Antioxidants

19 pages, 8516 KB

Open AccessArticle

Novel Resveratrol Derivatives as Dual PDE4 Inhibitors and Free Radical Scavengers: Rational Design, Synthesis, and Biological Evaluation

by Youzhi Wang, Huizhen Shen, Ying Liang, Guoqing Yang, Botao Zhang, Yunbao Zhi and Jinxin Wang

Antioxidants 2026, 15(7), 899; https://doi.org/10.3390/antiox15070899 - 20 Jul 2026

Abstract

A novel class of resveratrol derivatives as dual PDE4 (Phosphodiesterase 4) inhibitors and free radical scavengers for the treatment of COPD (chronic obstructive pulmonary disease) was developed in this study. In vitro, the most promising compound WYZ69 showed similar PDE4 inhibitory activity and [...] Read more.

A novel class of resveratrol derivatives as dual PDE4 (Phosphodiesterase 4) inhibitors and free radical scavengers for the treatment of COPD (chronic obstructive pulmonary disease) was developed in this study. In vitro, the most promising compound WYZ69 showed similar PDE4 inhibitory activity and anti-inflammatory activity to rolipram and better DPPH free radical scavenging ability and anti-lipid peroxidative activity than edaravone. In addition, compound WYZ69 turned out to be a novel ferroptosis inhibitor, which significantly inhibited ferroptosis as a free radical scavenger, decreased the levels of ROS (reactive oxygen species), increased the expression of GPX4 (Glutathione peroxidase 4), and decreased the expression of transferrin in A549 cells induced by a ferroptosis activator, RSL3 ((1S,3R)-RSL3). In vivo, it exhibited a half-life of 1.63 h in mice and moderate anti-inflammatory activity in mice induced by LPS (Lipopolysaccharide). Hence, these findings suggest that compound WYZ69 is a promising dual PDE4 inhibitor and free radical scavenger with anti-inflammatory and anti-ferroptosis activities for the treatment of COPD. Full article

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

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23 pages, 26676 KB

Open AccessArticle

Pectolinarigenin Attenuates LPS-Induced Lung Inflammation and Injury with Reduced HDAC3/NF-κB/NLRP3 Signaling

by Danbee Kim, Dong-Keon Lee and Jeong-Ran Park

Antioxidants 2026, 15(7), 898; https://doi.org/10.3390/antiox15070898 - 20 Jul 2026

Abstract

Pectolinarigenin (PEC), a naturally occurring flavonoid, exhibits anti-inflammatory and antioxidant activities in various experimental models. However, its protective effects against lipopolysaccharide (LPS)-induced lung inflammation and the underlying molecular mechanisms remain unclear. This study investigated the protective effects of PEC using LPS-treated MLE12 cells [...] Read more.

Pectolinarigenin (PEC), a naturally occurring flavonoid, exhibits anti-inflammatory and antioxidant activities in various experimental models. However, its protective effects against lipopolysaccharide (LPS)-induced lung inflammation and the underlying molecular mechanisms remain unclear. This study investigated the protective effects of PEC using LPS-treated MLE12 cells and RAW264.7 macrophages, as well as a prophylactic mouse model in which PEC was administered before LPS exposure. In LPS-treated MLE12 cells and RAW264.7 macrophages, PEC reduced inflammatory responses and cellular injury, accompanied by decreased reactive oxygen species production and modulation of the histone deacetylase 3 (HDAC3)/nuclear factor κB (NF-κB)/NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) signaling. Consistent with these findings, PEC pretreatment attenuated pulmonary edema, inflammatory cell infiltration, pro-inflammatory cytokine production, oxidative stress, pyroptosis-associated signaling, and histopathological lung injury in LPS-exposed mice. These protective effects were accompanied by reduced HDAC3 expression and nuclear localization, together with reduced NF-kB/NLRP3 signaling in lung tissues. Overall, PEC attenuated LPS-induced lung inflammation and injury, accompanied by reduced oxidative stress and modulation of HDAC3/NF-κB/NLRP3 signaling. These findings support the potential of PEC as a preventive agent against excessive pulmonary inflammation. Full article

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

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43 pages, 4185 KB

Open AccessReview

Microbiota-Derived Metabolites in the Epigenetic Regulation of Redox Homeostasis

by Patricia Mester, Sara Martina Steinmann, Simon Mehler, Martina Müller and Karsten Gülow

Antioxidants 2026, 15(7), 897; https://doi.org/10.3390/antiox15070897 - 20 Jul 2026

Abstract

Redox homeostasis is essential for intestinal and systemic health and is regulated by antioxidant defense systems and redox-sensitive signaling pathways such as the nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells (NF-κB). Disturbances in this balance [...] Read more.

Redox homeostasis is essential for intestinal and systemic health and is regulated by antioxidant defense systems and redox-sensitive signaling pathways such as the nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells (NF-κB). Disturbances in this balance promote oxidative stress, chronic inflammation, and disease progression. Increasing evidence indicates that microbiota-derived metabolites act as key modulators of redox biology by shaping host gene expression through receptor-mediated signaling, metabolic regulation, and chromatin-associated mechanisms, including histone modifications, DNA methylation, and changes in chromatin accessibility. This review discusses how major classes of microbiota-derived and microbiota-modulated metabolites, including short-chain fatty acids (SCFAs), secondary bile acids, tryptophan-derived metabolites, polyphenol metabolites, hydrogen sulfide, and lipid mediators, influence redox-sensitive signaling and epigenetic regulation. We highlight their effects on intestinal barrier integrity and immune cell function, with particular emphasis on macrophage polarization and T-cell differentiation. Finally, we consider the emerging translational relevance of the microbiota–metabolite–epigenetic axis, while emphasizing that biomarker development and therapeutic applications require further mechanistic validation and clinical studies. Full article

(This article belongs to the Special Issue Interplay Between Gut Microbiota and Oxidative Stress)

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14 pages, 1450 KB

Open AccessSystematic Review

Effects of Melatonin in Women with Polycystic Ovary Syndrome Undergoing ART: A Systematic Review

by Sapna Jaiswar, Mahadev Bhise and Pallavi Shukla

Antioxidants 2026, 15(7), 896; https://doi.org/10.3390/antiox15070896 - 20 Jul 2026

Abstract

Polycystic ovary syndrome (PCOS), newly named as Polyendocrine Metabolic Ovarian Syndrome (PMOS) is the most common endocrinopathy affecting women of reproductive age, which often leads to infertility due to anovulation and poor oocyte quality. Poor oocyte quality is a major reason for women’s [...] Read more.

Polycystic ovary syndrome (PCOS), newly named as Polyendocrine Metabolic Ovarian Syndrome (PMOS) is the most common endocrinopathy affecting women of reproductive age, which often leads to infertility due to anovulation and poor oocyte quality. Poor oocyte quality is a major reason for women’s infertility in humans and a barrier to efficient assisted reproduction technology (ART) treatment. Supplementation of melatonin, a free radical scavenger, has been reported to show satisfactory results in women undergoing ART. This review investigates whether the endogenous melatonin or supplementation of melatonin impact on oocyte/embryo quality and pregnancy rate in PCOS patients undergoing ART treatment. Articles published between 2010 and 2025 were reviewed to perform a comprehensive search on observational studies and clinical trials that evaluated the use of melatonin in PCOS patients undergoing in vitro fertilization (IVF) or intrauterine insemination (IUI) or intracytoplasmic sperm injection (ICSI). The databases searched included PubMed, Google Scholar, Science Direct, and Cochrane Library. This systematic review indicates that the group that received melatonin had significantly higher clinical pregnancy probabilities than the control group. Similarly, the melatonin administration significantly enhanced the endometrium thickness (p < 0.001) and the chemical pregnancy rate (30% versus 18%, p = 0.012). Additionally, in comparison to the control group that received metformin alone, the group that received melatonin (3 mg) significantly increased the proportion of top-quality embryos (40.3% vs. 29.9%; p < 0.001). According to this systematic review, melatonin significantly improves endometrial thickness, mature oocytes, high-quality embryos, and pregnancy rates, all of which improve ART outcomes in PCOS patients. Because of its safety, affordability, and efficacy, it is a useful supplement to ART procedures. The most popular and well-tolerated dosage is still 3 mg per day, despite variations in research. Full article

(This article belongs to the Special Issue Oxidative Stress and Human Reproduction)

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29 pages, 832 KB

Open AccessReview

Chasing the FoxO in Metabolic Disorders: Novel Considerations for Oxidative Stress, Programmed Cell Death, Wnt, and the Gut Microbiome

by Kenneth Maiese

Antioxidants 2026, 15(7), 895; https://doi.org/10.3390/antiox15070895 - 20 Jul 2026

Abstract

Lifespan is increasing throughout the world leading to a rise in non-communicable diseases in the global population that impacts over 800 million individuals with metabolic disorders, such as diabetes mellitus. Metabolic disease presents a significant challenge for clinical care since multi-organ disease progression [...] Read more.

Lifespan is increasing throughout the world leading to a rise in non-communicable diseases in the global population that impacts over 800 million individuals with metabolic disorders, such as diabetes mellitus. Metabolic disease presents a significant challenge for clinical care since multi-organ disease progression ensues despite a broad array of treatment protocols. The pursuit of innovative strategies with mammalian forkhead transcription factors of the “O” class (FoxOs) and intimately related pathways of aging, cellular senescence, telomere integrity, oxidative stress, programmed cell death with apoptosis, autophagy, ferroptosis, pyroptosis, and cuproptosis, Wnt/β-catenin signaling, Wnt1 inducible signaling pathway protein 1, and the gut microbiome becomes vital to address the clinical hurdles of metabolic disorders. Platforms incorporating novel diagnostics with artificial intelligence and machine learning can further address the underlying mechanisms tied to FoxOs that include the mechanistic target of rapamycin, AMP activated protein kinase, silent mating type information regulation 2 homolog 1 (S. cerevisiae), and glucagon-like peptide-1 receptor agonists that can markedly influence biological outcomes. Given the premise that it is essential to comprehend the intimate relationship that FoxO signaling pathways hold, FoxOs offer an exciting and promising approach to address the clinical aspects of disease onset, progression, and treatment with metabolic disorders. Full article

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16 pages, 1431 KB

Open AccessReview

Oxidative Stress in Inflammatory Bowel Disease: From Redox Dysregulation to Translational Targeting

by Alexandra Laura Mederle, Ana Lascu, Andrei Raul Manzur, Alexandru Caraba, Raluca Elisabeta Staicu, Lavinia Noveanu and Oana Maria Aburel

Antioxidants 2026, 15(7), 894; https://doi.org/10.3390/antiox15070894 - 20 Jul 2026

Abstract

Oxidative stress has emerged as an important component of the complex pathophysiology of inflammatory bowel disease (IBD), where increasing evidence suggests an interaction between redox imbalance, immune activation, epithelial dysfunction, and chronic intestinal inflammation. This structured narrative review critically synthesizes current evidence regarding [...] Read more.

Oxidative stress has emerged as an important component of the complex pathophysiology of inflammatory bowel disease (IBD), where increasing evidence suggests an interaction between redox imbalance, immune activation, epithelial dysfunction, and chronic intestinal inflammation. This structured narrative review critically synthesizes current evidence regarding the biological basis of oxidative stress in IBD, with emphasis on cellular and molecular mechanisms, oxidative biomarkers, therapeutic modulation of redox pathways, and their translational relevance. Current evidence indicates that oxidative stress is associated with immune-cell activation, mitochondrial dysfunction, impairment of epithelial homeostasis, and dysregulation of redox-sensitive signaling pathways. Biomarkers including nitric oxide metabolites, malondialdehyde, myeloperoxidase, total antioxidant capacity, serum thiols, and antioxidant enzymes have demonstrated associations with inflammatory activity, while anti-inflammatory, antioxidant, and dietary interventions have been reported to modulate oxidative biomarkers in selected clinical studies. However, substantial methodological heterogeneity, variability in analytical techniques, and limited prospective validation currently restrict their routine clinical application. Moreover, many mechanistic pathways have been characterized predominantly in experimental models, highlighting the need to distinguish biological plausibility from evidence supporting clinical implementation. Overall, oxidative stress represents a promising area of investigation that may contribute to a better understanding of IBD biology and support future biomarker-guided and precision medicine approaches. Nevertheless, further standardized translational and longitudinal clinical studies are required before oxidative biomarkers and redox-targeted strategies can be integrated into routine patient care. Full article

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23 pages, 4015 KB

Open AccessArticle

Curcumin Attenuates Glyphosate-Induced Mammary Toxicity via Suppression of ER Stress and the TNFα/MAPK/STAT3 Axis

by Yonglong He, Hanbing Yan, Zesheng Gan, Ziwei Cheng, Binyun Cao, Jiangang Wang and Xiaopeng An

Antioxidants 2026, 15(7), 893; https://doi.org/10.3390/antiox15070893 - 19 Jul 2026

Abstract

Curcumin, a natural polyphenol with well-established antioxidant and anti-inflammatory properties, was evaluated for its protective effects against glyphosate (GLY)-induced mammary toxicity. Pregnant mice received GLY (50 or 250 mg/kg/day) with or without curcumin (150 mg/kg/day) by oral gavage; GLY dose-dependently disrupted alveolar architecture, [...] Read more.

Curcumin, a natural polyphenol with well-established antioxidant and anti-inflammatory properties, was evaluated for its protective effects against glyphosate (GLY)-induced mammary toxicity. Pregnant mice received GLY (50 or 250 mg/kg/day) with or without curcumin (150 mg/kg/day) by oral gavage; GLY dose-dependently disrupted alveolar architecture, caused marked inflammatory infiltration, and downregulated tight-junction proteins. In parallel, goat mammary epithelial cells (GMECs) were treated with GLY (1 or 7 mM) and curcumin (1 µM) to dissect acute cellular stress pathways. These complementary models address distinct aspects of GLY toxicity: the in vivo system reflects defined oral exposure, whereas the in vitro setting employs high concentrations to probe mechanistic events. Transcriptomic profiling combined with functional assays demonstrated that GLY triggered oxidative stress, endoplasmic reticulum stress, and intracellular Ca²⁺ overload, activated the TNFα/MAPK axis, suppressed STAT3 phosphorylation, and ultimately promoted apoptosis. Curcumin co-treatment alleviated these alterations at both structural and molecular levels. These findings indicate that curcumin can combat GLY-induced mammary injury by restoring cellular homeostasis and inhibiting apoptotic and inflammatory signaling, thereby protecting breast health. Full article

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21 pages, 13185 KB

Open AccessArticle

Effects of Different Temperatures on Flavonoid Secondary Metabolites and Antioxidant Activities of Paecilomyces hepiali

by Bing Jia, Chuyu Tang, Haoxu Tang, Yan Tong, Jinxuan Yan, Yuling Li and Xiuzhang Li

Antioxidants 2026, 15(7), 892; https://doi.org/10.3390/antiox15070892 - 19 Jul 2026

Abstract

To explore the physiological and metabolic response mechanism of Paecilomyces hepiali (P. hepiali) under varying temperatures, five temperature gradients were established in this study. Combined with in vitro antioxidant assays and untargeted and targeted metabolomics analyses, the variations in antioxidant system and flavonoid [...] Read more.

To explore the physiological and metabolic response mechanism of Paecilomyces hepiali (P. hepiali) under varying temperatures, five temperature gradients were established in this study. Combined with in vitro antioxidant assays and untargeted and targeted metabolomics analyses, the variations in antioxidant system and flavonoid secondary metabolites were investigated. Results showed that temperature significantly affected the accumulation of active substances and antioxidant capacity, including of peroxidase (POD), total flavonoids, soluble protein and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Metabolomics analysis revealed distinct metabolic profiles among groups, and flavonoids and phenolic acids were identified as pivotal responsive metabolites. KEGG enrichment analysis revealed that flavonoid biosynthesis, linoleic acid metabolism and arachidonic acid metabolism served as core regulatory pathways. Nineteen common differential flavonoid metabolites were screened out. Correlation analysis revealed that vanillin, cryptochlorogenic acid and sinapinic acid strongly correlated with antioxidant capacity, acting as key regulators for temperature-induced antioxidant responses in P. hepiali. This study verified that temperature modulates the antioxidant system and flavonoid metabolism of P. hepiali, offering references for industrial optimization of its fermentation. Full article

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24 pages, 14828 KB

Open AccessArticle

Wogonin Suppresses Non-Small Cell Lung Cancer Growth in Association with Oxidative Stress, c-Myc/GPX4 Downregulation and Ferroptosis-Related Responses

by Hairong Xiang, Haoshu Liu, Ruyu Jiang, Xiaomeng Tang, Linfeng Zhao, Dawei Zeng, Yue Zhang, Jiazhen Xie, Liangqin Shi and Lan Yang

Antioxidants 2026, 15(7), 891; https://doi.org/10.3390/antiox15070891 - 19 Jul 2026

Abstract

Reactive oxygen species (ROS)-regulated antioxidant defense is closely linked to non-small cell lung cancer (NSCLC) progression and therapy resistance. Wogonin (WGN), a flavonoid from Scutellaria baicalensis, has antitumor activity, but whether it is associated with ROS-dependent ferroptotic and mitochondrial stress in NSCLC [...] Read more.

Reactive oxygen species (ROS)-regulated antioxidant defense is closely linked to non-small cell lung cancer (NSCLC) progression and therapy resistance. Wogonin (WGN), a flavonoid from Scutellaria baicalensis, has antitumor activity, but whether it is associated with ROS-dependent ferroptotic and mitochondrial stress in NSCLC remains incompletely defined. A549 and BEAS-2B cells, male BALB/c nude mouse A549 xenografts, patient-derived NSCLC organoids, and public transcriptomic cohorts were analyzed using viability, colony formation, migration/invasion, DCFH-DA ROS, JC-1, Annexin V/PI, Fe²⁺ and lipid ROS probes, RT-qPCR, Western blotting, immunofluorescence, inhibitor rescue, and c-Myc gain- and loss-of-function assays. WGN suppressed A549 growth and motility with weaker effects on BEAS-2B cells. WGN markedly increased intracellular ROS, Fe²⁺ accumulation and lipid peroxidation, decreased mitochondrial membrane potential, promoted Caspase-related apoptosis, reduced c-Myc/GPX4 and SLC7A11, and increased ACSL4. N-acetylcysteine, Z-VAD-FMK and Ferrostatin-1 partially rescued WGN-induced injury. c-Myc overexpression partially restored GPX4 and reduced lipid ROS/Fe²⁺ accumulation, whereas c-Myc knockdown decreased GPX4. Xenografts and organoids reproduced tumor inhibition and selected redox-associated molecular changes. Collectively, WGN suppresses A549-associated NSCLC phenotypes in association with ROS accumulation, ferroptosis-related lipid injury, mitochondrial dysfunction-associated apoptosis, and c-Myc/GPX4 downregulation. Full article

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

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14 pages, 371 KB

Open AccessReview

Intrinsic Antioxidant Capacity of Fish Muscle as Potential Link Between Pre-Harvest Biology and Post Mortem Flesh Quality in Farmed Fish

by Cosmas I. Nathanailides and Michael G. Kontominas

Antioxidants 2026, 15(7), 890; https://doi.org/10.3390/antiox15070890 - 18 Jul 2026

Abstract

The present review examines markers of intrinsic antioxidant capacity in fish muscle, how these markers change after death, and the point to which their post mortem evolution is related to flesh quality and shelf life in farmed fish. Aquaculture parameters such as temperature, [...] Read more.

The present review examines markers of intrinsic antioxidant capacity in fish muscle, how these markers change after death, and the point to which their post mortem evolution is related to flesh quality and shelf life in farmed fish. Aquaculture parameters such as temperature, salinity and fish feeds can affect intrinsic antioxidant systems throughout the fish life cycle, but, in addition to the effect of aquaculture variables, the redox starting point of muscle at death can be affected by pre-slaughter stressors such as transportation, crowding, fasting, and handling. Based on the results of the studies reviewed in this work, it can be postulated that the rate of post mortem lipid and protein oxidation of fish fillets is not determined only by processes occurring after death or during storage, but may also be influenced by the antioxidant status of axial skeletal muscle. This postulation offers an important mechanistic link between (i) pre-slaughter conditions (such as aquaculture production systems, environmental factors, feeding regime, handling stress) and (ii) harvesting methods, with these two determining the oxidative stability of fish fillets via shaping the antioxidant capacity of muscle tissue. This approach highlights the value of linking nutritional, husbandry, harvesting and processing practices in order to improve fish welfare, flesh quality and shelf life. Full article

(This article belongs to the Section Aberrant Oxidation of Biomolecules)

25 pages, 3246 KB

Open AccessArticle

Characterization of Spent Coffee Grounds’ Polyphenol Fraction and Its Potential as a Low-Cost Tool for Bioactivity-Guided Nephroprotective Modulation of Gut–Kidney Axis and NF-κB/Nrf2/TGF-β Signaling in Hypertension-Associated Kidney Injury

by Fahrul Nurkolis, Dante Saksono Harbuwono, Yulia Wardhani, Edwin Hadinata, Siti Nur Rohmah, Metalia Puspitasari, Lucia De Luca, Raffaele Romano, Danny Pratama Kuswadi, Raymond Rubianto Tjandrawinata, Eka Ginanjar, Pringgodigdo Nugroho and Antonello Santini

Antioxidants 2026, 15(7), 889; https://doi.org/10.3390/antiox15070889 - 17 Jul 2026

Abstract

Background: Hypertension-associated kidney injury is driven by oxidative stress, inflammation, fibrosis, and gut-derived uremic toxins via the gut–kidney axis. Spent coffee grounds (SCG) represent a sustainable source of bioactive polyphenols with potential nephroprotective effects. This study aimed to characterize a bioactivity-guided SCG polyphenol [...] Read more.

Background: Hypertension-associated kidney injury is driven by oxidative stress, inflammation, fibrosis, and gut-derived uremic toxins via the gut–kidney axis. Spent coffee grounds (SCG) represent a sustainable source of bioactive polyphenols with potential nephroprotective effects. This study aimed to characterize a bioactivity-guided SCG polyphenol fraction and evaluate its therapeutic potential. Methods: Bioactivity-guided fractionation was performed to enrich active polyphenols, followed by in silico target prediction and in vivo validation using L-NAME-induced hypertensive rats treated for 8 weeks. Renal function, oxidative stress, inflammatory and fibrotic markers, gut-derived metabolites, and endothelial function were assessed. Results: The enriched fraction was dominated by chlorogenic acid derivatives and showed predicted interactions with NF-κB, Keap1/Nrf2, TGF-β receptor, ACE, and AT1 receptor. In hypertensive rats, treatment significantly lowered blood pressure, improved renal function, reduced oxidative stress, inflammation, fibrosis, and gut-derived uremic toxins, while restoring Nrf2 activity, short-chain fatty acid production, and endothelial function. Across multiple biological endpoints, the polyphenol-enriched fraction consistently demonstrated greater efficacy than the crude extract. Conclusion: SCG polyphenol fraction shows strong nephroprotective potential via gut–kidney axis modulation and NF-κB/Nrf2/TGF-β regulation, supporting its development as a low-cost therapeutic candidate. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Kidney Diseases)

26 pages, 77986 KB

Open AccessArticle

Danshen (Salvia miltiorrhiza Buge)–Gegen (Pueraria lobata (Willd.) Ohwi) Herb Pair Inhibits Ferroptosis After Ischemia–Reperfusion Injury Involving the Nrf2/System xc-/GPX4 Axis

by Yin Liu, Yan Wang, Xinyu Shi, Ruomei Che and Xiaoli He

Antioxidants 2026, 15(7), 888; https://doi.org/10.3390/antiox15070888 - 17 Jul 2026

Abstract

Background: Danshen–Gegen is a classic herb pair in traditional Chinese medicine, which has been used to treat cardiovascular and cerebrovascular diseases. Ischemic stroke (IS) is a prevalent cerebrovascular condition; ferroptosis is one of the contributing factors driving the progression of IS. This study [...] Read more.

Background: Danshen–Gegen is a classic herb pair in traditional Chinese medicine, which has been used to treat cardiovascular and cerebrovascular diseases. Ischemic stroke (IS) is a prevalent cerebrovascular condition; ferroptosis is one of the contributing factors driving the progression of IS. This study aims to determine the underlying mechanism and examine if Danshen–Gegen (DG) extract may prevent cerebral ischemia–reperfusion injury by preventing ferroptosis. Methods: The comprehensive compositional characterization of DG was analyzed by ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry (UPLC-Q-orbitrap MS). The experiments were conducted in middle cerebral artery occlusion/reperfusion (MCAO/R) rats and oxygen-glucose deprivation/re-oxygenation (OGD/R) cells. The neuroprotective effects of DG on IS were assessed by examining rat survival rates, infarct volume, behavioral scores, and cerebral water content. Then, we tested the accumulation of Fe²⁺ and lipid peroxidation products such as reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and 4-hydroxynonenal (4-HNE) in rats and cells. The expression of nuclear factor erythroid-derived 2-like 2 (Nrf2), Solute Carrier Family 7 Member 11 (-xCT), Glutathione peroxidase 4 (GPX4), Cyclooxygenase-2 (COX-2), Transferrin Receptor 1 (TFR1), and Long-chain-fatty-acid–CoA ligase 4 (ACSL4) was also assessed in vivo and in vitro. Results: UPLC-Q-orbitrap MS analysis was performed to characterize the chemical profile of DG, and a total of 33 chemical constituents were successfully identified. DG significantly alleviated the ischemic damage to brain tissue, reduced infarct volume, and improved neurological dysfunction. The content of Fe²⁺ and lipid peroxidation products was markedly decreased. Furthermore, DG could restore the expression of Nrf2, -xCT, and GPX4 with the inhibition of COX-2, TFR1, and ACSL4, thus achieving a suppressive effect on ferroptosis. Conclusions: The regulatory influence of DG via the Nrf2/System xc-/GPX4 axis may play a crucial role in alleviating ferroptosis and enhancing recovery from cerebral ischemia injury. Full article

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

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17 pages, 1613 KB

Open AccessArticle

Comparison of Nutritional Profiles and Antioxidant Capacity in the Muscle of Procambarus clarkii Farmed Across Various Rice Paddy Regions in Eastern China

by Linjun Zhou, Chonghang Ding, Rui Jia, Yiran Hou, Chengfeng Zhang, Liqiang Zhang, Bing Li and Jian Zhu

Antioxidants 2026, 15(7), 887; https://doi.org/10.3390/antiox15070887 - 17 Jul 2026

Abstract

The aim of the study was to assess the regional differences in Procambarus clarkii via analyzing amino acid and fatty acid profiles, minerals, antioxidant capacity, and metabolic profiles from ten major producing areas in China. The results showed that P. clarkii cultured in [...] Read more.

The aim of the study was to assess the regional differences in Procambarus clarkii via analyzing amino acid and fatty acid profiles, minerals, antioxidant capacity, and metabolic profiles from ten major producing areas in China. The results showed that P. clarkii cultured in rice fields was a high-quality source of amino acids and fatty acids. The P. clarkii collected from Feixi and Suqian city exhibited higher amino acids and polyunsaturated fatty acids, whereas those from Honghu and Jianli city displayed lower unsaturated fatty acids. Mineral profiles showed clear regional heterogeneity, with K and Na as the predominant elements; Feixi city was characterized by relatively high K and Mg levels, while Nanxian and Honghu city showed higher Zn and Fe accumulation. Moreover, antioxidant-related indicators showed region-specific and mixed patterns, indicating that antioxidant status should be interpreted based on multiple biomarkers rather than any single indicator. Metabolomic profiling also revealed clear geographic clustering, with regional differences mainly associated with amino acid and lipid metabolism. Overall, the nutritional composition and antioxidant capacity of P. clarkii muscle exhibited clear regional variability. Our findings provide a theoretical basis for quality evaluation in P. clarkii aquaculture and offer practical guidance for refining the development models and strategic direction of integrated rice–crayfish farming across different regions. Full article

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

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21 pages, 3834 KB

Open AccessArticle

Comparative Evaluation of Oxidative Stress, Cortisol, Inflammatory Response, and Systemic CO₂ Dynamics in Dogs Undergoing Laparoscopic and Open Ovariectomy

by Sandra Čechovičienė, Ieva Šidlauskaitė, Birutė Karvelienė, Ieva Sarapinienė, Ieva Čiapienė, Vita Riškevičienė and Dalia Juodžentė

Antioxidants 2026, 15(7), 886; https://doi.org/10.3390/antiox15070886 - 17 Jul 2026

Abstract

A key distinction between open and laparoscopic surgery is the use of CO₂ insufflation to create pneumoperitoneum and establish the operative field. This study compared the effects of laparoscopic and open ovariectomy (OVE) on plasma cortisol, oxidative stress (OS), systemic inflammation, and [...] Read more.

A key distinction between open and laparoscopic surgery is the use of CO₂ insufflation to create pneumoperitoneum and establish the operative field. This study compared the effects of laparoscopic and open ovariectomy (OVE) on plasma cortisol, oxidative stress (OS), systemic inflammation, and systemic CO₂ dynamics in healthy dogs anesthetized under a standardized protocol. Thirty-eight healthy female dogs were enrolled in the study and allocated to the laparotomy (LPTOVE, n = 19) or laparoscopic (LAPOVE, n = 19) OVE group. OS was assessed using total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI). Systemic inflammation was evaluated by TNF-α and IL-6 concentrations, whereas systemic CO₂ dynamics were assessed using plasma total CO₂ (TCO₂) and end-tidal CO₂ (EtCO₂). Blood samples were collected prior to sedation (T0), prior to surgical incision (T1), prior to surgical closure in the LPTOVE group or CO₂ desufflation in the LAPOVE group (T2), and 2 h postoperatively (T3). Cortisol concentrations at T2 and T3 were significantly higher in the LPTOVE group than in the LAPOVE group. No significant intergroup differences were observed in TOS, TAS, OSI, or TCO₂. In the LPTOVE group, TOS significantly decreased at T3, whereas in the LAPOVE group, TOS mildly increased at T1 and OSI significantly decreased at T2. No measurable TNF-α or IL-6 concentrations were detected at the evaluated time points. EtCO₂ levels were higher in the LAPOVE group at the end of surgery. These findings suggest that laparoscopic OVE was associated with lower perioperative cortisol concentrations, while systemic redox status, TNF-α and IL-6 concentrations, and carbon dioxide-related parameters remained largely comparable between surgical approaches. Full article

(This article belongs to the Special Issue Oxidative Stress and Biomarkers in Veterinary Medicine)

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25 pages, 3463 KB

Open AccessArticle

Multifunctional System with Ferulic Acid: Increased Safety, Antioxidant Activity, and Efficacy of Sunscreen Formulations

by Jamile Vitória Alves Freire, Fernanda Ílary Costa Duarte, Lívia Maria da Costa Dantas, Júlia Luíza André Santana, Patrícia Prado Augusto, Cristiane Fernandes de Assis, Francisco Caninde de Sousa Junior, Ana Paula Barreto Gomes, Fernando Henrique Andrade Nogueira, Patricia Santos Lopes, André Rolim Baby, Ádley Antonini Neves de Lima and Elissa Arantes Ostrosky

Antioxidants 2026, 15(7), 885; https://doi.org/10.3390/antiox15070885 - 17 Jul 2026

Abstract

The topical application of ferulic acid (FA) is limited by its low solubility and high susceptibility to oxidation. To overcome these limitations, the multicomponent system Cicloferulic^® (CF) was developed by mixing FA, hydroxypropyl β-cyclodextrin (HPβ-CD), and polyvinylpyrrolidone K30 (PVP K30), which demonstrated [...] Read more.

The topical application of ferulic acid (FA) is limited by its low solubility and high susceptibility to oxidation. To overcome these limitations, the multicomponent system Cicloferulic^® (CF) was developed by mixing FA, hydroxypropyl β-cyclodextrin (HPβ-CD), and polyvinylpyrrolidone K30 (PVP K30), which demonstrated greater safety and antioxidant efficacy than FA alone. The physicochemical characterization of FA, CF, and their components showed greater thermal stability and reduced crystallinity of CF, indicating the formation of the system. In cytotoxicity assays on HaCaT cells, FA maintained cell viability only up to 500 µg/mL, while CF maintained viability even at 10.000 µg/mL, demonstrating 20 times greater safety than FA. In cellular antioxidant activity assays, FA and CF showed similar effects at low concentrations. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method, CF and FA reduced more than 70% of DPPH; however, CF contains only 12% FA, indicating an eightfold greater efficiency than FA. Formulations containing FA and CF increased the Sun Protection Factor (SPF) in vitro, even with a 50% reduction in UV filters. However, they did not stabilize formulations with intrinsically photolabile UV filters. In release studies, FA exhibited rapid flow, while CF promoted a modified release profile. Thus, CF stands out as an innovative, multifunctional system that can improve the stability, safety, and efficacy of FA for topical applications. Full article

(This article belongs to the Special Issue Antioxidants and Multifunction Photoprotection—2nd Edition)

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18 pages, 1923 KB

Open AccessArticle

Effect of a Nutraceutical-Oriented Dietary Intervention on Serum Carotenoids and Antioxidant Vitamin Concentrations in Patients with Neovascular Age-Related Macular Degeneration

by Daria Szulim, Elżbieta Kucharska, Anna Machalińska, Leszek Kuprjanowicz, Piotr Czupryński and Małgorzata Szczuko

Antioxidants 2026, 15(7), 884; https://doi.org/10.3390/antiox15070884 - 16 Jul 2026

Abstract

Background: Age-related macular degeneration (AMD) is one of the most common causes of irreversible impairment of central vision in the elderly population. Although anti-VEGF therapy remains the standard treatment for neovascular AMD, nutritional factors may influence disease progression and retinal health. The aim [...] Read more.

Background: Age-related macular degeneration (AMD) is one of the most common causes of irreversible impairment of central vision in the elderly population. Although anti-VEGF therapy remains the standard treatment for neovascular AMD, nutritional factors may influence disease progression and retinal health. The aim of this prospective controlled study was to evaluate the effects of an individualized dietary intervention with nutraceutical characteristics on serum concentrations of lutein, zeaxanthin, lycopene, vitamin A, and vitamin E in patients with neovascular AMD receiving anti-VEGF therapy. Methods: This prospective controlled study included 43 patients with neovascular AMD who completed a six-month follow-up period. Participants were allocated to either a control group receiving anti-VEGF therapy alone or an intervention group receiving anti-VEGF therapy combined with an individualized dietary plan. The dietary intervention emphasized foods naturally rich in carotenoids, antioxidant vitamins, trace elements, dietary fiber, and omega-3 fatty acids. Serum concentrations of lutein + zeaxanthin, lycopene, vitamin A, and vitamin E were determined using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) at baseline and after six months. Results: Serum lutein + zeaxanthin concentrations increased significantly within both groups (control 0.31 ± 0.61 to 0.49 ± 0.69 mg/L; intervention 0.51 ± 0.54 to 0.87 ± 0.89 mg/L). The increase was numerically larger in the intervention group, but the between-group difference was not statistically significant after adjustment for baseline concentrations (ANCOVA, p = 0.30). Lycopene increased significantly within the intervention group only (0.20 ± 0.15 to 0.43 ± 0.30 μmol/L); the between-group difference was not significant after baseline adjustment (p = 0.24). Vitamin A increased significantly within both groups and vitamin E within the intervention group only; however, no between-group difference remained significant after baseline adjustment (vitamin A p ≈ 1.00, vitamin E p = 0.96). The greatest increase in lutein + zeaxanthin concentrations was observed among participants with improved retinal status. These descriptive findings should be interpreted cautiously because subgroup analyses were not powered. Correlation analyses performed after six months demonstrated positive associations between serum lutein + zeaxanthin, lycopene, and vitamin A concentrations. Conclusions: An individualized dietary intervention rich in naturally occurring bioactive compounds was associated with within-group improvements in serum carotenoid and antioxidant vitamin status. After adjustment for baseline values, between-group differences did not reach statistical significance, consistent with the exploratory, non-powered pilot design. These preliminary findings, including the observed effect sizes, are intended to inform the design of an adequately powered future study rather than to establish a between-group benefit of dietary management. Particularly pronounced changes were observed for lutein + zeaxanthin and lycopene concentrations. These findings support the potential role of dietary management as an adjunct to anti-VEGF therapy. However, given the nature of the study and the relatively small sample size, larger multicenter studies are needed to confirm these observations. 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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26 pages, 2098 KB

Open AccessArticle

Differential Temperature Effects on Phenolic Recovery and Antioxidant Capacity During the Hydroethanolic Extraction of Chilean Blueberry Pomace

by Franco Espinoza-Cartagena, Manuel Benítez-Fajardo, Sebastián Ormazábal-Latorre, Laura M. Cuellar, Camilo Sánchez-Baeza, Gonzalo A. Núñez and Andrés F. Arroyo-Avirama

Antioxidants 2026, 15(7), 883; https://doi.org/10.3390/antiox15070883 - 16 Jul 2026

Abstract

Blueberry pomace is a polyphenol-rich by-product of fruit processing. A face-centered central composite design (FCCCD) optimized hydroethanolic extraction across time (20–60 min), temperature (20–60 °C) and ethanol (20–80%), evaluating total phenolic content (TPC), yield and selectivity. The selected condition (40 min, 60 °C, [...] Read more.

Blueberry pomace is a polyphenol-rich by-product of fruit processing. A face-centered central composite design (FCCCD) optimized hydroethanolic extraction across time (20–60 min), temperature (20–60 °C) and ethanol (20–80%), evaluating total phenolic content (TPC), yield and selectivity. The selected condition (40 min, 60 °C, 50% ethanol) reached 20.0 mg GAE/g dry biomass, a yield of 27% and a selectivity of 75.2 mg GAE/g dry extract. Peleg’s model adequately described the kinetics at 20 and 60 °C; pseudo-equilibrium was reached within 5 min, with equilibrium concentration rising from 9.9 to 20.8 mg GAE/g DW, and initial rate tripling. Based on the kinetic analysis (t₉₉ ≈ 2.5 min), 5 min was adopted as the operational reference for phytochemical characterization; extracts were characterized by FRAP, DPPH, total anthocyanin content (TAC), and HPLC-DAD anthocyanin profiling. Increasing the temperature from 20 to 60 °C raised FRAP 3.4-fold and TAC 1.9-fold while reducing DPPH by 14%, decoupling bulk phenolic recovery from antioxidant capacity. HPLC-DAD identified five glycosylated anthocyanins, with petunidin-3-glucoside as the dominant constituent. Antimicrobial screening confirmed activity against Staphylococcus aureus. These results provide foundational process and compositional data to guide GRAS-compatible valorization of Chilean blueberry pomace and caution against bulk phenolic indicators as the sole quality criteria. Full article

(This article belongs to the Special Issue Antioxidant Research in Chile—2nd Edition)

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23 pages, 8501 KB

Open AccessArticle

Lactobacillus reuteri DSM 17938 and Its Supernatant Ameliorate Parkinson’s Disease in Association with Modulation of Gut Microbiota and Its Tryptophan Metabolism

by Bin Su, Fanying Meng, Yao Lu, Yunlong Zhang, Tingting Wang, Yuxin Zhang, Jiajia Liu and Lianbing Lin

Antioxidants 2026, 15(7), 882; https://doi.org/10.3390/antiox15070882 - 16 Jul 2026

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder associated with gut dysbiosis and tryptophan metabolism disturbance, but the mechanisms of probiotic action are unclear. We orally administered Lactobacillus reuteri DSM 17938 live bacteria (1.0 × 10⁹ CFU/mL, 0.2 mL) or its fermentation supernatant [...] Read more.

Parkinson’s disease (PD) is a neurodegenerative disorder associated with gut dysbiosis and tryptophan metabolism disturbance, but the mechanisms of probiotic action are unclear. We orally administered Lactobacillus reuteri DSM 17938 live bacteria (1.0 × 10⁹ CFU/mL, 0.2 mL) or its fermentation supernatant lyophilized powder at three concentrations to MPTP-induced PD male C57BL/6J mice. Treatments increased locomotor distance and speed, elevated serum SOD and GSH, reduced MDA, TNF-α, IL-6, and IL-1β, promoted neuronal survival, and tended to increase TH expression in the substantia nigra. 16S rRNA sequencing showed that treatments altered gut microbiota composition. PD mice had increased Lactobacillus and Allobaculum but decreased Oscillospira and Helicobacter; treatments restored Oscillospira. Fecal untargeted metabolomics revealed disturbed tryptophan metabolism in PD, with elevated indoleacetic acid and reduced kynurenic acid, xanthurenic acid, indole-3-ethanol, and α-oxo-1H-indole-3-propanoic acid. Treatments significantly restored neuroprotective metabolites including kynurenic acid, xanthurenic acid, and serotonin. PICRUSt2 predicted tryptophan synthesis pathway-associated microbes (Oscillospira, Ruminococcus, Coprococcus). Treatments ameliorated motor deficits, oxidative stress, inflammation, and dopaminergic neuron death, correlating with gut microbiota modulation and accumulation of microbiota-derived tryptophan metabolites. Live bacteria showed superior antioxidant and neuroprotective efficacy compared to supernatant, likely due to sustained colonization and continuous metabolic activity. These findings suggest that targeting key tryptophan-metabolizing bacteria or their metabolites may be a potential PD therapy. Full article

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29 pages, 25142 KB

Open AccessArticle

Knockouts of Sulfur Metabolism Genes Induce Chronic Inflammation and Immune Dysregulation in Drosophila melanogaster

by Victoria Shilova, Alexander Rezvykh, Victoria Aristova, Artem Davletshin, Anna Andreeva, Ksenia Ponomareva, David Garbuz, Michael Evgen’ev and Olga Zatsepina

Antioxidants 2026, 15(7), 881; https://doi.org/10.3390/antiox15070881 - 16 Jul 2026

Abstract

Hydrogen sulfide (H₂S) is a vital gasotransmitter essential for maintaining redox homeostasis and modulating inflammatory responses. Herein, we examined a collection of Drosophila melanogaster knockout (KO) lines generated in our laboratory, lacking key genes involved in transsulfuration (cbs, cse [...] Read more.

Hydrogen sulfide (H₂S) is a vital gasotransmitter essential for maintaining redox homeostasis and modulating inflammatory responses. Herein, we examined a collection of Drosophila melanogaster knockout (KO) lines generated in our laboratory, lacking key genes involved in transsulfuration (cbs, cse) and sulfide metabolism (tst1), to elucidate the role of this adaptive system in immunity. Genetic ablation of these pathways results in profound H₂S deficiency and hyperhomocysteinemia, leading to chronic oxidative stress. This leads to constitutive activation of major immune pathways—including IMD, Toll, and JAK-STAT—even in the absence of infection, a hallmark of chronic inflammation. Indeed, transcriptomic analysis and qRT-PCR studies revealed significant upregulation of these pathways in double (cbs; cse) and triple (cbs; cse; tst1) KO flies under control conditions. Following septic injury with Bacillus subtilis, double and triple KO flies exhibited increased expression of antimicrobial peptides (AMPs) and pattern recognition receptors compared to control and TST1-/- single KO lines. Notably, double and triple KO lines showed more prolonged immune activation. The triple KO flies exhibited the worst survival rate following septic injury. These results demonstrate that H₂S deficiency causes chronic inflammation through the sustained activation of immune pathways, highlighting sulfur metabolism as a crucial regulator of homeostasis and innate immunity in Drosophila. Full article

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

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