Antioxidants

24 pages, 52994 KiB

Open AccessArticle

The Naturally Bioactive Vicine Extracted from Faba Beans Is Responsible for the Transformation of Grass Carp (Ctenopharyngodon idella) into Crisp Grass Carp

by Xinyu Zheng, Minyi Luo, Bing Fu, Gen Kaneko, Jingjing Tian, Jun Xie, Jilun Hou and Ermeng Yu

Antioxidants 2025, 14(7), 813; https://doi.org/10.3390/antiox14070813 (registering DOI) - 1 Jul 2025

Abstract

While faba bean feeding improves grass carp muscle texture via reactive oxygen species (ROS), the main bioactive compound was unclear. In this study, vicine—a pro-oxidant glycoside—was isolated from faba beans using cation-exchange column chromatography and supplemented into the feed of grass carp at [...] Read more.

While faba bean feeding improves grass carp muscle texture via reactive oxygen species (ROS), the main bioactive compound was unclear. In this study, vicine—a pro-oxidant glycoside—was isolated from faba beans using cation-exchange column chromatography and supplemented into the feed of grass carp at 0.6%. To assess the impact of vicine on muscle texture, the grass carp were fed for 150 days with three treatments: control group, faba bean group, and vicine group. The results showed that vicine improved muscle texture similarly to faba beans but caused fewer adverse effects on muscle, liver, and intestinal health. Vicine improved grass carp muscle texture in the following ways: (1) induced ROS overproduction, activating the Caspase apoptosis pathway and downregulating Pax-7 to promote satellite cell-mediated myofiber regeneration; (2) vicine-mediated intestinal microbiota alterations increased lipopolysaccharide (LPS) levels, indirectly elevating muscle ROS via the gut–muscle axis to further affect muscle structure. This study demonstrated that vicine improved muscle texture by activating ROS-dependent myofiber regeneration but also induced oxidative stress and gut microbiota perturbation. While vicine mitigated the severe toxicity of faba beans, its application requires careful evaluation of its toxicological properties to balance benefits and risks. This study offers new insights for enhancing the quality of aquatic animals. Full article

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

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38 pages, 5469 KiB

Open AccessReview

Alzheimer’s Disease Pathogenic Mechanisms: Linking Redox Homeostasis and Mitochondria-Associated Metabolic Pathways Through Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)

by Agueda Rostagno and Jorge Ghiso

Antioxidants 2025, 14(7), 812; https://doi.org/10.3390/antiox14070812 (registering DOI) - 1 Jul 2025

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia, with a prevalence expected to escalate with the aging of the world population as life expectancy increases. In spite of significant progress made in the investigation of the etiology and pathogenesis of the disease, [...] Read more.

Alzheimer’s disease (AD) is the leading cause of dementia, with a prevalence expected to escalate with the aging of the world population as life expectancy increases. In spite of significant progress made in the investigation of the etiology and pathogenesis of the disease, many mechanistic aspects that could support the implementation of novel therapeutic avenues remain unresolved. Research during the last decade has revealed a crucial role for mitochondria-mediated pathways dysregulation as significant contributors to the disease, highlighting the relevance of changes in brain metabolism and bioenergetics as well as the induction of oxidative stress conditions for neurodegeneration. This review summarizes mitochondrial functional changes associated with AD with emphasis in the dysregulation of redox homeostasis and the role of nuclear factor erythroid 2-related factor 2 (Nrf2), not only as a central regulator of the antioxidant response but also as a more recently described modulator of cellular metabolic pathways. Potential therapeutic strategies targeting oxidative stress and mitochondrial dysfunction are also discussed, with particular emphasis on the use of small molecules Nrf2 activators. Exploiting the multifactorial properties of the transcription factor in either novel or combination-based pharmacological approaches targeting multiple genes and pathways may contribute to providing more definitive and precise therapeutic perspectives. Full article

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

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23 pages, 2149 KiB

Open AccessArticle

Liposomal Delivery of a Biotechnological Lavandula angustifolia Miller Extract Rich in Rosmarinic Acid for Topical Herpes Simplex Therapy

by Federica Fulgheri, Fabrizio Angius, Matteo Perra, Ilenia Delogu, Silvia Puxeddu, Milen I. Georgiev, Renáta Novotná, Jana Franková, Misia Lobina, Aldo Manzin, Maria Manconi and Maria Letizia Manca

Antioxidants 2025, 14(7), 811; https://doi.org/10.3390/antiox14070811 (registering DOI) - 30 Jun 2025

Abstract

Herpes simplex virus type 1 (HSV-1) is a widespread pathogen responsible for recurrent infections, primarily affecting the skin and mucous membranes. With the aim of targeting both the viral infection and the associated inflammatory response, biotechnologically produced Lavandula angustifolia Miller (L. angustifolia [...] Read more.

Herpes simplex virus type 1 (HSV-1) is a widespread pathogen responsible for recurrent infections, primarily affecting the skin and mucous membranes. With the aim of targeting both the viral infection and the associated inflammatory response, biotechnologically produced Lavandula angustifolia Miller (L. angustifolia) extract, rich in rosmarinic acid, was incorporated into liposomal formulations intended for topical application. Lavender is known for its strong anti-inflammatory, antioxidant, wound-healing, and antiviral properties. However, its low stability under certain conditions limits its therapeutic potential. Four different formulations were developed: conventional liposomes, glycerosomes, hyalurosomes, and glycerohyalurosomes. The vesicles were characterized for size, stability, and entrapment efficiency. Glycerosomes were the smallest (~58 nm), while the other formulations ranged around 77 nm, all maintaining a highly negative surface charge, ensuring stability and reduced aggregation. Glycerol-containing formulations demonstrated superior stability over 12 months, while liposomes and hyalurosomes increased their size after only two months. Entrapment efficiency reached up to 100% for most vesicles, except for glycerohyalurosomes (~54%). In vitro studies on Normal Human Dermal Fibroblasts (NHDFs) demonstrated that all formulations were biocompatible and enhanced cell viability under oxidative stress. Glycerosomes, hyalurosomes, and glycerohyalurosomes exhibited significant anti-inflammatory activity by reducing MMP-1 and IL-6 levels in LPS-stimulated fibroblasts. Furthermore, these preliminary results highlighted promising antiviral activity against HSV-1 of the obtained formulations, particularly when applied during or post-infection. Overall, these phospholipid vesicles offer a dual therapeutic approach, combining antioxidant, anti-inflammatory, and antiviral effects, positioning them as promising candidates for the treatment of HSV-induced skin lesions and related inflammatory conditions. Full article

(This article belongs to the Special Issue Recent Trends in Nanoantioxidants—2nd Edition)

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22 pages, 6678 KiB

Open AccessArticle

Pharmaco-Toxicological Effects of Cachrys libanotis Extract: Antioxidant, Antimicrobial, and Cytotoxic Activities in Human Cell Lines and Embryonic Models

by Mary Fucile, Ioana Gabriela Macasoi, Monica Negrea, Diana Obistioiu, Mariangela Marrelli, Ersilia Alexa, Cristina Dehelean, Giancarlo Statti, Filomena Conforti and Iulia Pinzaru

Antioxidants 2025, 14(7), 810; https://doi.org/10.3390/antiox14070810 (registering DOI) - 30 Jun 2025

Abstract

We conducted a study to explore the potential of an enriched coumarin extract from Cachrys libanotis for the prevention and treatment of various diseases. The extract was prepared using pressurized cyclic solid–liquid extraction, and its safety profile was thoroughly evaluated using both cellular [...] Read more.

We conducted a study to explore the potential of an enriched coumarin extract from Cachrys libanotis for the prevention and treatment of various diseases. The extract was prepared using pressurized cyclic solid–liquid extraction, and its safety profile was thoroughly evaluated using both cellular and embryonic models. Our main goal was to uncover a mixture of bioactive compounds that could offer therapeutic benefits. The following parameters were assessed: (i) extract composition; (ii) antioxidant activity; (iii) effects on cell viability and morphology; (iv) irritant potential (in ovo); and (v) antimicrobial activity against nine microbial strains. Chromatographic and spectrometric analyses confirmed that the main specialized metabolites in C. libanotis extract were furanocoumarins, with xanthotoxin, bergapten, and isopimpinellin identified as the three predominant constituents. Treatment with the C. libanotis extract did not induce significant alterations in the adherent human keratinocytes, with confluence and epithelial morphology comparable to control cells. Conversely, viable cells declined in the breast carcinoma cell line (MDA-MB-231). Moreover, the C. libanotis extract exhibited a promising antimicrobial activity against two Gram-negative pathogens, Shigella flexneri and Salmonella typhimurium. Full article

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

20 pages, 3618 KiB

Open AccessReview

Superoxide Dismutases in Immune Regulation and Infectious Diseases

by Tong Liu, Jiajin Shang and Qijun Chen

Antioxidants 2025, 14(7), 809; https://doi.org/10.3390/antiox14070809 (registering DOI) - 30 Jun 2025

Abstract

Superoxide dismutases (SODs) maintain redox homeostasis through the catalytic dismutation of superoxide anions, thereby affording protection to organisms against oxidative damage. The SOD family, encompassing Cu/Zn-SOD, Mn-SOD, Fe-SOD, and Ni-SOD, exhibits structural diversity and constitutes a multilevel antioxidant defense system with discrete subcellular [...] Read more.

Superoxide dismutases (SODs) maintain redox homeostasis through the catalytic dismutation of superoxide anions, thereby affording protection to organisms against oxidative damage. The SOD family, encompassing Cu/Zn-SOD, Mn-SOD, Fe-SOD, and Ni-SOD, exhibits structural diversity and constitutes a multilevel antioxidant defense system with discrete subcellular localizations. Beyond their antioxidant functions, SODs also function as immunomodulatory proteins, regulating the maturation, proliferation, and differentiation of immune cells. They further fulfill a crucial role in host responses to parasitic infections. The current review synthesizes and critically evaluates extant research to comprehensively delineate the molecular architecture of SODs, their intricate post-translational modification (PTM) networks, and their dual regulatory mechanisms at the interface of immunomodulation and pathological processes. This review establishes a critical framework for elucidating the biological significance of redox homeostasis maintenance. Full article

(This article belongs to the Special Issue Advances in Oxidoreductases)

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20 pages, 3091 KiB

Open AccessArticle

Carnosol, a Rosemary Ingredient Discovered in a Screen for Inhibitors of SARM1-NAD⁺ Cleavage Activity, Ameliorates Symptoms of Peripheral Neuropathy

by Hitoshi Murata, Kazuki Ogawa, Yu Yasui, Toshiki Ochi, Nahoko Tomonobu, Ken-Ichi Yamamoto, Rie Kinoshita, Yoji Wada, Hiromichi Nakamura, Masahiro Nishibori and Masakiyo Sakaguchi

Antioxidants 2025, 14(7), 808; https://doi.org/10.3390/antiox14070808 (registering DOI) - 30 Jun 2025

Abstract

Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a nicotinamide adenine dinucleotide (NAD⁺) hydrolase involved in axonal degeneration and neuronal cell death. SARM1 plays a pivotal role in triggering the neurodegenerative processes that underlie peripheral neuropathies, traumatic brain injury, [...] Read more.

Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a nicotinamide adenine dinucleotide (NAD⁺) hydrolase involved in axonal degeneration and neuronal cell death. SARM1 plays a pivotal role in triggering the neurodegenerative processes that underlie peripheral neuropathies, traumatic brain injury, and neurodegenerative diseases. Importantly, SARM1 knockdown or knockout prevents the degeneration; as a result, SARM1 has been attracting attention as a potent therapeutic target. In recent years, the development of several SARM1 inhibitors derived from synthetic chemical compounds has been reported; however, no dietary ingredients with SARM1 inhibitory activity have been identified. Therefore, we here focused on dietary ingredients and found that carnosol, an antioxidant contained in rosemary, inhibits the NAD⁺-cleavage activity of SARM1. Purified carnosol inhibited the enzymatic activity of SARM1 and suppressed neurite degeneration and cell death induced by the anti-cancer medicine vincristine (VCR). Carnosol also inhibited VCR-induced hyperalgesia symptoms, suppressed the loss of intra-epidermal nerve fibers in vivo, and reduced the blood fluid level of phosphorylated neurofilament-H caused by an axonal degeneration event. These results indicate that carnosol has a neuroprotective effect via SARM1 inhibition in addition to its previously known antioxidant effect via NF-E2-related factor 2 and thus suppresses neurotoxin-induced peripheral neuropathy. Full article

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

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13 pages, 1303 KiB

Open AccessReview

Positive Role of Trichoderma harzianum in Increasing Plant Tolerance to Abiotic Stresses: A Review

by Yueyao Geng, Shuying Chen, Pinke Lv, Yankai Li, Jingxuan Li, Fangling Jiang, Zhen Wu, Qirong Shen and Rong Zhou

Antioxidants 2025, 14(7), 807; https://doi.org/10.3390/antiox14070807 (registering DOI) - 30 Jun 2025

Abstract

As a beneficial fungus, Trichoderma harzianum (T. harzianum) has been widely applied for growth promotion and biocontrol. Recently, it has attracted much attention with regard to improving stress tolerance in plants under abiotic stress. In this paper, the multiple mechanisms of [...] Read more.

As a beneficial fungus, Trichoderma harzianum (T. harzianum) has been widely applied for growth promotion and biocontrol. Recently, it has attracted much attention with regard to improving stress tolerance in plants under abiotic stress. In this paper, the multiple mechanisms of T. harzianum for alleviating abiotic stress damage in plants are reviewed. T. harzianum can regulate the synthesis of key phytohormones, such as abscisic acid (ABA), indole-3-acetic acid (IAA), etc., thereby enhancing the physiological response ability of plants under stress conditions such as drought, salt stress, and high temperature. These are associated with antioxidant system regulation in plants, which reduces levels of reactive oxygen species (ROS) and oxidative damage and maintains intracellular redox balance. T. harzianum can also improve plant nutrient uptake and root development, secondary metabolism, soil environment and structure, and expression of related genes. In addition, in this paper, the characteristics of T. harzianum application in field and horticultural crops are summarized and compared, revealing differences in the methods, concentrations, time, and effects of applying T. harzianum to various crops. We further explore the synergistic regulation effect of T. harzianum and plant–microbiome interaction on the stress microenvironment. Future perspectives on the molecular mechanism of T. harzianum and its field application potential are discussed. This review provides a theoretic and practical reference for the application of T. harzianum in agricultural production. Full article

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19 pages, 4889 KiB

Open AccessArticle

The Antioxidant and Skin-Brightening Effects of a Novel Caffeic Acid Derivative, Caffeic Acid-3,4-Dihydroxyphenylpropanolester

by Kyu-lim Kim, Ju-hee Jeon, Yeonjoon Kim and Kyung-Min Lim

Antioxidants 2025, 14(7), 806; https://doi.org/10.3390/antiox14070806 (registering DOI) - 29 Jun 2025

Abstract

Caffeic acid (CA) is a naturally occurring polyphenol antioxidant found in coffee, tea, fruits, and vegetables, known for its strong antioxidant, anti-inflammatory, and anti-aging properties. However, its cosmetic application is limited because of poor dermal absorption due to its high polarity. This study [...] Read more.

Caffeic acid (CA) is a naturally occurring polyphenol antioxidant found in coffee, tea, fruits, and vegetables, known for its strong antioxidant, anti-inflammatory, and anti-aging properties. However, its cosmetic application is limited because of poor dermal absorption due to its high polarity. This study aimed to evaluate the antioxidant and skin-brightening effects of a novel lipophilic CA derivative, CAD (caffeic acid-3,4-dihydroxyphenylpropanolester). CAD was synthesized by conjugating CA with 3,4-DHPEA, a lipophilic antioxidant derived from olive oil. In both DPPH and ABTS assays, CAD exhibited more potent antioxidant activity than CA. In B16F10 melanoma cells, CAD significantly inhibited melanin production without cytotoxicity at concentrations lower than those required for CA. Cellular assays using DCF-DA staining demonstrated that CAD effectively reduced intracellular ROS levels. Mechanistic studies revealed that CAD inhibited tyrosinase activity and downregulated the expression of TYR, TRP-1, and TRP-2. Additionally, CAD suppressed MITF phosphorylation, along with reduced phosphorylation of ERK and JNK, elucidating its anti-melanogenic mechanism. Importantly, CAD showed dose-dependent skin-brightening effects in the 3D human skin model Melanoderm™, as evidenced by increased lightness and histological evaluation. In conclusion, CAD demonstrates strong potential as a safe and effective antioxidant and skin-brightening agent for cosmetic applications. Full article

(This article belongs to the Special Issue Methodologies for Improving Antioxidant Properties and Absorption)

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20 pages, 6973 KiB

Open AccessArticle

Bioactive Properties of Enzymatically Hydrolyzed Mulberry Leaf Proteins: Antioxidant and Anti-Inflammatory Effects

by Yichen Zhou, Tianxu Liu, Rijun Zhang, Junyong Wang, Jing Zhang, Yucui Tong, Haosen Zhang, Zhenzhen Li, Dayong Si and Xubiao Wei

Antioxidants 2025, 14(7), 805; https://doi.org/10.3390/antiox14070805 (registering DOI) - 28 Jun 2025

Abstract

Oxidative stress and inflammatory responses often occur concomitantly, and they are key causative factors in various human and animal diseases. Evidence suggests that mulberry leaf protein (MLP) may have potential antioxidant and anti-inflammatory properties, but there are significant challenges in enhancing their bioactivities. [...] Read more.

Oxidative stress and inflammatory responses often occur concomitantly, and they are key causative factors in various human and animal diseases. Evidence suggests that mulberry leaf protein (MLP) may have potential antioxidant and anti-inflammatory properties, but there are significant challenges in enhancing their bioactivities. In this study, MLP was enzymatically hydrolyzed using papain, protamex, alkaline protease, trypsin, and neutral protease, followed by comprehensive evaluation of the antioxidant capacity, anti-inflammatory properties, and cytotoxicity of the hydrolysates. Our findings revealed that some enzymes significantly enhanced the peptide production and antioxidant activity of MLP (p < 0.01), and its activity was positively correlated with the degree of hydrolysis. Among the five hydrolysates, neutral protease hydrolysate (NeuH) exhibited the best antioxidant properties, with free radical scavenging rates of 71.58 ± 0.42% (ABTS), 26.38 ± 0.15% (OH), and 73.91 ± 0.37% (DPPH) at a concentration of 0.1 mg/mL. In addition, NeuH significantly suppressed IL-6 secretion (p < 0.01) and downregulated mRNA expression of IL-6, iNOS, and COX-2 inflammatory markers. This study not only establishes a correlation between enzymatic parameters and MLP biological functions but also demonstrates the potential of optimized MLP hydrolysates, particularly NeuH, as valuable natural antioxidant and anti-inflammatory ingredients for functional foods or nutraceuticals aimed at mitigating oxidative stress and inflammation-related disorders. Full article

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

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25 pages, 7791 KiB

Open AccessArticle

Argan Callus Extract Restores Skin Cells via AMPK-Dependent Regulation of Energy Metabolism, Autophagy, and Inflammatory Pathways

by Ramona Hartinger, Felix Quirin Fenzl, Vanessa Martina Nalewaja and Karima Djabali

Antioxidants 2025, 14(7), 804; https://doi.org/10.3390/antiox14070804 (registering DOI) - 28 Jun 2025

Abstract

Skin aging is driven by cellular senescence, oxidative stress, and diminished regenerative capacity. In this study, we investigated the effects of PhytoCellTec™ Argan, an argan callus extract (PC), on primary human fibroblasts and adult stem cells. PC treatment (0.1% and 0.5%) significantly enhanced [...] Read more.

Skin aging is driven by cellular senescence, oxidative stress, and diminished regenerative capacity. In this study, we investigated the effects of PhytoCellTec™ Argan, an argan callus extract (PC), on primary human fibroblasts and adult stem cells. PC treatment (0.1% and 0.5%) significantly enhanced fibroblast proliferation, reduced senescence-associated β-galactosidase activity, and decreased the expression of p16, p21, and phosphorylated NFκB. PC treatment lowered intracellular ROS levels, increased ATP production, and promoted autophagy via LC3B-II accumulation and p62 reduction. In skin-derived precursor cells (SKPs), as well as mesenchymal stem cells (MSCs), PC treatment improved spheroid formation and growth while preserving the expression of key stemness markers, including Sox2, Oct4, and Nestin. Furthermore, PC exhibited antioxidant capacity (TEAC assay) and inhibited elastase, supporting its anti-aging potential. These findings suggest that PC is safe at concentrations below 1% and may serve as an effective natural compound to restore cellular homeostasis, reduce senescence and inflammation, and support stem cell health during aging. Full article

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17 pages, 2607 KiB

Open AccessArticle

Unveiling the Cardioprotective Potential of Hydroxytyrosol: Insights from an Acute Myocardial Infarction Model

by Alejandra Bermúdez-Oria, Eugenia Godoy, Virginia Pérez, Camila Musci Ferrari, Martin Donato, Juan Fernández-Bolaños, Tamara Zaobornyj and Verónica D’Annunzio

Antioxidants 2025, 14(7), 803; https://doi.org/10.3390/antiox14070803 (registering DOI) - 28 Jun 2025

Abstract

Cardiovascular diseases remain the leading cause of death worldwide, highlighting the urgent need for novel therapeutic strategies. The Mediterranean diet is renowned for its cardiovascular benefits, largely attributed to extra virgin olive oil (EVOO) and its phenolic compounds, particularly hydroxytyrosol (HT). HT, a [...] Read more.

Cardiovascular diseases remain the leading cause of death worldwide, highlighting the urgent need for novel therapeutic strategies. The Mediterranean diet is renowned for its cardiovascular benefits, largely attributed to extra virgin olive oil (EVOO) and its phenolic compounds, particularly hydroxytyrosol (HT). HT, a potent antioxidant and anti-inflammatory agent, has demonstrated significant therapeutic potential in mitigating myocardial damage following acute myocardial infarction (AMI). However, there is a notable lack of published evidence regarding the effects of HT administration in the context of acute ischemia/reperfusion (I/R) injury, making this study a novel contribution to the field. This study aimed to evaluate the cardioprotective effects of HT using the Langendorff technique in an isolated mouse heart ischemia/reperfusion (I/R) model. Mice were administered a single intraperitoneal dose of HT (10 mg/kg) 24 h prior to the I/R protocols, and parameters such as the infarct size, mitochondrial function, and redox balance were assessed. The results revealed a remarkable 57% reduction in infarct size in HT-treated mice compared to untreated controls. HT treatment also improved mitochondrial bioenergetics, as evidenced by the increased membrane potential (ΔΨm), enhanced oxygen consumption, and reduced hydrogen peroxide (H₂O₂) production. Furthermore, HT restored the activity of the mitochondrial respiratory complexes, notably Complex I, even under I/R conditions. These findings highlight the efficacy of HT in reducing oxidative stress and preserving mitochondrial function, critical factors in cardiac disease. In conclusion, HT emerges as a promising therapeutic agent for ischemic heart disease, demonstrating both preventive and restorative potential. Future research should explore its clinical applicability to advance cardiovascular disease management. Full article

(This article belongs to the Special Issue Antioxidant Activity of Olive Extracts and Their Applications)

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Graphical abstract

12 pages, 232 KiB

Open AccessArticle

Oxidative Stress and Semen Quality Among Night- and Day-Shift Workers: A Cross-Sectional Study

by Luca Boeri, Federica Passarelli, Ludovico Maria Basadonna, Edoardo Sorba, Giorgio Graps, Fabio Ciamarra, Damiano Dagnino, Valentina Parolin, Marco Nizzardo, Gianpaolo Lucignani and Emanuele Montanari

Antioxidants 2025, 14(7), 802; https://doi.org/10.3390/antiox14070802 (registering DOI) - 28 Jun 2025

Abstract

Introduction: Infertility affects 15% of couples, with oxidative stress recognized as a key contributor to male infertility. Night-shift work, through circadian disruption, may exacerbate oxidative imbalance and impair reproductive function. This study investigates the impact of night-shift work on oxidative stress and semen [...] Read more.

Introduction: Infertility affects 15% of couples, with oxidative stress recognized as a key contributor to male infertility. Night-shift work, through circadian disruption, may exacerbate oxidative imbalance and impair reproductive function. This study investigates the impact of night-shift work on oxidative stress and semen quality and evaluates the potential benefits of antioxidant supplementation in this context. Materials and Methods: We retrospectively analysed 96 white-European men aged 18–45, seeking fertility assessment at a single academic centre. Participants were classified as day or night workers based on their shift schedule, and all underwent standardised clinical, hormonal, and semen evaluations. Oxidative stress was assessed using the d-ROMs test. A subgroup of 40 patients (20 per group) treated for 3 months with antioxidant supplementation (Drolessano) to evaluate changes in oxidative stress and semen parameters was also considered. Statistical comparisons were performed using non-parametric tests and logistic regression analyses. Results: Night-shift workers exhibit significantly higher oxidative stress levels compared to day workers (median D-ROMs values of 340 vs. 280 U.CARR, p = 0.01), and a greater proportion of men exceeding the oxidative stress threshold (74.4% vs. 24.4%, p = 0.01). Logistic regression confirmed night-shift work as an independent predictor of elevated oxidative stress (OR 2.1, p = 0.001), even after adjusting for age and smoking. Following three months of antioxidant supplementation with Drolessano, both groups experienced significant reductions in oxidative stress (all p < 0.01), but night workers showed a substantially greater decrease (mean change −58.5 vs. −15.4 U.CARR, p = 0.001). Improvements in semen quality, including sperm concentration, motility, and morphology, were also more pronounced in the night group after treatment. Conclusions: At baseline, night-shift workers had significantly higher oxidative stress than day workers, likely due to circadian disruption. Both groups improved after antioxidant treatment, but night workers showed a greater reduction in D-ROMs. This pilot study might suggest a potential benefit of antioxidant therapy particularly in night workers. Full article

(This article belongs to the Special Issue Oxidative Stress and Male Reproductive Health)

35 pages, 5399 KiB

Open AccessReview

Non-Bovine Milk as Functional Foods with Focus on Their Antioxidant and Anti-Inflammatory Bioactivities

by Yan Li, Qingshan Ma, Mengmeng Li, Wenqiang Liu, Yihong Liu, Menghan Wang, Changfa Wang and Muhammad Zahoor Khan

Antioxidants 2025, 14(7), 801; https://doi.org/10.3390/antiox14070801 (registering DOI) - 27 Jun 2025

Abstract

The growing interest in functional foods has directed scientific attention toward alternative milk sources, particularly camel and donkey milk, which have been traditionally consumed for their purported health benefits across diverse cultures. These milk sources possess unique nutritional profiles and bioactive compositions that [...] Read more.

The growing interest in functional foods has directed scientific attention toward alternative milk sources, particularly camel and donkey milk, which have been traditionally consumed for their purported health benefits across diverse cultures. These milk sources possess unique nutritional profiles and bioactive compositions that differ substantially from conventional bovine milk. This review examines the current scientific understanding of the anti-inflammatory and antioxidant bioactivities of camel and donkey milk, exploring their bioactive constituents and therapeutic potential. Camel and donkey milk demonstrate notable antioxidant and anti-inflammatory properties that may exceed those of conventional milk sources. Key bioactive compounds include lactoferrin, lysozyme, immunoglobulins, bioactive peptides, vitamins C and E, and polyunsaturated fatty acids. Mechanistic studies reveal that milk from donkeys and camels suppresses inflammatory pathways through NF-κB inhibition, cytokine modulation (reducing IL-6, IL-1β, and TNF-α while enhancing IL-10), and antioxidant pathway activation via Nrf2-ARE signaling. Donkey milk exhibits particularly high lysozyme content and demonstrates significant immunomodulatory effects, while camel milk shows remarkable therapeutic potential in diabetes management, nephroprotection, and hepatoprotection. Preclinical studies demonstrate efficacy in treating oxidative stress-related disorders, inflammatory conditions, metabolic dysfunction, and tissue injury models. Altogether, the published data show that camel and donkey milk represent promising functional foods with significant antioxidant and anti-inflammatory bioactivities mediated through multiple molecular pathways. Their unique bioactive profiles offer therapeutic potential for various health conditions, warranting further clinical investigation and development as nutraceutical interventions. Full article

(This article belongs to the Special Issue Potential Health Benefits of Dietary Antioxidants)

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20 pages, 1617 KiB

Open AccessArticle

Evolution of COQ-Synthome Transcripts and CoQ Levels in Mice Tissues Along Aging: Effect of Resveratrol and Exercise

by Catherine Meza-Torres, Iván Reyes-Torres, Tung Bui Thanh, Carmen Campos-Silva, Elisabet Rodriguez-Bies, Plácido Navas and Guillermo López-Lluch

Antioxidants 2025, 14(7), 800; https://doi.org/10.3390/antiox14070800 (registering DOI) - 27 Jun 2025

Abstract

The balanced control of the synthesis of CoQ along the life of the organism is essential to maintain the respiratory capacity at the mitochondria and the antioxidant protection of cell membranes and plasma lipoproteins. For this reason, we determined the levels of the [...] Read more.

The balanced control of the synthesis of CoQ along the life of the organism is essential to maintain the respiratory capacity at the mitochondria and the antioxidant protection of cell membranes and plasma lipoproteins. For this reason, we determined the levels of the transcripts of the CoQ-synthome along the life of mice in comparison with the levels of antioxidant enzymes and the levels of CoQ in these animals. Surprisingly, we found that some organs such as liver, kidney and heart show great differences in mRNA levels of some COQ-genes along life whereas others such as the brain or gastrocnemius muscle do not show differences. Interestingly, these differences were not related to the total amount of CoQ in these tissues, indicating a discrepancy between the transcript activity of the CoQ-synthome and the level of the product, CoQ. This likely responds to different regulatory levels including mRNA lifespan and CoQ turnover. Further, resveratrol and physical activity in old animals can modulate some transcripts but many of them are in an organ-dependent effect, indicating a different response to the regulators. Full article

(This article belongs to the Special Issue CoQ10 and Aging and Age-Related Diseases—2nd Edition)

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28 pages, 1506 KiB

Open AccessArticle

Exploring the Functional Properties of Leaves of Moringa oleifera Lam. Cultivated in Sicily Using Precision Agriculture Technologies for Potential Use as a Food Ingredient

by Carlo Greco, Graziella Serio, Enrico Viola, Marcella Barbera, Michele Massimo Mammano, Santo Orlando, Elena Franciosi, Salvatore Ciulla, Antonio Alfonzo, Rosario Schicchi, Daniela Piazzese, Carla Gentile, Luca Settanni, Giuseppe Mannino and Raimondo Gaglio

Antioxidants 2025, 14(7), 799; https://doi.org/10.3390/antiox14070799 (registering DOI) - 27 Jun 2025

Abstract

This study aimed to evaluate the microbiological quality and functional properties of Moringa oleifera Lam. leaves from plants cultivated in Sicily, with the objective of exploring their potential use in functional food production. Precision agriculture techniques, including unmanned aerial vehicle-based multispectral remote sensing, [...] Read more.

This study aimed to evaluate the microbiological quality and functional properties of Moringa oleifera Lam. leaves from plants cultivated in Sicily, with the objective of exploring their potential use in functional food production. Precision agriculture techniques, including unmanned aerial vehicle-based multispectral remote sensing, were used to determine the optimal harvesting time for M. oleifera. After harvesting, leaves were dried using a smart solar dryer system based on a wireless sensor network and milled with a laboratory centrifugal mill to produce powdered M. oleifera leaves (PMOLs). Plate counts showed no colonies of undesired microorganisms in PMOLs. The MiSeq Illumina analysis revealed that the class Alphaproteobacteria was dominant (83.20% of Relative Abundance) among bacterial groups found in PMOLs. The hydroalcoholic extract from PMOLs exhibited strong redox-active properties in solution assays and provided antioxidant protection in a cell-based lipid peroxidation model (CAA₅₀: 5.42 μg/mL). Additionally, it showed antiproliferative activity against three human tumour epithelial cell lines (HepG2, Caco-2, and MCF-7), with GI₅₀ values ranging from 121.03 to 237.75 μg/mL. The aromatic profile of PMOLs includes seven phytochemical groups: alcohols, aldehydes, ketones, esters, acids, terpenes, and hydrocarbons. The most representative compounds were terpenes (27.5%), ketones (25.3%), and alcohols (14.5%). Results suggest that PMOLs can serve as a natural additive for functional foods. Full article

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

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24 pages, 1239 KiB

Open AccessArticle

Upcycling of By-Products from Autochthonous Red Grapes and Commercial Apples as Ingredients in Baked Goods: A Comprehensive Study from Processing to Consumer Consumption

by Gaetano Cardone, Martina Magni, Veronica Marin, Andrea Pichler, Daniele Zatelli, Peter Robatscher, Ombretta Polenghi, Virna Lucia Cerne, Michael Oberhuber and Silvano Ciani

Antioxidants 2025, 14(7), 798; https://doi.org/10.3390/antiox14070798 (registering DOI) - 27 Jun 2025

Abstract

Lagrein grape (Vitis vinifera L.) pomace and Scilate apple (Malus domestica Borkh.) skin are polyphenol- and antioxidant-rich by-products with promising applications in the food industry. This study investigated the impact of drying and grinding on their antioxidant properties for use in [...] Read more.

Lagrein grape (Vitis vinifera L.) pomace and Scilate apple (Malus domestica Borkh.) skin are polyphenol- and antioxidant-rich by-products with promising applications in the food industry. This study investigated the impact of drying and grinding on their antioxidant properties for use in gluten-free baked goods. Regardless of the by-product analysis, the results showed that processing conditions effectively preserved most of the polyphenols. Furthermore, the grape pomace and apple skin flours produced retained approximately 86% and 66% of anthocyanins, respectively. Incorporating these flours into breadsticks, focaccia, and cookies significantly enhanced their polyphenol content (300–727%), anthocyanin content (600–1718%), and antioxidant capacity (280–1200%). The addition of these by-products to baked goods led to a slight decrease in texture and sensory properties. However, adding both grape pomace and apple skin flours significantly improved consumer acceptance compared to products containing only grape pomace flour. This study highlights the potential of upcycling by-products from grapes and apples to enhance the nutritional profile of gluten-free products while supporting a circular economy approach. Full article

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39 pages, 1558 KiB

Open AccessReview

Antioxidant Intervention Against Microplastic Hazards

by Zhihua Wang, Yunting Wang, Jian Zhang, Guoquan Feng, Shuhan Miao, Rongzhu Lu, Xinyu Tian and Yang Ye

Antioxidants 2025, 14(7), 797; https://doi.org/10.3390/antiox14070797 (registering DOI) - 27 Jun 2025

Abstract

Microplastic pollution (<5 mm) poses a serious threat to the environment and human health, inducing cellular stress damage in organisms (especially through oxidative stress). The damage results from excessive reactive oxygen species and impaired defense mechanisms, affecting energy production, organelles, and triggering inflammation. [...] Read more.

Microplastic pollution (<5 mm) poses a serious threat to the environment and human health, inducing cellular stress damage in organisms (especially through oxidative stress). The damage results from excessive reactive oxygen species and impaired defense mechanisms, affecting energy production, organelles, and triggering inflammation. Antioxidants (such as vitamin C, curcumin, and quercetin) reduce stress markers and inflammation by neutralizing harmful molecules, activating protective pathways, and regulating autophagy, providing potential protection. However, practical applications face challenges such as low absorption rates, large individual variations, and unclear long-term safety. Research needs to delve into the molecular interaction mechanisms, develop effective delivery systems for antioxidant combinations, and formulate evidence-based strategies. Addressing the complexity of microplastics (size, shape, additives) and their cross-ecosystem impacts requires multidisciplinary collaboration. This review explores the oxidative stress mechanisms induced by microplastics, assesses the potential and limitations of antioxidant interventions, and provides a basis for environmental health risk management. Full article

(This article belongs to the Special Issue Oxidative Stress Induced by Micro(Nano)plastics)

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28 pages, 4695 KiB

Open AccessArticle

From Chemistry to Pharmacology: Exploring the Anti-Inflammatory and Antioxidant Potential of Novel Dexketoprofen Amide Derivatives

by Marko Karović, Miloš Nikolić, Nikola Nedeljković, Marina Vesović, Marina Nikolić, Marijana Anđić, Nevena Lazarević, Vladimir Jakovljević, Jelena Nedeljković, Sanja Đaković, Jelena Bošković and Vladimir Dobričić

Antioxidants 2025, 14(7), 796; https://doi.org/10.3390/antiox14070796 - 27 Jun 2025

Abstract

In the present study, five novel dexketoprofen amide derivatives with a free carboxyl group in their side chains were synthesized. The in vivo anti-inflammatory potential of dexketoprofen derivatives was evaluated using a carrageenan-induced paw edema model of acute inflammation. Additionally, the local and [...] Read more.

In the present study, five novel dexketoprofen amide derivatives with a free carboxyl group in their side chains were synthesized. The in vivo anti-inflammatory potential of dexketoprofen derivatives was evaluated using a carrageenan-induced paw edema model of acute inflammation. Additionally, the local and systemic redox status in rats following acute administration of the compounds was assessed by measuring levels of pro-oxidative markers and the activity of antioxidant enzymes. Among the analyzed molecules, derivatives 2 and 4 exhibited the most potent in vivo anti-inflammatory activity, showing effects comparable to those of the parent compound dexketoprofen. In vitro results revealed that all newly synthesized compounds exhibited low inhibitory activity toward COX-1, whereas only compound 4 showed significant COX-2 inhibition. The stronger binding affinity of derivative 4 for COX-2 in comparison to other tested compounds is likely attributed to its ability to form multiple electrostatic interactions within the enzyme’s active site. Furthermore, compounds 2 and 5 demonstrated efficacy comparable to the parent drug in restoring redox balance, indicating their potential antioxidant properties under acute inflammatory conditions. The findings of this study underscore the therapeutic potential of the novel dexketoprofen amide derivatives as dual-function agents with the capacity to modulate both inflammatory responses and oxidative stress. Full article

(This article belongs to the Special Issue Synthetic Compounds: Antioxidant and Anti-Inflammatory Activities, Biomedical Properties and Formulations)

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21 pages, 5821 KiB

Open AccessArticle

Integration of Transcriptomic Analysis, Network Pharmacology, and Experimental Validation Demonstrates Enhanced Muscle-Protective Effects of Ethanol Extract of Jakyak-Gamcho-Tang

by Aeyung Kim, Minh Nhat Tran, A Yeong Lee, Heerim Yeo, Su-Jin Baek, No Soo Kim, Seongwon Cha and Sang-Min Park

Antioxidants 2025, 14(7), 795; https://doi.org/10.3390/antiox14070795 - 27 Jun 2025

Abstract

Muscle atrophy, characterized by progressive loss of skeletal muscle mass and strength, remains a significant therapeutic challenge. Jakyak-gamcho-tang (JGT) is a traditional herbal formulation that has demonstrated promising muscle-protective effects; however, the key bioactive constituents and the influence of different extraction methods have [...] Read more.

Muscle atrophy, characterized by progressive loss of skeletal muscle mass and strength, remains a significant therapeutic challenge. Jakyak-gamcho-tang (JGT) is a traditional herbal formulation that has demonstrated promising muscle-protective effects; however, the key bioactive constituents and the influence of different extraction methods have not yet been fully elucidated. This study compared the muscle-protective effects of the ethanol and water extracts of JGT (JGT-E and JGT-W, respectively), while also identifying the principal bioactive compounds that contribute to the enhanced efficacy of JGT-E. An integrative methodological approach was adopted, incorporating transcriptomic profiling, network pharmacology analysis, antioxidant activity assays, and in vitro validation using C2C12 myoblasts and myotubes. This comprehensive investigation enabled a detailed assessment of the biological activities of both JGT-E and JGT-W. Transcriptomic analysis revealed that JGT-E significantly modulates key pathways involved in oxidative phosphorylation, mitochondrial biogenesis, and signaling cascades related to PGC-1α, mTORC1, and ERRα, while simultaneously inhibiting TGF-β-mediated muscle atrophic signaling. Functional assays demonstrated that under oxidative stress conditions, JGT-E preserved mitochondrial content more effectively, reduced reactive oxygen species levels, and enhanced both myoblast viability and myotube integrity. Network pharmacology analysis identified isoliquiritigenin, catechin, and glabridin as major bioactive compounds enriched in JGT-E, all of which play critical roles in mitigating oxidative stress and supporting mitochondrial function. These findings were further substantiated by antioxidant assays that confirmed the contribution of these compounds to the observed muscle-protective effects of JGT-E. Overall, JGT-E exhibited superior efficacy in preventing muscle atrophy compared to JGT-W, likely due to its enriched profile of potent bioactive constituents. These results highlight the critical role of extraction methods in herbal medicine research and support the potential of JGT-E as a promising candidate for the treatment of muscle atrophy. Full article

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

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