Antioxidants

17 pages, 33185 KB

Open AccessArticle

Fluorescent-Conjugated ZnO Nanostructures Exhibited 3D Anti-Tumor Efficacy Against Drug-Resistant Cancers Through Cholesterol-Mediated ROS Regulation

by Salida Ali, Yu Li, Ontana Yotnarong, Ruofan Shi, Ruochen Ma, Chi Yao, Xiaohao Ruan, Jingyi Huang, Da Huang, Yongle Zhan, Theeranan Tangthong and Rong Na

Antioxidants 2026, 15(8), 935; https://doi.org/10.3390/antiox15080935 - 28 Jul 2026

Abstract

ZnO nanoparticles (ZnO NPs) have been widely investigated in the biomedical field, particularly their anti-tumor efficacy. The potential of ZnO hierarchical structures (ZnO HSs) in tumor cell eradication remains largely unexplored in prostate cancer (PCa) and thyroid cancer (TC). In this study, we [...] Read more.

ZnO nanoparticles (ZnO NPs) have been widely investigated in the biomedical field, particularly their anti-tumor efficacy. The potential of ZnO hierarchical structures (ZnO HSs) in tumor cell eradication remains largely unexplored in prostate cancer (PCa) and thyroid cancer (TC). In this study, we successfully synthesized and characterized ZnO NPs and ZnO HSs using green tea extract (Camellia sinensis) as a reducing agent and conjugation of FIT-C tracking for both ZnO NPs and ZnO HSs. UV-vis spectrophotometry, Dynamic Light Scattering (DLS), FTIR, XDR, SEM and TEM revealed significant differences in morphology between ZnO NPs and ZnO HSs. Our in vitro experiments demonstrated that SNPs were more effective on aggressive PCa and TC cell lines compared to ZnO NPs. Notably, ZnO HSs exhibited enhanced cytotoxicity in 3D tumor cell spheroid models. Mechanistically, ZnO HSs induced apoptosis through cholesterol-mediated reactive oxygen species (ROS) generation. Our in vivo study revealed no histopathological changes in major organs (liver, kidneys, spleen and lungs), emphasizing the safe administration of both ZnO NPs and ZnO HSs. Our study synthesized FITC-conjugated non-spherical ZnO nanoparticles, providing evidence for a novel treatment strategy for hormone-related cancers and prospective fluorescent-guided nanomedicine. Full article

(This article belongs to the Topic Advanced Nanocarriers for Targeted Drug and Gene Delivery)

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12 pages, 17724 KB

Open AccessArticle

Baicalin Protects ARPE-19 Cells Against BRVO-Related Hypoxic Injury by Preserving Mitochondrial Function and Inhibiting Ferroptosis

by Yuchang Yang, Gaiyue Yue, Jie Bai, Jingwen Yang, Ziheng Wang, Qi Chen, Shuchang Yao, Lisha Yi, Xinzhu Wang, Jian Zhou, Jingyi Gao, Yaxuan Li, Ting Huang, Jian Ni and Changhai Qu

Antioxidants 2026, 15(8), 934; https://doi.org/10.3390/antiox15080934 - 28 Jul 2026

Abstract

Branch retinal vein occlusion (BRVO) is a retinal vascular disorder characterized by ischemia and hypoxia. These pathological conditions contribute to retinal pigment epithelial (RPE) cell injury through oxidative stress and ferroptosis. However, whether baicalin (BC) protects against hypoxia-induced RPE injury remains unclear. CoCl [...] Read more.

Branch retinal vein occlusion (BRVO) is a retinal vascular disorder characterized by ischemia and hypoxia. These pathological conditions contribute to retinal pigment epithelial (RPE) cell injury through oxidative stress and ferroptosis. However, whether baicalin (BC) protects against hypoxia-induced RPE injury remains unclear. CoCl₂-induced hypoxic ARPE-19 cells were used to evaluate the protective effects and potential mechanisms of BC. BC improved cell viability and reduced LDH release under hypoxic conditions. BC markedly suppressed hypoxia-induced inflammatory responses, as evidenced by reduced p65 and ICAM-1 expression and decreased release of pro-inflammatory cytokines. Moreover, BC alleviated oxidative stress by reducing ROS and MDA accumulation and restoring SOD and GSH activity. BC attenuated mitochondrial dysfunction, accompanied by restoration of mitochondrial membrane potential, oxygen consumption rate (OCR), and ATP production. Transmission electron microscopy (TEM) results further confirmed the protective effect of BC on mitochondrial integrity. Mechanistically, BC suppressed ferroptosis by reducing intracellular Fe²⁺ accumulation and lipid peroxidation, accompanied by downregulation of TFR1, ACSL4, and p53, as well as upregulation of SLC7A11 and GPX4. These findings suggest that BC protects ARPE-19 cells against hypoxia-induced injury through preservation of mitochondrial function and inhibition of ferroptosis. Full article

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23 pages, 5666 KB

Open AccessArticle

Effects of Dietary Luteolin on the Growth Performance and Intestinal Health of Juvenile GIFT Tilapia

by Xiangli Li, Huige Ren, Jianting Lu, Yonggang Mo, Jingyi Du, Ye Qian, Xiao Peng, Zihe Guo, Chanxia Qin, Chengrui Huang, Kai Huang, Yinghui Zhang and Weihao Ou

Antioxidants 2026, 15(8), 933; https://doi.org/10.3390/antiox15080933 - 28 Jul 2026

Abstract

This study aimed to investigate the effects of luteolin on the growth performance and intestinal health of juvenile Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus). A total of 450 juvenile GIFT tilapia (initial body weight 8.12 ± 0.04 g) were randomly assigned [...] Read more.

This study aimed to investigate the effects of luteolin on the growth performance and intestinal health of juvenile Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus). A total of 450 juvenile GIFT tilapia (initial body weight 8.12 ± 0.04 g) were randomly assigned to five groups (90 fish per group; three replicate tanks of 30 fish each) and fed diets containing luteolin at 0, 50, 150, 300, or 600 mg/kg (CG, LG50, LG150, LG300, and LG600, respectively) for 56 days. The results showed that with increasing luteolin supplementation, the weight gain rate (WGR) and specific growth rate (SGR) first increased and then decreased; the LG300 group had the highest WGR and SGR (significantly higher than the CG and LG600 groups, p < 0.05) and the lowest feed conversion ratio. Based on broken-line and quadratic polynomial regression analyses of the WGR and SGR, the optimal dietary luteolin supplementation level was determined to be 274.14–303.39 mg/kg. For intestinal antioxidant enzyme activities and oxidative stress, total superoxide dismutase (T-SOD) activity in the LG150 and LG300 groups was significantly higher than in the CG and LG600 groups (p < 0.05), and superoxide anion (O₂⁻) content in the LG300 group was significantly lower than in the CG, LG50, and LG600 groups (p < 0.05). Histological analysis of the intestine revealed that muscular layer thickness was significantly greater in the LG300 group than in the CG group (p < 0.05). Intestinal microbiota analysis indicated that compared with the CG group, the LG300 group showed lower relative abundances of the potential pathogens Plesiomonas and Bosea, whereas it had a higher relative abundance of the potentially beneficial bacteria Bacteroidota and Romboutsia. Intestinal untargeted metabolomics revealed that, compared with the CG group, the beneficial metabolites Chrysoeriol, Laricitrin, and Docosahexaenoylethanolamine were significantly up-regulated, whereas the biotoxins Aplysiatoxin, 17-Debromo- and Pectenotoxin 3 were significantly down-regulated in the LG300 group (p-adjust < 0.05), with the up-regulated metabolites significantly enriched in the flavone and flavonol biosynthesis pathway (p-adjust < 0.05). Collectively, dietary supplementation with an appropriate level (300 mg/kg) of luteolin can effectively improve the growth performance and intestinal health of juvenile GIFT tilapia. Full article

(This article belongs to the Special Issue Natural Antioxidants and Aquatic Animal Health—3rd Edition)

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21 pages, 2549 KB

Open AccessArticle

A 12-Week Structured Antioxidant-Focused Dietary Intervention Improves Cognitive Function and Oxidative Stress Biomarkers in Lung Cancer Patients with Cancer-Related Cognitive Impairment: A Randomized Controlled Trial

by Zhenzhen Huang, Xinxin Cheng, Jianyun He, Lan Cheng, Yuting Wang, Xiaoxia Lin, Xinyi Miao, Ran Wang and Shufang Xia

Antioxidants 2026, 15(8), 932; https://doi.org/10.3390/antiox15080932 - 28 Jul 2026

Abstract

Patients with lung cancer are at increased risk of developing cancer-related cognitive impairment (CRCI), and oxidative stress may contribute to its development. We conducted an assessor-blinded randomized controlled trial to evaluate whether a 12-week antioxidant-focused dietary intervention improved cognitive function, oxidative stress biomarkers, [...] Read more.

Patients with lung cancer are at increased risk of developing cancer-related cognitive impairment (CRCI), and oxidative stress may contribute to its development. We conducted an assessor-blinded randomized controlled trial to evaluate whether a 12-week antioxidant-focused dietary intervention improved cognitive function, oxidative stress biomarkers, and quality of life (QoL) in lung cancer patients with CRCI. One hundred participants were randomized to standard dietary counseling or an antioxidant-focused dietary intervention. Continuous outcomes were assessed at baseline and week 12 and analyzed using linear mixed-effects models under the intention-to-treat principle. The mean age was 66.10 ± 5.39 years, and 78.0% of participants were male. Ninety-one participants completed the week-12 assessment. Participants receiving the intervention demonstrated greater increases in Montreal Cognitive Assessment scores (β = 2.626; 95% CI: 0.825, 4.427; p = 0.005), dietary oxidative balance score (β = 2.292; 95% CI: 0.656, 3.928; p = 0.006), and physical and mental QoL component scores than those in the control group (p < 0.05). In the complete-case analysis (n = 91), the proportion meeting CRCI criteria was lower in the intervention group (60.0% vs. 93.5%; p < 0.001). Biomarker analyses showed increases in glutathione and superoxide dismutase and a reduction in malondialdehyde in the intervention group (p < 0.05). The intervention demonstrated a large effect on cognitive function (Cohen’s d = 0.84), supporting antioxidant-focused dietary intervention as a promising supportive-care strategy for managing CRCI in lung cancer patients. Full article

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27 pages, 2408 KB

Open AccessArticle

Anti-Thrombotic and Metabolic Protective Effects of Ginseng in High-Fat Diet-Induced Obese Rats: In Vivo Evaluation with In Silico Mechanistic Prediction

by Eun-Jin Lee, Dahye Yoon, Woo-Cheol Shin, Bo-Ram Choi, Dash Oyunbileg, Hye Yoon Do, Sun-Seek Min, Jin Seong Kim, Dae Young Lee and Dae-Yong Song

Antioxidants 2026, 15(8), 931; https://doi.org/10.3390/antiox15080931 - 27 Jul 2026

Abstract

Cardiovascular disease (CVD) is closely linked to metabolic disorders such as obesity, dyslipidemia, and hepatic steatosis. This study investigated the anti-thrombotic and metabolic effects of KoreaGinseng F Max (KGF), a standardized extract rich in ginsenosides, in high-fat diet (HFD)-induced obese rats, and complementary [...] Read more.

Cardiovascular disease (CVD) is closely linked to metabolic disorders such as obesity, dyslipidemia, and hepatic steatosis. This study investigated the anti-thrombotic and metabolic effects of KoreaGinseng F Max (KGF), a standardized extract rich in ginsenosides, in high-fat diet (HFD)-induced obese rats, and complementary in silico analyses were used to explore putative molecular targets and pathways. The extract was standardized to contain 36.97 mg/g of ginsenosides Rg1, Rb1, and Rf. Male rats were administered KGF (50, 100, or 200 mg/kg) orally for six weeks. KGF significantly improved lipid profiles by reducing serum triglycerides, total cholesterol, and low-density lipoprotein (LDL) levels. Histological analysis revealed a dose-dependent reduction in hepatic steatosis and adipocyte size. Potential anti-thrombotic activity was evaluated using a FeCl₃-induced carotid artery thrombosis model, with aspirin (30 mg/kg) included as a positive control. KGF200 delayed thrombus formation and produced a carotid blood flow pattern comparable to that observed in the aspirin-treated group, without significant alterations in serum ALT, AST, BUN, or creatinine levels. To further generate mechanistic hypotheses, complementary in silico analyses, including target prediction, GO/KEGG enrichment, network analysis, and molecular docking, were performed using the marker compounds. Eight overlapping genes, including STAT3, PTAFR, VEGFA, FGF2, HPSE, IL2, HSP90AA1, and LGALS3, associated with thrombotic regulation were identified. Pathway analysis suggested that PI3K–Akt signaling, calcium signaling, Th17 cell differentiation, and proteoglycan/ECM-related signaling may represent putative pathway-level mechanisms underlying the observed protective effects. Molecular docking suggested possible interactions between the marker ginsenosides and several predicted hub targets. Collectively, these findings suggest that KGF may have potential for further investigation as a natural product-derived material for improving HFD-associated metabolic and thrombotic dysfunction, while the predicted multi-target and multi-pathway effects require further experimental validation. Full article

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

48 pages, 4387 KB

Open AccessReview

From Exposure to Outcome: Air Pollution-Induced Oxidative Stress as a Determinant of Early and Late Outcomes After Coronary Artery Bypass Grafting

by Tomasz Urbanowicz and Krzysztof J. Filipiak

Antioxidants 2026, 15(8), 930; https://doi.org/10.3390/antiox15080930 - 27 Jul 2026

Abstract

Coronary artery bypass grafting (CABG) remains one of the most effective treatments for advanced coronary artery disease; however, substantial variability persists in both perioperative and long-term outcomes despite advances in surgical technique, myocardial protection, and risk stratification. Oxidative stress is a central mediator [...] Read more.

Coronary artery bypass grafting (CABG) remains one of the most effective treatments for advanced coronary artery disease; however, substantial variability persists in both perioperative and long-term outcomes despite advances in surgical technique, myocardial protection, and risk stratification. Oxidative stress is a central mediator of tissue injury during cardiac surgery, contributing to ischemia–reperfusion injury, endothelial dysfunction, systemic inflammation, and postoperative organ complications. At the same time, chronic exposure to ambient air pollution has emerged as an important environmental determinant of cardiovascular disease through mechanisms that converge on many of the same redox-sensitive pathways. We propose the concept of environmental oxidative priming, whereby long-term exposure to particulate matter, nitrogen oxides, ozone, and other pollutants establishes a persistent state of endothelial dysfunction, mitochondrial impairment, chronic inflammation, nitric oxide depletion, and reduced antioxidant reserve before surgery. Within this framework, CABG represents a second oxidative challenge superimposed on a pre-existing environmentally conditioned phenotype. We discuss the mechanistic overlap between air pollution-induced cardiovascular injury and cardiac surgical stress and examine how this interaction may contribute to postoperative complications, graft adaptation, major adverse cardiovascular events, and long-term survival. Recognition of air pollution as a modifier of biological resilience provides a novel framework for understanding outcome heterogeneity after CABG and may support future precision-based risk stratification and preventive strategies. Full article

(This article belongs to the Special Issue Oxidative Stress Induced by Air Pollution, 3rd Edition)

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18 pages, 3648 KB

Open AccessArticle

Comparative Efficacy of Monobutyrin, Tributyrin, Sodium Butyrate, and Poly-β-hydroxybutyrate on Growth, Intestinal Health, and Nitrite Stress Resistance in Penaeus monodon

by Yafei Duan, Ruijie Zhu, Yun Wang, Jianhua Huang, Song Jiang, Qibin Yang, Yundong Li, Jianzhi Shi, Yukai Yang, Lishi Yang, Yangyang Ding and Falin Zhou

Antioxidants 2026, 15(8), 929; https://doi.org/10.3390/antiox15080929 - 27 Jul 2026

Abstract

Intestinal health is crucial for the growth and stress resistance of shrimp. Butyrate, a beneficial metabolite of intestinal microbiota and the primary energy substrate for enterocytes, exerts regulatory effects on intestinal health. Butyrates exist in various chemical forms, yet their application in shrimp [...] Read more.

Intestinal health is crucial for the growth and stress resistance of shrimp. Butyrate, a beneficial metabolite of intestinal microbiota and the primary energy substrate for enterocytes, exerts regulatory effects on intestinal health. Butyrates exist in various chemical forms, yet their application in shrimp remains limited. Therefore, in this study, Penaeus monodon were fed diets supplemented with 1% four types of butyrate (monobutyrin, MB; tributyrin, TB; sodium butyrate, SB; poly-β-hydroxybutyrate, PHB) for 56 days, followed by 48 h of acute nitrite stress. A systematic investigation into their influences on the shrimp growth, intestinal health and nitrite stress resistance was conducted. The results showed that the four butyrate types significantly increased the weight gain rate of the shrimp by more than 25% and improved the survival rate under nitrite stress by more than 28% when compared with the control group (p < 0.05). They also improved intestinal mucosal integrity, and enhanced intestinal antioxidant and immune capacities through the activation of the Nrf2 pathway and the upregulation of immune gene expression. Specifically, T-AOC and SOD activities, as well as the expression levels of Nrf2, GPx, Trx, ALF, Pen3, and serP genes, were significantly upregulated in all four butyrate groups, while MDA content was significantly decreased (p < 0.05). In addition, LPO content, CAT and ASC activities, and the expression of HO1, SOD, Crus, and proPO genes exhibited differential changes among the four butyrate groups. Furthermore, the intestinal microflora structure was reshaped by all four butyrate variants, with notable reductions in pathogenic Vibrio alongside elevated abundances of advantageous taxa including Rhodobacteraceae. In conclusion, butyrate can facilitate the growth and anti-stress capacity of P. monodon by improving intestinal health, with the overall efficacy ranked as TB, PHB, MB and SB under the present study conditions. Full article

(This article belongs to the Special Issue Natural Antioxidants and Aquatic Animal Health—3rd Edition)

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41 pages, 9340 KB

Open AccessReview

Urtica dioica L. Phytochemistry, Green Extraction Techniques, Molecular Mechanisms, and Gene Expression Modulation: A Comprehensive Review

by Noor Alriyahi, Ammar Badran Ramddan, Nawfal Alhelfi, Asad Abbas, Ralf Weiskirchen, Farhang Hameed Awlqadr, Ghalia Arshad and Hassan Raza

Antioxidants 2026, 15(8), 928; https://doi.org/10.3390/antiox15080928 - 27 Jul 2026

Abstract

Urtica dioica L. (stinging nettle) is a perennial herb with a long ethnomedicinal history and diverse pharmacological potential. This comprehensive review consolidates current knowledge on its phytochemistry, extraction technologies, bioactivities, and molecular mechanisms. However, recent reviews have generally addressed these aspects separately, and [...] Read more.

Urtica dioica L. (stinging nettle) is a perennial herb with a long ethnomedicinal history and diverse pharmacological potential. This comprehensive review consolidates current knowledge on its phytochemistry, extraction technologies, bioactivities, and molecular mechanisms. However, recent reviews have generally addressed these aspects separately, and an integrated assessment linking green extraction technologies and phytochemical profiles to molecular mechanisms and gene expression modulation is still lacking. U. dioica contains abundant polyphenols (rutin, quercetin, kaempferol, and chlorogenic acid), sterols (β-sitosterol and stigmasterol), vitamins, carotenoids, and the antiviral lectin Urtica dioica agglutinin (UDA). Advances in green extraction technologies, such as ultrasound-assisted extraction, microwave-assisted extraction (MAE), pressurized liquid extraction, and natural deep eutectic solvent (NADES)-based systems, have significantly improved yield, purity, and environmental sustainability compared to conventional maceration and Soxhlet methods. Comprehensive chromatographic and spectroscopic profiling (HPLC, GC–MS, FTIR, NMR, and LC–MS/MS) has established detailed chemical fingerprints linking bioactive constituents to antioxidant, anti-inflammatory, antimicrobial, and antiviral properties. Mechanistic studies reveal that U. dioica exerts its therapeutic effects through modulation of oxidative stress, inhibition of the NF-κB and COX-2 pathways, enhancement of endogenous antioxidant enzymes, and regulation of apoptotic gene expression. Moreover, NADES–MAE extracts demonstrate potential as sustainable, high-efficacy formulations for nutraceutical and cosmetic applications. Despite extensive preclinical evidence, clinical standardization and dosage optimization remain major challenges. This review underscores U. dioica as a multifunctional medicinal plant with significant promise for next-generation phytotherapeutics and molecular nutrition. Full article

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

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17 pages, 1046 KB

Open AccessArticle

Shelf Temperature and Depressurisation Strategy Affect Bioactive Retention and Functionality of Freeze-Dried Pumpkin Powder

by Daniela Sumczynski, Libor Červenka, Helena Velichová, Ludmila Hrabalíková and Jiří Mlček

Antioxidants 2026, 15(8), 927; https://doi.org/10.3390/antiox15080927 - 26 Jul 2026

Abstract

Background: Pumpkin is a source of phenolics and carotenoids, but their retention during freeze-drying may depend on the drying programme. Methods: Pumpkin flesh was freeze-dried using two schedules: a stepwise schedule (SWS; gradual pressure decrease and shelf heating) or a rapid schedule (RS; [...] Read more.

Background: Pumpkin is a source of phenolics and carotenoids, but their retention during freeze-drying may depend on the drying programme. Methods: Pumpkin flesh was freeze-dried using two schedules: a stepwise schedule (SWS; gradual pressure decrease and shelf heating) or a rapid schedule (RS; deep vacuum and direct shelf heating). Final shelf temperatures of 20, 30 and 40 °C were tested. The powders were analysed for phenolic and carotenoid profiles, residual moisture, colour and basic powder functionality. Results: RS produced lower residual moisture (4.7–5.4%) than SWS (6.2–8.8%). Flowability remained poor but improved at higher shelf temperatures. Water-holding capacity increased, while swelling decreased. Higher levels of protocatechuic acid (121–130 μg/g dry weight), (-)-epicatechin (36–39 μg/g dry weight), and ethyl protocatechuate (7.7–8.8 μg/g dry weight) were determined in samples dried at the lowest shelf temperature, regardless of the drying schedule. SWS30 and SWS40 were associated with caffeic acid, syringic acid and trans-2-hydroxycinnamic acid, and all SWS samples had higher quercetin content. RS gave higher carotenoid levels at 20 °C, while responses at 30 and 40 °C depended on the compound. Conclusions: Final shelf temperature and drying schedule affected antioxidant retention and functional properties of pumpkin powder. Full article

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

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14 pages, 2108 KB

Open AccessArticle

NRF2 Deletion Results in Mobility Impairment in A53TSyn Model of Synucleinopathy

by Noah Gladen-Kolarsky, Lucas Kuhnau, Wyatt Hack, Joseph F. Quinn and Nora E. Gray

Antioxidants 2026, 15(8), 926; https://doi.org/10.3390/antiox15080926 - 25 Jul 2026

Abstract

Parkinson’s Disease (PD) is the second most diagnosed neurological disorder globally, affecting millions of people worldwide. Oxidative stress is implicated in the progression of PD, yet its direct effects on motor function, particularly in the context of synucleinopathy, are not fully understood. Here, [...] Read more.

Parkinson’s Disease (PD) is the second most diagnosed neurological disorder globally, affecting millions of people worldwide. Oxidative stress is implicated in the progression of PD, yet its direct effects on motor function, particularly in the context of synucleinopathy, are not fully understood. Here, we investigated the effects of the loss of the antioxidant regulatory transcription factor NRF2 in the A53TSyn mouse model of synucleinopathy. Motor function was evaluated in separate cohorts of A53TSyn mice without NRF2 (A53TSyn/NRF2KO), as well as A53TSyn mice expressing NRF2 (A53TSyn/NRF2+) and healthy wild-type (WT) mice at four, six, and eight months of age. The overall mobility decreased in A53TSyn/NRF2KO mice relative to WT mice at all ages. Significant alterations in gait were also apparent in A53TSyn/NRF2KO mice compared to A53TSyn mice without NRF2 deletion. Expression of tyrosine hydroxylase (TH) was also quantified in the brains of those mice. While there were no differences in cortical pSyn expression between A53TSyn/NRF2+ and A53TSyn/NRF2KO mice, a reduction in TH abundance in the striatum was evident in A53TSyn/NRF2KO mice at all ages. In summary, our data suggest that NRF2 plays a role in maintaining mobility and gait in the context of synucleinopathy and may represent a therapeutic target to mitigate mobility decline in PD-affected individuals. Full article

(This article belongs to the Special Issue Oxidative Stress in Age-Related Diseases)

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16 pages, 1403 KB

Open AccessReview

Oral Microbiota, the Oral–Brain Axis, and Neurodegeneration: Mechanisms and Dietary Modulation

by Justyna Godos, Giuseppe Caruso, Giuseppe Mainas, Agnieszka Micek, Andrea Di Mauro, Lucia Buccarello, Nohora Milena Martínez López, Evelyn Frias-Toral, Francesca Giampieri, Andrea Lehoczki, Gaetano Isola, Fabio Galvano, Zoltan Ungvari, José L. Quiles, Maurizio Battino and Giuseppe Grosso

Antioxidants 2026, 15(8), 925; https://doi.org/10.3390/antiox15080925 - 25 Jul 2026

Abstract

The oral microbiota represents a complex and dynamic microbial ecosystem that plays a critical role in preserving both oral and systemic homeostasis. Emerging evidence suggests that alterations in oral microbial milieu (dysbiosis) may contribute to the pathogenesis of neurodegenerative disorders, especially Alzheimer’s disease [...] Read more.

The oral microbiota represents a complex and dynamic microbial ecosystem that plays a critical role in preserving both oral and systemic homeostasis. Emerging evidence suggests that alterations in oral microbial milieu (dysbiosis) may contribute to the pathogenesis of neurodegenerative disorders, especially Alzheimer’s disease (AD), through the oral–brain axis. This review synthesizes current evidence on the pathways linking oral microbiota to cognitive decline, integrating microbial, immunological, and vascular perspectives. Oral pathogens may access the central nervous system via hematogenous dissemination or neural routes, including the trigeminal nerve, while simultaneously promoting systemic inflammation, immune activation, and blood–brain barrier disruption. These processes converge on key neurodegenerative mechanisms, including chronic neuroinflammation, amyloid-β accumulation, and tau pathology. In parallel, alterations in oral microbial composition have been linked to disease severity, supporting a potential role of dysbiosis in both initiation and progression of cognitive impairment. Diet emerges as a critical modifiable determinant of oral microbial ecology. Diets rich in refined sugars may promote dysbiosis and inflammatory signaling, whereas (poly)phenols, probiotics, and prebiotics may support microbial eubiosis and exert neuroprotective effects through modulation of host–microbe interactions. Although current evidence remains largely observational and mechanistic, the diet–oral microbiota–brain axis represents a promising target for preventive and therapeutic strategies aimed at mitigating cognitive decline and promoting healthy aging. Future longitudinal and interventional studies are required to establish causality and translate these insights into clinical practice. Full article

(This article belongs to the Special Issue Interplay of Microbiome and Oxidative Stress)

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19 pages, 11349 KB

Open AccessArticle

Transcriptomic Analysis Reveals the Antioxidant and Anti-Inflammatory Mechanisms of EGCG-Zn Nanoparticles in Dextran Sulfate Sodium-Induced Colitis in Mice

by Tingting Liu, Mohan Zhou, Yuhang Deng, Feifei Huang and Jie Feng

Antioxidants 2026, 15(8), 924; https://doi.org/10.3390/antiox15080924 - 25 Jul 2026

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease characterized by persistent colonic inflammation, excessive oxidative stress, and impaired barrier function. Transition metal-based nanoparticles offer promising antioxidant platforms to address oxidative stress-related pathologies. To overcome the poor gastrointestinal stability of the potent dietary antioxidant [...] Read more.

Ulcerative colitis (UC) is a chronic inflammatory disease characterized by persistent colonic inflammation, excessive oxidative stress, and impaired barrier function. Transition metal-based nanoparticles offer promising antioxidant platforms to address oxidative stress-related pathologies. To overcome the poor gastrointestinal stability of the potent dietary antioxidant epigallocatechin gallate (EGCG), we utilized zinc-coordinated EGCG (EGCG-Zn) nanoparticles (NPs), which function as a transition metal–phenolic network, to achieve sustained colonic release and overcome the poor gastrointestinal stability of free EGCG. The therapeutic efficacy and underlying mechanisms were evaluated in dextran sulfate sodium (DSS)-induced colitis in mice. Oral administration of EGCG-Zn NPs effectively reduced oxidative stress, suppressed pro-inflammatory cytokine production, alleviated colitis symptoms, and repaired the intestinal mucus and mechanical barriers. Mechanistically, transcriptomic analysis revealed that EGCG-Zn NPs pretreatment markedly reversed DSS-induced transcriptional alterations. Integrated K-means clustering and KEGG enrichment analyses further demonstrated that these protective effects were mediated by down-regulating inflammation-associated genes and up-regulating tight junction proteins, primarily involving the modulation of calcium signaling, T-cell differentiation, and the PI3K-Akt, Wnt, NF-κB, and TNF pathways. Collectively, these findings suggest that EGCG-Zn NPs alleviate DSS-induced colitis by mitigating inflammation, suppressing oxidative stress, and promoting epithelial barrier repair, supporting their potential as a functional nutraceutical for UC management. Full article

(This article belongs to the Special Issue Transition Metal-Based Nanoparticles as Antioxidant Platforms for Biomedical and Cosmetic Applications)

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13 pages, 770 KB

Open AccessArticle

Plasma SH Concentrations and Mortality in Patients with Newly Diagnosed Idiopathic Pulmonary Fibrosis

by Panagiotis Paliogiannis, Stefano Zoroddu, Simona Fois, Chiara Scala, Elisabetta Zinellu, Arduino A. Mangoni, Ciriaco Carru, Pietro Pirina, Angelo Zinellu and Alessandro G. Fois

Antioxidants 2026, 15(8), 923; https://doi.org/10.3390/antiox15080923 - 24 Jul 2026

Abstract

Introduction. Oxidative stress plays a critical role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), yet its prognostic significance remains unclear. This study investigated the association between plasma sulfhydryl (SH) group concentrations and thiobarbituric acid reactive substances (TBARS), systemic markers of oxidative stress, [...] Read more.

Introduction. Oxidative stress plays a critical role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), yet its prognostic significance remains unclear. This study investigated the association between plasma sulfhydryl (SH) group concentrations and thiobarbituric acid reactive substances (TBARS), systemic markers of oxidative stress, and mortality in patients with IPF. Materials and methods. Eighty-eight patients with newly diagnosed IPF were recruited between 2016 and 2023 for the purposes of the study. Plasma SH and TBARS were measured at baseline under standardized conditions and normalized to plasma protein content. Survival analyses were performed using Kaplan–Meier curves and Cox regression models, adjusting for lung function parameters and IPF stage. Results. Patients with lower SH concentrations had significantly higher mortality (log-rank p = 0.012). SH group concentrations, but not TBARS, were independently and negatively associated with survival in multivariate models adjusting for %TLC, %FVC, %DLCO, and IPF stage (HR: 0.606, 95% CI: 0.443–0.830, p = 0.0018). Conclusions. Low plasma SH concentrations, reflecting systemic redox imbalance, are independently associated with increased mortality in newly diagnosed IPF. SH quantification represents a promising prognostic biomarker in IPF. Full article

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27 pages, 89758 KB

Open AccessArticle

Curcumin-Loaded Milk-Derived Exosomes Improve the Developmental Competence of Yak Oocytes by Regulating Mitophagy

by Tingting Lu, Xin Ma, Meng Wang, Yangyang Pan, Xiaoqing Yang, Shantong Qiu, Xueru Yang and Sijiu Yu

Antioxidants 2026, 15(8), 922; https://doi.org/10.3390/antiox15080922 - 24 Jul 2026

Abstract

Yaks are a distinctive livestock species native to the Qinghai–Tibet Plateau. However, the low in vitro maturation rate of their oocytes significantly limits the efficiency of assisted reproductive technologies. Curcumin (CUR), known for its bioactive functions, including antioxidant and anti-inflammatory properties, suffers from [...] Read more.

Yaks are a distinctive livestock species native to the Qinghai–Tibet Plateau. However, the low in vitro maturation rate of their oocytes significantly limits the efficiency of assisted reproductive technologies. Curcumin (CUR), known for its bioactive functions, including antioxidant and anti-inflammatory properties, suffers from low water solubility and bioavailability, which restricts its practical applications. This study aimed to develop a curcumin-loaded bovine milk-derived exosome nanodelivery system (CUR-mEXOs) and investigate its effects on the in vitro maturation of yak oocytes and the embryonic development of parthenogenetic embryos, leveraging its natural biocompatibility and targeted delivery properties. The results indicated that the isolated mEXOs exhibited typical exosome morphology and nanoscale particle size characteristics and were effectively internalized by the oocytes. During in vitro maturation, treatment with 10 μM CUR produced optimal outcomes. Compared to free CUR, CUR-mEXOs significantly enhanced the cumulus expansion index and the rate of first polar body expulsion, reduced intracellular ROS accumulation and mitochondrial superoxide levels, and improved mitochondrial function and spindle morphology, while simultaneously upregulating the expression of factors related to mitochondrial autophagy and oocyte maturation. Following intervention with the mitochondrial autophagy inhibitor CsA, the promotive effect of CUR-mEXOs was significantly diminished, leading to increased blastocyst apoptosis and a decrease in the total cell count. In summary, CUR-mEXOs can enhance the quality of in vitro maturation of yak oocytes and their embryonic developmental capacity following parthenogenesis by regulating mitochondrial autophagy. This study established an experimental foundation for optimizing the in vitro maturation system of yak oocytes and developing strategies for the delivery of natural bioactive substances. Additionally, this study provides a theoretical basis for enhancing the efficiency of assisted reproductive technologies in yaks. Full article

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18 pages, 16089 KB

Open AccessFeature PaperArticle

Pyrroloquinoline Quinone Improves Cognitive-Related Behavioral Performance Associated with Enhanced Mitochondrial Bioenergetics in Naturally Aged Mice

by Yun Yan, Di Deng, Chunxia Tan, Qi Lu, Jiutang Sun, Shaoliang Wu, Zhanhua Jiang, Yibo Li and Tao Lu

Antioxidants 2026, 15(8), 921; https://doi.org/10.3390/antiox15080921 - 24 Jul 2026

Abstract

We investigated whether pyrroloquinoline quinone (PQQ) could improve cognitive performance in twenty-month-old naturally aged mice and explored the potential mechanisms involved. Results showed that PQQ supplementation improved spatial working memory and recognition memory without inducing anxiety-like behavior, and was associated with better preservation [...] Read more.

We investigated whether pyrroloquinoline quinone (PQQ) could improve cognitive performance in twenty-month-old naturally aged mice and explored the potential mechanisms involved. Results showed that PQQ supplementation improved spatial working memory and recognition memory without inducing anxiety-like behavior, and was associated with better preservation of hippocampal neuronal integrity. In HT-22 hippocampal neuronal cells, PQQ reduced reactive oxygen species (ROS) accumulation, restored mitochondrial membrane potential, and enhanced mitochondrial respiratory capacity. Hippocampal transcriptomic analysis and upstream regulator prediction identified sirtuin 1 (SIRT1) as a major regulator associated with the PQQ-induced transcriptional response, while uncoupling protein 2 (UCP2) emerged as a candidate downstream mitochondrial effector. Consistently, PQQ increased hippocampal SIRT1 protein expression and downregulated UCP2 at both mRNA and protein levels. Pharmacological inhibition of SIRT1 attenuated the PQQ-induced increase in ATP production and partially weakened the regulatory effect of PQQ on UCP2, supporting the involvement of SIRT1 in PQQ-associated mitochondrial bioenergetic regulation. Collectively, these findings indicate that PQQ improves cognitive-related behavioral performance in naturally aged mice and is associated with mitochondrial bioenergetic regulation, and suggest that modulation of a SIRT1–UCP2-associated pathway may contribute to its neuroprotective effects. Full article

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23 pages, 6013 KB

Open AccessArticle

Comparative Phytochemical Profiling and Phenotypic Senolytic Screening of Botanical Extracts for Oxidative-Stress-Induced Skin-Cell Senescence

by Somi Park, Ji Eun Lee, Hyeontae Kang, Kyoung-Min Choi, Hee Cheol Kang and Jin Woo Min

Antioxidants 2026, 15(8), 920; https://doi.org/10.3390/antiox15080920 - 24 Jul 2026

Abstract

Cellular senescence contributes to skin aging through the accumulation of senescent cells and the secretion of senescence-associated secretory phenotype (SASP) factors. Although numerous botanical flavonoids have been reported to possess antioxidant and anti-aging properties, the relationship between phytochemical composition, antioxidant capacity, and senolytic [...] Read more.

Cellular senescence contributes to skin aging through the accumulation of senescent cells and the secretion of senescence-associated secretory phenotype (SASP) factors. Although numerous botanical flavonoids have been reported to possess antioxidant and anti-aging properties, the relationship between phytochemical composition, antioxidant capacity, and senolytic activity in complex botanical extracts remains poorly understood. In this study, twenty botanical extracts were systematically compared using a standardized screening platform that integrated total flavonoid quantification, UPLC-Q-TOF-MS phytochemical profiling, antioxidant evaluation, cytotoxicity assessment, and phenotypic senolytic screening in oxidative-stress-induced human foreskin fibroblast (HFF) senescence models. Among the tested extracts, chlorella, water lily, green tea, and rosemary exhibited the most pronounced senolytic-associated activities while maintaining minimal cytotoxicity toward non-senescent fibroblasts. UPLC-Q-TOF-MS analysis revealed that these extracts possessed distinct flavonoid-enriched phytochemical fingerprints despite producing comparable biological responses. Notably, green tea extract exhibited the strongest antioxidant activity, whereas its phytochemical composition differed substantially from those of the other highly active extracts, indicating that antioxidant capacity alone does not predict senolytic efficacy. Collectively, the findings demonstrate that total flavonoid content, antioxidant activity, and senolytic activity are not necessarily directly correlated and highlight the importance of comprehensive phytochemical characterization combined with phenotypic biological screening for identifying botanical resources with senescence-modulating potential. These results provide a practical comparative strategy for discovering multifunctional botanical ingredients applicable to oxidative-stress-associated skin aging. Full article

(This article belongs to the Special Issue Phytochemical Analysis and Evaluation of Antioxidant Properties in Medicinal Plants)

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39 pages, 1604 KB

Open AccessReview

From Oxidative Stress to Fibrotic Remodeling: Integrating Redox Biology, Galectin-3, and Imaging Phenotypes in Heart Failure

by Samuel Ardelean, Andrada Ardelean, Diana-Evelyne Buzzi, Andrei-Catalin Zavragiu, Daniel Rus, Elena-Larisa Zimbru, Vlad Ioan Morariu, Ruxandra Maria Christodorescu, Adrian Sturza and Minodora Andor

Antioxidants 2026, 15(8), 919; https://doi.org/10.3390/antiox15080919 - 24 Jul 2026

Abstract

Oxidative stress contributes to heart failure (HF) progression by mechanisms that go beyond hemodynamic overload, including mitochondrial dysfunction, endothelial injury, inflammation, and fibrotic remodeling. This review evaluates the relationship between redox imbalance, Galectin-3 (Gal-3), fibrosis, and imaging findings in HF. Reactive oxygen species [...] Read more.

Oxidative stress contributes to heart failure (HF) progression by mechanisms that go beyond hemodynamic overload, including mitochondrial dysfunction, endothelial injury, inflammation, and fibrotic remodeling. This review evaluates the relationship between redox imbalance, Galectin-3 (Gal-3), fibrosis, and imaging findings in HF. Reactive oxygen species (ROS) generated by mitochondria, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and xanthine oxidase may disturb calcium handling, impair mitochondrial function, activate fibroblasts, and promote ferroptosis. Biomarkers of oxidative injury and antioxidant reserve, including malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and circulating thiols, provide information complementary to natriuretic peptides. Experimental evidence supports a context-dependent role of Gal-3 in fibro-inflammatory remodeling, whereas circulating Gal-3 should be regarded as a complementary biomarker rather than as a direct measure of myocardial fibrosis. Echocardiography assesses functional remodeling through diastolic indices, myocardial deformation, and right ventricular–pulmonary arterial (RV–PA) coupling, while cardiac magnetic resonance characterizes focal scar and diffuse interstitial remodeling using late gadolinium enhancement, native T1 mapping, and extracellular volume fraction. Therapeutic strategies are increasingly shifting from nonspecific antioxidant supplementation toward targeting ROS sources and downstream pathways, with SGLT2 inhibitors emerging as clinically relevant agents with indirect redox-modulating effects. Integrated redox, fibro-inflammatory, hemodynamic, and imaging phenotyping may refine risk stratification, although prospective validation is required before routine implementation. Full article

(This article belongs to the Special Issue Role of Oxidative Stress in Cardiac Remodeling and Heart Failure—3rd Edition)

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16 pages, 1551 KB

Open AccessArticle

Gill Tissue Tolerance Remodeling and Compensatory Regulatory Mechanisms Under Acute Hypoxic Stress in Topmouth Culter (Culter alburnus)

by Jinmei Tang, Huali Zhao, Hao Zhang, Kabba Koroma and Di’an Fang

Antioxidants 2026, 15(8), 918; https://doi.org/10.3390/antiox15080918 - 24 Jul 2026

Abstract

Topmouth culter (Culter alburnus) is highly sensitive to hypoxic conditions, but its regulatory mechanisms remain poorly understood. In this study, C. alburnus were exposed to hypoxia (DO: 0.60 ± 0.05 mg·L⁻¹) for 0, 2, 4, 6, 12, and 24 [...] Read more.

Topmouth culter (Culter alburnus) is highly sensitive to hypoxic conditions, but its regulatory mechanisms remain poorly understood. In this study, C. alburnus were exposed to hypoxia (DO: 0.60 ± 0.05 mg·L⁻¹) for 0, 2, 4, 6, 12, and 24 h to investigate the gill tissue responses and the underlying regulatory mechanisms. Results showed that gill lamellae of C. alburnus exhibited distortion and thickening under hypoxic stress for 2–6 h. Between 12 and 24 h of hypoxia, the gill tissue exhibited changes characterized by sinusoidal dilatation and an increased number of red blood cells. Interestingly, the apoptosis rates significantly increased in all experimental groups in response to the hypoxic environment. The plasma glucose (Glu) level increased rapidly at the early stage and then gradually declined. The total protein (TP) level showed a slight elevation. Meanwhile, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) exhibited sustained increases. Hypoxia stress may induce a metabolic transition from early reliance on glucose for energy to later reliance on lipid metabolism. SOD activity gradually increased under hypoxia, while MDA content exhibited an overall upward trend. Oxidative stress-related genes (foxo1b, mapkapk2, irs2, ppargc1b) were significantly upregulated to enhance antioxidant capacity during the early phase of hypoxic stress. However, during the late phase of hypoxia, the expression of these genes was significantly downregulated. In conclusion, this study offers a new theoretical basis for gill tolerance remodeling and molecular regulation in C. alburnus under acute hypoxic stress. Full article

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

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57 pages, 2802 KB

Open AccessReview

Role of Antioxidant Systems and Heat Shock Response in Aquatic Animals Under Multistress Conditions

by Konstantinos Feidantsis, Marina Minari, Víctor Cubillos, Peter D. Dijkstra, Olivia D. K. Buzinski, Daniel C. Moreira and Marcelo Hermes-Lima

Antioxidants 2026, 15(8), 917; https://doi.org/10.3390/antiox15080917 - 23 Jul 2026

Abstract

The multistress concept is a recent approach developed to better understand the effects of environmental stress in animals under real-world conditions. In nature, animals are exposed to simultaneous environmental fluctuations on daily and seasonal time scales, and interactions among stressors can produce antagonistic, [...] Read more.

The multistress concept is a recent approach developed to better understand the effects of environmental stress in animals under real-world conditions. In nature, animals are exposed to simultaneous environmental fluctuations on daily and seasonal time scales, and interactions among stressors can produce antagonistic, additive, or synergistic physiological responses. Consequently, studies examining only one stressor under controlled laboratory conditions may fail to reflect responses in natural habitats. This review discusses the effects of multiple stressors on redox metabolism and heat shock protein (HSP) responses, focusing on aquatic environments. We discuss the multistress approach in laboratory and field studies, highlighting major abiotic stressors such as salinity changes, solar radiation, temperature, and low oxygen availability, including hypoxia and aerial exposure. The effects of multiple stressors on HSPs and antioxidants are summarized using examples from the literature. Finally, the role of social stress and life history stage in shaping responses to multiple abiotic stressors is considered. Overall, the review highlights the application of the multistress approach in laboratory and field experiments, emphasizing key stress responses involving endogenous antioxidants and HSPs, both initiated by reactive oxygen species (ROS). Full article

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

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