Antioxidants

26 pages, 18184 KB

Open AccessArticle

Viridicatin from the Antarctic Fungus Penicillium sp. Protects Human Microglia and Patient-Derived Peripheral Immune Cells Against Oxidative Stress

by Cristian Paz, Muhammad Javid Iqbal, Andrea Cristina Paula Lima, Alejandro Luarte, Pablo Lazcano, Ursula Wyneken, María Isabel Behrens, Daniela Ponce, Nicole Jeraldo, Sigisfredo Garnica, Cecilia Villegas, Vaderament-A. Nchiozem-Ngnitedem, Bernd Schmidt, Eric Sperlich, Nicole Cortez and Viviana Burgos

Antioxidants 2026, 15(9), 1089; https://doi.org/10.3390/antiox15091089 (registering DOI) - 30 Aug 2026

Abstract

Neurodegenerative diseases remain a major therapeutic challenge, with oxidative stress playing a central role in central and peripheral immune system dysfunction that leads to neuronal loss. Natural products from extreme environments represent an underexplored source of neuroprotective agents. In this study, viridicatin, a [...] Read more.

Neurodegenerative diseases remain a major therapeutic challenge, with oxidative stress playing a central role in central and peripheral immune system dysfunction that leads to neuronal loss. Natural products from extreme environments represent an underexplored source of neuroprotective agents. In this study, viridicatin, a quinoline-derived alkaloid, was isolated from the Antarctic fungus Penicillium sp. collected from sediments taken from Deception Island, and its structure was unambiguously confirmed by 1D/2D-NMR spectroscopy and single-crystal X-ray diffraction. Viridicatin (100 µM) significantly attenuated H₂O₂-induced cytotoxicity in HMC-3 human microglial cells, preserving cell viability and mitochondrial membrane potential. Viridicatin modulated the Nrf2 antioxidant signaling pathway, accompanied by increased expression of the downstream antioxidant enzymes HO-1 and NQO1. Moreover, molecular docking revealed preferential binding to the KEAP1 Kelch domain (−8.0 kcal/mol), suggesting indirect Nrf2 pathway modulation. A 100 ns molecular dynamics simulation with MM-GBSA analysis supported the stability of the viridicatin–KEAP1 complex. Notably, viridicatin rescued peripheral immune cells, i.e., peripheral blood mononuclear cells (PBMCs) obtained from older adults with mild cognitive impairment from H₂O₂-induced cell death, bridging the gap between in vitro mechanistic evidence and clinically relevant human cellular models. This is the first report of neuroprotective activity for viridicatin, positioning this Antarctic-derived alkaloid as a compelling candidate for further preclinical development against age-related neurodegeneration. Full article

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

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20 pages, 2784 KB

Open AccessArticle

Genome-Wide Association Study Reveals Novel Loci and Candidate Genes of Vitamin E Content in Sesame (Sesamum indicum L.)

by Zishu Luo, Jianglong Zhou, Yijia Zhang, Huan Li, Rong Zhou, Ting Zhou, Yanxin Zhang, Jun You and Linhai Wang

Antioxidants 2026, 15(9), 1088; https://doi.org/10.3390/antiox15091088 (registering DOI) - 29 Aug 2026

Abstract

Sesame is a significant oilseed crop whose exceptional oxidative stability is closely associated with its abundant endogenous antioxidants. As one of the most predominant lipid-soluble antioxidants in sesame, vitamin E (VE) plays a critical role in scavenging lipid peroxyl radicals, terminating lipid peroxidation [...] Read more.

Sesame is a significant oilseed crop whose exceptional oxidative stability is closely associated with its abundant endogenous antioxidants. As one of the most predominant lipid-soluble antioxidants in sesame, vitamin E (VE) plays a critical role in scavenging lipid peroxyl radicals, terminating lipid peroxidation chain reactions, and protecting cellular membranes from oxidative damage, thereby maintaining intracellular redox homeostasis and attenuating the development of oxidative stress-related disorders. Although VE is a potent natural antioxidant with significant pharmacological activities in mitigating oxidative stress-related disorders, the genetic mechanisms underlying the natural variation in VE content in sesame remain incompletely understood. Here, variation in VE content was evaluated across 400 sesame accessions grown in two environments. Ultra-high-performance liquid chromatography (UHPLC) analysis revealed that only γ-tocopherol was detected in sesame seeds, with concentrations between 169.33 and 463.31 mg/kg, averaging 316.28 mg/kg. The newly acquired SNP and InDel data from whole-genome resequencing were associated with the phenotypic data, leading to the identification of five significant loci associated with VE content. Comparative transcriptomic profiling of two sesame accessions with distinct VE contents revealed the differential expression of key biosynthetic enzyme genes (such as GGDR, PDS1, VTE2, and VTE4) between the two accessions. By integrating a genome-wide association study with transcriptomic data, two primary candidate effector genes, SINPZ1100015/SiNST1 and SINPZ0901927, were identified, with SiNST1 being particularly prominent. Functional validation further showed that overexpression of SiNST1 in the hairy root of sesame significantly decreased VE content. This investigation advances the comprehension of variations in VE content and the regulatory mechanisms governing its biosynthetic metabolism in sesame, supporting the development of functional sesame varieties for dietary antioxidant supplementation. Full article

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

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16 pages, 1371 KB

Open AccessArticle

Skin Histology of Pithecopus spp. and Modulation of Glutathione Status by the Antioxidant Tryptophyllin PaT-2

by Flávia G. D. Araújo, Henrique L. L. de Araújo, Maria da Gloria da Silva, João B. Nunes, João G. T. L. Resende, Fernanda L. Silva, Miguel G. Cardoso, Eder A. Barbosa, Andreanne G. Vasconcelos, Guilherme D. Brand, Tatiana K. S. Borges, Amilcar S. Damazo, Daniel C. Moreira and José R. S. A. Leite

Antioxidants 2026, 15(9), 1087; https://doi.org/10.3390/antiox15091087 (registering DOI) - 29 Aug 2026

Abstract

Amphibians of the family Phyllomedusidae produce complex cutaneous secretions with ecological and pharmacological relevance. Here, we investigated the skin morphology of Pithecopus oreades and P. azureus and the antioxidant function of the tryptophyllin PaT-2 in microglial cells. Histological and histochemical analyses revealed a [...] Read more.

Amphibians of the family Phyllomedusidae produce complex cutaneous secretions with ecological and pharmacological relevance. Here, we investigated the skin morphology of Pithecopus oreades and P. azureus and the antioxidant function of the tryptophyllin PaT-2 in microglial cells. Histological and histochemical analyses revealed a conserved glandular organization, with mucous glands rich in neutral mucopolysaccharides and serous glands containing acidic and sulfated polysaccharides, concentrated predominantly in the dorsal and cephalic regions. MALDI mass spectrometry imaging showed that PaT-2 (m/z 696.4) is heterogeneously distributed. A second ion (m/z 1626.8), assigned to a truncated form of a phylloseptin-like antimicrobial peptide, was predominantly localized in limb tissues and partially overlapped with PaT-2, suggesting co-deployment of antioxidant and antimicrobial molecules on the skin. In BV2 microglial cells, menadione (10 µM) induced oxidative stress reflected by increased oxidized glutathione (GSSG) and higher total glutathione levels, consistent with a compensatory increase in glutathione synthesis. Synthetic PaT-2 (50 µM) was associated with numerically lower GSSG accumulation and a smaller increase in total glutathione when co-administered with menadione, showing no cytotoxicity while demonstrating modulation of endogenous glutathione status. These findings advance the integumentary biology of Pithecopus, suggest differences in peptide distribution between the specimens examined, and extend the antioxidant characterization of PaT-2 to the level of glutathione status, supporting its further investigation as a candidate molecule for oxidative stress-related research. Full article

(This article belongs to the Special Issue Antioxidant Peptides)

36 pages, 8341 KB

Open AccessArticle

Synthetic Cyclic C₅-Curcuminoids Mitigate Oxidative, Apoptotic and Inflammatory Damage in a 6-OHDA-Induced Neuron–Microglia Co-Culture Model of Neuronal Damage

by Edina Pandur, Zsombor Bence Tóth, Levente Tyukodi, Ilona Gróf, Szilvia Veszelka, Mária A. Deli, Zsuzsanna Rozmer and Imre Huber

Antioxidants 2026, 15(9), 1085; https://doi.org/10.3390/antiox15091085 (registering DOI) - 29 Aug 2026

Abstract

Curcumin and natural curcuminoids possess numerous beneficial properties, including antioxidant, antitumor, and anti-inflammatory effects. However, their application is challenging because of instability and rapid metabolism. Cyclic C₅-curcuminoids, a subgroup of curcuminoids, are chemically more stable and less susceptible to hydrolysis or [...] Read more.

Curcumin and natural curcuminoids possess numerous beneficial properties, including antioxidant, antitumor, and anti-inflammatory effects. However, their application is challenging because of instability and rapid metabolism. Cyclic C₅-curcuminoids, a subgroup of curcuminoids, are chemically more stable and less susceptible to hydrolysis or metabolism. In our study, seven synthetic compounds—five cyclic C₅-curcuminoids (compounds 8, 9, 11, 12, and 13) and two cyclic chalcones (compounds 4 and 5)—were examined using an in vitro 6-hydroxydopamine-induced neuronal damage model established with all-trans retinoic acid-differentiated SH-SY5Y and BV-2 microglial cells. The antioxidant, anti-apoptotic (including ferroptosis markers (iron, GSH/GSSG, and malondialdehyde)), apoptotic (PARP, cytochrome c, caspase 9, active caspase-3, and oligonucleosome release), and anti-inflammatory effects of these compounds were also investigated. Compounds 5, 9, 12, and 13 significantly decreased reactive oxygen species production (percentage changes: 5: 28.9%; 9: 32%; 12: 29.8%; 13: 49.2%) and increased antioxidant capacity (percentage changes: 5: 63.4%; 9: 85.8%; 12: 31.2%; 13: 85.9%) and antioxidant enzyme activity (catalase, superoxide dismutase, and glutathione peroxidase) in SH-SY5Y cells. Compounds 5, 9, and 12 decreased microglial activation by downregulating Iba1 expression (fold changes: 5: 0.73; 9: 0.39; 12: 0.33) and decreasing glutamate concentration (percentage changes: 5: 26.5%; 9: 41.2%; 12: 27.3%). Together with compound 13, they reduced pro-inflammatory cytokine (IL-6, TNFα) secretion and induced anti-inflammatory cytokine (IL-10) release in SH-SY5Y and BV-2 cells. Based on these results, the blood–brain barrier penetrations of compounds 5, 9, 12, and 13 were also investigated. The highest blood–brain barrier penetration was observed for compound 12 (P_app value 13.6 × 10⁻⁶ cm/s). Synthetic cyclic C₅-curcuminoids derived from curcumin overcome the limitations of stability and bioavailability and exhibit strong antioxidant, anti-inflammatory, and anti-apoptotic effects, making them promising candidates for treating neurodegenerative diseases. Full article

(This article belongs to the Special Issue Innovative Approaches to Neuroprotective Strategies: Targeting Oxidative Stress in Neurodegenerative Disorders)

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21 pages, 3134 KB

Open AccessArticle

L-Histidine Improves Boar Sperm Quality by Alleviating Oxidative Stress During Preservation at 17 °C

by Qingzhe Meng, Yongjin Liu, Xiaohong Duan, Xifei Zhang, Guijiang Wang, Lingjiang Min, Eslam M. Bastawy, Fei Luo and Zhendong Zhu

Antioxidants 2026, 15(9), 1086; https://doi.org/10.3390/antiox15091086 - 28 Aug 2026

Abstract

Oxidative damage is closely associated with the gradual decline in boar sperm quality during liquid storage at 17 °C. To determine whether L-histidine (L-His) could limit this deterioration, semen was diluted with an extender containing 0, 1, 10, 100, or 1000 μM L-His. [...] Read more.

Oxidative damage is closely associated with the gradual decline in boar sperm quality during liquid storage at 17 °C. To determine whether L-histidine (L-His) could limit this deterioration, semen was diluted with an extender containing 0, 1, 10, 100, or 1000 μM L-His. Motility and acrosomal integrity were measured throughout storage. On day 7, mitochondrial membrane potential (MMP) and ATP content were determined together with intracellular probe oxidation, membrane lipid oxidation, and Annexin V-FITC/PI staining patterns. The stored sperm were subsequently exposed to capacitating conditions and tested for their ability to bind to oviductal explants. The most favorable responses were observed with 100 μM L-His. Compared with untreated semen, this group retained higher motility and acrosomal integrity and showed higher MMP and ATP content (p < 0.05). It also exhibited less intracellular probe oxidation and membrane lipid oxidation, together with lower proportions of Annexin V-positive and membrane-compromised sperm. Following capacitation induction, sperm stored with 100 μM L-His showed increased tyrosine phosphorylation and higher proportions of capacitated sperm. Their binding index to oviductal explants was also higher than that of the control group. These findings indicate that supplementation with 100 μM L-His can improve the preservation quality of boar sperm during extended liquid storage at 17 °C and maintain functional characteristics of stored sperm, providing new insights into the potential use of L-His as a semen extender supplement for prolonged storage. Full article

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

26 pages, 6522 KB

Open AccessArticle

Bioactive Phenolics from Medemia argun: Biological Activities, Molecular Docking, Encapsulation in Alginate–Whey Protein Hydrogel Beads, and Functional Yoghurt Fortification

by Mohammad S. Mohammad, Sally S. Sakr, Marwa A. Kamel, Amira A. Gamal, Eman S. Abou-Amra, Asmahan A. Ali and Marwa M. El-Said

Antioxidants 2026, 15(9), 1084; https://doi.org/10.3390/antiox15091084 - 28 Aug 2026

Abstract

Medemia argun is a rare desert palm rich in phenolic compounds with promising biological activities; however, the instability and poor compatibility of phenols in dairy systems limit their functional application. This study characterized the phenolic composition and biological activities of M. argun phenolic [...] Read more.

Medemia argun is a rare desert palm rich in phenolic compounds with promising biological activities; however, the instability and poor compatibility of phenols in dairy systems limit their functional application. This study characterized the phenolic composition and biological activities of M. argun phenolic extract (MAPE), developed sodium alginate–whey protein concentrate (SAlg/WP) hydrogel beads for phenolic encapsulation, and evaluated their application in fortified yoghurt. HPLC identified quercetin and gallic acid as the predominant phenolic compounds. Antioxidant, antimicrobial, antiviral, and molecular docking analyses were performed, while SAlg/WP–MAPE beads were characterized by encapsulation efficiency analysis, FTIR, and scanning electron microscopy. Fortified yoghurt containing different concentrations of encapsulated MAPE was evaluated for color, syneresis, pH, and antioxidant activity during 14 days of refrigerated storage. MAPE exhibited strong antioxidant and broad-spectrum antimicrobial activities against bacterial and fungal strains, as well as promising antiviral activity against hepatitis A virus (HAV), with an IC₅₀ of 104.89 μg/mL and a selectivity index of 1.6. Molecular docking revealed favorable interactions of rutin, chlorogenic acid, and rosmarinic acid with the HAV 3C protease. SAlg/WP beads achieved 78.92% encapsulation efficiency, while FTIR and SEM confirmed successful phenolic entrapment. Encapsulation effectively preserved MAPE functionality and significantly enhanced yoghurt antioxidant activity during storage, demonstrating its potential for functional dairy applications. Full article

(This article belongs to the Special Issue Food Antioxidants: From Chemistry to Health—Analysis, Bioactivity, and Processing)

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31 pages, 16456 KB

Open AccessArticle

Comparative Phytochemical Profiling, Antioxidant Activity, and Chondrocyte Cytocompatibility of Water and Ethanolic Extracts from Different Organs of Golden Gardenia (Gardinia sootepensis)

by Thitinun Tarathipayakul, Pattaranee Srichairatanakool, Pornpawee Sreechomphu, Vanichaya Sinpiang, Onsaya Kerdto, Peraphan Pothacharoen, Somdet Srichairatanakool and Wachiraporn Tipsuwan

Antioxidants 2026, 15(9), 1083; https://doi.org/10.3390/antiox15091083 - 28 Aug 2026

Abstract

Gardenia sootepensis Hutch. (Golden Gardinia) has received limited scientific attention despite the chemical diversity of its specialized metabolites. In this study, aqueous and 70% ethanolic preparations derived from the leaves, peel plus pulp, and seeds were systematically evaluated for extraction efficiency, total phenolic [...] Read more.

Gardenia sootepensis Hutch. (Golden Gardinia) has received limited scientific attention despite the chemical diversity of its specialized metabolites. In this study, aqueous and 70% ethanolic preparations derived from the leaves, peel plus pulp, and seeds were systematically evaluated for extraction efficiency, total phenolic content (TPC), flavonoid content (TFC), ABTS and DPPH radical-scavenging capacity, HPLC–ESI–MS phytochemical profiles, and cytocompatibility with C28/I2 cells and primary human articular chondrocytes. The largest extract recovery was obtained from seed material, whereas the ethanolic leaf preparation contained the greatest TPC (81.08 ± 4.60 mg GAE/g), and TFC (28.36 ± 3.63 mg QE/g), and showed the strongest ABTS antioxidant activity (272.92 ± 10.95 mg TE/g). HPLC–ESI–MS analysis based on nominal-mass measurements enable the provisional annotation of 34 phytochemical features encompassing iridoids and iridoid glycosides, phenolic acids, flavonoids and their glycosides, xanthones, and benzophenone-related constituents. Overall, extraction with aqueous ethanol yielded a wider spectrum of detectable metabolites than extraction with water, while seed-derived preparations displayed the greatest chemical diversity. Under the experimental conditions and concentration range tested, viability of both immortalized C28/I2 cells and primary human articular chondrocytes remained above 80%. Collectively, these findings demonstrate that the botanical tissue selected and the extraction solvent substantially influence the phytochemical composition and antioxidant properties of G. sootepensis. The observed cytocompatibility provides a basis for subsequent mechanistic investigations but does not establish chondroprotective activity. Further confirmation and quantitative characterization of the provisionally annotated metabolites using high-resolution MS/MS and authentic reference standards are warranted. Full article

(This article belongs to the Special Issue Natural Bioactive Compounds with Antioxidant and Anti-Inflammatory Potential: From Mechanisms to Applications)

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17 pages, 1419 KB

Open AccessArticle

Ergothioneine-Derived Carbon Dot Nanozymes Alleviate the Oxidative Stress Microenvironment to Delay Intervertebral Disc Degeneration

by Ziyang Zhang, Kehan Wang, Hao Chen, Yu Shi and Huihui Wang

Antioxidants 2026, 15(9), 1082; https://doi.org/10.3390/antiox15091082 - 28 Aug 2026

Abstract

Nucleus pulposus cells (NPCs) age mainly because reactive oxygen species (ROS) build up too much. Excess ROS is associated with intervertebral disc degeneration (IVDD). In this study, we prepared ergothioneine-derived carbon dots (EGT-Fe-CDs) as an antioxidant nanozyme. EGT-Fe-CDs showed good biocompatibility, superoxide dismutase-like [...] Read more.

Nucleus pulposus cells (NPCs) age mainly because reactive oxygen species (ROS) build up too much. Excess ROS is associated with intervertebral disc degeneration (IVDD). In this study, we prepared ergothioneine-derived carbon dots (EGT-Fe-CDs) as an antioxidant nanozyme. EGT-Fe-CDs showed good biocompatibility, superoxide dismutase-like and catalase-like activities, and high total antioxidant capacity. In H₂O₂-treated NPCs, EGT-Fe-CDs reduced cell damage. Local EGT-Fe-CDs treatment also reduced degeneration in the animal model, based on imaging, disc height index (DHI), and Pfirrmann grade. EGT-Fe-CDs also reduced mitochondrial damage associated with excess ROS. They slow down NPC ageing and help control IVDD. Based on these characteristics, the nanozyme could be a useful option for clinical therapy in the future. Full article

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

30 pages, 10364 KB

Open AccessArticle

Self-Assembled Carrier-Free Nanostructures of Anemoside B4 and Oleanolic Acid Alleviate Intestinal Injury Induced by Intraperitoneal Escherichia coli Challenge in Mice

by Jianchi Lun, Yuxin Yan, Junji Huang, Rong Chen, Yimu Ma, Mengjie Liu, Qian Qu, Weijie Lv and Shining Guo

Antioxidants 2026, 15(9), 1081; https://doi.org/10.3390/antiox15091081 - 28 Aug 2026

Abstract

Escherichia coli-induced enteritis imposes a substantial economic burden on the global livestock industry. In the current context of reducing and restricting antibiotic use, there is an urgent need for novel therapeutic strategies. Based on traditional Chinese medicine compatibility, anemoside B4 (AB4) and [...] Read more.

Escherichia coli-induced enteritis imposes a substantial economic burden on the global livestock industry. In the current context of reducing and restricting antibiotic use, there is an urgent need for novel therapeutic strategies. Based on traditional Chinese medicine compatibility, anemoside B4 (AB4) and oleanolic acid (OA) form nanoscale assemblies (AB4-OA NPs) through hydrogen bonds and van der Waals forces. Physicochemical characterization quantified the NPs as spherical particles with an average hydrodynamic diameter of 164.16 nm, a PDI of 0.280, zeta potential of −22.16 mV, and stable particle size for 28 days; the hemolysis ratio remained below 3.38% at concentrations up to 2 mg/mL, confirming favorable biosafety. In vitro assays confirmed that AB4-OA NPs outperformed AB4/OA physical mixtures in anti-inflammatory and antioxidant activity by restraining pro-inflammatory factors and activating antioxidant enzymes, verifying nanotechnology’s potency in boosting their bioactivity. In mice challenged intraperitoneally with E. coli, AB4-OA NPs elevated SOD, CAT, GSH-Px and lowered MDA; they inhibited the NF-κB pathway, activated the Nrf2 pathway, balanced inflammatory cytokines, alleviated intestinal leakage, upregulated tight junction proteins and reshaped gut microbiota by reducing Proteobacteria and enriching Firmicutes. Spearman’s correlation study indicated a strong positive relationship between Lactobacillus and Faecalibacterium with intestinal barrier function (Occludin and ZO-1) as well as antioxidant capacity, while Enterococcus was significantly and positively correlated with pro-inflammatory cytokines. These findings demonstrate that AB4-OA NPs exert pronounced protective therapeutic effects on E. coli-induced enteritis via inhibition of inflammation, attenuation of oxidative stress, protection of the intestinal barrier, and regulation of gut microbiota, and that these effects were greater than those of the corresponding physical mixture. This study proposes a novel therapeutic strategy for managing E. coli-induced enteritis and highlights the therapeutic potential of phytochemical-based self-assembled nanomedicines. Full article

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

24 pages, 8367 KB

Open AccessArticle

Dimethyl Fumarate and Cobalt Protoporphyrin IX Inhibit Fibromyalgia-Like Pain by Modulating Region-Specific Redox Pathways

by Sylmara Esther Negrini-Ferrari, Weitao Wang and Olga Pol

Antioxidants 2026, 15(9), 1080; https://doi.org/10.3390/antiox15091080 - 28 Aug 2026

Abstract

Fibromyalgia is a chronic nociplastic pain disorder characterized by widespread pain and affective disturbances, in which oxidative stress and neuroinflammation are now recognized as central pathogenic mechanisms. However, current therapies provide only limited symptomatic relief. This study compared the therapeutic and molecular effects [...] Read more.

Fibromyalgia is a chronic nociplastic pain disorder characterized by widespread pain and affective disturbances, in which oxidative stress and neuroinflammation are now recognized as central pathogenic mechanisms. However, current therapies provide only limited symptomatic relief. This study compared the therapeutic and molecular effects of dimethyl fumarate (DMF), an activator of nuclear factor erythroid 2-related factor 2 (NRF2), and cobalt protoporphyrin IX (CoPP), an inducer of heme oxygenase-1 (HO-1), in a reserpine-induced mouse model of fibromyalgia-like pain. Male and female C57BL/6J mice received repeated reserpine administration to induce mechanical allodynia, thermal hyperalgesia, cold allodynia, and depressive-like behaviors. Therapeutic efficacy was evaluated by behavioral testing and molecular analyses of the periaqueductal gray (PAG), anterior cingulate cortex (ACC), and spinal cord (SC). DMF produced a faster antinociceptive response than CoPP, although both compounds ultimately reversed nociceptive hypersensitivity and depressive-like behaviors in male and female mice. These behavioral alterations were associated with increased NLRP3 expression and activated AKT signaling, together with region-specific redox dysregulation involving differential regulation of NADPH oxidases and endogenous antioxidant defenses. Both treatments differentially modulated region-specific redox alterations, enhanced selected antioxidant defenses, and attenuated inflammatory and nociception-related signaling. These findings identify region-specific redox dysregulation as a prominent feature of fibromyalgia-like pathology, providing new mechanistic insight into the molecular basis of nociplastic pain. Collectively, these results demonstrate that DMF and CoPP treatments remodel region-specific redox networks while inhibiting both sensory and affective manifestations of fibromyalgia-like pain, supporting endogenous antioxidant pathways as promising mechanism-based therapeutic targets for fibromyalgia. Full article

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

24 pages, 3225 KB

Open AccessArticle

Paeonol and Its Metabolites Alleviate LPS/D-GalN-Induced Acute Liver Injury in Mice: Potential Involvement of NDUFS7 and Macrophage Mitochondrial Function

by Xin-Ru Lyu, Si-Tao Xu, Na Su, Min Lin, Zi-Ya Zhao, Zi-Han Xu, Xiang Li, Zhi-Hui Lu, Tong-Tong Wei, Shi-Yu Zhang, Qiang Fu, Guang-Ji Wang, Ying Peng and Jian-Guo Sun

Antioxidants 2026, 15(9), 1079; https://doi.org/10.3390/antiox15091079 - 28 Aug 2026

Abstract

Acute liver injury (ALI) is a severe clinical syndrome characterized by systemic inflammation and mitochondrial oxidative stress. This study investigated the hepatoprotective effects of paeonol (PA) in LPS/D-GalN-induced ALI and explored the potential involvement of macrophage mitochondrial function and NDUFS7. Proteomic analysis showed [...] Read more.

Acute liver injury (ALI) is a severe clinical syndrome characterized by systemic inflammation and mitochondrial oxidative stress. This study investigated the hepatoprotective effects of paeonol (PA) in LPS/D-GalN-induced ALI and explored the potential involvement of macrophage mitochondrial function and NDUFS7. Proteomic analysis showed that the expression of mitochondrial respiratory chain-related proteins was suppressed in the liver of ALI mice, while PA treatment was associated with increased expression of several of these proteins. Integrated metabolomic analysis further indicated that PA modulated metabolites associated with energy metabolism and redox processes. In vitro experiments suggested that inflammatory RAW264.7 macrophages contributed to hepatocyte injury, whereas PA attenuated inflammatory responses and reduced macrophage-mediated injury to AML12 cells. In RAW264.7 cells, PA attenuated ROS accumulation and modulated multiple mitochondrial functional parameters, including mitochondrial membrane potential, ATP levels, the NAD⁺/NADH ratio, and complex I activity. Metabolic studies in human liver microsomes and primary human hepatocytes identified three major PA glucuronide metabolite products with five possible structural assignments. Molecular docking and microscale thermophoresis further indicated that several proposed PA metabolite structures exhibited more favorable predicted interactions and stronger binding to recombinant NDUFS7 than the parent PA. Collectively, these findings support the hepatoprotective effects of PA and its modulation of macrophage mitochondrial function, as well as the potential involvement of PA metabolites and NDUFS7, while further functional validation is required to establish their causal roles. Full article

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

16 pages, 11187 KB

Open AccessArticle

Cord Blood Adductomic Profiling Provides Preliminary Insights on Perinatal Smoking Exposure: A Pilot Analysis

by Janu Newar, Elizabeth Brees, Erika T. Lin, Abhik Chakraborty, Aliyah Abanes, Kathleen M. Fisch, William Funk and Karen K. Mestan

Antioxidants 2026, 15(9), 1078; https://doi.org/10.3390/antiox15091078 - 28 Aug 2026

Abstract

Maternal smoking during pregnancy (MSDP) remains a significant public health concern. The molecular mechanisms underlying smoking-induced maternal-fetal impact remain incompletely understood. Newer omics platforms, such as cord blood adductomics, can provide preliminary insight into the “perinatal exposome” leading up to birth. The objective [...] Read more.

Maternal smoking during pregnancy (MSDP) remains a significant public health concern. The molecular mechanisms underlying smoking-induced maternal-fetal impact remain incompletely understood. Newer omics platforms, such as cord blood adductomics, can provide preliminary insight into the “perinatal exposome” leading up to birth. The objective of this study is to explore the adductomic signatures of oxidant stress in cord blood associated with MSDP. In a cohort of mother-infant dyads enrolled at a single birth center in Chicago, IL (2008–2021), we conducted a secondary analysis of self-reported maternal smoking exposure data that was linked to an existent adductomics database of 105 addition products (adducts) measured in cord blood plasma. Principal component analysis (PCA), volcano plots and PERMANOVA were used to visualize the variability in adductomic profiles and to compare significantly increased and decreased adduct concentrations according to self-reported current-smokers, former-smokers, and never-smokers. N = 158 participants (N = 6 current-smokers, 26 former-smokers, and 126 never-smokers) had documented self-reported smoking status and were included in the analysis. PCA demonstrated separation between current-smokers and the other groups (R² = 0.026 for current vs. never-smokers, R² = 0.115 for current vs. former-smokers; Padj = 0.0075 for both) and no difference between former vs. never-smokers. Among 56 annotated adducts, 27 were increased in current vs. never-smokers, and 32 in current vs. former-smokers. Mode of delivery (p = 0.02) and maternal hypertension (p = 0.001) were significantly different among the three groups. Matched analysis by chronic hypertension (yes/no) supported the main finding that current-smoker adductomic profiles were distinct from both former (p = 0.015) and never-smoker (p = 0.0225) profiles. Self-reported MSDP appears to be associated with cord blood adductomic signatures of oxidant stress. Further studies are needed to determine how the duration, extent and timing of exposure correlate with exposomic changes at birth. Full article

(This article belongs to the Special Issue The Role of Antioxidants in Pregnant Women’s and Children’s Health—3rd Edition)

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16 pages, 782 KB

Open AccessArticle

Association of Nutrient-, Food-, and Lifestyle-Based Oxidative Balance Scores with Liver Enzymes in Older Adults Across Cardiovascular-Risk Groups

by Hawa Sidibé, Mojgan Morvaridzadeh, Tamàs Fülöp, Hicham Berrougui, Slimane Belbraouet, Michel Nguyen and Abdelouahed Khalil

Antioxidants 2026, 15(9), 1077; https://doi.org/10.3390/antiox15091077 - 28 Aug 2026

Abstract

Diet and lifestyle are modifiable determinants of oxidative balance through their influence on exposure to antioxidant and pro-oxidant factors. The oxidative balance score (OBS) is a composite index that reflects the balance between these exposures, with higher scores indicating a predominance of antioxidant [...] Read more.

Diet and lifestyle are modifiable determinants of oxidative balance through their influence on exposure to antioxidant and pro-oxidant factors. The oxidative balance score (OBS) is a composite index that reflects the balance between these exposures, with higher scores indicating a predominance of antioxidant factors. In this exploratory pilot study, we examined three OBSs (nutrient-, food-, and lifestyle-based), as well as their combined versions (nutrient–lifestyle and food–lifestyle), across clinical subgroups and evaluated their associations with biomarkers of oxidative stress, inflammation, lipid metabolism, and liver-related biomarkers. A total of 44 older adults were enrolled and stratified into three subgroups (16 healthy, 14 hypercholesterolemia, and 14 post–myocardial infarction). Each participant completed a questionnaire, a 3-day food record, and underwent blood sampling. OBSs were calculated based on 15 nutrients, nine food groups, and two lifestyle components. Correlations and multiple linear regression analyses were performed to examine associations between OBSs and the following biomarkers: plasma total antioxidant capacity (TEAC and FRAP), C-reactive protein (CRP), HDL cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). The nutrient–lifestyle OBS (OBSN-L) was significantly associated with lower ALT and AST (adjusted ALT β = −1.06; p = 0.048; AST β = −0.54; p = 0.034). A similar association was observed for the nutrient OBS (OBSN) (adjusted AST β = −0.64; p = 0.022). No significant associations were observed for TEAC, FRAP, or CRP. Neither the OBSF nor the OBSF-L was associated with any circulating biomarkers. Higher nutrient-based OBSs, with or without lifestyle integration, were independently associated with lower liver transaminase levels in older adults with varying levels of cardiovascular risk. OBSs may help to capture dietary and lifestyle patterns associated with liver-related biomarkers. These exploratory findings warrant confirmation in larger, prospective studies. Full article

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19 pages, 3266 KB

Open AccessArticle

Co-Ingestion Timing, Rather than Food Matrix or Dose, Determines α-Tocopherol Bioavailability from Intrinsically Labeled Spinach in Healthy Adults: A Crossover Pharmacokinetic Study

by Shahabeddin Rezaei, Sisi Cao, Min Zeng, Maria L. Antonius, Jillian T. Pierson, Ariana H. Bond, Allyson Q. McHenry, Joshua J. Blakeslee and Richard S. Bruno

Antioxidants 2026, 15(9), 1076; https://doi.org/10.3390/antiox15091076 - 28 Aug 2026

Abstract

Dark green leafy vegetables, such as spinach, are rich sources of α-tocopherol (α-T), a lipid-soluble antioxidant, but may contribute little to α-T status due to low intake and limited bioavailability. This study investigated whether egg co-consumption enhances α-T bioavailability from spinach and whether [...] Read more.

Dark green leafy vegetables, such as spinach, are rich sources of α-tocopherol (α-T), a lipid-soluble antioxidant, but may contribute little to α-T status due to low intake and limited bioavailability. This study investigated whether egg co-consumption enhances α-T bioavailability from spinach and whether effects differ by egg dose, food matrix, or timing of intake. In a crossover study, healthy adults consumed deuterium-labeled (d_x)-spinach (containing 5 mg d_x-α-T) alone; or with 1, 2, or 3 hard-boiled eggs; 2 egg whites; or vegetable oil (9.6 g). Two exploratory trials evaluated delayed egg consumption 3 h after spinach intake. Compared with spinach alone, d_x-α-T AUC_0–72h (µmol/L × h) was 1.5–1.8-times higher when spinach was co-consumed with 1, 2, and 3 eggs (p ≤ 0.05), respectively, with no egg dose-dependent differences (p > 0.05). Co-ingestion of spinach with egg whites or vegetable oil increased d_x-α-T AUC_0–72h similar to whole eggs (p > 0.05). Delayed egg intake did not affect d_x-α-T AUC_0–72h relative to spinach alone (p > 0.05). Plant-derived α-T bioavailability can be improved through co-ingestion with other foods but is independent of egg dose and food matrix. Effective absorption requires concurrent intake, indicating that timing and associated digestive processes are key determinants and support food-pairing strategies to improve vitamin E bioavailability and its antioxidant contribution to plant-based diets. Registered at ClinicalTrials.gov (NCT04287816). Full article

(This article belongs to the Special Issue Natural Antioxidants in Functional Foods)

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21 pages, 2097 KB

Open AccessSystematic Review

Natural-Product-Derived Antioxidants and DNA Methylation-Based Epigenetic Aging: A Systematic Review of Human Intervention Studies

by Fatemeh Taktaz and Salar Hafez-Ghoran

Antioxidants 2026, 15(9), 1075; https://doi.org/10.3390/antiox15091075 - 28 Aug 2026

Abstract

DNA methylation clocks provide a tractable molecular readout for testing whether nutritional and natural-product interventions can modify biological aging. Natural-product-derived antioxidants are biologically plausible candidates because they influence redox signaling, inflammation, mitochondrial function, microbial metabolism and epigenetic regulation, yet their effects on DNA [...] Read more.

DNA methylation clocks provide a tractable molecular readout for testing whether nutritional and natural-product interventions can modify biological aging. Natural-product-derived antioxidants are biologically plausible candidates because they influence redox signaling, inflammation, mitochondrial function, microbial metabolism and epigenetic regulation, yet their effects on DNA methylation-based aging remain difficult to interpret. Here, we systematically synthesize human intervention studies evaluating antioxidant-rich dietary patterns, botanical and food-derived extracts, marine omega-3 fatty acids, multi-component nutraceuticals and related lifestyle-based interventions with DNA methylation-clock outcomes. The available evidence does not support a uniform epigenetic anti-aging effect. Instead, methylation-age responses were clock-specific, exposure-dependent and often most apparent in metabolically or biologically responsive subgroups. Longer randomized or trial-embedded studies provided the most credible signals, whereas small uncontrolled studies mainly generated hypotheses. Future trials should move beyond claims of epigenetic age reversal and test whether objectively verified natural-product-derived antioxidant exposures produce reproducible, mechanistically linked, and clinically meaningful changes in aging biology. Full article

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

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Graphical abstract

19 pages, 5099 KB

Open AccessArticle

SOD1 Overexpression Alleviates H₂O₂-Induced Oxidative Stress and Reshapes Transcriptomic Responses in Chicken DF-1 Cells

by Yidan Wang, Penghao Wei, Tinghao Gao, Zhiwei Li, Caiqin Deng, Hanjing Chen, Jianliang Zhang, Fengcai Zou and Haiyang Song

Antioxidants 2026, 15(9), 1074; https://doi.org/10.3390/antiox15091074 (registering DOI) - 27 Aug 2026

Abstract

Oxidative stress is a major consequence of environmental, metabolic, and disease-related challenges in poultry and can compromise cellular integrity and function. Although antioxidant defense mechanisms are broadly conserved across vertebrates, oxidative-stress responses in avian cells remain less well characterized than those in mammalian [...] Read more.

Oxidative stress is a major consequence of environmental, metabolic, and disease-related challenges in poultry and can compromise cellular integrity and function. Although antioxidant defense mechanisms are broadly conserved across vertebrates, oxidative-stress responses in avian cells remain less well characterized than those in mammalian systems. Superoxide dismutase 1 (SOD1) is a key antioxidant enzyme, but how elevated SOD1 expression influences both oxidative injury and stress-responsive transcription in chicken cells remains incompletely understood. In this study, we established a stable SOD1-overexpressing chicken DF-1 fibroblast cell line and induced acute oxidative stress using hydrogen peroxide (H₂O₂). Cellular responses were evaluated using CCK-8 viability assays and Hoechst 33342/propidium iodide staining, followed by RNA sequencing and transcriptomic analyses. SOD1 overexpression markedly improved cell viability under H₂O₂ challenge and substantially reduced necrotic cell death, whereas its effect on apoptosis-associated changes was comparatively limited. Transcriptomic profiling showed that H₂O₂ induced extensive transcriptional reprogramming, while SOD1 overexpression reshaped this response by attenuating a subset of stress-inducible gene programs. Trend clustering further identified an H₂O₂-responsive module associated mainly with basic amino acid transport and stress-related regulatory processes that was less strongly induced in SOD1-overexpressing cells. Collectively, these findings demonstrate that elevated SOD1 expression enhances resistance to acute oxidative injury and modifies stress-responsive transcription in chicken fibroblasts. This study extends our current understanding of SOD1-mediated antioxidant cytoprotection in an avian cellular model and provides a molecular basis for further investigation of oxidative-stress regulation in poultry. Full article

(This article belongs to the Special Issue Redox Homeostasis in Poultry/Animal Production―2nd Edition)

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20 pages, 4530 KB

Open AccessArticle

Dual Targeting of Galanin Receptor 3 Signaling and Redox Homeostasis Enhances Photoreceptor Survival in Retinas of rd10 Mice

by Maria Azam, Mingda Liu and Beata Jastrzebska

Antioxidants 2026, 15(9), 1073; https://doi.org/10.3390/antiox15091073 - 27 Aug 2026

Abstract

Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited retinal degenerative disorders characterized by progressive photoreceptor loss and vision impairment, for which broadly applicable mutation-independent therapies remain limited. To examine the therapeutic potential of combined galanin receptor 3 (GALR3) inhibition and antioxidant [...] Read more.

Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited retinal degenerative disorders characterized by progressive photoreceptor loss and vision impairment, for which broadly applicable mutation-independent therapies remain limited. To examine the therapeutic potential of combined galanin receptor 3 (GALR3) inhibition and antioxidant therapy in a mutation-independent context, we utilized the rd10 mouse model of RP. We first evaluated the effects of individual treatments with the GALR3 antagonist SNAP-37889 and the antioxidant quercetin, followed by a combined treatment regimen to determine whether simultaneous targeting of neuroinflammatory and oxidative stress pathways provides enhanced retinal protection. Treatment efficacy was assessed using functional and morphological analyses, including electroretinography (ERG) to measure retinal function, optical coherence tomography (OCT) to evaluate retinal structure in vivo, and histological and immunohistochemical analyses to quantify photoreceptor survival and markers of retinal oxidative stress and inflammation. Although the expression levels of individual inflammatory and oxidative stress markers did not consistently exhibit additive responses, the combined treatment produced greater photoreceptor survival and preservation of photopic retinal function than either monotherapy alone. These findings support the hypothesis that simultaneous modulation of oxidative stress and neuroinflammation provides greater neuroprotective benefits, establish a foundation for the development of mutation-independent therapeutic strategies for RP, and identify GALR3 as a promising therapeutic target. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Age-Related and Degenerative Eye Diseases)

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15 pages, 39533 KB

Open AccessArticle

Protective Effects of Antioxidant Mix Pre-Treatment Against Visible Light-Induced Damage in Dark Skin Phototype

by Anna Guiotto, Malak Alghamdi, Robyn Hickerson, Michael Conneely, Hina Choudhary, Patricia Brieva, Yunsook Lim, Alessandra Pecorelli and Giuseppe Valacchi

Antioxidants 2026, 15(9), 1072; https://doi.org/10.3390/antiox15091072 - 26 Aug 2026

Abstract

Visible light (VL) accounts for approximately 50% of the solar radiation reaching Earth’s surface and has emerged as a major contributor to skin photoaging and pigmentation disorders, particularly in individuals with darker Fitzpatrick skin phototypes. Increasing evidence suggests that VL exposure induces oxidative [...] Read more.

Visible light (VL) accounts for approximately 50% of the solar radiation reaching Earth’s surface and has emerged as a major contributor to skin photoaging and pigmentation disorders, particularly in individuals with darker Fitzpatrick skin phototypes. Increasing evidence suggests that VL exposure induces oxidative stress, inflammation, and melanogenesis by generating reactive oxygen species. In this study, we investigated the protective effects of a topical antioxidant formulation (AOX Mix) containing 15% ascorbic acid, 0.5% ferulic acid, and 1% tocopherol against VL exposure in ex vivo skin biopsies from donors with Fitzpatrick skin phototypes IV–V. To preserve physiological tissue tension and closely replicate in vivo skin responses, human skin explants were maintained using the TenSkin™ culture system. Samples were pretreated with AOX Mix for 30 min, then exposed to VL for 8 h, and collected on Days 2 and 7 for histological and molecular analyses. Our results demonstrated that prolonged exposure to VL disrupted redox homeostasis and induced structural alterations in skin explants, accompanied by increased markers of oxidative stress and pigmentation. In contrast, pre-treatment with AOX Mix significantly attenuated these effects, preserving tissue architecture and reducing molecular indicators of photodamage. In addition, we observed the co-localization of 4-hydroxynonenal and collagen type I, suggesting that oxidative post-translational modification of collagen may contribute to its loss. These findings suggest that antioxidant-based interventions, such as AOX Mix, may be a promising strategy for protecting dark skin against VL exposure. Full article

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

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17 pages, 3069 KB

Open AccessArticle

Green and Energy-Efficient Post-Harvest Enhancement: Low-Dose ⁶⁰Co-γ Irradiation Enhances the Bioactive Profile of Lily Bulbs (Lilium lancifolium Thunb.) as Functional Food Ingredients

by Yao Hu, Lihui Li, Xingyu Lei, Yiji Zhou, Wei Gong, Mengshan Sun and Rong Song

Antioxidants 2026, 15(9), 1071; https://doi.org/10.3390/antiox15091071 - 26 Aug 2026

Abstract

Edible lily bulbs (Lilium lancifolium Thunb.) are highly valued for their rich nutritional profile and significant medicinal properties. To further enhance these beneficial attributes, this study investigates a novel, green post-harvest enhancement strategy using low-dose ⁶⁰Co-γ irradiation (2–5 Gy) followed [...] Read more.

Edible lily bulbs (Lilium lancifolium Thunb.) are highly valued for their rich nutritional profile and significant medicinal properties. To further enhance these beneficial attributes, this study investigates a novel, green post-harvest enhancement strategy using low-dose ⁶⁰Co-γ irradiation (2–5 Gy) followed by immediate freeze-drying. Experimentally, fresh bulbs were exposed to varying irradiation doses, after which physiological parameters (enzyme activities, phytochemical contents) and metabolic profiles (via LC-MS/MS) were systematically evaluated. The results demonstrated that 4 Gy represented the optimal dose; compared to the non-irradiated control group (0 Gy), the 4 Gy treatment significantly enhanced the antioxidant defense system by eliciting oxidative stress responses, increasing superoxide dismutase (SOD) and catalase (CAT) activities by 1.55- to 1.86-fold, and elevating total phenolics and flavonoids by 1.31- and 2.69-fold, respectively. Untargeted metabolomic analysis identified 42 differential metabolites, revealing that 4 Gy irradiation primarily upregulated the phenylpropanoid and flavonoid biosynthetic pathways. Key antioxidants, specifically rosmarinic acid and the newly detected alkaloid jurubine, exhibited significant accumulation. Integrated correlation analysis and molecular docking simulations elucidated the underlying mechanisms, providing theoretical insights into their transient interactions with DPPH radicals. In conclusion, low-dose ⁶⁰Co-γ irradiation serves as a sustainable, green post-harvest processing strategy to improve the nutritional quality of edible lily bulbs by activating intrinsic metabolic defense mechanisms. Full article

(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)

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