArticle

Encapsulation of Polyphenolic Preparation in Gelatin Fruit Jellies Slows the Digestive Release of Cholinesterase Inhibitors In Vitro

by Dominik Szwajgier, Ewa Baranowska-Wójcik, Wirginia Kukula-Koch and Katarzyna Krzos

Antioxidants 2025, 14(5), 535; https://doi.org/10.3390/antiox14050535 (registering DOI) - 29 Apr 2025

Abstract

Peach, apricot, chokeberry, blueberry, cranberry, raspberry, and wild strawberry fruits were used to create a polyphenolic preparation (PP) after enzyme-assisted extraction, ultrafiltration, and concentration. The composition of PP was determined using LC-MS. Gelatin jellies produced with PP, as well as liquid PP, were [...] Read more.

Peach, apricot, chokeberry, blueberry, cranberry, raspberry, and wild strawberry fruits were used to create a polyphenolic preparation (PP) after enzyme-assisted extraction, ultrafiltration, and concentration. The composition of PP was determined using LC-MS. Gelatin jellies produced with PP, as well as liquid PP, were “digested” in an in vitro model. The entrapment of PP in the gelatin matrix delayed the release of total polyphenolics, flavonoids, flavanols, condensed tannins, and anthocyanins (predominantly during the “small intestinal” phase). PP entrapped in the jelly more effectively (p < 0.05) decreased the activity of acetylcholinesterase, butyrylcholinesterase, cyclooxygenase-2 and catalase (during the “small intestinal” phase). However, no significant (p < 0.05) effects on superoxide dismutase, glutathione peroxidase, and glutathione reductase activities were observed. FRAP, CUPRAC, HORAC, oxidation of linoleic acid, and ABTS-reducing activities were higher during the “intestinal” phase; however, the DPPH test and β-carotene bleaching tests did not confirm these results. The presented findings may be useful for designing nutraceuticals with programmed release of bioactive compounds during digestion. Full article

(This article belongs to the Special Issue Antioxidants from Sustainable Food Sources)

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20 pages, 5769 KiB

Open AccessArticle

Antioxidant Capacity and Disease Resistance Enhanced by Dietary D-Glucuronolactone Supplementation in Chinese Soft-Shelled Turtles (Pelodiscus sinensis)

by Tong Zhou, Wenyi Wu, Mingyang Xue, Yong Zhou, Hongwei Liang and Wei Liu

Antioxidants 2025, 14(5), 534; https://doi.org/10.3390/antiox14050534 (registering DOI) - 29 Apr 2025

Abstract

D-glucuronolactone (DGL), a hepatoprotective compound widely used in clinical and energy products, was evaluated for its effects on Chinese soft-shelled turtles (Pelodiscus sinensis) through an 8-week feeding trial with dietary supplementation (0, 200, and 400 mg kg⁻¹). DGL did [...] Read more.

D-glucuronolactone (DGL), a hepatoprotective compound widely used in clinical and energy products, was evaluated for its effects on Chinese soft-shelled turtles (Pelodiscus sinensis) through an 8-week feeding trial with dietary supplementation (0, 200, and 400 mg kg⁻¹). DGL did not alter survival or feed intake, but induced dose-dependent growth improvements, including increased final body weight, weight gain rate, specific growth rate, and muscle/liver glycogen, alongside reduced feed conversion ratio and muscle and liver fat. Serum analysis showed decreased activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and reduced low-density lipoprotein cholesterol, total cholesterol, and triacylglycerols. Antioxidant indices revealed elevated catalase and superoxide dismutase (SOD) activities in serum and intestine, coupled with reduced malondialdehyde, though hepatic SOD activity declined. Histologically, 400 mg kg⁻¹ DGL alleviated liver lesions without impacting intestinal morphology. Molecular analyses demonstrated upregulated muscle mTOR signaling genes (mTOR, IGF1, S6K1) but downregulated hepatic/intestinal mTOR and IGF1 expression. DGL also suppressed inflammatory cytokines (TNF-α, IL-1β, IL-10) in liver and intestine. Challenge tests with Aeromonas hydrophila confirmed the enhanced disease resistance in DGL-supplemented turtles. These findings highlight DGL’s potential as a nutritional strategy to enhance growth, antioxidant capacity, and health in intensive turtle farming. Full article

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

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20 pages, 3836 KiB

Open AccessArticle

Luteolin 7-Glucuronide in Artemisia rupestris L. Extract Attenuates Pulmonary Fibrosis by Inhibiting Fibroblast Activation and FMT via Targeting of TGF-β1

by Lingfeng Peng, Yimeng Fan, Luyao Wang, Chao Han and Zhihui Hao

Antioxidants 2025, 14(5), 533; https://doi.org/10.3390/antiox14050533 (registering DOI) - 29 Apr 2025

Abstract

Pulmonary fibrosis (PF) is a chronic pulmonary disease characterized by excessive extracellular matrix (ECM) deposition, with cigarette smoking being a major risk factor and no effective treatment at present. Transforming growth factor beta 1 (TGF-β1) plays a key role in PF and regulating [...] Read more.

Pulmonary fibrosis (PF) is a chronic pulmonary disease characterized by excessive extracellular matrix (ECM) deposition, with cigarette smoking being a major risk factor and no effective treatment at present. Transforming growth factor beta 1 (TGF-β1) plays a key role in PF and regulating oxidative stress. This study investigated the effects and mechanisms of Artemisia rupestris L. ethanol extract (ER) on cigarette smoke (CS)-induced PF. We used pull-down and LC–MS analyses to screen and identify compounds that bind to TGF-β1 in ER. We demonstrated that ER inhibits CS-induced PF, lung inflammation, and oxidative stress, thereby improving pulmonary structural injury. The ER inhibits fibroblast activation and fibroblast-to-myofibroblast transition (FMT), reducing collagen deposition for the treatment of PF. We identified the active ingredient in ER that binds to TGF-β1, namely, Luteolin 7-glucuronide (LG). LG inhibits the TGF-β1 signaling pathway through targeted binding to TGF-β1, downregulates the expression of downstream proteins (including collagen I, α-SMA, MMP-2, and MMP-9), and inhibits fibronectin expression. It also inhibits fibroblast activation and FMT, enhances E-cadherin expression to promote fibroblast adhesion, and suppresses collagen deposition, alleviating PF. Based on these findings, we propose that LG might be a promising therapeutic drug candidate for treating PF. Full article

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14 pages, 3680 KiB

Open AccessSystematic Review

Extracellular Vesicles as Epigenetic Regulators of Redox Homeostasis: A Systematic Review and Meta-Analysis

by Cristina Mas-Bargues, Javier Huete-Acevedo, Marta Arnal-Forné, Laura Sireno, Virgilio Pérez and Consuelo Borrás

Antioxidants 2025, 14(5), 532; https://doi.org/10.3390/antiox14050532 (registering DOI) - 29 Apr 2025

Abstract

Extracellular vesicles (EVs) are emerging as key regulators of cellular communication, with increasing evidence supporting their role in oxidative stress (OS) modulation. In particular, the miRNA cargo of EVs plays a crucial role in mitigating OS and promoting redox balance through both direct [...] Read more.

Extracellular vesicles (EVs) are emerging as key regulators of cellular communication, with increasing evidence supporting their role in oxidative stress (OS) modulation. In particular, the miRNA cargo of EVs plays a crucial role in mitigating OS and promoting redox balance through both direct antioxidant effects and epigenetic regulation. This study aimed to evaluate the impact of EVs on OS markers, influenced by their miRNA-mediated effects and potential epigenetic modifications in target cells. A systematic literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to identify studies reporting the effects of EVs on OS parameters. A meta-analysis was performed on key OS biomarkers, including reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA). The heterogeneity of EV isolation and characterization techniques was also analyzed. The included studies demonstrated that EVs exert significant antioxidant effects by reducing ROS levels, increasing SOD activity and GSH levels, and lowering MDA levels. These effects were largely attributed to EV-miRNAs, which induce epigenetic modifications that modulate redox-related signaling pathways. However, the variability in EV isolation methods and characterization approaches highlights the need for standardization to improve data comparability. Despite their therapeutic potential, this significant heterogeneity in EV research remains a barrier to translation. Moreover, further exploration of epigenetic mechanisms is essential to fully harness their benefits for OS-related diseases. Full article

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25 pages, 1241 KiB

Open AccessReview

An Overview of Oxidative Stress in Sex Chromosome Aneuploidies in Pediatric Populations

by Roberto Paparella, Fabiola Panvino, Francesca Tarani, Benedetto D’Agostino, Lucia Leonardi, Giampiero Ferraguti, Sabrina Venditti, Fiorenza Colloridi, Ida Pucarelli, Luigi Tarani and Marco Fiore

Antioxidants 2025, 14(5), 531; https://doi.org/10.3390/antiox14050531 (registering DOI) - 29 Apr 2025

Abstract

Background: Oxidative stress, defined as an imbalance between reactive oxygen species and antioxidant defenses, plays a pivotal role in the pathogenesis of sex chromosome aneuploidies (SCAs), such as Turner syndrome (TS) and Klinefelter syndrome (KS). Pediatric patients with SCAs are particularly susceptible due [...] Read more.

Background: Oxidative stress, defined as an imbalance between reactive oxygen species and antioxidant defenses, plays a pivotal role in the pathogenesis of sex chromosome aneuploidies (SCAs), such as Turner syndrome (TS) and Klinefelter syndrome (KS). Pediatric patients with SCAs are particularly susceptible due to hormonal deficiencies, metabolic disturbances, and systemic complications. Methods: A comprehensive literature search was conducted in November 2024 using PubMed, Scopus, and Web of Science. Keywords included “antioxidants”, “oxidative stress”, “pediatrics”, “Turner syndrome”, “Klinefelter syndrome”, and “sex chromosome aneuploidies”. English-language articles were included without publication year restrictions. Relevant data on oxidative stress mechanisms and antioxidant interventions were systematically extracted. Results: The relationship between oxidative stress and SCAs can be described as bidirectional, where oxidative stress both contributes to and is exacerbated by aneuploidies. TS is marked by estrogen deficiency, cardiovascular anomalies, and metabolic dysfunction, all linked to heightened oxidative stress. KS is associated with hypogonadism, metabolic syndrome, and neurocognitive challenges, further exacerbated by oxidative damage. The aneuploid condition predisposes to increased oxidative stress in other SCAs, including 47,XXX and 47,XYY, as well as in high-grade aneuploidies. Emerging evidence highlights the therapeutic potential of antioxidants, including vitamin C, vitamin E, glutathione precursors, polyphenols, and melatonin. These interventions, when combined with hormonal therapies such as estrogen replacement in TS or testosterone replacement in KS, demonstrate synergistic effects in restoring redox balance and mitigating systemic complications. Conclusions: Oxidative stress significantly impacts the progression of SCAs in pediatric populations, amplifying risks across metabolic, cardiovascular, and neurocognitive domains. Early, tailored antioxidant strategies, integrated with syndrome-specific hormonal therapies, could reduce long-term complications and improve patient outcomes. Future research should focus on standardizing protocols to optimize these interventions for pediatric patients with SCAs. Full article

(This article belongs to the Special Issue Development and Validation of Methods for Analysis of Oxidative Stress in Humans and Animals—2nd Edition)

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25 pages, 1261 KiB

Open AccessReview

Regenerative Organic Agriculture and Human Health: The Interconnection Between Soil, Food Quality, and Nutrition

by Giulia Feliziani, Laura Bordoni and Rosita Gabbianelli

Antioxidants 2025, 14(5), 530; https://doi.org/10.3390/antiox14050530 (registering DOI) - 29 Apr 2025

Abstract

Regenerative organic agriculture (ROA) combines ecological and organic principles to promote soil health, biodiversity, and long-term sustainability. This narrative review explores the connection between soil quality, food nutritional value, and human health, highlighting how ROA can enhance phytochemical content and reduce harmful residues [...] Read more.

Regenerative organic agriculture (ROA) combines ecological and organic principles to promote soil health, biodiversity, and long-term sustainability. This narrative review explores the connection between soil quality, food nutritional value, and human health, highlighting how ROA can enhance phytochemical content and reduce harmful residues in plant-based foods. Empirical studies report increases in vitamin C, zinc, and polyphenols in crops such as leafy greens, grapes, and carrots grown under regenerative systems, along with reductions in nitrates and pesticide residues. We summarize recent literature (2000–2025) that links soil-driven improvements in food composition to antioxidant activity and potential health benefits. By addressing current research gaps, this review supports the role of ROA in building resilient food systems and preventing chronic disease. Full article

(This article belongs to the Special Issue Bioactive Compounds in Functional Foods and Their Role in Combating Oxidative Stress)

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22 pages, 2075 KiB

Open AccessReview

The Role of Oxidative Stress-Induced Senescence in the Pathogenesis of Preeclampsia

by Alexandra Barbouti, Dimitrios N. Varvarousis and Panagiotis Kanavaros

Antioxidants 2025, 14(5), 529; https://doi.org/10.3390/antiox14050529 (registering DOI) - 28 Apr 2025

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Abstract

Preeclampsia is a hypertension condition of human pregnancy that poses a significant risk to pregnant women and their fetus. It complicates about 2–8% of human pregnancies worldwide and displays multifactorial pathogenesis, including increased placental oxidative stress because of disturbed utero-placental blood flow. Recent [...] Read more.

Preeclampsia is a hypertension condition of human pregnancy that poses a significant risk to pregnant women and their fetus. It complicates about 2–8% of human pregnancies worldwide and displays multifactorial pathogenesis, including increased placental oxidative stress because of disturbed utero-placental blood flow. Recent evidence suggests that increased oxidative stress promotes acceleration of the placental senescence which is implicated in the pathogenesis of preeclampsia. This review focuses on the mechanisms that lead to oxidative stress in preeclamptic patients and examines the role of oxidative stress-induced placental senescence in the pathogenesis of the disease. Full article

(This article belongs to the Special Issue Implication of Oxidative Stress in Promoting Cellular Senescence and Associated Pathologies—2nd Edition)

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21 pages, 4449 KiB

Open AccessArticle

Zearalenone Exposure Damages Skeletal Muscle Through Oxidative Stress and Is Alleviated by Glutathione, Nicotinamide Mononucleotide, and Melatonin

by Dandan Li, Wei Fu, Jiyue Zhang, Yaqiu Lin, Xianrong Xiong, Jian Li and Yan Xiong

Antioxidants 2025, 14(5), 528; https://doi.org/10.3390/antiox14050528 (registering DOI) - 28 Apr 2025

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Abstract

Zearalenone (ZEN), a mycotoxin, is toxic to skeletal muscle, and the solution to alleviate its damage remains unknown. Here, we analyzed the toxic effect of ZEN on muscle and the mitigation of antioxidants (GSH, NMN, and melatonin) for this toxicity. The results showed [...] Read more.

Zearalenone (ZEN), a mycotoxin, is toxic to skeletal muscle, and the solution to alleviate its damage remains unknown. Here, we analyzed the toxic effect of ZEN on muscle and the mitigation of antioxidants (GSH, NMN, and melatonin) for this toxicity. The results showed that 0.02 mmol/L ZEN inhibited myoblast viability and myogenic differentiation, accompanied by reducing Type I and Type IIA and increasing Type IIX myofibers. Antioxidants (NMN with 0.5 mmol/L, GSH with 1 mmol/L, and melatonin with 1 mmol/L) rescued these phenotypes. Mice that were delivered 3 mg/kg body weight (BW)/day of ZEN by gavage for 35 days exhibited a similar trend of muscle fiber composition, but the gavage of antioxidants (NMN with 500 mg/kg BW/day, GSH with 300 mg/kg BW/day, and melatonin with 100 mg/kg BW/day) abolished this phenotype. Mechanistically, ZEN treatment increased ROS production, resulting in oxidative stress, mitochondrial dysfunction, and, subsequently, myofiber changes. Additionally, ZEN indirectly contributed to its damage, decreasing the abundance of Lactobacillus at the genus level and increasing Streptococcus sp. at the species level, which was associated with lactic acid production. Antioxidants partially rescued this microbiota composition. This study explores ZEN toxicity effects and alleviation of antioxidants, which provides new insights and attenuation solutions for ZEN damage to skeletal muscle. However, the underlying molecular mechanism of ZEN and antioxidants in the skeletal muscle still needs to be explored. Full article

(This article belongs to the Special Issue Antioxidant Response in Skeletal Muscle)

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37 pages, 2373 KiB

Open AccessReview

Ferroptosis and Iron Homeostasis: Molecular Mechanisms and Neurodegenerative Disease Implications

by Nurzhan Abdukarimov, Kamilya Kokabi and Jeannette Kunz

Antioxidants 2025, 14(5), 527; https://doi.org/10.3390/antiox14050527 (registering DOI) - 28 Apr 2025

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Abstract

Iron dysregulation has emerged as a pivotal factor in neurodegenerative pathologies, especially through its capacity to promote ferroptosis, a unique form of regulated cell death driven by iron-catalyzed lipid peroxidation. This review synthesizes current evidence on the molecular underpinnings of ferroptosis, focusing on [...] Read more.

Iron dysregulation has emerged as a pivotal factor in neurodegenerative pathologies, especially through its capacity to promote ferroptosis, a unique form of regulated cell death driven by iron-catalyzed lipid peroxidation. This review synthesizes current evidence on the molecular underpinnings of ferroptosis, focusing on how disruptions in iron homeostasis interact with key antioxidant defenses, such as the system Xc⁻-glutathione-GPX4 axis, to tip neurons toward lethal oxidative damage. Building on these mechanistic foundations, we explore how ferroptosis intersects with hallmark pathologies in Alzheimer’s disease (AD) and Parkinson’s disease (PD) and examine how iron accumulation in vulnerable brain regions may fuel disease-specific protein aggregation and neurodegeneration. We further surveyed the distinct components of ferroptosis, highlighting the role of lipid peroxidation enzymes, mitochondrial dysfunction, and recently discovered parallel pathways that either exacerbate or mitigate neuronal death. Finally, we discuss how these insights open new avenues for neuroprotective strategies, including iron chelation and lipid peroxidation inhibitors. By highlighting open questions, this review seeks to clarify the current state of knowledge and proposes directions to harness ferroptosis modulation for disease intervention. Full article

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26 pages, 4026 KiB

Open AccessArticle

Enhanced Extraction of Bioactive Compounds from Red Grape Pomace: Optimizing Ultrasound-Assisted Extraction with Ethanol and NaDES as Solvents

by Nicoleta Balan, Silviu Măntăilă, Gabriela Râpeanu and Nicoleta Stănciuc

Antioxidants 2025, 14(5), 526; https://doi.org/10.3390/antiox14050526 (registering DOI) - 27 Apr 2025

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Abstract

This study aims to investigate two types of solvents, ethanol and natural deep eutectic solvent (NaDES), using the ultrasound-assisted extraction techniques, in order to analyze their efficiency and ability to extract polyphenolic compounds from red grape pomace. The optimization and validation of the [...] Read more.

This study aims to investigate two types of solvents, ethanol and natural deep eutectic solvent (NaDES), using the ultrasound-assisted extraction techniques, in order to analyze their efficiency and ability to extract polyphenolic compounds from red grape pomace. The optimization and validation of the most feasible extraction conditions leading to maximization of the dependent variables (total anthocyanins, polyphenols, flavonoids and antioxidant activity), were carried out using response surface methodology with a central composite design. For ethanol extraction, the validated optimal conditions were at 35 °C for 22.5 min and a concentration of 70% ethanol. The values obtained under these conditions were 105.32 mg cyanindin-3-glucoside (C3G)/g DW, 465.81 mg gallic acid equivalents (GAE)/100 g DW, 15.3 mg catechin equivalents (CE)/100 g DW and 1414.15 mMol Trolox/g DW, respectively. Concerning the extraction using NaDES, consisting of a 1:2:1 molar mixture of choline chloride, lactic acid and water, the optimal conditions that led to a profile consisting in 57.58 mg C3G/g DW, 414.04 mg GAE/100 g DW, 15.8 mg CE/100 g DW and 7.28 mMol Trolox/g DW, respectively, were at 60 °C for 60 min and a solvent volume of 10 mL. Two different chromatographic profiles were obtained, with 12 polyphenolic compounds identified in ethanolic extracts and only 5 in NaDES, respectively. The in vitro digestion study revealed the high bioaccessibility of polyphenols in the gastric environment, with a drastic decrease in simulated intestinal fluid. The results are valuable in terms of identifying the best extraction conditions for polyphenols using alternative, non-toxic, ecofriendly solvents. Full article

(This article belongs to the Special Issue Green Extraction of Antioxidant from Natural Source)

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18 pages, 4617 KiB

Open AccessArticle

Hydroxy-Selenomethionine Supplementation During Gestation and Lactation Improve Reproduction of Sows by Enhancing the Antioxidant Capacity and Immunity Under Heat Stress Conditions

by Juan Wang, Hua Sun, Zhe Peng, Shao-Qing Wang, Yi-Qin Yan, Wei-Cai Luo, Ren-Gui Yang, Wei-Cheng Bei, Lv-Hui Sun and Jia-Cheng Yang

Antioxidants 2025, 14(5), 525; https://doi.org/10.3390/antiox14050525 (registering DOI) - 27 Apr 2025

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Abstract

The objective of this study was to determine whether hydroxy-selenomethionine (OH-SeMet) exerts better protective effects on sows against heat stress than sodium selenite (SeNa) or seleno-yeast (SeY). A total of 60 sows (Landrace × Yorkshire) were randomly allocated into the three groups and [...] Read more.

The objective of this study was to determine whether hydroxy-selenomethionine (OH-SeMet) exerts better protective effects on sows against heat stress than sodium selenite (SeNa) or seleno-yeast (SeY). A total of 60 sows (Landrace × Yorkshire) were randomly allocated into the three groups and fed a base diet supplemented with SeNa, SeY, or OH-SeMet at 0.3 mg Se/kg under a heat stress condition for a reproductive cycle. Compared to SeNa or SeY, OH-SeMet could more effectively sustain offspring growth performance, as evidenced by an increased number of live-born piglets, higher litter weight at day 21, and greater litter body weight gain from days 1 to 21. OH-SeMet was more effective in supporting endogenous redox systems, as shown by enhanced levels of TXNRD and GSH and reduced levels of GSSG in the serum of sows, improved T-AOC, TXNRD, and GSH alongside decreased MDA and GSSG in the serum of piglets, and heightened T-AOC in the jejunum of piglets. Furthermore, among the two tested organic Se sources, OH-SeMet was more effective than SeY in regulating immune responses compared to SeNa. OH-SeMet reduced inflammation-related markers CRP, HP, MAP, LPS, IL-1β, IL-6, and TNF-α, some or all of which were reduced in the serum of sows and their offspring. In addition, OH-SeMet also showed reduced glucose, TG, and NEFA levels, along with elevated insulin levels in the serum of sows. Correspondingly, among the two organic forms of Se, particularly those sows fed OH-SeMet showed better gut protection for the sows’ offspring, as indicated by a reduced crypt depth and increased villus height/crypt depth ratio in the duodenum, jejunum, and ileum than those fed SeNa. Specifically, compared to SeNa or SeY, OH-SeMet upregulated the expression of selenoproteins (GPX6, TXNRD3, GPX4, and SELENON), the tight junction protein (ZO-1), and host defense peptide gene (pBD1, pBD2, pBD3, NPG3, NPG4), along with downregulating levels of inflammation factor (IL-1β, IL-6 and TNF-α) and pro-apoptotic factor (P53) in the jejunum of piglets. Taken together, OH-SeMet more effectively mitigated the adverse effects induced by heat stress in sows and their offspring. Full article

(This article belongs to the Special Issue Redox Homeostasis in Poultry/Animal Production)

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20 pages, 23873 KiB

Open AccessArticle

Engeletin Targets Mitochondrial Dysfunction to Attenuate Oxidative Stress and Experimental Colitis in Intestinal Epithelial Cells Through AMPK/SIRT1/PGC-1α Signaling

by Jing Li, Zhijun Geng, Lixia Yin, Ju Huang, Minzhu Niu, Keni Zhang, Xue Song, Yueyue Wang, Lugen Zuo and Jianguo Hu

Antioxidants 2025, 14(5), 524; https://doi.org/10.3390/antiox14050524 (registering DOI) - 27 Apr 2025

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Abstract

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is characterized by chronic intestinal inflammation and epithelial barrier disruption. Emerging evidence highlights mitochondrial dysfunction as a pivotal contributor to IBD pathogenesis, where impaired mitochondrial homeostasis in intestinal epithelial cells (IECs) disrupts redox [...] Read more.

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is characterized by chronic intestinal inflammation and epithelial barrier disruption. Emerging evidence highlights mitochondrial dysfunction as a pivotal contributor to IBD pathogenesis, where impaired mitochondrial homeostasis in intestinal epithelial cells (IECs) disrupts redox balance, exacerbates oxidative stress, and triggers apoptosis, further compromising barrier integrity. This study investigated the therapeutic effects of Engeletin (Eng), a dihydroflavonoid from Smilax glabra Roxb., in dextran sulfate sodium (DSS)-induced colitis mice and colonic organoid models. Eng administration (10, 20, 40 mg/kg) significantly alleviated colitis symptoms, including weight loss, disease activity index (DAI) scores, and colon shortening, while restoring intestinal barrier integrity through the upregulation of tight junction proteins (ZO-1, claudin-1) and goblet cell preservation. Eng suppressed NF-κB-mediated inflammation and activated the Nrf2 antioxidant pathway, as well as reduced oxidative stress markers (MDA, CAT, GSH, and SOD). It attenuated epithelial apoptosis by balancing pro- and anti-apoptotic proteins (Bax/Bcl2, c-caspase3) and ameliorated mitochondrial dysfunction via enhanced ATP production, mtDNA levels, and complex I/IV activity. Mechanistically, Eng activated the AMPK/SIRT1/PGC-1α axis, and pharmacological inhibition of PGC-1α abolished its mitochondrial protective and anti-apoptotic effects. These findings demonstrate that Eng alleviates colitis by targeting mitochondrial homeostasis and oxidative stress through AMPK/SIRT1/PGC-1α signaling, offering a multitargeted strategy for IBD therapy. Full article

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

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24 pages, 11921 KiB

Open AccessArticle

Optimized Fermentation Conditions of Pulses Increase Scavenging Capacity and Markers of Anti-Diabetic Properties

by Andrea Jimena Valdés-Alvarado, Erick Damián Castañeda-Reyes and Elvira Gonzalez de Mejia

Antioxidants 2025, 14(5), 523; https://doi.org/10.3390/antiox14050523 (registering DOI) - 27 Apr 2025

Viewed by 65

Abstract

Fermented pulses offer health benefits due to their antioxidant and antidiabetic properties. The objective was to optimize the fermentation conditions of black bean (BB), black eyed pea (BEP), green split pea (GSP), red lentil (RL), and pinto bean (PB), using Lactiplantibacillus plantarum 299v [...] Read more.

Fermented pulses offer health benefits due to their antioxidant and antidiabetic properties. The objective was to optimize the fermentation conditions of black bean (BB), black eyed pea (BEP), green split pea (GSP), red lentil (RL), and pinto bean (PB), using Lactiplantibacillus plantarum 299v (Lp299v), based on the antioxidant-scavenging capacity and the ability to modulate type-2 diabetes markers. Pulses were grounded, dispersed in water, hydrolyzed with α-amylase, and pasteurized and inoculated with Lp299v. Optimization was performed by using the Box–Behnken response surface methodology, with the fermentation time, bacterial concentration, and flour concentration as variables. The values of antioxidant capacity measured as 2,2-diphenyl-1-picrylhydrazyl (DPPH)-radical scavenging of RL, BEP, PB, BB, and GSP were 57%, 68%, 71%, 72%, and 83%, respectively, under optimal conditions (8–9 h, 0.76–3.5 × 10⁹ a colony-forming unit (CFU)/mL, and 5.5–15 g flour/100 mL). These models demonstrated strong predictive power (p < 0.01) and a non-significant lack of fit (p ≥ 0.05). Additionally, fermentation increased the soluble protein content (3–10 mg/mL) and significantly inhibited dipeptidyl peptidase-IV and α-glucosidase activities by 40–70% and 30–60%, respectively. These results suggest that fermentation with Lp299v enhances the nutritional and functional quality of pulses, producing bioactive ingredients with antioxidant and antidiabetic potential. These functional ingredients may be used in the development of dietary interventions or as part of health-promoting foods, especially those targeted at the management of type-2 diabetes. Full article

(This article belongs to the Special Issue Antioxidants from Sustainable Food Sources)

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17 pages, 1092 KiB

Open AccessReview

Takotsubo Syndrome and Oxidative Stress: Physiopathological Linkage and Future Perspectives

by Alfredo Mauriello, Carmen Del Giudice, Gerardo Elia Del Vecchio, Adriana Correra, Anna Chiara Maratea, Martina Grieco, Arianna Amata, Vincenzo Quagliariello, Nicola Maurea, Riccardo Proietti, Antonio Giordano, Antonello D’Andrea and Vincenzo Russo

Antioxidants 2025, 14(5), 522; https://doi.org/10.3390/antiox14050522 (registering DOI) - 27 Apr 2025

Viewed by 95

Abstract

Takotsubo syndrome (TTS) is an acute coronary syndrome of unknown prevalence with a physiopathological mechanism that is not yet fully understood. The course is generally benign. Current therapeutic management is based on limited evidence. Oxidative stress seems to play a role in the [...] Read more.

Takotsubo syndrome (TTS) is an acute coronary syndrome of unknown prevalence with a physiopathological mechanism that is not yet fully understood. The course is generally benign. Current therapeutic management is based on limited evidence. Oxidative stress seems to play a role in the pathogenesis of cardiovascular diseases, especially regarding the endothelial dysfunction underlying TTS. The present review aims to describe the pathophysiological mechanisms linking oxidative stress and TTS, explore the impact of oxidative stress on TTS, and evaluate the efficacy of anti-oxidative stress therapies on TTS. Full article

(This article belongs to the Special Issue New Insight into Redox Homeostasis and Oxidative Stress in Health and Disease: Focus on Cardiac and Vascular Function)

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34 pages, 4688 KiB

Open AccessArticle

Optimized Sambucus nigra L., Epilobium hirsutum L., and Lythrum salicaria L. Extracts: Biological Effects Supporting Their Potential in Wound Care

by Diana Antonia Safta, Ana-Maria Vlase, Anca Pop, Julien Cherfan, Rahela Carpa, Sonia Iurian, Cătălina Bogdan, Laurian Vlase and Mirela-Liliana Moldovan

Antioxidants 2025, 14(5), 521; https://doi.org/10.3390/antiox14050521 (registering DOI) - 27 Apr 2025

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Abstract

This study aimed to optimize the extraction of phytocompounds intended for wound care applications from three plant species, Sambucus nigra L. flowers and Epilobium hirsutum L. and Lythrum salicaria L. aerial parts, by using a Quality by Design approach. The effects of different [...] Read more.

This study aimed to optimize the extraction of phytocompounds intended for wound care applications from three plant species, Sambucus nigra L. flowers and Epilobium hirsutum L. and Lythrum salicaria L. aerial parts, by using a Quality by Design approach. The effects of different extraction methods (ultra-turrax and ultrasonic-assisted extraction), ethanol concentrations (30%, 50%, 70%), and extraction times (3, 5, 10 min) were studied, and during the optimization step, the polyphenol and flavonoid contents were maximized. The phytochemical profiles of the optimized HEs (herbal extracts) were assessed using LC-MS/MS methods. The antioxidant capacity of the optimized HEs was determined using DPPH (2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity) TEAC (Trolox equivalent antioxidant capacity), and FRAP (ferric reducing antioxidant power) assays, while the antibacterial activity was evaluated against Escherichia coli, Pseudomonas aeruginosa, and MSSA—methicillin-sensitive Staphylococcus aureus and MRSA—methicillin-resistant Staphylococcus aureus). Cell viability and antioxidant and wound healing potential were assessed on keratinocytes and fibroblasts. The anti-inflammatory effect was assessed on fibroblasts by measuring levels of interleukins IL-6 and IL-8 and the production of nitric oxide from RAW 264.7 cells. The major compounds of the optimized HEs were rutin and chlorogenic acid. The Lythrum salicaria optimized HE showed the strongest antibacterial activity, while the Sambucus nigra optimized HE demonstrated high cell viability. Lythrum salicaria and Epilobium hirsutum optimized HEs showed increased antioxidant capacities. All extracts displayed anti-inflammatory effects, and the Epilobium hirsutum optimized HE exhibited the best in vitro wound-healing effect. Full article

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

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26 pages, 2059 KiB

Open AccessArticle

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 8-Week Pilot Study of Tuna-Byproduct-Derived Novel Supplements for Managing Cellular Senescence and Cognitive Decline in Perimenopausal and Postmenopausal Women

by Jintanaporn Wattanathorn, Wipawee Thukham-mee, Terdthai Tong-un, Weerapon Sangartit, Woraluck Somboonporn and Pongsatorn Paholpak

Antioxidants 2025, 14(5), 520; https://doi.org/10.3390/antiox14050520 (registering DOI) - 27 Apr 2025

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Abstract

Due to the lack of clinical data, we aimed to assess the anti-cellular senescence and cognition-enhancing effects and the mechanisms of novel tuna-byproduct-derived supplements. An 8-week, three-arm, randomized, double-blind, placebo-controlled parallel study was performed. A total of 60 female perimenopausal and postmenopausal women [...] Read more.

Due to the lack of clinical data, we aimed to assess the anti-cellular senescence and cognition-enhancing effects and the mechanisms of novel tuna-byproduct-derived supplements. An 8-week, three-arm, randomized, double-blind, placebo-controlled parallel study was performed. A total of 60 female perimenopausal and postmenopausal women (45–60 years old) were randomly assigned to placebo, low (2600 mg/day), and high (6000 mg/day) doses of the supplement. The N100 and P300 brain waves, working memory, serum levels of MDA, SOD, CAT, GPx TNF-α, IL-6, eNOS, AChE, MAO, GABA-T, and SIRT1, and density of Lactobacillus and Bifidobacterium spp. in feces were assessed before consumption and every 4 weeks throughout the study period. The telomere length and total phenolic compound and DHA levels were assessed before and at the end of the study. The low dose increased the N100 amplitude, working memory, telomere length, and SIRT1, whereas high doses improved the amplitudes of N00 and P300, P300 latency, and working memory; suppressed AChE, MAO, and GABA-T; and improved MDA, SOD, GPx, TNF-α, and IL-6 levels in the serum, further exhibiting an increase in DHA. Therefore, the novel supplement could be a potential remedy for managing cellular senescence and cognitive decline in perimenopausal and postmenopausal women; however, studies with larger sample sizes are required. Full article

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

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23 pages, 1292 KiB

Open AccessReview

Antioxidant and Anti-Inflammatory Properties of Mushroom-Based Food Additives and Food Fortified with Them—Current Status and Future Perspectives

by Agata Michalska, Małgorzata Sierocka, Beata Drzewiecka and Michał Świeca

Antioxidants 2025, 14(5), 519; https://doi.org/10.3390/antiox14050519 (registering DOI) - 26 Apr 2025

Viewed by 90

Abstract

Due to an aging population and the prevalence of illnesses associated with modern lifestyles, mushrooms, well known for their nutritional value and health-promoting properties, are becoming an increasingly important part of the diet. They are consumed in various forms, including food, nutraceuticals, and [...] Read more.

Due to an aging population and the prevalence of illnesses associated with modern lifestyles, mushrooms, well known for their nutritional value and health-promoting properties, are becoming an increasingly important part of the diet. They are consumed in various forms, including food, nutraceuticals, and dietary supplements. A relatively new trend involves incorporating mushrooms or their components as additives and supplements to enhance the quality and functionality of traditional food products. The processing and preservation methods of fresh mushrooms can significantly impact the activity of resulting powders, extracts, or other functional forms used in food additives, supplements, and fortified foods. The functional benefits of mushrooms are frequently attributed to their antioxidant and anti-inflammatory properties. However, to date, the literature lacks comprehensive reviews that consolidate existing knowledge on mushroom-based food additives and products enriched with them. Therefore, this review aims to compile and methodically analyze the existing data in this field, identify existing knowledge gaps, and outline future perspectives for the development and application of such products. Special attention is given to food supplementation with microencapsulated additives, which represent a promising form of functional powders. All these aspects are evaluated in terms of their antioxidant and anti-inflammatory properties. Finally, future perspectives on improving the health benefits of food through mushroom-based additives are discussed. Full article

(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Properties of Mushrooms: From Structure to Functionality)

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23 pages, 4545 KiB

Open AccessArticle

The Manifestation of the Dual ROS-Processing and Redox Signaling Roles of Glutathione Peroxidase-like Enzymes in Development of Arabidopsis Seedlings

by Krisztina Bela, Bernát Tompa, Riyazuddin Riyazuddin, Edit Horváth, Krisztián Jász, Ádám Hajnal, Sajid Ali Khan Bangash, Ágnes Gallé and Jolán Csiszár

Antioxidants 2025, 14(5), 518; https://doi.org/10.3390/antiox14050518 (registering DOI) - 25 Apr 2025

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Abstract

Plant glutathione peroxidase-like (GPXL) enzymes are thiol-based peroxidases that reduce H₂O₂ or hydroperoxides to water or alcohols using electrons principally from thioredoxin. Arabidopsis thaliana possesses eight isoenzymes (AtGPXL1−8) located in different plant organelles and have various roles in redox-dependent processes. [...] Read more.

Plant glutathione peroxidase-like (GPXL) enzymes are thiol-based peroxidases that reduce H₂O₂ or hydroperoxides to water or alcohols using electrons principally from thioredoxin. Arabidopsis thaliana possesses eight isoenzymes (AtGPXL1−8) located in different plant organelles and have various roles in redox-dependent processes. The determination of the redox potential of 6-day-old T-DNA insertional mutants (Atgpxl1–Atgpxl8) using a cytosolic redox-sensitive fluorescent probe (roGFP2) uncovered more oxidized redox status in the shoot and/or root of the untreated mutants, except for Atgpxl5. To investigate the involvement of AtGPXLs in the growth and abiotic stress responses of seedlings, the 4-day-old Atgpxls were exposed to salt and osmotic stresses for two weeks. The evaluation of the reactive oxygen species (ROS) levels of untreated 18-day-old plants using fluorescent microscopy revealed the elevated accumulation of total ROS in the shoots and, in some cases, the roots of the mutants. Regarding the growth of roots, both the length of primary roots and/or the number of lateral roots were affected by the mutation of AtGPXLs. A strong negative correlation was observed between the ROS level of wild type shoots and the development of lateral roots, but it was altered in mutants, while in the case of Atgpxl1, Atgpxl5, and Atgpxl7 seedlings, it disappeared; in other mutants (Atgpxl4, Atgpxl6, and Atgpxl8), the correlation became stronger. Our analysis underpins the discrete role of AtGPXL enzymes in controlling the growth and development of plants by fine tuning the ROS contents and redox status in an organ-specific way. Differences in root phenotype and metabolic activity between Atgpxl mutants and wild type plants highlight the essential role of AtGPXLs in ROS processing to support growth, which is particularly evident when one GPXL isoenzyme is absent or its activity is reduced, both under normal and abiotic stress conditions. Full article

(This article belongs to the Special Issue Oxidative Stress in Various Forms and Efficient Antioxidant Pathways in Prokaryotic and Eukaryotic Cells)

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16 pages, 1463 KiB

Open AccessArticle

Trimethylamine N-Oxide (TMAO) Acts as Inhibitor of Endothelial Nitric Oxide Synthase (eNOS) and Hampers NO Production and Acetylcholine-Mediated Vasorelaxation in Rat Aortas

by Alma Martelli, Federico Abate, Michele Roggia, Giada Benedetti, Eugenio Caradonna, Vincenzo Calderone, Gian Carlo Tenore, Sandro Cosconati, Ettore Novellino and Mariano Stornaiuolo

Antioxidants 2025, 14(5), 517; https://doi.org/10.3390/antiox14050517 - 25 Apr 2025

Viewed by 106

Abstract

Trimethylamine N-oxide (TMAO) is an endogenous osmolyte produced by enzymatic reactions starting in the human gut, where microbiota release trimethylamine (TMA) from foods, and ending in the liver, where TMA is oxidized to TMAO by flavin-containing monooxygenase 3 (FMO3). While physiological concentrations of [...] Read more.

Trimethylamine N-oxide (TMAO) is an endogenous osmolyte produced by enzymatic reactions starting in the human gut, where microbiota release trimethylamine (TMA) from foods, and ending in the liver, where TMA is oxidized to TMAO by flavin-containing monooxygenase 3 (FMO3). While physiological concentrations of TMAO help proteins preserve their folding, high levels of this metabolite are harmful and promote oxidative stress, inflammation, and atherosclerosis. In humans, elevated levels of circulating TMAO predispose individuals to cardiovascular diseases and chronic kidney disease and increase mortality risk, especially in the elderly. How TMAO exerts its negative effects has been only partially elucidated. In hypertensive rats, the eNOS substrate L-arginine and Taurisolo^®, a nutraceutical endowed with TMAO-reducing activity, act synergistically to reduce arterial blood pressure. Here, we investigate the molecular mechanisms underpinning this synergism and prove that TMAO, the target of Taurisolo^®, acts as direct inhibitor of endothelial nitric oxide synthase (eNOS) and competes with L-arginine at its catalytic site, ultimately inhibiting NO production and acetylcholine (Ach)-induced relaxation in murine aortas. Full article

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

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12 pages, 251 KiB

Open AccessArticle

The Effect of Chokeberry Juice and Fiber Consumption on the Concentration of Antioxidant Minerals in Serum

by Ewa Olechno, Małgorzata Elżbieta Zujko, Katarzyna Socha and Anna Puścion-Jakubik

Antioxidants 2025, 14(5), 516; https://doi.org/10.3390/antiox14050516 - 25 Apr 2025

Viewed by 153

Abstract

Aronia is a fruit that has become increasingly popular in recent years. Numerous health-promoting effects resulting from consumption have been indicated, including the possibility of using aronia as a functional food in the prevention and support of therapy for various ailments. For the [...] Read more.

Aronia is a fruit that has become increasingly popular in recent years. Numerous health-promoting effects resulting from consumption have been indicated, including the possibility of using aronia as a functional food in the prevention and support of therapy for various ailments. For the first time, we assessed the effects of the impact of a 90-day nutritional intervention on the level of selected minerals in the serum of women (n = 67) and men (n = 35). The consumption of 100 mL of juice for 60 days resulted in a significant increase in the levels of copper, manganese, and selenium. The addition of 10 g of aronia fiber resulted in a further increase in the concentration of these elements with antioxidant properties. An interesting observation is that the concentration of zinc decreased, which may indicate the operation of compensatory mechanisms. The above results indicate that regular consumption of aronia bio-products may have a beneficial effect on the concentration of microelements in the serum. Full article

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

20 pages, 2143 KiB

Open AccessReview

Argan Oil: A Natural Bioactive Lipid Modulating Oxidative Stress and Inflammation

by Soufiane Rabbaa, Habiba Bouchab, Yassir Laaziouez, Youness Limami, Boubker Nasser, Pierre Andreoletti, Mustapha Cherkaoui-Malki and Riad El Kebbaj

Antioxidants 2025, 14(5), 515; https://doi.org/10.3390/antiox14050515 - 25 Apr 2025

Viewed by 255

Abstract

Nutrition is a key determinant in modulating disease risk, with numerous studies highlighting the role of antioxidants and lipids, particularly the micronutrient and fatty acid composition of natural oils and their bioactive metabolites. In this context, argan oil—a vegetable oil extracted from the [...] Read more.

Nutrition is a key determinant in modulating disease risk, with numerous studies highlighting the role of antioxidants and lipids, particularly the micronutrient and fatty acid composition of natural oils and their bioactive metabolites. In this context, argan oil—a vegetable oil extracted from the kernels of Argania spinosa—has gained significant attention due to its well-balanced fatty acid profile, rich in oleic and linoleic acids, and its high levels of antioxidant compounds, including tocopherols, polyphenols, and phytosterols, particularly schottenol and spinasterol. Thanks to its unique composition, argan oil exhibits protective properties against harmful biological processes, such as oxidative stress and inflammation, both of which play a significant role in various diseases. Preclinical studies, both in vitro and in vivo, have demonstrated that argan oil reduces oxidative stress by preventing DNA damage, protein carbonylation, and lipid peroxidation, while simultaneously increasing antioxidant defenses. Furthermore, it modulates inflammatory responses by decreasing pro-inflammatory biomarkers, increasing anti-inflammatory markers, and limiting immune cell infiltration across different tissues. These antioxidant and anti-inflammatory effects are thought to be linked to argan oil’s ability to regulate key signaling pathways, such as Nrf-2 and NF-κB. Although direct evidence remains limited, studies suggest that its main bioactive components—fatty acid, γ-tocopherol, ferulic acid, and campesterol—can influence these pathways, either by activating Nrf2 to boost antioxidant defenses or by inhibiting NF-κB to suppress inflammation. This review explores the antioxidant and anti-inflammatory properties of argan oil, drawing insights from a range of scientific studies to better understand its therapeutic potential. Full article

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15 pages, 3532 KiB

Open AccessArticle

Carbon Monoxide Stimulates Chondrocyte Mitochondria and Protects Mitochondria During Cartilage Injury

by Suryamin Liman, Madeline R. Hines, Piedad C. Gómez-Contreras, Emily Witt, Jacob S. Fisher, Kevin J. Lu, Lauren D. McNally, Alicia T. Cotoia, Maxwell Y. Sakyi, Brett A. Wagner, Michael S. Tift, Douglas Fredericks, Jessica E. Goetz, James D. Byrne and Mitchell C. Coleman

Antioxidants 2025, 14(5), 514; https://doi.org/10.3390/antiox14050514 - 25 Apr 2025

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Abstract

Objective: Joint injury precipitates post-traumatic osteoarthritis (PTOA) via chondrocyte mitochondrial oxidative damage. Carbon monoxide (CO) is a small molecule with potent antioxidant and mitochondrial benefits in other tissues that have not been explored in healthy chondrocytes. We hypothesized that CO would subvert the [...] Read more.

Objective: Joint injury precipitates post-traumatic osteoarthritis (PTOA) via chondrocyte mitochondrial oxidative damage. Carbon monoxide (CO) is a small molecule with potent antioxidant and mitochondrial benefits in other tissues that have not been explored in healthy chondrocytes. We hypothesized that CO would subvert the mitochondrial effects of articular cartilage injuries upon resident chondrocytes. Design: We evaluated intra-articular delivery of a novel carbon monoxide-containing foam (COF). We used in vitro impact injuries to explore mitochondrial and redox endpoints after CO exposure. We then applied intra-articular injections of COF or control room air foam (RAF) to assess safety, efficacy, and other intra-articular responses. Results: COF increased the expression of HO1 and mitofusin-1 within 1 h and this increase was sustained for 12 h in vitro. COF increased chondrocyte mitochondrial respiration by 40% and increased reduced (not oxidized) thiols by 50% following in vitro injury to osteochondral explants. After cartilage injury, COF prevented the formation of 3-nitrotyrosine and the loss of articular chondrocyte mitochondria. When injected intra-articularly, COF was retained for 24 h post-injection in mouse stifle joints. It increased HO1 in those joints, enhanced reduced thiol levels in rabbit stifle joints, and exhibited no toxicity 1 and 4 weeks after injection. Conclusions: This study supports the hypothesis that CO functions as an antioxidant for articular chondrocytes by supporting mitochondria and intracellular GSH in the presence or absence of cartilage injury. Challenges in delivering exogenous CO have limited its preclinical development, but new CO-releasing materials like COF may enable new examinations of this promising small molecule. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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20 pages, 2179 KiB

Open AccessReview

Ganoderma lucidum—From Ancient Remedies to Modern Applications: Chemistry, Benefits, and Safety

by Mădălina-Paula Plosca, Maria Simona Chiș, Anca Corina Fărcaș and Adriana Păucean

Antioxidants 2025, 14(5), 513; https://doi.org/10.3390/antiox14050513 - 25 Apr 2025

Viewed by 289

Abstract

Ganoderma lucidum (G. lucidum), commonly known as Reishi or Lingzhi, is a medicinal mushroom with a rich history in traditional Asian medicine. This review examines diverse bioactive components supporting therapeutic properties, including polysaccharides, triterpenoids, phenolic compounds, fatty acids, peptides and proteins, [...] Read more.

Ganoderma lucidum (G. lucidum), commonly known as Reishi or Lingzhi, is a medicinal mushroom with a rich history in traditional Asian medicine. This review examines diverse bioactive components supporting therapeutic properties, including polysaccharides, triterpenoids, phenolic compounds, fatty acids, peptides and proteins, vitamins, minerals, and sterols. The mushroom offers numerous health benefits, including immunomodulation, antioxidant and anti-inflammatory effects, liver protection, and anti-cancer activities. In addition, it shows potential in managing diabetes, cardiovascular disease, and viral infections. Advances in extraction technologies, such as ultrasound and microwave-assisted methods, have improved the bioavailability and efficacy of compounds. While G. lucidum is an excellent functional food and therapeutic agent it remains an unexploited source of nutrients. Further research is needed to optimize the industrial applications and evaluate the safety in specific populations. Full article

(This article belongs to the Special Issue Advances in Analytical Chemistry in Antioxidant-Rich Functional Foods and Food Supplements)

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19 pages, 2722 KiB

Open AccessArticle

Nitazoxanide Modulates Mitochondrial Function and Inflammatory Metabolism in Chondrocytes from Patients with Osteoarthritis via AMPK/mTORC1 Signaling

by Ha Eun Kim, Jong Yeong Lee, Ga-Yeon Son, Jun-Young Park, Ki Bum Kim, Chul-Min Choi, Young Jae Moon and Jin Kyeong Choi

Antioxidants 2025, 14(5), 512; https://doi.org/10.3390/antiox14050512 - 24 Apr 2025

Viewed by 181

Abstract

Osteoarthritis (OA) is a long-term degenerative condition of the joints, characterized by persistent inflammation, progressive cartilage breakdown, and impaired mitochondrial function. Recent studies have shown that hyperactivation of the mTORC1 pathway and metabolic reprogramming of chondrocytes contribute to disease progression. Nitazoxanide (NTZ), an [...] Read more.

Osteoarthritis (OA) is a long-term degenerative condition of the joints, characterized by persistent inflammation, progressive cartilage breakdown, and impaired mitochondrial function. Recent studies have shown that hyperactivation of the mTORC1 pathway and metabolic reprogramming of chondrocytes contribute to disease progression. Nitazoxanide (NTZ), an oral antiparasitic agent approved by the Food and Drug Administration, has shown anti-inflammatory and mitochondrial protective effects in various disease situations; despite this, its application in osteoarthritis has yet to be fully investigated. Here, we assessed the therapeutic efficacy of NTZ using IL-1β-stimulated primary chondrocytes derived from patients with OA. NTZ substantially reduced the expression of proinflammatory cytokines and matrix metalloproteinases, restored mitochondrial membrane potential, and reduced mitochondrial reactive oxygen species levels. NTZ also effectively reversed IL-1β-induced glycolytic metabolic changes by inhibiting glucose uptake and GLUT1 expression. Mechanistically, NTZ inhibited the activation of the mTORC1 pathway and substantially increased AMPK phosphorylation. The siRNA-mediated AMPK knockdown negated NTZ-induced mitochondrial and metabolic improvements, suggesting that AMPK is a key upstream regulator of the protective actions of NTZ. NTZ can, therefore, effectively inhibit inflammatory metabolic reprogramming and mitochondrial dysfunction in OA chondrocytes through AMPK-dependent mTORC1 signaling inhibition, highlighting its potential as a disease-modifying therapy for OA. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Bone Metabolism and Diseases)

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16 pages, 932 KiB

Open AccessArticle

Elevated Oxidative Stress in Patients with Coexisting Multiple Sclerosis and Migraine: A Cross-Sectional Study

by Iwona Rościszewska-Żukowska, Marek Biesiadecki, Mateusz Mołoń, Aleksandra Rożek, Halina Bartosik-Psujek and Sabina Galiniak

Antioxidants 2025, 14(5), 511; https://doi.org/10.3390/antiox14050511 - 24 Apr 2025

Viewed by 110

Abstract

One potential association that is gaining increasing attention is the link between multiple sclerosis (MS) and migraine, which are suggested to frequently coexist in young patients. This is the first study to analyze the levels of multiple markers of oxidative stress in sociodemographically [...] Read more.

One potential association that is gaining increasing attention is the link between multiple sclerosis (MS) and migraine, which are suggested to frequently coexist in young patients. This is the first study to analyze the levels of multiple markers of oxidative stress in sociodemographically similar groups of patients with migraine, MS, and both MS and migraine. A single cross-sectional study was conducted at the Department of Neurology, Rzeszów University. The study included 110 participants, comprising 26 healthy controls, 24 subjects with migraines, 30 with MS, and 30 with both MS and migraine. Oxidative stress markers were measured in patients’ serum. Patients with MS and migraines had statistically elevated levels of 3-nitrotyrosine, Amadori products, 4-hydroxy-nonenal, and oxidative damage to amino acids. Moreover, we observed reduced levels of thiol groups and total antioxidant capacity in the serum of patients with MS and migraines compared to healthy controls. The co-occurrence of migraines in MS leads to greater oxidative stress than MS alone. The impact of chronic oxidative stress on both MS and migraines may exacerbate symptoms and deteriorate the quality of life. Full article

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

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21 pages, 4917 KiB

Open AccessArticle

Intestinal Microbiota and Gene Expression Alterations in Chinese Mitten Crab (Eriocheir sinensis) Under Deltamethrin Exposure

by Chunyi Zhong, Jinliang Du, Haojun Zhu, Jiancao Gao, Gangchun Xu and Pao Xu

Antioxidants 2025, 14(5), 510; https://doi.org/10.3390/antiox14050510 - 24 Apr 2025

Viewed by 220

Abstract

The intestine is an important immune organ of aquatic animals and it plays an essential role in maintaining body health and anti-oxidative stress. To investigate the toxic effects of deltamethrin in intestinal tissue of Chinese mitten crabs (Eriocheir sinensis), 120 healthy [...] Read more.

The intestine is an important immune organ of aquatic animals and it plays an essential role in maintaining body health and anti-oxidative stress. To investigate the toxic effects of deltamethrin in intestinal tissue of Chinese mitten crabs (Eriocheir sinensis), 120 healthy crabs were randomly divided into two experimental groups (blank control group and deltamethrin-treated group), with three replicates in each group. After being treated with deltamethrin for 24 h, 48 h, 72 h, and 96 h, intestinal tissues were collected aseptically to assess the effects of deltamethrin on oxidative stress, immunity, apoptosis-related genes, and the structure of microflora in intestinal tissues. Additionally, correlations between gut microbiota composition and intestinal tissue damage-associated genes were analyzed. The results demonstrated that prolonged exposure to deltamethrin induced oxidative stress damage in intestinal tissue. Compared with the blank control group, the expression of autophagy-related genes B-cell lymphoma/Leukemia-2 (bcl-2), c-Jun N-terminal kinase (jnk), Microtuble-associated protein light chain 3 (lc3c), Cysteine-dependent Aspartate-specific Protease 8 (caspase 8), BECN1(beclin1), oxidative stress damage-related genes MAS1 proto-oncogene (mas), Glutathione Peroxidase (gpx), kelch-like ECH-associated protein 1 (keap1), Sequestosome 1 (p62), Interleukin-6 (il-6), and immune-related genes Lipopolysaccharide-induced TNF-alpha Factor (litaf), Heat shock protein 90 (hsp90) and prophenoloxidase (propo) in the deltamethrin treatment group were significantly up-regulated at 96 h (p < 0.05 or p < 0.01). Additionally, 16S rRNA sequencing showed that the diversity of intestinal flora in the deltamethrin-treated group was significantly higher compared with the blank control group (p < 0.01). Analysis of the differences in the composition of intestinal flora at the genus level showed that the relative abundance of Candidatus Bacilloplasma in the deltamethrin treatment group was significantly lower than that in the blank control group (p < 0.01). In contrast, the relative abundances of Flavobacterium, Lachnospiraceae_NK4A136_group, Acinetobacter, Chryseobacterium, Lacihabitans, Taibaiella, Hydrogenophaga, Acidovorax, and Undibacterium were significantly higher than those in the blank control group (p < 0.05 or p < 0.01). Pearson correlation analysis revealed that Malaciobacter, Shewanella, and Prevotella exhibited significant positive correlations with gene indicators (jnk, gpx, lc3c, litaf, hsp90), while Dysgonomonas, Vibrio, and Flavobacterium demonstrated significant negative correlations with multiple gene indicators (caspase 8, p62, il-16, keap1, jnk, etc). These results demonstrate that deltamethrin significantly impacts the gut microbiota, immune function, and antioxidant capacity of E. sinensis. The changes in gut microbiota have correlations with the biomarkers of intestinal tissue injury genes, indicating that gut microbiota plays a crucial role in deltamethrin-induced intestinal tissue damage. These insights contribute to a better understanding of the ecological risks associated with deltamethrin exposure in aquatic organisms. Full article

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16 pages, 3921 KiB

Open AccessArticle

Alleviating Effects of Ethanol Extract from Acremonium terricola Culture on Patulin Toxicity

by Haiyan Lin, Savindi Kaushalya Edirisinghe, Ijeoma Esther Okolo, Zhen Chen, Juan Sun, Wei Hong and Ruiyu Zhu

Antioxidants 2025, 14(5), 509; https://doi.org/10.3390/antiox14050509 - 24 Apr 2025

Viewed by 174

Abstract

Exposure to patulin (PAT) poses a significant health risk to animals, emphasizing the need for natural, safe substances to mitigate toxicity. Acremonium terricola culture (ATC), a fungal fermentation-derived feed additive, is known for its antioxidant properties, yet its potential to alleviate mycotoxin-induced toxicity [...] Read more.

Exposure to patulin (PAT) poses a significant health risk to animals, emphasizing the need for natural, safe substances to mitigate toxicity. Acremonium terricola culture (ATC), a fungal fermentation-derived feed additive, is known for its antioxidant properties, yet its potential to alleviate mycotoxin-induced toxicity remains largely uninvestigated. In this study, the ethanol extracts from the ATC (EEAT) were prepared with a total phenolic content of 67.9 mg GAE/g and a total flavonoid content of 32.7 mg RE/g. Ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-ESI-MS/MS) analysis was employed to investigate the bioactive components in EEAT. In PAT-exposed Caenorhabditis elegans models, EEAT treatment significantly enhanced locomotory capacity and elevated antioxidant enzyme activities by 63.1% (SOD) and 90.1% (GSH-ST), respectively. Molecular docking analysis revealed that key active compounds in EEAT, such as coumarin, succinic acid, and trigonelline, exhibited effective binding affinities to potential targets SIR-2.1 and DAF-2. Notably, coumarin and trigonelline were most effective in alleviating PAT toxicity, as evidenced by rescued locomotor rates and oxidative impairment in C. elegans. Our findings not only elucidate the molecular basis of EEAT-mediated PAT mitigation but also establish A. terricola culture as a sustainable antioxidant. Full article

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

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Antioxidants, Volume 14, Issue 5 (May 2025) – 39 articles

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