Antioxidants

17 pages, 1404 KiB

Open AccessArticle

The Mechanism of Protective Action of Plant-Derived Squalane (2,6,10,15,19,23-Hexamethyltetracosane) Against UVA Radiation-Induced Apoptosis in Human Dermal Fibroblasts

by Katarzyna Wolosik, Magda Chalecka, Gabriela Gasiewska, Jerzy Palka and Arkadiusz Surazynski

Antioxidants 2025, 14(7), 853; https://doi.org/10.3390/antiox14070853 - 11 Jul 2025

Abstract

Ultraviolet A (UVA) radiation has been identified as a significant factor contributing to skin photoaging and skin diseases, operating through the excessive generation of reactive oxygen species (ROS) and the subsequent induction of DNA damage. Plant-derived antioxidants have demonstrated efficacy in mitigating UVA-induced [...] Read more.

Ultraviolet A (UVA) radiation has been identified as a significant factor contributing to skin photoaging and skin diseases, operating through the excessive generation of reactive oxygen species (ROS) and the subsequent induction of DNA damage. Plant-derived antioxidants have demonstrated efficacy in mitigating UVA-induced damage; nevertheless, their instability limits their therapeutic potential. This study investigates the mechanisms of antioxidant and cytoprotective effects of squalane (Sq), a stable, plant-derived triterpene, in human dermal fibroblasts (HDFs) exposed to UVA radiation. Sq was administered at concentrations ranging from 0.005% to 0.015% prior to UVA exposure (10 J/cm²). It has been found that Sq counteracted UVA-induced ROS formation, decreased the level of reduced thiol groups, activated apoptosis, and inhibited DNA biosynthesis. Immunofluorescence analysis revealed that Sq suppressed the UVA-induced expression of p53, caspase-3, caspase-9, and PARP, while restoring the activity of the pro-survival p-Akt/mTOR pathway. The findings indicate that Sq exerts protective effects on UVA-induced fibroblast damage through a combination of antioxidant and anti-apoptotic mechanisms. Full article

(This article belongs to the Special Issue Antioxidant Phytochemicals for Promoting Human Health and Well-Being)

22 pages, 2242 KiB

Open AccessArticle

Quercetin Can Alleviate ETECK88-Induced Oxidative Stress in Weaned Piglets by Inhibiting Quorum-Sensing Signal Molecule Autoinducer-2 Production in the Cecum

by Hailiang Wang, Min Yao, Dan Wang, Mingyang Geng, Shanshan Nan, Xiangjian Peng, Yuyang Xue, Wenju Zhang and Cunxi Nie

Antioxidants 2025, 14(7), 852; https://doi.org/10.3390/antiox14070852 - 11 Jul 2025

Abstract

This study evaluated the inhibitory activity of quercetin at sub-inhibitory concentrations on quorum-sensing (QS) molecules in vitro and the effects of dietary supplementation with quercetin (for 24 consecutive days) on enterotoxigenic Escherichia coli (ETEC)-induced inflammatory and oxidative stress responses in weaned piglets. The [...] Read more.

This study evaluated the inhibitory activity of quercetin at sub-inhibitory concentrations on quorum-sensing (QS) molecules in vitro and the effects of dietary supplementation with quercetin (for 24 consecutive days) on enterotoxigenic Escherichia coli (ETEC)-induced inflammatory and oxidative stress responses in weaned piglets. The piglets were fed one of three diets: the basal diet (Con), ETEC challenge (K88) after the basal diet, or ETEC challenge (quercetin + K88) after the basal diet supplemented with 0.2% quercetin. In vitro experiments revealed that 5 mg/mL quercetin exhibited the strongest QS inhibitory activity and reduced pigment production by Chromobacterium violaceum ATCC12472 by 67.70%. In vivo experiments revealed that quercetin + K88 significantly increased immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) levels in the serum, ileum mucosa, and colon mucosa; increased glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) levels in the serum, liver, and colon mucosa; and decreased cluster of differentiation 3 (CD3) and cluster of differentiation 8 (CD8)activity in the serum compared with K88 alone. Quercetin + K88 significantly alleviated pathological damage to the liver and spleen and upregulated antioxidant genes (nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1(HO-1), CAT, SOD, and glutathione s-transferase (GST)). Inducible nitric oxide synthase (iNOS) and kelch-like ech-associated protein 1 (Keap1), which cause oxidative damage to the liver and spleen, were significantly downregulated. The acetic acid content in the cecum was significantly increased, and the E. coli count and QS signal molecule autoinducer-2 (AI-2) yield were significantly reduced. In conclusion, 0.2% dietary quercetin can alleviate ETEC-induced inflammation and oxidative stress in weaned piglets. Full article

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22 pages, 937 KiB

Open AccessReview

Early-Life Prevention of Cardiovascular–Kidney–Metabolic Syndrome: The DOHaD Perspective on Resveratrol and Short-Chain Fatty Acids

by Chien-Ning Hsu, Ying-Jui Lin, Chih-Yao Hou, Yu-Wei Chen and You-Lin Tain

Antioxidants 2025, 14(7), 851; https://doi.org/10.3390/antiox14070851 - 10 Jul 2025

Abstract

Cardiovascular–kidney–metabolic (CKM) syndrome underscores the interconnected biology of cardiovascular disease, kidney disease, and metabolic disorders such as obesity and type 2 diabetes. Although now recognized as a growing global health burden, accumulating preclinical evidence suggests that CKM syndrome may originate in early life—a [...] Read more.

Cardiovascular–kidney–metabolic (CKM) syndrome underscores the interconnected biology of cardiovascular disease, kidney disease, and metabolic disorders such as obesity and type 2 diabetes. Although now recognized as a growing global health burden, accumulating preclinical evidence suggests that CKM syndrome may originate in early life—a concept rooted in the developmental origins of health and disease (DOHaD) framework. Animal studies have greatly enhanced our comprehension of these mechanisms, emphasizing the promise of early interventions that focus on antioxidants and gut microbiota modulation to mitigate the development of CKM conditions. Resveratrol, a natural antioxidant and prebiotic, alongside short-chain fatty acids (SCFAs), a postbiotic, have demonstrated the ability to modulate gut microbiota and oxidative stress in experimental models. Various resveratrol derivatives have also been engineered to improve bioavailability, though their effects remain largely confined to animal studies. This review synthesizes preclinical findings on the impact of perinatal oxidative stress and gut dysbiosis on CKM outcomes, critically examining the roles of resveratrol, SCFAs, and their derivatives in animal models. Finally, we highlight the significant translational gap between experimental research and clinical application, underscoring the need for human studies to validate these early-life intervention strategies. Full article

(This article belongs to the Special Issue Modulation of Gut Microbiota and Oxidative Stress to Counteract or Prevent Human Disease)

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20 pages, 2742 KiB

Open AccessReview

Therapeutic Potential of Proanthocyanidins in Dentistry: A Focus on Periodontal Disease and on Dental Implants in Osteoporotic Patients

by Yoshimi Niwano, Shunichi Shishido, Midori Shirato, Hidetsugu Kohzaki and Keisuke Nakamura

Antioxidants 2025, 14(7), 850; https://doi.org/10.3390/antiox14070850 - 10 Jul 2025

Abstract

Proanthocyanidins (PACs), also called condensed tannins, are oligomers or polymers composed of flavan-3-ols. This review aimed to explore the potential role of PACs in ameliorating oral health problems, with a particular focus on their effects within the intestine—especially the colon, where most orally [...] Read more.

Proanthocyanidins (PACs), also called condensed tannins, are oligomers or polymers composed of flavan-3-ols. This review aimed to explore the potential role of PACs in ameliorating oral health problems, with a particular focus on their effects within the intestine—especially the colon, where most orally ingested PACs are believed to accumulate. Previous studies suggest that PACs can be beneficial in periodontal disease as well as in the osseointegration of dental implants in patients with osteoporosis. Periodontal disease is worsened by lipopolysaccharides (LPS) that enter the bloodstream due to disrupted tight junctions of intestinal epithelial cells, along with inflammatory cytokines released by activated macrophages. A similar mechanism is thought to affect osseointegration: LPS-induced inflammatory cytokines originating in the intestine can enter the bloodstream, contributing to bone loss and impaired integration of dental implants. PACs absorbed by intestinal epithelial cells can function as prooxidants, triggering the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which strengthens the gut barrier. This enhanced barrier reduces the levels of LPS and inflammatory cytokines in the blood, leading to the alleviation of periodontal inflammation and increased alveolar bone density, thereby promoting better osseointegration of dental implants. Full article

(This article belongs to the Special Issue Antioxidant Capacity of Anthocyanins and Other Vegetal Pigments: Properties, Intake and Health Benefits)

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15 pages, 882 KiB

Open AccessArticle

Propolis Extract with Activity Against Cutibacterium acnes Biofilm Targeting the Expression of Virulence Genes

by Sophia Athanasopoulou, Eleni Panagiotidou, Eleni Spanidi, Maria Gkika, Danai Georgiou, Athanasios K. Anagnostopoulos, Christos Ganos, Ioanna Chinou, Evangelos Beletsiotis and Konstantinos Gardikis

Antioxidants 2025, 14(7), 849; https://doi.org/10.3390/antiox14070849 - 10 Jul 2025

Abstract

Acne is a highly prevalent skin condition with multifactorial pathophysiology, where Cutibacterium acnes (C. acnes) overgrowths generate inflammation. C. acnes can grow and adhere, through the formation of biofilms, to almost any surface, which enables chronic infections. Acne treatment with antibiotics [...] Read more.

Acne is a highly prevalent skin condition with multifactorial pathophysiology, where Cutibacterium acnes (C. acnes) overgrowths generate inflammation. C. acnes can grow and adhere, through the formation of biofilms, to almost any surface, which enables chronic infections. Acne treatment with antibiotics can induce topical antimicrobial resistance, impair microbiome biodiversity and cause cutaneous dysbiosis. In this study, we assess the effect of a standardized propolis extract (PE) from Greece against C. acnes, whilst maintaining skin’s microbiome biodiversity, and we investigate its effect against genes related to the attachment and colonization of C. acnes, as well as against biofilm formation. The extract has been chemically characterized by GC-MS and was additionally tested for its antioxidant properties by the Folin–Ciocalteu method and the 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) assay and its regulatory activity on the expression of antimicrobial and anti-inflammatory genes in normal human epidermal keratinocytes (NHEKs). The suggested efficacy of PE in targeting pathogenic C. acnes biofilm, via downregulation of virulence genes, represents an alternative strategy to modulate the behavior of skin microbiota in acne, paving the way for next-generation acne-targeting products. Full article

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

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27 pages, 1565 KiB

Open AccessReview

Manganese Superoxide Dismutase: Structure, Function, and Implications in Human Disease

by Jovan Grujicic and Antiño R. Allen

Antioxidants 2025, 14(7), 848; https://doi.org/10.3390/antiox14070848 - 10 Jul 2025

Abstract

Manganese superoxide dismutase (MnSOD) is a vital mitochondrial antioxidant enzyme that preserves cellular integrity by catalyzing the dismutation of superoxide radicals into hydrogen peroxide. Its central role in maintaining redox homeostasis has positioned it as a key target in biomedical research. This review [...] Read more.

Manganese superoxide dismutase (MnSOD) is a vital mitochondrial antioxidant enzyme that preserves cellular integrity by catalyzing the dismutation of superoxide radicals into hydrogen peroxide. Its central role in maintaining redox homeostasis has positioned it as a key target in biomedical research. This review provides an in-depth examination of MnSOD’s structural and functional properties, regulatory mechanisms, and its involvement in the pathogenesis of various human diseases. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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25 pages, 4666 KiB

Open AccessArticle

Taurine Attenuates Disuse Muscle Atrophy Through Modulation of the xCT-GSH-GPX4 and AMPK-ACC-ACSL4 Pathways

by Xi Liu, Yifen Chen, Linglin Zhang, Zhen Qi, Longhe Yang, Caihua Huang, Li Wang and Donghai Lin

Antioxidants 2025, 14(7), 847; https://doi.org/10.3390/antiox14070847 - 10 Jul 2025

Abstract

Disused muscle atrophy (DMA) is characterized by skeletal muscle loss and functional decline due to prolonged inactivity. Though evidence remains limited, recent studies suggest that ferroptosis, an iron-dependent, lipid peroxidation-driven form of cell death, may contribute to DMA. Taurine, a natural amino acid [...] Read more.

Disused muscle atrophy (DMA) is characterized by skeletal muscle loss and functional decline due to prolonged inactivity. Though evidence remains limited, recent studies suggest that ferroptosis, an iron-dependent, lipid peroxidation-driven form of cell death, may contribute to DMA. Taurine, a natural amino acid enriched in energy drinks, can improve the proliferation and myogenic differentiation potential of myoblasts. This study aimed to investigate whether taurine supplementation could protect against DMA and explore its potential role in modulating ferroptosis. Using a hindlimb suspension-induced DMA model in male C57BL/6J mice (6–8 weeks old), we assessed muscle mass, function, ferroptosis-related markers, histopathological changes, and metabolic alterations. The results showed that taurine supplementation improved muscle strength and morphology while attenuating markers of ferroptosis, including iron accumulation, lipid peroxidation, and glutathione and related protein (NRF2, GPX4, and xCT) depletion. Metabolomic analysis suggested that taurine modulates disorders in glutathione and lipid metabolism, potentially associated with the regulation of the xCT-GSH-GPX4 and AMPK-ACC-ACSL4 pathways. While these findings support a protective role for taurine and a possible link between ferroptosis and DMA, further functional studies are needed to confirm causality and assess the compound’s translational potential. This study provides initial in vivo evidence implicating ferroptosis in DMA and highlights taurine as a promising candidate for future therapeutic exploration. Full article

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16 pages, 2268 KiB

Open AccessArticle

Hydnocarpin, a Natural Flavonolignan, Induces the ROS-Mediated Apoptosis of Ovarian Cancer Cells and Reprograms Tumor-Associated Immune Cells

by Jae-Yoon Kim, Yejin Kim, Soo-Yeon Woo, Jin-Ok Kim, Hyunsoo Kim, So-Ri Son, Dae Sik Jang and Jung-Hye Choi

Antioxidants 2025, 14(7), 846; https://doi.org/10.3390/antiox14070846 - 10 Jul 2025

Abstract

Ovarian cancer, the most lethal form of gynecological cancer worldwide with a poor prognosis, is largely driven by an immunosuppressive tumor microenvironment. In this study, we investigated the anticancer effects of hydnocarpin, a natural flavonolignan derived from the flowers of Pueraria lobata, [...] Read more.

Ovarian cancer, the most lethal form of gynecological cancer worldwide with a poor prognosis, is largely driven by an immunosuppressive tumor microenvironment. In this study, we investigated the anticancer effects of hydnocarpin, a natural flavonolignan derived from the flowers of Pueraria lobata, focusing on its effects on ovarian cancer and tumor-associated immune cells, including ovarian cancer-stimulated macrophages (MQs) and T cells. Hydnocarpin exhibited potent cytotoxicity against multiple ovarian cancer cell lines but only minimal toxicity against normal ovarian surface epithelial cells. Mechanistically, hydnocarpin triggered caspase-dependent apoptosis, as evidenced by the activation of caspase-9 and -3, with limited involvement of caspase-8, indicating the activation of the intrinsic apoptotic pathway. Experimental data implicated reactive oxygen species generation as a key mediator of hydnocarpin cytotoxicity, and reactive oxygen species inhibition significantly inhibited this cytotoxicity. In addition to its direct tumoricidal effects, hydnocarpin reprogrammed the tumor-associated immune cells, ovarian cancer-stimulated macrophages and T cells, by downregulating the levels of M2 MQ markers and pro-tumoral factors (matrix metalloproteinase-2/9, C–C motif chemokine ligand 5, transforming growth factor-β, and vascular endothelial growth factor) and enhancing MQ phagocytosis. Additionally, hydnocarpin promoted T-cell activation (interferon-γ and interleukin-2) and reduced the expression levels of immune evasion markers (CD80, CD86, and VISTA). Overall, this study demonstrated the dual anti-tumor effects of hydnocarpin on both ovarian cancer cells and immunosuppressive immune components in the tumor microenvironment, highlighting its potential as a novel therapeutic candidate for ovarian cancer. Full article

(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Potential of Plants in Cancer Treatment)

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25 pages, 9865 KiB

Open AccessArticle

Microencapsulation of Propolis by Complex Coacervation with Chia Mucilage and Gelatin: Antioxidant Stability and Functional Potential

by Carlos A. Ligarda-Samanez, David Choque-Quispe, Henry Palomino-Rincón, Elibet Moscoso-Moscoso, Rodrigo J. Guzmán Gutiérrez and Ismael Banda Mozo

Antioxidants 2025, 14(7), 845; https://doi.org/10.3390/antiox14070845 - 10 Jul 2025

Abstract

Propolis is a bee-derived resin rich in phenolic compounds known for their antioxidant, anti-inflammatory, and antimicrobial properties; however, its limited solubility and stability hinder its incorporation into food matrices. This study aimed to optimize the microencapsulation of ethanolic propolis extract through complex coacervation [...] Read more.

Propolis is a bee-derived resin rich in phenolic compounds known for their antioxidant, anti-inflammatory, and antimicrobial properties; however, its limited solubility and stability hinder its incorporation into food matrices. This study aimed to optimize the microencapsulation of ethanolic propolis extract through complex coacervation using chia mucilage and gelatin as wall materials, followed by spray drying. A 3² factorial design was applied to evaluate the effects of coacervate concentration and inlet temperature on various microcapsule properties. The optimal formulation (3.13% coacervate and 120 °C) exhibited high phenolic retention (15.36 mg GAE/g), notable antioxidant capacity (60.10 µmol TE/g), good solubility, thermal stability, and sustained in vitro release. Phenolic compounds were identified and quantified by UPLC-PDA-QDa, including gallic acid, catechin, epicatechin, epigallocatechin gallate, rutin, myricetin, resveratrol, quercetin, and kaempferol. Incorporating the microcapsules into functional gummy candies significantly enhanced their antioxidant activity without compromising sensory attributes. These findings support the use of complex coacervation as an effective strategy for stabilizing propolis bioactives, with promising applications in the development of functional foods that offer potential health benefits. Full article

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

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26 pages, 1980 KiB

Open AccessReview

The Destructive Cycle in Bronchopulmonary Dysplasia: The Rationale for Systems Pharmacology Therapeutics

by Mia Teng, Tzong-Jin Wu, Kirkwood A. Pritchard, Jr., Billy W. Day, Stephen Naylor and Ru-Jeng Teng

Antioxidants 2025, 14(7), 844; https://doi.org/10.3390/antiox14070844 - 10 Jul 2025

Abstract

Bronchopulmonary dysplasia (BPD) remains a significant complication of premature birth and neonatal intensive care. While much is known about the drivers of lung injury, few studies have addressed the interrelationships between oxidative stress, inflammation, and downstream events, such as endoplasmic reticulum (ER) stress. [...] Read more.

Bronchopulmonary dysplasia (BPD) remains a significant complication of premature birth and neonatal intensive care. While much is known about the drivers of lung injury, few studies have addressed the interrelationships between oxidative stress, inflammation, and downstream events, such as endoplasmic reticulum (ER) stress. In this review, we explore the concept of a “destructive cycle” in which these drivers self-amplify to push the lung into a state of maladaptive repair. Animal models, primarily the hyperoxic rat pup model, support a sequential progression from the generation of reactive oxygen species (ROS) and inflammation to endoplasmic reticulum (ER) stress and mitochondrial injury. We highlight how these intersecting pathways offer not just therapeutic targets but also opportunities for interventions that reprogram system-wide responses. Accordingly, we explore the potential of systems pharmacology therapeutics (SPTs) to address the multifactorial nature of BPD. As a prototype SPT, we describe the development of N-acetyl-L-lysyl-L-tyrosyl-L-cysteine amide (KYC), a systems chemico-pharmacology drug (SCPD), which is selectively activated in inflamed tissues and modulates key nodal targets such as high-mobility group box-1 (HMGB1) and Kelch-like ECH-associated protein-1 (Keap1). Collectively, the data suggest that future therapies may require a coordinated, network-level approach to break the destructive cycle and enable proper regeneration rather than partial repair. Full article

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

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28 pages, 5899 KiB

Open AccessArticle

Sex-Specific Cardiovascular Protection in Developing Metabolic Syndrome: The Role of AMPK

by Miroslava Kvandova, Anna Zemancikova, Andrea Berenyiova, Iveta Waczulikova, Silvia Magyarova, Andrea Micurova, Jozef Torok, Marian Grman, Lenka Tomasova, Anton Misak, Zuzana Vysoka, Martina Manikova, Milan Zvarik, Patrick Mydla, Jana Vlkovicova, Peter Balis and Angelika Puzserova

Antioxidants 2025, 14(7), 843; https://doi.org/10.3390/antiox14070843 - 9 Jul 2025

Abstract

Metabolic syndrome (MetS) increases the risk of cardiovascular disease development, with sex differences playing a significant role. AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, becomes dysregulated in MetS, making it a potential therapeutic target. Therefore, we aimed to investigate [...] Read more.

Metabolic syndrome (MetS) increases the risk of cardiovascular disease development, with sex differences playing a significant role. AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, becomes dysregulated in MetS, making it a potential therapeutic target. Therefore, we aimed to investigate the role of AMPK in the development of cardiovascular comorbidities in male and female rats with MetS. MetS was induced in young Wistar–Kyoto (WKY) rats through a high-fat diet (HFD; 10 weeks), and the function of AMPK was studied using Compound C (Cmpd C; 1.5 mg/kg, twice per week, during the last 4 weeks). An HFD induced MetS in males, but, in females, it did not affect body weight, blood pressure, or glycemia until AMPK inhibition occurred. Endothelial dysfunction, oxidative stress, and inflammation developed in both HFD male groups, while, in females, these arose only with AMPK inhibition. In both sexes, α1-AMPK activation decreased with eNOS and Nrf2 protein levels after HFD + Cmpd C treatment. Estradiol levels significantly dropped in HFD and Cmpd C females, whereas testosterone levels remained unchanged. Our results suggest that MetS and related cardiovascular comorbidities in males are driven by oxidative stress, inflammation, and endothelial dysfunction, with minimal additive effect of AMPK. In females, MetS arose only when inhibition of AMPK impaired estrogen signalling, emphasising their protective roles. Targeting AMPK-estrogen pathways may provide a therapeutic strategy, particularly for high-risk cardiovascular females and menopausal women. Full article

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

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21 pages, 2551 KiB

Open AccessArticle

SOD1 Deficiency Reveals Indirect Redox Stress Mechanisms Underlying Vanillin Toxicity in Saccharomyces cerevisiae Yeast

by Sabina Bednarska, Magdalena Kwolek-Mirek, Roman Maslanka, Dominika Graboś, Gabriela Świniuch and Renata Zadrag-Tecza

Antioxidants 2025, 14(7), 842; https://doi.org/10.3390/antiox14070842 - 9 Jul 2025

Abstract

Vanillin is a compound of great utility, and its production is, among others, based on using microorganisms such as Saccharomyces cerevisiae yeast. The effect of vanillin on cells is not fully understood. It has been demonstrated that vanillin induces oxidative stress; however, evidence [...] Read more.

Vanillin is a compound of great utility, and its production is, among others, based on using microorganisms such as Saccharomyces cerevisiae yeast. The effect of vanillin on cells is not fully understood. It has been demonstrated that vanillin induces oxidative stress; however, evidence also suggests its beneficial effects, including antioxidant and anti-inflammatory properties. For this reason, the present study was designed to elucidate the mechanism of vanillin’s action and to ascertain the extent to which its toxic effect is attributable to oxidative stress. The studies were conducted using wild-type and Δsod1 mutant strains. SOD1 deficiency results in cell hypersensitivity to oxidative factors, thus making the mutant strain a valuable model for investigating various aspects of oxidative stress. Based on an evaluation of cell vitality, Yap1p activation, ROS content, and glutathione and NADP(H) content, it can be concluded that oxidative stress is a secondary effect of metabolic and redox perturbations in cells rather than a direct consequence of vanillin reactivity. Furthermore, alterations observed in the redox couples GSH/GSSG and NADPH/NADP⁺ are one of the reasons for oxidative stress and suggest that vanillin may induce the utilization of NADPH for cellular needs other than antioxidant effects. Full article

(This article belongs to the Special Issue Super Oxide Dismutase (SOD) Isoenzymes and Reactive Oxygen Species (ROS) in Immuno-Pathophysiology)

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15 pages, 4245 KiB

Open AccessArticle

Oxidative Stress and Complement Activation in Aqueous Cells and Vitreous from Patient with Vitreoretinal Diseases: Comparison Between Diabetic ERM and PDR

by Lucia Dinice, Pamela Cosimi, Graziana Esposito, Fabio Scarinci, Andrea Cacciamani, Concetta Cafiero, Luca Placentino, Guido Ripandelli and Alessandra Micera

Antioxidants 2025, 14(7), 841; https://doi.org/10.3390/antiox14070841 - 8 Jul 2025

Abstract

Background: Epiretinal membrane (ERM) and proliferative diabetic retinopathy (PDR) belong to the group of vitreoretinal diseases, characterized by impairments at both the retina and the vitreous. The non-diabetic and diabetic forms of ERM (no-dERM and dERM) as well as the PDR are caused [...] Read more.

Background: Epiretinal membrane (ERM) and proliferative diabetic retinopathy (PDR) belong to the group of vitreoretinal diseases, characterized by impairments at both the retina and the vitreous. The non-diabetic and diabetic forms of ERM (no-dERM and dERM) as well as the PDR are caused by microvascular disorder, which frequently occurs in association with inflammation and oxidative stress. To better characterize no-dERM, dERM, and PDR at the biomolecular level, we compared the expression of inflammatory, oxidative, lipidic peroxidation products, and complement receptors. Methods: Twenty-seven ocular fluids from patients who underwent phaco-vitrectomy were categorized as no-dERM (9, 4M/5F; 70.4 ± 6.4), dERM (6, 3M/3F; 73.2 ± 4.9), and PDR (6, 5M/1F; 63.7 ± 7.4). Six cataracts (CTR; 3M/3F; 77.7 ± 9.0) were collected for internal control of aqueous cells. Results: In aqueous cells, p65NFkB, iNOS, Nox1/Nox4, and Nrf2 were significantly upregulated, and Keap1 was downregulated in dERM compared with PDR and no-dERM. In aqueous cells, a significant upregulation for C3aR1mRNA, C5aR1mRNA, and CFHmRNA were observed in dERM. In vitreous, C3a, C5b9, and MDA levels were significantly increased in dERM compared with PDR and no-dERM. Conclusions: Inflammatory and ROS products, as well as C3aR1/C5aR1 and soluble MDA, appear of great interest, as their expression in aqueous and vitreous might have potential prognostic and therapeutic values. Full article

(This article belongs to the Special Issue Diabetic Retinopathy and Oxidative Stress: Molecular Mechanisms, Diagnostic Strategies, and Advances in Antioxidant Therapies)

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25 pages, 330 KiB

Open AccessReview

Post-COVID Condition and Neuroinflammation: Possible Management with Antioxidants

by Noemí Cárdenas-Rodríguez, Iván Ignacio-Mejía, César Miguel Mejía-Barradas, Daniel Ortega-Cuellar, Felipe Muñoz-González, Marco Antonio Vargas-Hernández, Exsal Manuel Albores-Méndez, Gabriela Ibáñez-Cervantes, Roberto Medina-Santillán, Aarón Hernández-Ortiz, Elizabeth Herrera-López and Cindy Bandala

Antioxidants 2025, 14(7), 840; https://doi.org/10.3390/antiox14070840 - 8 Jul 2025

Abstract

Post-COVID condition (PCC) is a complex syndrome characterized by the persistence of diverse symptoms—including respiratory, neurological, and psychiatric manifestations—that last for weeks or months after acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Epidemiological data indicate a higher prevalence among women and [...] Read more.

Post-COVID condition (PCC) is a complex syndrome characterized by the persistence of diverse symptoms—including respiratory, neurological, and psychiatric manifestations—that last for weeks or months after acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Epidemiological data indicate a higher prevalence among women and older adults, with significant impacts on daily functioning. The pathophysiology of PCC is multifactorial, involving immune dysregulation, viral persistence, mitochondrial dysfunction, and oxidative stress, all of which contribute to sustained neuroinflammation. This narrative review examines the clinical features, risk factors, and current evidence on antioxidant-based interventions as potential therapeutic strategies for PCC. A wide range of compounds—including vitamins, polyphenols, and endogenous antioxidants—have shown promise in mitigating neuroinflammation and oxidative damage in both clinical and experimental settings. Antioxidants may help restore redox balance and improve neurological outcomes in affected patients. However, further clinical research is essential to determine their efficacy, safety, and optimal therapeutic protocols. Full article

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36 pages, 848 KiB

Open AccessReview

Oxidative Stress and Inflammation in Hypoxemic Respiratory Diseases and Their Comorbidities: Molecular Insights and Diagnostic Advances in Chronic Obstructive Pulmonary Disease and Sleep Apnea

by Jorge Rodríguez-Pérez, Rosa Andreu-Martínez, Roberto Daza, Lucía Fernández-Arroyo, Ana Hernández-García, Elena Díaz-García, Carolina Cubillos-Zapata, Alicia Lozano-Diez, Aythami Morales, Daniel Ramos, Julián Aragonés, Ángel Cogolludo, Luis del Peso, Francisco García-Río and María J. Calzada

Antioxidants 2025, 14(7), 839; https://doi.org/10.3390/antiox14070839 - 8 Jul 2025

Abstract

In chronic respiratory diseases (CRDs), oxidative stress and inflammation are closely linked, driving disease onset, progression, and comorbidities. Oxidative stress activates inflammatory pathways, while chronic inflammation promotes further reactive oxygen species (ROS) production, creating a vicious cycle leading to airway remodeling, reduced lung [...] Read more.

In chronic respiratory diseases (CRDs), oxidative stress and inflammation are closely linked, driving disease onset, progression, and comorbidities. Oxidative stress activates inflammatory pathways, while chronic inflammation promotes further reactive oxygen species (ROS) production, creating a vicious cycle leading to airway remodeling, reduced lung function, and exacerbations. This review highlights the central roles of inflammation and oxidative stress in chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA). In COPD, chronic hypoxemia associates with emphysema, appearing with disease progression. In OSA, beyond systemic consequences, pulmonary inflammation and oxidative stress contribute to lung injury as well. Although COPD and OSA are distinct conditions, some patients present with “overlap syndrome”, a term used in this review to describe the coexistence of both. This combination poses unique diagnostic and therapeutic challenges. We also examine the role of hypoxia and its transcriptional effects via hypoxia-inducible factors (HIFs) in promoting oxidative stress and inflammation. Finally, we explore how artificial intelligence (AI) offers promising tools to improve diagnosis, monitoring, and management of CRDs and may help elucidate mechanistic links between hypoxia, inflammation, and oxidative stress, contributing to more personalized therapeutic strategies. Full article

(This article belongs to the Special Issue Oxidative Stress and Immune Regulation in Respiratory Diseases)

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17 pages, 2498 KiB

Open AccessArticle

Lemongrass Alleviates Primary Dysmenorrhea Symptoms by Reducing Oxidative Stress and Inflammation and Relaxing the Uterine Muscles

by Sheikh Safeena Sidiq, Qaiser Jabeen, QurratUlAin Jamil, Muhammad Saeed Jan, Iram Iqbal, Fatima Saqib, Mohammed Aufy and Shahid Muhammad Iqbal

Antioxidants 2025, 14(7), 838; https://doi.org/10.3390/antiox14070838 - 8 Jul 2025

Abstract

Primary dysmenorrhea (PD) is characterized by lower abdominal spasms and painful cramps during menstruation in females with a normal pelvic anatomy. Cymbopogon citratus (DC.) Stapf, commonly known as lemongrass, is consumed in the form of herbal tea around the world. It has been [...] Read more.

Primary dysmenorrhea (PD) is characterized by lower abdominal spasms and painful cramps during menstruation in females with a normal pelvic anatomy. Cymbopogon citratus (DC.) Stapf, commonly known as lemongrass, is consumed in the form of herbal tea around the world. It has been traditionally used for menstrual disorders in several communities. This study aims to evaluate the traditional use of C. citratus for its efficacy in alleviating the symptoms of PD. C. citratus extract (CcE) was chemically characterized using HPLC and GCMS, which indicated the presence of several phenolic compounds and long-chain fatty acids. The anti-inflammatory activity of CcE was assessed by COX-I, COX-II, and 5-LOX enzyme inhibition with IC₅₀ values of 143.7, 91.7, and 61.5 µg/mL, respectively, and showed good total antioxidant capacity and free radical scavenging activity. PD was induced in female Wistar rats by administering estradiol valerate followed by oxytocin to induce PD symptoms. CcE efficacy was assessed at 30, 100, and 300 mg/kg concentrations and compared with ibuprofen. CcE 300 mg/kg reduced abdominal contortions and inflammation in the rat uterus. The inflammatory (COX-II, TNFα and IL-10) and oxidative stress (TAC, TOS, MDA and SOD) markers in uterine tissue homogenate were also improved. An in vivo analgesic assessment through hot-plate, tail-flick, and acetic acid-induced writhing assays showed good analgesic activity by CcE, while ex vivo experiments described tocolytic effects in rat uterine muscles. CcE alleviates PD by its antioxidant, anti-inflammatory, analgesic, and tocolytic effects. Full article

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

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19 pages, 2466 KiB

Open AccessArticle

Agmatine Mitigates Diabetes-Related Memory Loss in Female Mice by Targeting I₂/I₃ Imidazoline Receptors and Enhancing Brain Antioxidant Defenses

by Luis E. Cobos-Puc and Hilda Aguayo-Morales

Antioxidants 2025, 14(7), 837; https://doi.org/10.3390/antiox14070837 - 8 Jul 2025

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Abstract

Cognitive decline is a common complication of diabetes mellitus, driven in part by oxidative stress and impaired glucose–insulin homeostasis. This study examined the neuroprotective effects of agmatine (200 mg/kg intraperitoneally) in female BALB/c diabetic mice. Several receptor pathways were examined using commercially available [...] Read more.

Cognitive decline is a common complication of diabetes mellitus, driven in part by oxidative stress and impaired glucose–insulin homeostasis. This study examined the neuroprotective effects of agmatine (200 mg/kg intraperitoneally) in female BALB/c diabetic mice. Several receptor pathways were examined using commercially available antagonists. Behavioral performance was evaluated using the novel object recognition test. Metabolic parameters, such as glucose and insulin levels, as well as antioxidants, including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), were measured in blood and brain tissue. The diabetic mice exhibited impaired recognition memory (discrimination index = 0.08), hyperglycemia (24.3 mmol/L), decreased insulin levels (38.4 µU/mL), and diminished antioxidant defenses (CAT: 75.4 U/g tissue, SOD: 32.6 U/g tissue, and GSH: 8.3 mmol/g tissue). Agmatine treatment improved cognitive function and reversed the biochemical alterations. However, these effects were reduced when agmatine was co-administered with imidazoline I₂/I₃ receptor antagonists. Correlation analysis revealed that cognitive performance positively correlated with antioxidant enzyme levels and insulin levels and negatively correlated with glucose concentrations. Strong intercorrelations among CAT, SOD, and GSH levels suggest a coordinated antioxidant response. Overall, these results imply that agmatine’s neuroprotective effects are partially mediated by modulation of the oxidative balance and glucose–insulin regulation via imidazoline receptors. Full article

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

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17 pages, 2007 KiB

Open AccessReview

Modulation of Redox-Sensitive Cardiac Ion Channels

by Razan Orfali, Al Hassan Gamal El-Din, Varnika Karthick, Elisanjer Lamis, Vanna Xiao, Alena Ramanishka, Abdullah Alwatban, Osama Alkhamees, Ali Alaseem, Young-Woo Nam and Miao Zhang

Antioxidants 2025, 14(7), 836; https://doi.org/10.3390/antiox14070836 - 8 Jul 2025

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Abstract

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function [...] Read more.

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function and support excitation–contraction coupling. However, when ROS accumulate, they modify a variety of important channel proteins in cardiomyocytes, which commonly results in reducing potassium currents, enhancing sodium and calcium influx, and enhancing intracellular calcium release. These redox-driven alterations disrupt the cardiac rhythm, promote after-depolarizations, impair contractile force, and accelerate the development of heart diseases. Experimental models demonstrate that oxidizing agents reduce repolarizing currents, whereas reducing systems restore normal channel activity. Similarly, oxidative modifications of calcium-handling proteins amplify sarcoplasmic reticulum release and diastolic calcium leak. Understanding the precise redox-dependent modifications of cardiac ion channels would guide new possibilities for targeted therapies aimed at restoring electrophysiological homeostasis under oxidative stress, potentially alleviating myocardial infarction and cardiovascular dysfunction. 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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22 pages, 17031 KiB

Open AccessArticle

AZU1 as a DNA Methylation-Driven Gene: Promoting Oxidative Stress in High-Altitude Pulmonary Edema

by Qiong Li, Zhichao Xu, Qianhui Gong, Liyang Chen, Xiaobing Shen and Xiaowei Chen

Antioxidants 2025, 14(7), 835; https://doi.org/10.3390/antiox14070835 - 8 Jul 2025

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Abstract

High-altitude pulmonary edema (HAPE) is a severe condition associated with high-altitude environments, and its molecular mechanism has not been fully elucidated. This study systematically analyzed the DNA methylation status of HAPE patients and healthy controls using reduced-representation bisulfite sequencing (RRBS) and 850K DNA [...] Read more.

High-altitude pulmonary edema (HAPE) is a severe condition associated with high-altitude environments, and its molecular mechanism has not been fully elucidated. This study systematically analyzed the DNA methylation status of HAPE patients and healthy controls using reduced-representation bisulfite sequencing (RRBS) and 850K DNA methylation chips, identifying key differentially methylated regions (DMRs). Targeted bisulfite sequencing (TBS) revealed significant abnormalities in DMRs of five genes, azurocidin 1 (AZU1), growth factor receptor bound protein 7 (GRB7), mannose receptor C-type 2 (MRC2), RUNX family transcription factor 3 (RUNX3), and septin 9 (SEPT9). The abnormal expression of AZU1 was validated using peripheral blood leukocytes from HAPE patients and normal controls, as well as rat lung tissue, indicating its potential importance in the pathogenesis of HAPE. To further validate the function of AZU1, we conducted experimental studies using a hypobaric hypoxia injury model in Human Umbilical Vein Endothelial Cells (HUVEC). The results showed that AZU1 was significantly upregulated under hypobaric hypoxia. Knocking down AZU1 mitigates the reduction in HUVEC proliferation, angiogenesis, and oxidative stress damage induced by acute hypobaric hypoxia. AZU1 induces cellular oxidative stress via the p38/mitogen-activated protein kinase (p38/MAPK) signaling pathway. This study is the first to elucidate the mechanism of AZU1 in HAPE via the p38/MAPK pathway, offering novel insights into the molecular pathology of HAPE and laying a foundation for future diagnostic and therapeutic strategies. Full article

(This article belongs to the Topic Cardiovascular Disease in Special Populations: From Basic Science to Clinical Practice)

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27 pages, 3139 KiB

Open AccessArticle

Distinctive Effects of Fullerene C₆₀ and Fullerenol C₆₀(OH)₂₄ Nanoparticles on Histological, Molecular and Behavioral Hallmarks of Alzheimer’s Disease in APPswe/PS1E9 Mice

by Sholpan Askarova, Kseniia Sitdikova, Aliya Kassenova, Kirill Chaprov, Evgeniy Svirin, Andrey Tsoy, Johannes de Munter, Anna Gorlova, Aleksandr Litavrin, Aleksei Deikin, Andrey Nedorubov, Nurbol Appazov, Allan Kalueff, Anton Chernopiatko and Tatyana Strekalova

Antioxidants 2025, 14(7), 834; https://doi.org/10.3390/antiox14070834 - 8 Jul 2025

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Abstract

Fullerenes and fullerenols exhibit antioxidant and anti-inflammatory properties, making them promising candidates for Alzheimer’s disease (AD) therapy. Unlike conventional anti-inflammatory drugs, these compounds have multitargeted effects, including their ability to inhibit amyloid fibril formation. However, few studies have explored their efficacy in high-validity [...] Read more.

Fullerenes and fullerenols exhibit antioxidant and anti-inflammatory properties, making them promising candidates for Alzheimer’s disease (AD) therapy. Unlike conventional anti-inflammatory drugs, these compounds have multitargeted effects, including their ability to inhibit amyloid fibril formation. However, few studies have explored their efficacy in high-validity AD models. Female APPswe/PS1E9 (APP/PS1) mice and their wild-type (WT) littermates were orally administered with fullerene C₆₀ (0.1 mg/kg/day) or fullerenol C₆₀(OH)₂₄ (0.15 mg/kg/day) for 10 months starting at 2 months of age. Behavioral assessments were performed at 12 months of age. Amyloid plaque density and size were analyzed in the brain regions using Congo red staining. The expression of genes related to inflammation and plasticity was examined, and an in vitro assay was used to test the toxicity of fullerenol and its effect on amyloid β peptide 42 (Aβ42)-induced reactive oxygen species (ROS) production. Fullerenol reduced the maximum plaque size in the cortex and hippocampus, decreased the small plaque density in the hippocampus and thalamus, and prevented an increase in glial fibrillary acidic protein (GFAP) positive cell density in the mutants. Both treatments improved cognitive and emotional behaviors and reduced Il1β and increased Sirt1 expression. In vitro, fullerenol was non-toxic across a range of concentrations and reduced Aβ42-induced ROS production in brain endothelial cells and astrocytes. Long-term administration of fullerene or fullerenol improved behavioral and molecular markers of AD in APP/PS1 mice, with fullerenol showing additional benefits in reducing amyloid burden. Full article

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

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31 pages, 4367 KiB

Open AccessArticle

Serine-Driven Metabolic Plasticity Drives Adaptive Resilience in Pancreatic Cancer Cells

by Marcella Bonanomi, Sara Mallia, Mariafrancesca Scalise, Tecla Aramini, Federica Baldassari, Elisa Brivio, Federica Conte, Alessia Lo Dico, Matteo Bonas, Danilo Porro, Cesare Indiveri, Christian M. Metallo and Daniela Gaglio

Antioxidants 2025, 14(7), 833; https://doi.org/10.3390/antiox14070833 - 7 Jul 2025

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Abstract

Pancreatic cancer is one of the most lethal malignancies, in part due to its profound metabolic adaptability, which underlies drug resistance and therapeutic failure. This study explores the metabolic rewiring associated with resistance to treatment using a systems metabolomics approach. Exposure to the [...] Read more.

Pancreatic cancer is one of the most lethal malignancies, in part due to its profound metabolic adaptability, which underlies drug resistance and therapeutic failure. This study explores the metabolic rewiring associated with resistance to treatment using a systems metabolomics approach. Exposure to the redox-disrupting agent erastin revealed key metabolic vulnerabilities but failed to produce lasting growth suppression. Combinatorial treatments with methotrexate or alpelisib significantly impaired proliferation and triggered marked metabolic shifts. Systems-level analyses identified serine metabolism as a central adaptive pathway in resilient cells. Metabolic tracing and gene expression profiling showed increased de novo serine biosynthesis and uptake, supporting redox homeostasis, biosynthetic activity, and epigenetic regulation. Notably, cells that resumed growth after drug withdrawal exhibited transcriptional reprogramming involving serine-driven pathways, along with elevated expression of genes linked to survival, proliferation, and migration. These findings establish serine metabolism as a functional biomarker of metabolic plasticity and adaptive resilience in pancreatic cancer, suggesting that targeting this adaptive axis may enhance therapeutic efficacy. Full article

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

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21 pages, 325 KiB

Open AccessArticle

Antioxidant and Quality Effects of Red Grape Pomace in Barbecued Pork Burgers: Implications for PAH Formation

by María Jesús Petrón, María Jesús Martín-Mateos, Miriam Sánchez-Ordóñez, Belén Godoy and María Rosario Ramírez-Bernabé

Antioxidants 2025, 14(7), 832; https://doi.org/10.3390/antiox14070832 - 7 Jul 2025

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Abstract

The growing concern over the presence of polycyclic aromatic hydrocarbons (PAHs) in grilled meats has intensified the search for natural mitigation strategies. This study evaluates the effect of red grape pomace (RGP), a natural by-product with antioxidant properties, on the lipid stability, color, [...] Read more.

The growing concern over the presence of polycyclic aromatic hydrocarbons (PAHs) in grilled meats has intensified the search for natural mitigation strategies. This study evaluates the effect of red grape pomace (RGP), a natural by-product with antioxidant properties, on the lipid stability, color, fatty acid profile, volatile compounds, and PAHs formation in barbecued pork burgers. Unlike previous studies focusing on polyphenol extracts, this work investigates, for the first time, the direct incorporation of whole RGP stabilized by high hydrostatic pressure (HHP), a method that preserves its bioactive profile and ensures food safety. Incorporation of RGP at different levels (0.5%, 1%, and 3%) demonstrates its potential as a functional ingredient in meat products. Our results show that RGP effectively inhibits lipid oxidation, as indicated by significantly lower malondialdehyde (MDA) levels (p < 0.001) compared to control batches. It also modified the fatty acid profile by reducing saturated fatty acids and increasing the linoleic acid content (up to 15.56% at the 3% level). As the RPG concentration increased, color parameters (lightness, redness, yellowness, chroma, and hue) decreased significantly (p < 0.001), particularly at higher pomace levels (1% and 3%). The RGP did not significantly affect the PAH concentration, indicating its safe use in barbecued products. However, it selectively influenced volatile compounds, decreasing the hydrocarbon levels at higher concentrations, likely due to its antioxidant properties. These findings suggest that stabilized RGP may serve as a natural additive that enhances the nutritional quality and reduces lipid oxidation, without promoting PAH formation in thermally processed meats. Full article

(This article belongs to the Special Issue Natural Antioxidants from Plant-Based By-Products: Mechanisms and Applications in Food Systems)

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20 pages, 7960 KiB

Open AccessArticle

Optimisation of Phenolic Compound Extraction from Agrimonia eupatoria L. Using Response Surface Methodology for Enhanced Yield of Different Phenolics and Maximised Antioxidant Activity

by Justinas Sukackas, Modestas Žilius, Gerda Šaltytė and Lina Raudonė

Antioxidants 2025, 14(7), 831; https://doi.org/10.3390/antiox14070831 - 7 Jul 2025

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Abstract

Agrimonia eupatoria L. is a traditionally used medicinal plant rich in tannin compounds with antioxidant, anti-inflammatory, and antimicrobial activities. This study aimed to optimise the extraction of individual phenolic acids, flavonoids, and tannins from A. eupatoria and maximise their antioxidant activity using response [...] Read more.

Agrimonia eupatoria L. is a traditionally used medicinal plant rich in tannin compounds with antioxidant, anti-inflammatory, and antimicrobial activities. This study aimed to optimise the extraction of individual phenolic acids, flavonoids, and tannins from A. eupatoria and maximise their antioxidant activity using response surface methodology (RSM). A central composite design was applied to evaluate the influence of acetone concentration, solvent ratio, and extraction time on the yield of total phenolics, total radical scavenging and reducing capacities, and individual compounds. Acetone concentration, solvent ratio, and extraction time were varied in a central composite design. The optimal conditions yielded high levels of agrimoniin (9.16 mg/g), total identified phenolics (33.61 mg/g), and strong antioxidant activity. These findings provide a scientific basis for standardising bioactive-rich extracts for nutraceutical and pharmaceutical applications. Full article

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

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24 pages, 5180 KiB

Open AccessArticle

Resolvin D2 Reduces UVB Skin Pathology by Targeting Cytokines, Oxidative Stress, and NF-κB Activation

by Ingrid C. Pinto, Priscila Saito, Camilla C. A. Rodrigues, Renata M. Martinez, Cristina P. B. Melo, Maiara Piva, Clovis M. Kumagai, David L. Vale, Telma Saraiva-Santos, Allan J. C. Bussmann, Marcela M. Baracat, Sandra R. Georgetti, Fabiana T. M. C. Vicentini, Waldiceu A. Verri and Rubia Casagrande

Antioxidants 2025, 14(7), 830; https://doi.org/10.3390/antiox14070830 - 6 Jul 2025

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Abstract

UVB skin pathology is initiated by reactive oxygen species (ROS), differentiating this condition from other inflammatory diseases involving first the immune cell activation by danger or pathogen molecular patterns followed by oxidative stress. Resolvin D2 (RvD2) has been found to reduce inflammation in [...] Read more.

UVB skin pathology is initiated by reactive oxygen species (ROS), differentiating this condition from other inflammatory diseases involving first the immune cell activation by danger or pathogen molecular patterns followed by oxidative stress. Resolvin D2 (RvD2) has been found to reduce inflammation in preclinical models. However, whether or not RvD2 reduces skin pathology caused by UVB irradiation is not yet known. Therefore, the efficacy of RvD2 on skin pathology triggered by UVB irradiation in female hairless mice was assessed. RvD2 (0.3, 1 or 3 ng/mouse, i.p.) was found to protect the skin against UVB inflammation, as observed in the reduction in edema (46%), myeloperoxidase activity (77%), metalloproteinase-9 activity (39%), recruitment of neutrophils/macrophages (lysozyme⁺ cells, 76%) and mast cells (106%), epidermal thickening (93%), sunburn cell formation (68%), collagen fiber breakdown (55%), and production of cytokines such as TNF-α (100%). Considering the relevance of oxidative stress to UVB irradiation skin pathologies, an important observation was that the skin antioxidant capacity was recovered by RvD2 according to the results that show the ferric reducing antioxidant power (68%), cationic radical scavenges (93%), catalase activity (74%), and the levels of reduced glutathione (48%). Oxidative damage was also attenuated, as observed in the reduction in superoxide anion production (69%) and lipid hydroperoxides (71%). The RvD2 mechanism involved the inhibition of NF-κB activation, as observed in the diminished degradation of IκBα (48%) coupled with a reduction in its downstream targets that are involved in inflammation and oxidative stress, such as COX-2 (66%) and gp91^phox (77%) mRNA expression. In conclusion, RvD2 mitigates the inflammatory and oxidative pathologic skin aggression that is triggered by UVB. Full article

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

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19 pages, 2098 KiB

Open AccessArticle

Influence of an Antioxidant Nanomaterial on Oral Tablet Formulation: Flow Properties and Critical Quality Attributes

by Andrea C. Ortiz, Javiera Carrasco-Rojas, Sofía Peñaloza, Mario J. Simirgiotis, Lorena Rubio-Quiroz, Diego Ruiz, Carlos F. Lagos, Javier Morales and Francisco Arriagada

Antioxidants 2025, 14(7), 829; https://doi.org/10.3390/antiox14070829 - 5 Jul 2025

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Abstract

Antioxidant nanomaterials, particularly mesoporous silica nanoparticles (MSNs) functionalized with polyphenols, offer innovative solutions for protecting oxidation-sensitive components and enhancing bioavailability in pharmaceuticals or extending the shelf life of nutraceutical and food products. This study investigates the influence of MSNs functionalized with caffeic acid [...] Read more.

Antioxidant nanomaterials, particularly mesoporous silica nanoparticles (MSNs) functionalized with polyphenols, offer innovative solutions for protecting oxidation-sensitive components and enhancing bioavailability in pharmaceuticals or extending the shelf life of nutraceutical and food products. This study investigates the influence of MSNs functionalized with caffeic acid (MSN-CAF) on powder flow properties and their tableting performance. Aminated MSNs were synthesized via co-condensation and conjugated with caffeic acid using EDC/NHS chemistry. Antioxidant capacity was evaluated using DPPH^●, ABTS^●+, ORAC, and FRAP assays. Powder blends with varying MSN-CAF concentrations (10–70%) were characterized for flow properties (angle of repose, Hausner ratio, Carr’s index), tablets were produced via direct compression, and critical quality attributes (weight uniformity, hardness, friability, disintegration, nanoparticle release) were assessed. MSN-CAF exhibited reduced antioxidant capacity compared with free caffeic acid due to pore entrapment but retained significant activity. Formulation F1 (10% MSN-CAF) showed excellent flowability (angle of repose: 12°, Hausner ratio: 1.16, Carr’s index: 14%), enabling robust tablet production with rapid disintegration, low friability, and complete nanoparticle release in 10 min. Additionally, the antioxidant nanomaterial demonstrated biocompatibility with the HepG2 cell line. MSN-CAF is a versatile nanoexcipient for direct compression tablets, offering potential as an active packaging agent and delivery system in the nutraceutical and food industries. Full article

(This article belongs to the Special Issue Natural Antioxidants from Plant-Based By-Products: Mechanisms and Applications in Food Systems)

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24 pages, 2920 KiB

Open AccessArticle

The MiBlend Randomized Trial: Investigating Genetic Polymorphisms in Personalized Responses to Fruit and Vegetable Interventions for Chronic Disease Prevention

by Julia N. DeBenedictis, Na Xu, Theo M. de Kok and Simone G. van Breda

Antioxidants 2025, 14(7), 828; https://doi.org/10.3390/antiox14070828 - 4 Jul 2025

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Abstract

Background: The MiBlend Study investigated the effect of consuming different combinations of fruits and vegetables (F&Vs) blends on markers of chronic disease risk and gene expression changes in healthy human subjects. Overall, the increase in F&Vs led to reduced susceptibility to the induction [...] Read more.

Background: The MiBlend Study investigated the effect of consuming different combinations of fruits and vegetables (F&Vs) blends on markers of chronic disease risk and gene expression changes in healthy human subjects. Overall, the increase in F&Vs led to reduced susceptibility to the induction of DNA damage ex vivo, higher antioxidant capacity of plasma, and improved microvasculature as reflected by retinal analysis. As with most dietary intervention studies, inter-individual variability was observed in the responses, which might be the consequence of genetic differences. Therefore, this study aims to identify if genetic variants in relevant genes affect outcomes and responses to the dietary interventions. Methods: The literature review identified 15 polymorphic genes related to phytochemical metabolism, oxidative stress, and detoxification, which were tested in 146 participant samples using TaqMan and PCR analysis. The effect of genotypes on study outcomes was determined via analysis of variance. Results: XRCC1 wildtype carriers were more protected from ex vivo-induced DNA damage after consuming flavanol-rich F&Vs than other variants. XRCC1 is involved in DNA repair, particularly oxidative damage, and its wildtype allele enhances repair efficiency. GSTP1 wildtype carriers had a larger improvement in microvasculature after all F&V blends, especially those rich in polyphenols. GSTP1 polymorphisms likely affect microvascular responses to polyphenol-rich F&V intake by modulating detoxification and fiber-derived butyrate that can influence arterial dilation and endothelial function. Conclusions: Stratifying participants by relevant genetic polymorphisms can reveal predisposed responses to nutrients and guide efforts to personalize disease prevention strategies. Full article

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

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24 pages, 2490 KiB

Open AccessArticle

Hydrogen Sulfide (H₂S)-Donating Formyl Peptide Receptor 2 (FPR2) Agonists: Design, Synthesis, and Biological Evaluation in Primary Mouse Microglia Culture

by Leonardo Brunetti, Fabio Francavilla, Mauro Niso, Jakub Kosma Frydrych, Ewa Trojan, Igor A. Schepetkin, Liliya N. Kirpotina, Beata Grygier, Krzysztof Łukowicz, Mark T. Quinn, Agnieszka Basta-Kaim, Enza Lacivita and Marcello Leopoldo

Antioxidants 2025, 14(7), 827; https://doi.org/10.3390/antiox14070827 - 4 Jul 2025

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Abstract

Chronic neuroinflammation and oxidative stress play an important role in the onset and progression of neurodegenerative disorders, including Alzheimer’s disease, which can ultimately lead to neuronal damage and loss. The mechanisms of sustained neuroinflammation and the coordinated chain of events that initiate, modulate, [...] Read more.

Chronic neuroinflammation and oxidative stress play an important role in the onset and progression of neurodegenerative disorders, including Alzheimer’s disease, which can ultimately lead to neuronal damage and loss. The mechanisms of sustained neuroinflammation and the coordinated chain of events that initiate, modulate, and then lead to the resolution of inflammation are increasingly being elucidated, offering alternative approaches for treating pathologies with underlying chronic neuroinflammation. Here, we propose a new multitarget approach to address chronic neuroinflammation and oxidative stress in neurodegenerative disorders by activating the formyl peptide receptor 2 (FPR2) combined with the potentiation of hydrogen sulfide (H₂S) release. FPR2 is a key player in the resolution of inflammation because it mediates the effects of several endogenous pro-resolving mediators. At the same time, H₂S is an endogenous gaseous transmitter with anti-inflammatory and pro-resolving properties, and it can protect against oxidative stress. Starting from potent FPR2 agonists identified in our laboratories, we prepared hybrid compounds by embedding an H₂S-donating moiety within the molecular scaffold of these FPR2 agonists. Following this approach, we identified several compounds that combined potent FPR2 agonism with the ability to release H₂S. The release of H₂S was assessed in buffer and intracellularly. Compounds 7b and 8b combined potent FPR2 agonist activity, selectivity over FPR1, and the ability to release H₂S. Compounds 7b and 8b were next studied in murine primary microglial cells stimulated with lipopolysaccharide (LPS), a widely accepted in vitro model of neuroinflammation. Both compounds were able to counterbalance LPS-induced cytotoxicity and the release of pro-inflammatory (IL-18, IL-6) and anti-inflammatory (IL-10) cytokines induced by LPS stimulation. Full article

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

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17 pages, 1910 KiB

Open AccessArticle

Production of Lambic-like Fruit Sour Beer with Lachancea thermotolerans

by Rubén Bartolomé, Elena Alonso, Antonio Morata and Carmen López

Antioxidants 2025, 14(7), 826; https://doi.org/10.3390/antiox14070826 - 4 Jul 2025

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Abstract

Consumer demand for low-alcohol acidic beers is driving the use of non-conventional yeasts in the brewing process. In this study, the addition of mixed berries and fermentation with L. thermotolerans L31 are performed in crafting a low-alcohol acidic beer. Four different beers were [...] Read more.

Consumer demand for low-alcohol acidic beers is driving the use of non-conventional yeasts in the brewing process. In this study, the addition of mixed berries and fermentation with L. thermotolerans L31 are performed in crafting a low-alcohol acidic beer. Four different beers were brewed in the primary stage with either Saccharomyces cerevisiae or L. thermotolerans and with or without added berry mixture. Beer was fermented for 8 days at 20 °C, stored, and bottled. pH, density, alcoholic content, bitterness, and color of final beer were analyzed for all samples using analytical methods. Volatile compounds, anthocyanin content, and antioxidant activity were also evaluated. Sensory analysis was performed and correlated (PCA) with the analytical results. The obtained data indicated that beers brewed with L. thermotolerans were significantly more acidic and less bitter than S. cerevisiae beers. No difference in alcoholic content was found. Fruity aroma-associated compounds were present in L. thermotolerans beers, which correlated with the sensory analysis. Fruit beers were also redder and showed higher anthocyanin content and stronger antioxidant activity due to the presence of anthocyanins such as cyanidin, delphinidin, and malvidin from fruit, and other antioxidant compounds. Full article

(This article belongs to the Special Issue Antioxidant Capacity of Anthocyanins and Other Vegetal Pigments: Properties, Intake and Health Benefits)

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23 pages, 1771 KiB

Open AccessReview

Reactive Nitrogen Species and Fibrinogen: Exploring the Effects of Nitration on Blood Clots

by Francesca Nencini, Serena Borghi, Elvira Giurranna, Ilenia Barbaro, Niccolò Taddei, Claudia Fiorillo and Matteo Becatti

Antioxidants 2025, 14(7), 825; https://doi.org/10.3390/antiox14070825 - 4 Jul 2025

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Abstract

Reactive nitrogen species (RNS), particularly peroxynitrite (ONOO⁻), play a central role in post-translational modifications (PTMs) of proteins, including fibrinogen, a key component of the coagulation cascade. This review explores the structural and functional consequences of fibrinogen nitration, with a focus on [...] Read more.

Reactive nitrogen species (RNS), particularly peroxynitrite (ONOO⁻), play a central role in post-translational modifications (PTMs) of proteins, including fibrinogen, a key component of the coagulation cascade. This review explores the structural and functional consequences of fibrinogen nitration, with a focus on its impact on clot formation, morphology, mechanical stability, and fibrinolysis. Nitration, primarily targeting tyrosine residues within functional domains of the Aα, Bβ, and γ chains, induces conformational changes, dityrosine crosslinking, and aggregation into high molecular weight species. These modifications result in altered fibrin polymerization, the formation of porous and disorganized clot networks, reduced mechanical resilience, and variable susceptibility to fibrinolysis. Moreover, nitrated fibrinogen may affect interactions with platelets and endothelial cells, although current evidence remains limited. Emerging clinical studies support its role as both a prothrombotic mediator and a potential biomarker of oxidative stress in cardiovascular and inflammatory diseases. Finally, we explore both pharmacological interventions, such as NOX inhibitors, and natural antioxidant strategies at counteracting fibrinogen nitration. Overall, fibrinogen nitration emerges as a critical molecular event linking oxidative stress to thrombotic risk. Full article

(This article belongs to the Special Issue Antioxidants in Cardiovascular Medicine: Emerging Trends and Future Perspectives)

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36 pages, 3577 KiB

Open AccessArticle

Screening of a Plant Extract Library from the Greek Flora for Biological Activities Related to Anti-Aging Applications

by Harris Pratsinis, Despoina D. Gianniou, Gabriela Belén Lemus Ringele, Adamantia Agalou, Asimina Fotopoulou, Xanthippi P. Louka, Christos Nastos, Eleftherios Kalpoutzakis, Aikaterini Argyropoulou, Dimitris Michailidis, Antonia Theodoridi, Ioanna Eleftheriadou, Adamantia Papadopoulou, Sentiljana Gumeni, Stavros Beteinakis, Konstantina Karamanou, Eleni Mavrogonatou, Georgios Stavropoulos, Dimitris Beis, Maria Halabalaki, Ioannis P. Trougakos and Dimitris Kletsas Show full author list Hide full author list

Antioxidants 2025, 14(7), 824; https://doi.org/10.3390/antiox14070824 - 4 Jul 2025

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Abstract

Characteristic manifestations of skin aging, due to either intrinsic or extrinsic factors, such as ultraviolet (UV) radiation and oxidative stress, include cell senescence, alterations in collagen and elastin networks, and melanogenesis disorders. Natural products are considered a rich source of anti-aging molecules. Accordingly, [...] Read more.

Characteristic manifestations of skin aging, due to either intrinsic or extrinsic factors, such as ultraviolet (UV) radiation and oxidative stress, include cell senescence, alterations in collagen and elastin networks, and melanogenesis disorders. Natural products are considered a rich source of anti-aging molecules. Accordingly, the screening of a plant extract library from the Greek flora for a panel of biological activities related to skin aging is presented herein. In particular, 52 plant materials extracted using Accelerated Solvent Extraction (ASE) and Supercritical Fluid Extraction (SFE) were assessed for their effects on (1) human skin cell viability, (2) antioxidant activity—using both cell-free and cell-based methods—(3) photoprotective capacity, and (4) interference with collagenase, elastase, and tyrosinase, as well as with proteasomal and lysosomal activities of human skin cells. In vivo phenotypic screens on Danio rerio (zebrafish) embryos were also used for assessing melanogenesis. Many active extracts were identified, some of them for the first time, and others in agreement with previous reports. In general, ASE extracts exhibited higher activities than SFE ones. Seven extracts showed multiple activities, being highly effective in at least four different assays. These data support the potential use of these extracts against skin aging in medicinal and cosmetic applications. Full article

(This article belongs to the Special Issue Natural Products: Biological, Antioxidant Properties and Health Effects—4th Edition)

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Antioxidants, Volume 14, Issue 7 (July 2025) – 97 articles

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