Antioxidants

17 pages, 2585 KB

Open AccessArticle

Novel Hybrid Peptide DEFB126 (1-39)-TP5 Inhibits LPS-Induced Inflammatory Responses and Oxidative Stress by Neutralizing LPS and Blocking the TLR4/MD2-NFκB Signaling Axis

by Yuan Tang, Xuelian Zhao, Zetao Ding, Junyong Wang, Jing Zhang, Yichen Zhou, Marhaba Ahmat, Hao Wang, Yang Zhu, Baseer Ahmad, Zaheer Abbas, Dayong Si, Rijun Zhang and Xubiao Wei

Antioxidants 2025, 14(9), 1117; https://doi.org/10.3390/antiox14091117 (registering DOI) - 14 Sep 2025

Abstract

Lipopolysaccharide (LPS), an essential structural molecule in the outer membrane of Gram-negative bacteria, is recognized as a principal trigger of inflammatory responses and oxidative stress. Thus, the control and clearance of LPS is essential to inhibit LPS-induced excessive inflammation, oxidative stress, and liver [...] Read more.

Lipopolysaccharide (LPS), an essential structural molecule in the outer membrane of Gram-negative bacteria, is recognized as a principal trigger of inflammatory responses and oxidative stress. Thus, the control and clearance of LPS is essential to inhibit LPS-induced excessive inflammation, oxidative stress, and liver injury. In recent years, some native bioactive peptides, such as human β-defensin 126 (DEFB126) and thymopentin (TP5), have been reported to have inhibitory effects against LPS-induced inflammation and oxidative stress. However, the cytotoxicity, weak stability, and poor biological activity have hindered their practical application and clinical development. The development of novel hybrid peptides is a promising approach for overcoming these problems. In this study, we designed a novel hybrid peptide [DTP, DEFB126 (1-39)-TP5] that combines the active center of DEFB126 and full-length thymopentin (TP5). Compared to the parental peptides, DTP has a longer half-life, lower cytotoxicity, and greater anti-inflammatory and antioxidant activity. The anti-inflammatory and antioxidant effects of DTP were demonstrated in a murine LPS-induced sepsis model, which showed that DTP successfully inhibited the indicators associated with LPS-induced liver injury; decreased the contents of TNF-α, IL-6, and IL-1β; increased the level of glutathione (GSH); and improved the activities of catalase (CAT) and superoxide dismutase (SOD). Furthermore, our study revealed that the anti-inflammatory and antioxidant activities of DTP were associated with LPS neutralization, blockade of LPS binding to the Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD-2) complex, reduction in reactive oxygen species content, and inhibition of the activation of the nuclear factor kappa-B (NF-кB) signaling pathway. These results elucidate the structural and functional properties of the peptide DTP, reveal its underlying molecular mechanisms, and shed light on its potential as a multifunctional agent for applications in agriculture, food technology, and clinical therapeutics. Full article

(This article belongs to the Special Issue Antioxidant Peptides)

► Show Figures

Figure 1

25 pages, 7590 KB

Open AccessArticle

A Study of the Fruits of Catalpa bignonioides Walt.: Evaluation of the Antioxidant, Anti-Inflammatory, and Anti-Cancer Activities in Colorectal Adenocarcinoma Cells in Relation to Phytochemical Profile

by Clizia Bernardi, Thomas Gaslonde, Federica Finetti, Salim Benmaouche, Giulia Macrì, Annabelle Dugay, Claire Cuyamendous, Chouaha Bouzidi, Monica Rosa Loizzo, Philippe Belmont, Rosa Tundis, Lorenza Trabalzini and Brigitte Deguin

Antioxidants 2025, 14(9), 1116; https://doi.org/10.3390/antiox14091116 (registering DOI) - 14 Sep 2025

Abstract

The chemical profiles and potential anti-inflammatory, antioxidant, and anticancer activities of the aqueous extract and fractions of fresh Catalpa bignonioides fruits were studied. Iridoids, flavonoids, and phenolic compounds represent the main phytochemical classes. Nine of the ten iridoids detected are acyl-iridoids. Significant amounts [...] Read more.

The chemical profiles and potential anti-inflammatory, antioxidant, and anticancer activities of the aqueous extract and fractions of fresh Catalpa bignonioides fruits were studied. Iridoids, flavonoids, and phenolic compounds represent the main phytochemical classes. Nine of the ten iridoids detected are acyl-iridoids. Significant amounts of catalpol and catalposide were found. The antioxidant activity of iridoids was demonstrated by HPTLC analysis coupled with a DPPH derivatization and by applying four in vitro tests, such as DPPH, ABTS, FRAP, and the β-carotene bleaching test. C. bignonioides extract and fractions were also evaluated for their anti-cancer activity using in vitro models of colorectal cancer (HT29 and HCT166 cell lines), and focusing on the effect of the different fractions on inflammation and oxidative stress, key factors that drive the onset and progression of colon cancer. Full article

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

► Show Figures

Figure 1

23 pages, 4376 KB

Open AccessArticle

Integrated Metabolomics and Transcriptomics Reveals Metabolic Pathway Changes in Common Carp Muscle Under Oxidative Stress

by Yongxiang Liu, Bing Li, Yiran Hou, Linjun Zhou, Qiqin Yang, Chengfeng Zhang, Hongwei Li, Jian Zhu and Rui Jia

Antioxidants 2025, 14(9), 1115; https://doi.org/10.3390/antiox14091115 (registering DOI) - 14 Sep 2025

Abstract

Hydrogen peroxide (H₂O₂), a ubiquitous reactive oxygen species in aquatic ecosystems, has been shown to induce toxicological effects in aquatic animals. However, the molecular mechanisms underlying H₂O₂-mediated alterations in muscle quality and metabolic homeostasis remain [...] Read more.

Hydrogen peroxide (H₂O₂), a ubiquitous reactive oxygen species in aquatic ecosystems, has been shown to induce toxicological effects in aquatic animals. However, the molecular mechanisms underlying H₂O₂-mediated alterations in muscle quality and metabolic homeostasis remain largely unexplored. In this study, we performed integrated metabolomic and transcriptomic analyses to characterize the molecular mechanisms underlying H₂O₂-induced oxidative stress in fish muscle tissue. Common carp (Cyprinus carpio) were randomized into two groups: a control group (0.0 mM H₂O₂) and an H₂O₂-treated group (1.0 mM H₂O₂) for a 14-day exposure. Following the exposure, comprehensive analyses, including fatty acid composition, amino acid profiles, and multi-omics sequencing, were conducted to elucidate the metabolic responses to oxidative stress. The results showed neither the amino acid nor the fatty acid composition exhibited significant modifications following H₂O₂ exposure. Metabolomic profiling identified 83 upregulated and 89 downregulated metabolites, predominantly comprising organic acids and derivatives, lipids and lipid-like molecules. These differential metabolites were associated with histidine and purine-derived alkaloid biosynthesis, glyoxylate and dicarboxylate metabolism pathways. Transcriptomic analysis identified 470 upregulated and 451 downregulated differentially expressed genes (DEGs). GO enrichment analysis revealed that these DEGs were significantly enriched in muscle tissue development and transcriptional regulatory activity. KEGG analysis revealed significant enrichment in oxidative phosphorylation, adipocytokine signaling, and PPAR signaling pathways. The elevated oxidative phosphorylation activity and upregulated adipocytokine/PPAR signaling pathways collectively indicate H₂O₂-induced metabolic dysregulation in carp muscle. Through the integration of metabolomics and transcriptomics, this study offers novel insights into the toxicity of H₂O₂ in aquatic environments, elucidates adaptive mechanisms of farmed fish to oxidative stress, and provides a theoretical basis for developing antioxidant strategies. Full article

(This article belongs to the Special Issue Natural Antioxidants and Aquatic Animal Health—2nd Edition)

► Show Figures

Figure 1

31 pages, 9126 KB

Open AccessArticle

Integrated Phytochemical Profiling, GC-MS Characterization, and In Silico, In Vitro Evaluation of Synergistic Antimicrobial, Antioxidant, and Anti-Inflammatory Activities of Morus alba Bark and Pinus densiflora Extracts with Methyl Gallate

by Muhammad Aleem Abbas, Ga-Yeong Lee, Syed Al Jawad Sayem, Seung-Jin Lee and Seung-Chun Park

Antioxidants 2025, 14(9), 1114; https://doi.org/10.3390/antiox14091114 (registering DOI) - 13 Sep 2025

Abstract

The growing challenge of antibiotic resistance and inflammation-related disorders calls for safe, multi-target therapeutic strategies. Morus alba (MOAL) and Pinus densiflora (PIDE) are known for their medicinal properties, yet their combined potential with methyl gallate (MG) has not been fully explored. In this [...] Read more.

The growing challenge of antibiotic resistance and inflammation-related disorders calls for safe, multi-target therapeutic strategies. Morus alba (MOAL) and Pinus densiflora (PIDE) are known for their medicinal properties, yet their combined potential with methyl gallate (MG) has not been fully explored. In this study, the phytochemical composition of MOAL and PIDE was characterized using GC–MS, and their combined antimicrobial, antioxidant, and anti-inflammatory activities were evaluated. Hydroethanolic extracts were prepared and assessed for antioxidant activity (DPPH assay), antibacterial activity (disk diffusion, MIC, time kill), and nitric oxide (NO) suppression in Lipopolysaccharide (LPS)-stimulated macrophages, alongside MTT cytotoxicity screening. MOAL exhibited a higher extraction efficiency, reaching 500 mg/mL at 4 h, whereas Pinus achieved 450 mg/mL at the same time point. Both exhibited a diverse and abundant phytochemical profile. The optimized blend (MOAL:PIDE:MG, 1:1:0.1) demonstrated significantly enhanced bioactivity, with over 90% DPPH scavenging with the low IC₅₀ value (66.62 mg/mL), potent inhibition of both Gram-positive and Gram-negative bacteria, and the strongest effect against Staphylococcus aureus (264 μg/mL). Time-kill assays confirmed rapid bactericidal action, and NO production was reduced by approximately 75% without cytotoxicity. Molecular docking identified a lead multi-target compound exhibiting strong binding affinities to COX-2, TNF-α, and Keap1, supporting its observed anti-inflammatory and antioxidant potential. These findings highlight the promise of synergistic phytochemical formulations as broad-spectrum, multifunctional therapeutic candidates, supporting further in vivo and clinical validation. Full article

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

► Show Figures

Figure 1

18 pages, 4016 KB

Open AccessArticle

The Supersulfide-Producing Activity of Rat Cystathionine γ-Lyase Is Irreversibly Inactivated by L-CysNO but Not by L-GSNO

by Shoma Araki, Tsuyoshi Takata, Sunghyeon Yoon, Shingo Kasamatsu, Hideshi Ihara, Hidehiko Nakagawa, Takaaki Akaike, Yukihiro Tsuchiya and Yasuo Watanabe

Antioxidants 2025, 14(9), 1113; https://doi.org/10.3390/antiox14091113 (registering DOI) - 13 Sep 2025

Abstract

Cystathionine γ-lyase (CSE) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that catalyzes the final step of the transsulfuration pathway, converting cystathionine into cysteine. Additionally, CSE is also essential for the formation of cysteine hydropolysulfide (Cys-S-(S)n-H), known as supersulfides, by metabolizing cystine under pathological conditions. [...] Read more.

Cystathionine γ-lyase (CSE) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that catalyzes the final step of the transsulfuration pathway, converting cystathionine into cysteine. Additionally, CSE is also essential for the formation of cysteine hydropolysulfide (Cys-S-(S)n-H), known as supersulfides, by metabolizing cystine under pathological conditions. We previously reported that, during cystine metabolism, CSE undergoes self-inactivation through polysulfidation at the Cys136 residue. Here, contrary to the anticipated role of L-S-nitrosocysteine (L-CysNO) as a nitric oxide (NO) donor, we demonstrate that it serves as a substrate for CSE and that its metabolites inhibit the activity of the enzyme during L-CysNO metabolism. The in vitro incubation of CSE—but not the Cys136/171Val mutant—with L-CysNO resulted in the dose-dependent inhibition of supersulfide production, which was not reversed by the reducing agents. Notably, CSE activity remained unchanged upon preincubation with other NO donors, such as S-nitrosoglutathione or D-CysNO, but was inhibited when coincubated with cysteine. Furthermore, when PLP was removed from the CSE/L-CysNO premix, L-CysNO no longer inhibited CSE activity, suggesting that CSE metabolizes L-CysNO and that its metabolites contribute to enzyme inactivation. Indeed, we identified thionitrous acid and pyruvate as the primary CSE/L-CysNO reaction products. Thus, we establish L-CysNO as a CSE substrate and demonstrate that its metabolites act as enzyme inhibitors through a novel irreversible modification at the Cys136/171 residues. Full article

(This article belongs to the Special Issue Nitric Oxide (NO) and Hydrogen Sulfide (H₂S) in Biology, Illness, and Therapies—2nd Edition)

► Show Figures

Figure 1

20 pages, 5047 KB

Open AccessArticle

Physiological and Transcriptome Analyses Offer Insights into Revealing the Mechanisms of Red Tilapia (Oreochromis spp.) in Response to Carbonate Alkalinity Stress

by Wei Ye, Wen Wang, Jixiang Hua, Dongpo Xu and Jun Qiang

Antioxidants 2025, 14(9), 1112; https://doi.org/10.3390/antiox14091112 (registering DOI) - 13 Sep 2025

Abstract

The utilization of saline–alkali water resources presents a promising approach for freshwater aquaculture. Red tilapia (Oreochromis spp.) exhibits moderate salinity tolerance, but its adaptation mechanism to alkaline conditions remains poorly understood. In the current study, five alkaline carbonate concentrations in a 60-day [...] Read more.

The utilization of saline–alkali water resources presents a promising approach for freshwater aquaculture. Red tilapia (Oreochromis spp.) exhibits moderate salinity tolerance, but its adaptation mechanism to alkaline conditions remains poorly understood. In the current study, five alkaline carbonate concentrations in a 60-day chronic stress experiment on red tilapia were evaluated. The experimental design included a control group (CA0, 0 mmol/L) and three treatment groups (CA10, 20 mmol/L; CA30, 30 mmol/L; and CA40 40 mmol/L). The results indicated that at alkaline carbonate concentrations exceeding 20 mmol/L, the gill filaments exhibited curling and deformation, the hepatocytes displayed migration, and tissue damage increased significantly. The gill’s antioxidant capacity initially decreased and then increased, with severe gill injury in the CA40 group, leading to significantly reduced levels of SOD, CAT, and GSH-PX compared to the CA40 group (p < 0.05). Conversely, the enzymatic activities related to energy metabolism showed an opposite trend under alkaline carbonate stress. The transcriptome analyses of gill tissues across five groups identified significant alterations in key pathways, including the metabolic process (endocytosis, focal adhesion, PI3K−Akt signaling pathway, MAPK signaling pathway, and Citrate cycle (TCA cycle)), and immune responses (mTOR signaling and NOD−like receptor signaling pathways). Additionally, we screened 13 differentially expressed genes (DEGs) as potential regulators of alkaline stress and validated their expression levels using quantitative real-time PCR (qPCR). This study preliminarily elucidated the molecular mechanism of red tilapia in the physiological regulation process under chronic alkaline stress, and offers a theoretical foundation for breeding programs aimed at developing alkali-tolerant strains for aquaculture in alkaline water environments. Full article

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

► Show Figures

Figure 1

25 pages, 999 KB

Open AccessReview

Carotenoids and Their Interaction with the Immune System

by Miguel Medina-García, Andrés Baeza-Morales, Pascual Martínez-Peinado, Sandra Pascual-García, Carolina Pujalte-Satorre, Rosa María Martínez-Espinosa and José Miguel Sempere-Ortells

Antioxidants 2025, 14(9), 1111; https://doi.org/10.3390/antiox14091111 (registering DOI) - 12 Sep 2025

Abstract

Carotenoids are lipophilic pigments naturally occurring in plants and, to a lesser extent, in certain non-photosynthetic organisms. They play a critical role in human health due to their antioxidant and immunomodulatory properties. Key carotenoids such as β-carotene, lycopene, lutein, and zeaxanthin are capable [...] Read more.

Carotenoids are lipophilic pigments naturally occurring in plants and, to a lesser extent, in certain non-photosynthetic organisms. They play a critical role in human health due to their antioxidant and immunomodulatory properties. Key carotenoids such as β-carotene, lycopene, lutein, and zeaxanthin are capable of neutralizing reactive oxygen species, thereby mitigating oxidative stress—a major contributor to the onset and progression of chronic diseases. These compounds also modulate immune responses by influencing lymphocyte proliferation, enhancing natural killer cell activity, and regulating the production of pro- and anti-inflammatory cytokines. Such immunomodulatory effects are associated with a reduced risk of infectious diseases and have shown potential protective roles against inflammatory conditions, cardiovascular and neurodegenerative disorders, and certain types of cancer. Moreover, diets rich in carotenoids are linked to improved immune status, particularly in vulnerable populations such as the elderly and immunocompromised individuals. Despite strong epidemiological evidence, clinical trials involving carotenoid supplementation have produced mixed results, indicating that their effectiveness may depend on the broader dietary context and interactions with other nutrients. In summary, carotenoids are important dietary compounds that contribute to immune regulation and the prevention of various diseases, although further clinical research is needed to determine optimal intake levels and assess their full therapeutic potential. Full article

(This article belongs to the Special Issue Carotenoids in Health and Disease)

40 pages, 2910 KB

Open AccessReview

Engineering Antioxidants with Pharmacological Applications: Biotechnological Perspectives

by Mădălina Paraschiv, Delia Turcov, Anca Zbranca-Toporaş, Bianca-Iulia Ciubotaru, Irina Grădinaru and Anca-Irina Galaction

Antioxidants 2025, 14(9), 1110; https://doi.org/10.3390/antiox14091110 - 12 Sep 2025

Abstract

Oxidative stress, a state resulting from an imbalance between the generation of reactive oxygen species (ROS) and the body’s antioxidant capacity, is a significant contributor to the development of various human pathologies, including malignancies, cardiovascular conditions, neurodegenerative disorders, and the aging process. Antioxidants, [...] Read more.

Oxidative stress, a state resulting from an imbalance between the generation of reactive oxygen species (ROS) and the body’s antioxidant capacity, is a significant contributor to the development of various human pathologies, including malignancies, cardiovascular conditions, neurodegenerative disorders, and the aging process. Antioxidants, both enzymatic and non-enzymatic, are vital in neutralizing free radicals and protecting against cellular damage. Given the limitations of synthetic antioxidants, such as potential toxicity and variable effectiveness, there has been a growing focus on biotechnological methods for producing these essential compounds. This review, titled “Engineering Antioxidants with Pharmacological Applications: Biotechnological Perspectives”, explores the latest developments in this field by examining how biological systems are being utilized to create a wide range of antioxidants. We discuss key production strategies, including the use of microbial cell factories, enzyme-driven synthesis, plant cell cultures, and metabolic engineering. The review provides specific examples of biotechnologically derived antioxidants, such as enzymatic defenses like superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzymatic molecules like carotenoids, polyphenols, and vitamins. We also evaluate the therapeutic potential of these bio-engineered antioxidants, analyzing preclinical and clinical data on their effectiveness in disease prevention and treatment. The mechanisms by which these compounds combat oxidative stress are also discussed. Finally, we address the current hurdles in scaling up production and managing costs while also outlining future research avenues, such as the creation of new production systems, advanced delivery technologies, and the discovery of novel antioxidant compounds through bioprospecting and synthetic biology. This comprehensive review highlights the potential of biotechnology to offer sustainable and impactful solutions for managing oxidative stress and enhancing overall health. Full article

(This article belongs to the Special Issue Multi-Target Profile of Antioxidant Compounds, Including Repurposing and Combination Strategies—2nd Edition)

► Show Figures

Figure 1

18 pages, 1505 KB

Open AccessArticle

The Role of Inulin in Maintaining Antioxidant Capacity and Enzymatic Activities of Jerusalem Artichoke (Helianthus tuberosus L.) Cultivars During Cold Storage

by Yuwen Mu, Bohua Zhang, Shiqi Lv, Fencan Li and Changming Zhao

Antioxidants 2025, 14(9), 1109; https://doi.org/10.3390/antiox14091109 - 12 Sep 2025

Abstract

Jerusalem artichoke (Helianthus tuberosus L.) is valued for its high inulin content and adaptability to marginal lands. This study investigated the changes in inulin content, antioxidant capacity, polyphenol concentrations, and enzymatic activities of eight cultivars during 60 days of cold storage. Inulin [...] Read more.

Jerusalem artichoke (Helianthus tuberosus L.) is valued for its high inulin content and adaptability to marginal lands. This study investigated the changes in inulin content, antioxidant capacity, polyphenol concentrations, and enzymatic activities of eight cultivars during 60 days of cold storage. Inulin levels ranged from 582.43 g/kg (LZJ006) to 809.70 g/kg (LZJ055), with LZJ047 maintaining the highest content throughout storage. The antioxidant potential, as measured by ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, declined across all cultivars, correlating with the reduction in inulin content. The polyphenol content varied significantly, with LZJ119 having 2.17 times more than LZJ010. POD activity increased, while catalase (CAT) and superoxide dismutase (SOD) activities fluctuated during the storage period. Hierarchical Cluster Analysis identified three distinct antioxidant clusters, revealing significant correlations between inulin content and key antioxidant parameters (CAT, FRAP, DPPH). These findings highlight the pivotal role of inulin in preserving the antioxidant system and bioactive properties of Jerusalem artichoke tubers during extended cold storage, providing valuable insights for post-harvest management and cultivar selection. Full article

(This article belongs to the Special Issue Food Proteins and Peptides as Antioxidants: Resource, Extraction, Functional Property and Application)

24 pages, 11114 KB

Open AccessArticle

Deinoxanthin-Enriched Extracellular Vesicles from Deinococcus radiodurans Drive IL-10–Dependent Tolerogenic Programming of Dendritic Cells

by Jeong Moo Han, Jaeyoon Lim, Woo Sik Kim, Bo-Gyeong Yoo, Jong-Hyun Jung, Sangyong Lim and Eui-Baek Byun

Antioxidants 2025, 14(9), 1108; https://doi.org/10.3390/antiox14091108 - 12 Sep 2025

Abstract

Extracellular vesicles (EVs) derived from bacteria are emerging as potent bioactive carriers that affect host immunity. Deinococcus radiodurans, an extremophilic bacterium with strong antioxidant capacity, produces EVs enriched in deinoxanthin (DX), a carotenoid with a reactive oxygen species–scavenging activity. Here, we assessed [...] Read more.

Extracellular vesicles (EVs) derived from bacteria are emerging as potent bioactive carriers that affect host immunity. Deinococcus radiodurans, an extremophilic bacterium with strong antioxidant capacity, produces EVs enriched in deinoxanthin (DX), a carotenoid with a reactive oxygen species–scavenging activity. Here, we assessed the antioxidant activity of D. radiodurans-derived EVs (R1-EVs) in biochemical assays and their immunomodulatory effects on dendritic cells (DCs). R1-EVs exhibited significantly higher antioxidant activity than EVs from a DX-deficient mutant strain (ΔcrtI-EVs), consistent with DX enrichment. Bone marrow-derived DCs treated with R1-EVs in the presence of lipopolysaccharide displayed reduced expression of surface maturation markers and pro-inflammatory cytokines, while interleukin-10 (IL-10) production and antigen uptake were preserved, indicating a tolerogenic phenotype. This tolerogenic program led to decreased proliferation and cytokine production in allogeneic CD4⁺ and CD8⁺ T cells. Mechanistically, R1-EVs inhibited mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways, key regulators of the DC activation. Importantly, IL-10 neutralization reversed these effects, restoring DC and T cell activation. Notably, ΔcrtI-EVs showed weaker antioxidant and immunoregulatory activities. Together, our findings identify R1-EVs as dual-functions, DX- and IL-10-dependent nanoplatform that integrates antioxidant and tolerogenic properties, with potential applications in inflammatory and autoimmune disease control. Full article

(This article belongs to the Special Issue Redox Regulation of Immune and Inflammatory Responses)

► Show Figures

Figure 1

17 pages, 1677 KB

Open AccessArticle

Association Between Blood Free Fatty Acid Concentrations in Midlife and Cerebral Small Vessel Disease

by Ryotaro Nukata, Yorito Hattori, Kotaro Noda, Takeshi Yoshimoto and Masafumi Ihara

Antioxidants 2025, 14(9), 1107; https://doi.org/10.3390/antiox14091107 - 12 Sep 2025

Viewed by 40

Abstract

Free fatty acids (FFAs) are a risk factor for recurrent ischemic stroke, primarily via the overproduction of reactive oxygen species. However, the association between FFA concentrations and cerebral small vessel disease (SVD), including lacunes, cerebral microbleeds, and white matter lesions on brain magnetic [...] Read more.

Free fatty acids (FFAs) are a risk factor for recurrent ischemic stroke, primarily via the overproduction of reactive oxygen species. However, the association between FFA concentrations and cerebral small vessel disease (SVD), including lacunes, cerebral microbleeds, and white matter lesions on brain magnetic resonance imaging, remains unclear. This study included 95 patients with acute ischemic stroke (median age: 59 [interquartile range: 49–73] years). The patients were divided into two groups: those aged ≤59 years (midlife patients) and those aged ≥60 years (late-life patients). In the midlife patients, the low serum total FFA concentration was an independent risk factor of lacunes (adjusted odds ratio [aOR]: 0.82, 95% confidence interval [CI]: 0.69–0.96; p = 0.013). Among FFA fractions, low serum free C14:0 (aOR: 0.80, 95% CI: 0.66–0.98; p = 0.028), and free C18:3n-3 (aOR: 0.93, 95% CI: 0.87–0.99; p = 0.015) concentrations were independent risk factors of lacunes in the midlife patients. However, the serum total FFA concentrations did not differ according to the SVD findings in the late-life patients. Therefore, low blood FFA concentrations in midlife can be a novel “nonvascular,” nonatheromatous risk factor of SVD, including the presence of lacunes identified on brain magnetic resonance imaging. Full article

(This article belongs to the Special Issue The Implication of Oxidative Stress on Human Aging and Associated Pathologies)

► Show Figures

Figure 1

2 pages, 551 KB

Open AccessCorrection

Correction: D’Amico et al. Hidrox^® and Chronic Cystitis: Biochemical Evaluation of Inflammation, Oxidative Stress, and Pain. Antioxidants 2021, 10, 1046

by Ramona D’Amico, Angela Trovato Salinaro, Marika Cordaro, Roberta Fusco, Daniela Impellizzeri, Livia Interdonato, Maria Scuto, Maria Laura Ontario, Roberto Crea, Rosalba Siracusa, Salvatore Cuzzocrea, Rosanna Di Paola and Vittorio Calabrese

Antioxidants 2025, 14(9), 1106; https://doi.org/10.3390/antiox14091106 - 11 Sep 2025

Viewed by 103

Abstract

In the original publication [...] Full article

► Show Figures

Figure 6

22 pages, 1031 KB

Open AccessArticle

Relationship Between Bioactive Compounds and Biological Activities (Antioxidant, Antimicrobial, Antihaemolytic) of ‘Colcas’ Fruits at Different Stages of Maturity

by Elena Coyago-Cruz, Johana Zúñiga-Miranda, Gabriela Méndez, Aida Guachamin, Ruth Escobar-Quiñonez, Carlos Barba-Ostria and Jorge Heredia-Moya

Antioxidants 2025, 14(9), 1105; https://doi.org/10.3390/antiox14091105 - 10 Sep 2025

Viewed by 159

Abstract

The genus Miconia is used in traditional medicine, but there are few studies supporting the bioactive potential of Miconia crocea. This study aimed to evaluate the physicochemical properties, bioactive compound content, and antioxidant, antimicrobial and antihaemolytic activities at four different phenological stages [...] Read more.

The genus Miconia is used in traditional medicine, but there are few studies supporting the bioactive potential of Miconia crocea. This study aimed to evaluate the physicochemical properties, bioactive compound content, and antioxidant, antimicrobial and antihaemolytic activities at four different phenological stages of M. crocea. The pH, soluble solids, titratable acidity, moisture and ash content were determined. Mineral contents were determined by atomic absorption. Vitamin C, organic acids, carotenoids, chlorophylls and derivatives and phenols were determined by chromatography. Total anthocyanins were determined by spectrophotometry. The antioxidant capacity was evaluated using ABTS and DPPH assays, and the antimicrobial activity was tested against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus mutans, Candida albicans and Candida tropicalis. Potassium was the predominant mineral (>1000 mg/100 g DW), while malic acid was the predominant organic acid. Lutein was the most abundant carotenoid, as among the phenolic compounds, m-coumaric acid and chlorogenic acid were most abundant (>1000 mg/100 g DW). The optimal method for preparing the extract for antimicrobial and haemolytic activity, with a focus on phenols, involved using 50% ethanol, applying ultrasound for six minutes, and carrying out three extractions. The M0% extract exhibited the most potent antimicrobial activity against S. mutans (MIC: 7.8 mg/mL). Anti-haemolytic activity indicates biocompatibility. The results emphasise the bioactive and antimicrobial potential of M. crocea, suggesting its possible application in various industries. However, further research is needed in the form of in vivo studies. Full article

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

► Show Figures

Graphical abstract

17 pages, 1087 KB

Open AccessArticle

Non-Invasive Redox Biomarkers Detected in Organ Preservation Outflow Solution Enable Early Prediction of Human Liver Allograft Dysfunction

by Daniel Vidal-Correoso, María José Caballero-Herrero, Ana M. Muñoz-Morales, Sandra V. Mateo, Marta Jover-Aguilar, Felipe Alconchel, Laura Martínez-Alarcón, Víctor López-López, Antonio Ríos-Zambudio, Pedro Cascales, José Antonio Pons, Pablo Ramírez, Kristine Stromsnes, Juan Gambini, Santiago Cuevas and Alberto Baroja-Mazo

Antioxidants 2025, 14(9), 1104; https://doi.org/10.3390/antiox14091104 - 10 Sep 2025

Viewed by 148

Abstract

Liver transplantation is commonly used for end-stage liver disease, but the demand for organs exceeds the supply, leading to the use of expanded criteria donors (ECDs). Organs from ECDs, especially from donors after circulatory death (DCD), encounter challenges like increased ischemia damage. Biomarkers, [...] Read more.

Liver transplantation is commonly used for end-stage liver disease, but the demand for organs exceeds the supply, leading to the use of expanded criteria donors (ECDs). Organs from ECDs, especially from donors after circulatory death (DCD), encounter challenges like increased ischemia damage. Biomarkers, especially oxidative stress markers, may provide valuable insights for understanding and monitoring post-transplant events. Here, we highlight the unique value of organ preservation solution (OPS) as a non-invasive and early source of redox biomarkers, directly reflecting graft status during critical cold storage. This study investigated oxidative stress in 74 donated livers using OPS samples collected after cold storage, and also liver biopsies obtained before and after storage. We measured lipid peroxidation, protein carbonylation, DNA oxidation, and total antioxidant capacity from OPS, and performed gene expression analysis of liver biopsies. Oxidative stress markers differed based on donation type, with higher lipid peroxidation in DCD samples compared with donation after brain death (18.51 ± 2.77 vs. 11.03 ± 1.31 nmoles malondialdehyde (MDA)/mg protein; p = 0.049). Likewise, oxidative damage markers were associated with clinical outcomes: lipid peroxidation was increased in patients who developed biliary complications (21.86 ± 5.91 vs. 11.97 ± 1.12 nmol MDA/mg protein; p = 0.05), and protein carbonylation was elevated in those experiencing acute rejection (199.6 ± 22.02 vs. 141.6 ± 15.94 nmol carbonyl/mg protein; p = 0.005). Moreover, higher protein carbonylation levels showed a trend toward reduced survival (p = 0.091). Transcriptomic analysis revealed overexpression of genes associated with reactive oxygen species production in DCD livers. A predictive model for acute rejection integrating OPS biomarkers with clinical variables achieved 83% accuracy. Hence, this study underscores the importance of assessing oxidative stress status in preservation fluid as a biomarker for evaluating liver transplant outcomes and highlights the need for validation in larger, independent cohorts. Full article

(This article belongs to the Special Issue Oxidative Stress and Liver Disease)

► Show Figures

Figure 1

23 pages, 2470 KB

Open AccessArticle

Evaluation of Polyphenolic Compounds Common in Greek Medicinal Plants for Their Antioxidant Effects and Antiviral Activity Against Dengue and Yellow Fever Viruses

by Eirini Kyriakopoulou, Aliki Tsakni, Evangelos Korakidis, George Mpekoulis, Katerina I. Kalliampakou, Monika Polanska, Jan F. M. Van Impe, Efstathia Tsakali, Dimitra Houhoula and Niki Vassilaki

Antioxidants 2025, 14(9), 1103; https://doi.org/10.3390/antiox14091103 - 10 Sep 2025

Viewed by 230

Abstract

Polyphenolic compounds, commonly found in Greek medicinal plants, exhibit promising antiviral and antioxidant properties, making them potential candidates for therapeutic purposes. This study aims to evaluate the antiviral activity of nine selected polyphenols against Dengue virus (DENV) and Yellow Fever virus (YFV) life [...] Read more.

Polyphenolic compounds, commonly found in Greek medicinal plants, exhibit promising antiviral and antioxidant properties, making them potential candidates for therapeutic purposes. This study aims to evaluate the antiviral activity of nine selected polyphenols against Dengue virus (DENV) and Yellow Fever virus (YFV) life cycles, alongside their antioxidant capacity determined by the DPPH method and the ABTS assay, and their ability to inhibit DNA strand scission induced by peroxyl radicals. Kaempferol and caffeic acid demonstrated the most potent inhibitory effects on DENV genome replication, while coumaric acid blocked viral entry more effectively. Notably, among the nine compounds, kaempferol exhibited the strongest anti-DENV effect, especially at the level of virus-released infectivity, showing the lowest EC₅₀ (3.55 μΜ) and the highest selectivity index (SI = 25.45). In contrast, none of the compounds showed significant antiviral activity against YFV genome replication. Concomitantly, caffeic acid and kaempferol had the highest radical scavenging activity (DPPH and ABTS assays), highlighting their dual properties. Moreover, DNA scission inhibition assays confirmed the strong antioxidant potential of all tested compounds, with caffeic acid and kaempferol achieving the highest inhibition rate of 98.98% and 97.34% respectively. These findings underscore the potential of specific polyphenols, particularly kaempferol and caffeic acid, as antiviral and antioxidant agents targeting DENV and oxidative stress-related damage. Full article

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

► Show Figures

Figure 1

18 pages, 10187 KB

Open AccessArticle

High-Fat-Diet-Induced Kidney Injury in Rats: The Role of Tart Cherry Supplementation

by Ilenia Martinelli, Proshanta Roy, Vincenzo Bellitto, Maria Vittoria Micioni Di Bonaventura, Carlo Cifani, Seyed Khosrow Tayebati and Daniele Tomassoni

Antioxidants 2025, 14(9), 1102; https://doi.org/10.3390/antiox14091102 - 10 Sep 2025

Viewed by 154

Abstract

The kidney plays a crucial role in the complex inter-organ communication that occurs during obesity, leading to the development of oxidative stress, inflammation, and fibrosis. Dysfunction of the transient receptor potential (TRP) ion channels contributes to this pathophysiology. This study was designed to [...] Read more.

The kidney plays a crucial role in the complex inter-organ communication that occurs during obesity, leading to the development of oxidative stress, inflammation, and fibrosis. Dysfunction of the transient receptor potential (TRP) ion channels contributes to this pathophysiology. This study was designed to evaluate the effects of antioxidant-rich fruit tart cherry (Prunus cerasus L.) on kidney morphology and protein expression in rats with diet-induced obesity (DIO). Methods include histological staining and immunohistochemical and Western blot assays. Obese rodents were fed with seed powder (DS) and seed powder plus juice (DJS) of the tart cherry. Results demonstrated that rats fed a high-fat-diet (HFD) showed a significant reduction in renal expression of the pro-inflammatory cytokines interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) following tart cherry supplementation. Furthermore, the study provided evidence that TRP channels, specifically TRP canonical 1 (TRPC1) and TRP melastatin 2 (TRPM2), were significantly upregulated in obese animals (p < 0.05 vs. CHOW rats) and markedly downregulated following tart cherry supplementation (p < 0.05 vs. DIO rats). In conclusion, these TRP proteins offer new insights for identifying targets and biomarkers for developing therapeutic strategies against HFD-induced renal damage, characterized by glomerulosclerosis, fibrosis, and inflammation. Tart cherries supplementation exerted a protective effect on the kidneys by reducing protein oxidation and pro-inflammatory cytokine expression. Full article

(This article belongs to the Special Issue Antioxidant Therapy for Obesity-Related Diseases)

► Show Figures

Figure 1

27 pages, 3081 KB

Open AccessArticle

Vitamin D Protects Pancreatic Cancer (PC) Cells from Death and DNA Damage Induced by Oxidative Stress

by Izabela Szymczak-Pajor, Egle Morta Antanaviciute, Józef Drzewoski, Ireneusz Majsterek and Agnieszka Śliwińska

Antioxidants 2025, 14(9), 1101; https://doi.org/10.3390/antiox14091101 - 10 Sep 2025

Viewed by 499

Abstract

In addition to its well-recognized roles in immunomodulation and calcium phosphate homeostasis, growing evidence shows that Vitamin D (Vit. D) presents a wide range of other properties, including antioxidant and anticancer effects. However, the action of Vit. D is not fully recognized in [...] Read more.

In addition to its well-recognized roles in immunomodulation and calcium phosphate homeostasis, growing evidence shows that Vitamin D (Vit. D) presents a wide range of other properties, including antioxidant and anticancer effects. However, the action of Vit. D is not fully recognized in pancreatic cancer (PC) cells exposed to oxidative stress. Therefore, the aim of the present study was to investigate whether vitamin D₃ (Vit. D₃) protects PC cells from death induced by oxidative stress. PC cells are suggested to be resistant to oxidative stress since they demonstrate overexpression of superoxide dismutase (SOD) 1–3. The study measured PC cell viability, DNA damage level, the mRNA and protein expression of antioxidant enzymes, reactive oxygen species (ROS) level and activity of antioxidant enzymes after exposure to H₂O₂, Vit. D₃ and their combinations. N-Acetyl-L-Cysteine (NAC), a well-known direct ROS scavenger, was used as a positive control. Vit. D₃ exposure alone had no effect on PC cell viability, ROS level and DNA damage. Its impact on the mRNA and protein expression of antioxidant enzymes was also scarce. However, Vit. D₃ protected PC cells against H₂O₂-induced death, similarly to NAC. It also diminished the increase in ROS and DNA damage caused by H₂O₂. In addition, Vit. D₃ enhanced the mRNA expression of catalase (CAT), SOD 1–3 and glutathione peroxidase (Gpx)3, but did not affect their protein levels in PC cells exposed to oxidative stress. Interestingly, Vit. D₃ increased CAT activity after 24 h in 1.2B4 cells and elevated the activity of both CAT and Gpx after 2 h in PANC-1 cells, which could contribute to the observed reduction of H₂O₂-induced ROS level. To conclude, our findings show that antioxidant properties of Vit. D₃ may protect PC cells from oxidative stress-induced death. Therefore, further studies are needed to understand the action of Vit. D₃ in PC cells. Full article

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

► Show Figures

Figure 1

13 pages, 4338 KB

Open AccessArticle

A Nanoformulation of Ubiquinol and Selenium Promotes Proliferation of Human Induced Pluripotent Stem Cells

by Filomain Nguemo, Hai Zhang, Annette Koester, Susan Rohani, Sureshkumar Perumal Srinivasan and Jürgen Hescheler

Antioxidants 2025, 14(9), 1100; https://doi.org/10.3390/antiox14091100 - 10 Sep 2025

Viewed by 419

Abstract

Human induced pluripotent stem cells (hiPSCs) hold immense promise for regenerative medicine. However, a critical barrier to the clinical application of hiPSCs is the difficulty in promoting robust cell proliferation while preserving their pluripotent state. Efficient hiPSC expansion without loss of pluripotency is [...] Read more.

Human induced pluripotent stem cells (hiPSCs) hold immense promise for regenerative medicine. However, a critical barrier to the clinical application of hiPSCs is the difficulty in promoting robust cell proliferation while preserving their pluripotent state. Efficient hiPSC expansion without loss of pluripotency is crucial for generating high quality cells or therapeutic applications, disease modeling, and drug discovery. In our study, we investigated the effects of QuinoMit Q10^® fluid (QMF-Se), a nanoformulated supplement containing Ubiquinol (the active form of Coenzyme Q10) and Selenium, on hiPSC growth and maintenance in vitro. Interesting, QMF-Se supplementation significantly enhances hiPSC proliferation compared to control cultures. This increase in cell number was accompanied by heightened mitochondrial activity, suggesting improved cellular energy metabolism. Importantly, the expression of core pluripotency markers OCT4, NANOG, and SOX2 remained unaltered, confirming that the stem cells retained their undifferentiated status. Moreover, we observed that QMF-Se treatment conferred protective effects during the freeze–thaw process, reducing cell death and supporting post-thaw recovery. These results indicate that QMF-Se may improve both cell culture efficiency and cryopreservation outcomes. Overall, our findings highlight the potential of QMF-Se as a valuable additive for hiPSC culture systems, contributing to more efficient and reliable expansion protocols in regenerative medicine research. Full article

(This article belongs to the Special Issue Unveiling the Essential Role of Coenzyme Q in Health)

► Show Figures

Figure 1

18 pages, 1207 KB

Open AccessReview

Biochemical, Biological, and Clinical Properties of γ-Oryzanol

by Helena Juricic, Massimiliano Cuccioloni, Laura Bonfili, Mauro Angeletti, Daniela Uberti, Anna Maria Eleuteri, Giulia Abate and Valentina Cecarini

Antioxidants 2025, 14(9), 1099; https://doi.org/10.3390/antiox14091099 - 9 Sep 2025

Viewed by 403

Abstract

γ-Oryzanol is a complex mixture of ferulic acid esters of phytosterols and triterpene alcohols predominantly found in rice bran. It exhibits a wide range of biological activities, including antioxidant, anti-inflammatory, and lipid-lowering effects, as well as the ability to modulate cellular metabolic pathways [...] Read more.

γ-Oryzanol is a complex mixture of ferulic acid esters of phytosterols and triterpene alcohols predominantly found in rice bran. It exhibits a wide range of biological activities, including antioxidant, anti-inflammatory, and lipid-lowering effects, as well as the ability to modulate cellular metabolic pathways in both in vitro and in vivo models. The composition and concentration of γ-oryzanol vary significantly among rice varieties and are influenced by genetic, environmental, and technological factors. Advances in extraction methods, including traditional solvent extraction and innovative approaches such as supercritical fluid extraction, have improved yield and purity, supporting its use in functional foods, nutraceuticals, and cosmetics. Current research in the biological, biomedical, and cosmetic fields is actively investigating γ-oryzanol’s mechanisms of action in metabolic regulation and inflammation, as well as developing advanced formulation strategies to enhance its antioxidant, skin-protective, and functional properties. These efforts aim to optimize its delivery and efficacy by addressing challenges related to poor water solubility and bioavailability, thereby expanding its role as a multifunctional bioactive compound. This review provides a comprehensive overview on γ-oryzanol, focusing on its extraction techniques, chemical characterization, and biological/pharmacological activities. Additionally, clinical trials investigating its efficacy and safety have been thoroughly dissected, offering valuable insights into its therapeutic potential in human populations. Full article

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

► Show Figures

Figure 1

3 pages, 4994 KB

Open AccessCorrection

Correction: Ghareeb et al. Chemical Profiling of Polyphenolics in Eucalyptus globulus and Evaluation of Its Hepato–Renal Protective Potential Against Cyclophosphamide Induced Toxicity in Mice. Antioxidants 2019, 8, 415

by Mosad A. Ghareeb, Mansour Sobeh, Walaa H. El-Maadawy, Hala Sh. Mohammed, Heba Khalil, Sanaa Botros and Michael Wink

Antioxidants 2025, 14(9), 1098; https://doi.org/10.3390/antiox14091098 - 9 Sep 2025

Viewed by 156

Abstract

In the original publication [...] Full article

► Show Figures

Figure 5

25 pages, 3060 KB

Open AccessArticle

Maternal Hydroxytyrosol Supplementation Enhances Antioxidant Capacity and Immunometabolic Adaptations in Nutrient-Restricted Beef Cows and Their Offspring

by Nieves Escalera-Moreno, Javier Álvarez-Rodríguez, Leire López de Armentia, Alba Macià, Maria José Martín-Alonso, Ester Molina, Daniel Villalba, Albina Sanz and Beatriz Serrano-Pérez

Antioxidants 2025, 14(9), 1097; https://doi.org/10.3390/antiox14091097 - 8 Sep 2025

Viewed by 325

Abstract

The impact of maternal dietary restriction and hydroxytyrosol (HT) supplementation during the last third of gestation on plasma malondialdehyde (MDA) concentration, total antioxidant capacity (ABTS assay), and peripheral blood gene expression related to antioxidant defence, immune response, and energy metabolism was evaluated in [...] Read more.

The impact of maternal dietary restriction and hydroxytyrosol (HT) supplementation during the last third of gestation on plasma malondialdehyde (MDA) concentration, total antioxidant capacity (ABTS assay), and peripheral blood gene expression related to antioxidant defence, immune response, and energy metabolism was evaluated in beef cows and calves. Two feeding treatments in late gestation (T100% vs. T60% of nutrient requirements) and two HT levels (Control vs. HT at 180 mg/kg of diet) were evaluated during gestation (n = 46 cows) and lactation (n = 37 cows and calves). In pregnant cows, undernutrition led to inhibition of glucose oxidation (PDK4), decreased lipid synthesis (HMGCS1 and SCD) and TLR signalling; T60% cows showed higher plasma MDA (p < 0.05) with no positive effect of HT on antioxidant capacity. Contrarily, during lactation, earlier HT supplementation upregulated antioxidant capacity and modulated antioxidant gene expression (p < 0.05). In calves, there was an increase in SOD1, CAT, and GPX1, especially in the T60%-HT group (p < 0.05). Interestingly, HT supplementation increased glucose transport (SLC2A1/GLUT1) during pregnancy and lactation (p < 0.05). However, it caused different effects on immunometabolic regulation in both dams and calves, depending on maternal diet. Overall, maternal HT supplementation under restricted nutritional conditions promoted postpartum antioxidant capacity and modulated immune and metabolic gene expression in cows and calves. Full article

(This article belongs to the Special Issue Novel Antioxidants for Animal Nutrition—2nd Edition)

► Show Figures

Figure 1

16 pages, 3788 KB

Open AccessArticle

Castalin Induces ROS Production, Leading to DNA Damage and Increasing the Activity of CHK1 Inhibitor in Cancer Cell Lines

by Margherita D’Angelo, Annamaria Medugno, Maria Cuomo, Maria Carmen Ragosta, Andrea Russo, Giulio Mazzarotti, Giuseppe Maria Napolitano, Carmelina Antonella Iannuzzi, Francesco Errichiello, Luigi Frusciante, Martino Forino, Raffaele Cucciniello, Canio Martinelli, Annamaria Salvati, Domenico Memoli, Giovanni Nassa, Enrico Bucci, Michelino De Laurentiis, Antonio Giordano and Luigi Alfano

Antioxidants 2025, 14(9), 1096; https://doi.org/10.3390/antiox14091096 - 8 Sep 2025

Viewed by 460

Abstract

(1) Background: The use of cancer therapy is one of the most challenging arguments in cancer research and is in constant development. One of the principal problems connected with tumor therapy arises from the potential side effects connected with the classical chemotherapeutic treatment [...] Read more.

(1) Background: The use of cancer therapy is one of the most challenging arguments in cancer research and is in constant development. One of the principal problems connected with tumor therapy arises from the potential side effects connected with the classical chemotherapeutic treatment but also with molecular target therapy. The identification of novel molecules useful for the reduction of potential side effects but also as a new therapeutic opportunity is one of the hottest topics. (2) Methods: We identified castalin from chestnut shells by using NRM and LC-MS/MS. We treated different cancer cell lines with castalin alone or in combination with a CHK1 inhibitor. Finally, we performed an RNA-seq analysis of HeLa cells treated with castalin. (3) Results: We demonstrated the ability of castalin to induce DNA damage, probably by increasing ROS production. Consistently, antioxidant treatment, with ascorbic acid, reduced the DNA damage induced by castalin. Finally, we demonstrated the potential synergistic effect of castalin with SRA737, a CHK1 inhibitor currently used in clinical trials. (4) Conclusions: We demonstrated the ability of castalin to induce DNA damage favoring NHEJ repair. Moreover, the use of castalin in combination with SRA737 increased the efficacy of the CHK1 inhibitor, reducing its possible side effects. Full article

(This article belongs to the Section ROS, RNS and RSS)

► Show Figures

Graphical abstract

35 pages, 1698 KB

Open AccessReview

Carp-Derived Antioxidant Peptides and Hydrolysates: Biological Effects and Potential Applications in Health and Food

by Fai-Chu Wong, Wen-Jie Ng, Ai-Lin Ooi, Fui-Fui Lem and Tsun-Thai Chai

Antioxidants 2025, 14(9), 1095; https://doi.org/10.3390/antiox14091095 - 8 Sep 2025

Viewed by 254

Abstract

Oxidative stress is a factor implicated in chronic diseases and aging, motivating the search for natural antioxidants. Over the past ten years, food-derived peptides have been recognized as potent antioxidants. Carp, a globally farmed fish, is a protein-rich raw material for producing antioxidant [...] Read more.

Oxidative stress is a factor implicated in chronic diseases and aging, motivating the search for natural antioxidants. Over the past ten years, food-derived peptides have been recognized as potent antioxidants. Carp, a globally farmed fish, is a protein-rich raw material for producing antioxidant peptides and hydrolysates. This review summarizes the current knowledge on these antioxidant peptides and hydrolysates, including their production, bioactivity, and applications. We discuss how enzymatic hydrolysis of carp by-products (e.g., skin, scales, and swim bladders) represents a strategy for waste valorization. Cellular and in vivo findings demonstrate the effectiveness of carp peptides and hydrolysates in tackling oxidative stress by reducing reactive oxygen species and enhancing cellular antioxidant enzymes. In addition to their antioxidant properties, these peptides and hydrolysates also possess anti-inflammatory, anti-melanogenic, and wound-healing properties. Potential applications of carp peptides and hydrolysates include their use as natural food preservatives and as active ingredients for skincare, nutraceuticals, and sports nutrition. Future research should focus on validating the in vivo bioavailability and assessing the long-term safety of carp peptides and hydrolysates to support their potential application in health. Carp-derived peptides are a valuable resource for developing functional foods and health products, which can contribute to a more sustainable food industry. Full article

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

► Show Figures

Figure 1

15 pages, 4308 KB

Open AccessArticle

Prenatal Melatonin Therapy Enhances Postnatal Lung Development in a Mouse Model of Inflammation-Induced Preterm Birth

by So Hee Park, Hee Young Cho, Jin Hyun Jun, Haengseok Song and Ji Yeon Lee

Antioxidants 2025, 14(9), 1094; https://doi.org/10.3390/antiox14091094 - 8 Sep 2025

Viewed by 218

Abstract

Inflammation-induced preterm birth (PTB) significantly impacts neonatal development, particularly due to fetal lung immaturity. The lungs undergo critical development both in utero and postnatally, and PTB disrupts this process, leading to impaired pulmonary function. Current treatments for promoting lung maturation in preterm infants [...] Read more.

Inflammation-induced preterm birth (PTB) significantly impacts neonatal development, particularly due to fetal lung immaturity. The lungs undergo critical development both in utero and postnatally, and PTB disrupts this process, leading to impaired pulmonary function. Current treatments for promoting lung maturation in preterm infants have limited efficacy and safety. Melatonin, known for its potent antioxidant and anti-inflammatory properties, has shown promise in preventing PTB, but its effects on fetal and postnatal lung maturation remain unclear. This study evaluated the therapeutic efficacy of melatonin in a mouse model of intrauterine inflammation-induced PTB (IPTB). Pregnant mice (Pregnancy Day 17, [PD17]) were assigned to control, lipopolysaccharide (LPS), and LPS + melatonin groups. LPS (25 µg) was injected into the right uterine horn, with melatonin (10 mg/kg) administered intraperitoneally 30 min prior. Uterine tissues were collected at 6 and 24 h post-LPS administration for molecular and histological analyses. PTB occurred in seven out of eleven (63.6%) IPTB mice within 24 h of LPS injection, whereas melatonin significantly reduced this rate to 25% (2/8). In melatonin-treated mice, the downregulation of pro-inflammatory genes in uterine tissues, restoration of placental blood flow, increased lamellar body counts, and prevention of LPS-induced vacuolation in PD18 fetal lungs were observed. Furthermore, melatonin administration enhanced surfactant protein B expression and improved lung structure. In the offspring of IPTB mice that survived, melatonin further suppressed pro-inflammatory markers and promoted lung septal thickening at postnatal day 3. In conclusion, melatonin prevents PTB, mitigates inflammation, and supports fetal lung maturation in IPTB mice, highlighting its therapeutic potential for improving neonatal pulmonary outcomes. Full article

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

► Show Figures

Figure 1

19 pages, 4637 KB

Open AccessArticle

Integrated Lipidomics and Network Pharmacology Reveal the AMPK-Mediated Therapeutic Mechanism of 3,3′-Diindolylmethane in Hepatic Lipid Metabolism

by Xudong Li, Yunfeng Lin, Ruomei Niu, Siyuan Chen, Jingyun Pan, Yuquan Zhong, Junqiang Du, Qiuxia Dong, Hongfeng Zhang, Heng Fang, Huiyang Zhu and Wei Zhu

Antioxidants 2025, 14(9), 1093; https://doi.org/10.3390/antiox14091093 - 7 Sep 2025

Viewed by 564

Abstract

Dysregulation of hepatic lipid metabolism constitutes a central mechanism in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). 3,3′-Diindolylmethane (DIM), a bioactive compound abundant in dietary Brassica vegetables, exhibited protective effects on hepatocellular carcinoma and metabolic/inflammatory pathologies. Nevertheless, the effects of DIM [...] Read more.

Dysregulation of hepatic lipid metabolism constitutes a central mechanism in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). 3,3′-Diindolylmethane (DIM), a bioactive compound abundant in dietary Brassica vegetables, exhibited protective effects on hepatocellular carcinoma and metabolic/inflammatory pathologies. Nevertheless, the effects of DIM on hepatic lipid metabolism and its underlying mechanisms remain unclear. Administration of DIM (50 mg/kg bw/day) prevented oxidative stress and hepatic lipid deposition in both high-fat diet (HFD)-fed wild-type (WT) and ob/ob mice. Lipidomics revealed that DIM diminished the lipogenesis and reshaped the hepatic lipid profile. Network pharmacology analysis identified the AMPK signaling pathway as the underlying mechanistic target for DIM in treating MASLD. In both HepG2 cells and mouse primary hepatocytes (MPH), DIM attenuated palmitic acid (PA)-induced cellular lipid accumulation, ROS generation, and reduction in oxygen consumption rate (OCR). These protective effects of DIM were diminished by co-treatment with Compound C (CC), a specific AMPK inhibitor. DIM administration enhanced AMPKα phosphorylation in vivo (WT/ob/ob mice) and in vitro (HepG2/MPH), concomitant with PPARα upregulation and SREBP1/ACC1 downregulation. CC abolished all DIM-induced molecular changes in vitro. Collectively, DIM alleviates hepatic lipid accumulation and oxidative stress in MASLD models through AMPK activation, subsequently modulating PPARα and SREBP1/ACC1 pathways. Full article

► Show Figures

Graphical abstract

17 pages, 4777 KB

Open AccessArticle

Epigallocatechin Gallate Ameliorates Granulosa Cell Developmental via the Eukaryotic Initiation Factor 2 Alpha/Activating Transcription Factor 4 Pathway in Hyperthyroid Female Rats

by Ying Sun, Mingqi Wu, Haoyuan Feng, Yilin Yao, Rui Chen, Yanzhou Yang and Cheng Zhang

Antioxidants 2025, 14(9), 1092; https://doi.org/10.3390/antiox14091092 - 6 Sep 2025

Viewed by 1348

Abstract

Follicular development is recognized as a highly complex biological process regulated by multiple factors. Thyroid hormone (TH) is considered one of the key regulators of female reproduction, and its dysregulation can significantly impair follicular development. Epigallocatechin gallate (EGCG), the main active component of [...] Read more.

Follicular development is recognized as a highly complex biological process regulated by multiple factors. Thyroid hormone (TH) is considered one of the key regulators of female reproduction, and its dysregulation can significantly impair follicular development. Epigallocatechin gallate (EGCG), the main active component of green tea, possesses strong antioxidant properties. Numerous studies have demonstrated that EGCG positively influences reproductive function in both humans and animals. However, whether EGCG directly affects follicular development under conditions of TH dysregulation remains poorly understood. The primary objective of this study was to investigate the impact of hyperthyroidism on ovarian development, examine whether EGCG could mitigate the adverse effects of TH dysregulation, and elucidate the underlying molecular mechanisms. In the T₄-induced hyperthyroidism rat model, ovarian tissues were serially sectioned for Hematoxylin-Eosin (HE) and Masson’s trichrome staining to assess morphological changes, and follicle numbers were quantified at each developmental stage. Granulosa cell (GC) viability, proliferation, and apoptosis induced by T₃ were evaluated using CCK8, EdU, and TUNEL assays, respectively. Antioxidant enzyme activity was measured, and the expression levels of related proteins were analyzed via Western blotting. Results showed that hyperthyroidism altered ovarian structure, significantly increasing the number of atretic follicles. Levels of antioxidant enzymes, including Superoxide Dismutase (SOD), Glutathione Peroxidase (GSH-PX), and Catalase (CAT), were markedly decreased, whereas the lipid peroxidation product malondialdehyde (MDA) was significantly elevated. Furthermore, all ERS-related proteins, phosphorylated Eukaryotic Initiation Factor 2 Alpha (p-eIF2α), Activating Transcription Factor 4 (ATF4), C/EBP homologous protein (CHOP), and Caspase-3, were upregulated, accompanied by decreased glucose-regulated protein 78 (GRP78) expression. Treatment with EGCG alleviated these detrimental effects of hyperthyroidism. At the cellular level, high concentrations of T₃ reduced GC viability and proliferation while increasing apoptosis. Reactive oxygen species levels were elevated, and GRP78 expression was decreased. Notably, all T₃-induced effects were reversed by EGCG treatment. In summary, this study demonstrates that hyperthyroidism induces oxidative stress in GCs, which triggers endoplasmic reticulum stress via the eIF2α/ATF4 pathway and leads to apoptosis. EGCG mitigates apoptosis by enhancing antioxidant capacity, thereby preserving ovarian function. These findings establish EGCG as a protective agent for maintaining ovarian health and fertility. Full article

► Show Figures

Figure 1

18 pages, 1964 KB

Open AccessArticle

Synthesis, Characterization, Antioxidant Activity, Antibacterial Activity, and Cytotoxicity of Quaternized Inulin Derivatives Bearing Aromatic Amides

by Yuan Chen, Yingqi Mi, Zhanyong Guo and Hongwu Zhang

Antioxidants 2025, 14(9), 1091; https://doi.org/10.3390/antiox14091091 - 6 Sep 2025

Viewed by 424

Abstract

In this study, a total of 12 new quaternized inulin (QIL) derivatives bearing aromatic amides were synthesized according to the ion exchange method. All the derivatives exhibited higher antioxidant activities in scavenging hydroxyl radicals, DPPH radicals, and superoxide radicals compared to pure inulin. [...] Read more.

In this study, a total of 12 new quaternized inulin (QIL) derivatives bearing aromatic amides were synthesized according to the ion exchange method. All the derivatives exhibited higher antioxidant activities in scavenging hydroxyl radicals, DPPH radicals, and superoxide radicals compared to pure inulin. Most of the derivatives could fully eliminate hydroxyl radicals at 1.6 mg/mL. Meanwhile, QIL derivatives exhibited increased antibacterial activity against Escherichia coli and Staphylococcus aureus compared to unmodified inulin. The structure–function relationship of the synthesized derivatives was discussed. Moreover, assays conducted with L929 cells (mouse fibroblasts) by the cell counting kit-8 (CCK-8) method did not show toxicities for the derivatives. Thus, the derivatives show promise for biomedical materials, functional foods, and pharmaceutical applications because they combine excellent antioxidant and antibacterial activities without exhibiting cytotoxicity. Full article

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

► Show Figures

Figure 1

20 pages, 7254 KB

Open AccessArticle

A Genome-Wide Association Study Reveals QTLs and Candidate Genes Associated with the Carotenoid Content in the Flesh of Cucurbita pepo L. Fruit

by Alba López, Alicia García, Alejandro Castro-Cegrí, María Segura, Álvaro Benítez, Francisco Palma, Dolores Garrido, Cecilia Martínez and Manuel Jamilena

Antioxidants 2025, 14(9), 1090; https://doi.org/10.3390/antiox14091090 - 5 Sep 2025

Viewed by 510

Abstract

Considering the importance of carotenoids in the human diet, their enhancement is a key trait in current breeding programs. This study assessed lutein, zeaxanthin, α-carotene, and β-carotene levels in the flesh of mature fruits from 257 global C. pepo accessions. Lutein and β-carotene [...] Read more.

Considering the importance of carotenoids in the human diet, their enhancement is a key trait in current breeding programs. This study assessed lutein, zeaxanthin, α-carotene, and β-carotene levels in the flesh of mature fruits from 257 global C. pepo accessions. Lutein and β-carotene were the most prevalent, with top accessions identified for each carotenoid. A panel of 120 accessions with reliable carotenoid contents and genetic diversity was analyzed using 23,111 GBS-generated SNPs in genome-wide association studies (GWAS). Three genomic regions (qtl1, qtl3, and qtl13) on chromosomes 1, 3, and 13 were significantly linked to carotenoid levels, with alternative alleles increasing the carotenoid content, leading to yellowish–orange flesh. Seven candidate genes were identified: CpTIC56, CpHSHP70, and CpPDL8, which regulate carotenoid biosynthesis in chloroplasts; CpSPX and CpPHO1, associated with phosphate homeostasis and carotenoid buildup; CpMYB106, co-expressed with carotenoid biosynthesis genes; and a CpPPR RNA-binding protein. RNA-seq data from yellow- and white-fleshed fruits supported their involvement in carotenoid accumulation. These results improve our understanding of the genetic control of carotenoid buildup in C. pepo fruit, supporting breeding efforts for improved nutritional quality. Full article

► Show Figures

Figure 1

14 pages, 7808 KB

Open AccessBrief Report

Polynucleotide HPT^TM-Based Hydrogels Exhibit Scavenging Activity Against Reactive Oxygen Species

by Maria Teresa Colangelo, Silvana Belletti, Stefano Guizzardi and Carlo Galli

Antioxidants 2025, 14(9), 1089; https://doi.org/10.3390/antiox14091089 - 5 Sep 2025

Viewed by 343

Abstract

This study investigates the scavenger activity of Polynucleotide High Purification Technology (PN HPT^TM), alone or in combination with hyaluronic acid (PN HPT^TM + HA) against oxidative stress induced by hydrogen peroxide (H₂O₂). Since oxidative stress is [...] Read more.

This study investigates the scavenger activity of Polynucleotide High Purification Technology (PN HPT^TM), alone or in combination with hyaluronic acid (PN HPT^TM + HA) against oxidative stress induced by hydrogen peroxide (H₂O₂). Since oxidative stress is implicated in numerous pathological conditions, identifying effective antioxidants is crucial for therapeutic development. We employed a cell-free fluorometric assay based on Calcein-AM, a fluorescence probe whose signal increases proportionally to the generation of reactive oxygen species (ROS), to evaluate the ability to neutralize ROS under varying oxidative stress conditions and determine the dose- and time-dependent effects of these compounds. PN HPT^TM, HA, and PN HPT^TM + HA were tested at various concentrations over multiple time points. Our results demonstrated that all tested treatments significantly lowered ROS levels compared to the untreated control. Notably, the PN HPT^TM -based compounds exhibited robust scavenging activity, with PN HPT^TM + HA displaying the strongest and most consistent ROS-neutralizing effect across all concentrations and time points. This enhanced performance suggests a synergistic interaction between PN HPT^TM and HA, potentially due to complementary mechanisms of free radical scavenging and structural stabilization. These findings highlight the potential of PN HPT^TM and PN HPT^TM + HA as effective antioxidative agents, offering potential for therapeutic applications where oxidative stress is central, including wound healing and tissue regeneration. Full article

(This article belongs to the Section ROS, RNS and RSS)

► Show Figures

Figure 1

28 pages, 10207 KB

Open AccessArticle

Hydrogen Sulfide Deficiency Contributes to Tubular Damage and Calcium Oxalate Crystal Formation in Hyperoxaluria Nephropathy: Role of Osteopontin and Tamm–Horsfall Protein

by Chien-Lin Lu, Yi-Shiou Tseng, Wen-Bin Wu, Chun-Hou Liao and Ming-Chieh Ma

Antioxidants 2025, 14(9), 1088; https://doi.org/10.3390/antiox14091088 - 5 Sep 2025

Viewed by 458

Abstract

Hydrogen sulfide (H₂S) exerts regulatory functions in kidney diseases. However, its protective role against kidney stone formation remains unclear. Here, we demonstrate that hyperoxaluria or oxalate exposure impairs H₂S formation, leading to tubular injury and calcium oxalate (CaOx) crystal [...] Read more.

Hydrogen sulfide (H₂S) exerts regulatory functions in kidney diseases. However, its protective role against kidney stone formation remains unclear. Here, we demonstrate that hyperoxaluria or oxalate exposure impairs H₂S formation, leading to tubular injury and calcium oxalate (CaOx) crystal deposition in both in vivo and in vitro models. In male rats fed 5% hydroxy-L-proline (HP), time-dependent increases in urinary supersaturation, tubular damage, and renal CaOx deposition were observed compared to controls. These changes were associated with the decreased expression of H₂S-producing enzymes and elevated urinary secretion of osteopontin (OPN) and Tamm–Horsfall protein (THP). Notably, the protein level and activity of specificity protein 1 (Sp1), a transcription factor regulating these enzymes, were markedly decreased in HP-treated kidneys. Chronic supplementation with the H₂S donor GYY4137 (GYY) significantly attenuated HP-induced tubular injury and CaOx deposition by reducing OPN and THP secretion. Consistent with in vivo results, H₂S donors mitigated oxalate-induced tubular cell damage and CaOx formation in MDCK cells. Mechanistically, oxalate activated cyclic AMP/protein kinase A (PKA) signaling, which promoted OPN and THP secretion; these effects were eradicated by the PKA inhibitor H89 or GYY. These findings indicate that hyperoxaluria impairs Sp1 transcriptional activity, resulting in H₂S deficiency and compromised anticrystallization defense in oxalate-induced tubulopathy. Full article

(This article belongs to the Special Issue Nitric Oxide (NO) and Hydrogen Sulfide (H₂S) in Biology, Illness, and Therapies—2nd Edition)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Antioxidants, Volume 14, Issue 9 (September 2025) – 88 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI