Antioxidants

38 pages, 9093 KB

Open AccessReview

Mitochondrial Quality Control Links Exercise to Sterile Inflammation in the Cardiovascular System: A Narrative Review

by Ying Wen, Pengfei Zhang, Xinyu Liao, Jiankang Liu, Yang Zhang and Xuyun Liu

Antioxidants 2026, 15(9), 1134; https://doi.org/10.3390/antiox15091134 - 7 Sep 2026

Preservation of mitochondrial integrity has emerged as a central hub in the anti-inflammatory effect of exercise. This narrative review advances a framework in which mitochondrial damage-associated molecular patterns (mtDAMPs) serve as the mechanistic bridge between exercise and inflammation. Mitochondrial dysfunction releases mtDAMPs, including [...] Read more.

Preservation of mitochondrial integrity has emerged as a central hub in the anti-inflammatory effect of exercise. This narrative review advances a framework in which mitochondrial damage-associated molecular patterns (mtDAMPs) serve as the mechanistic bridge between exercise and inflammation. Mitochondrial dysfunction releases mtDAMPs, including mitochondrial DNA (mtDNA), reactive oxygen species, cardiolipin, N-formyl peptides, and ATP, which activate cGAS–STING, the NLRP3 inflammasome, TLR9, AIM2, ZBP1, and NF-κB signaling. Crosstalk among these pathways allows mild mitochondrial damage to escalate into chronic inflammation. Exercise opposes this cascade through the AMPK–PGC-1α axis, which coordinately activates four mitochondrial quality control (MQC) modules: biogenesis, antioxidant defense, dynamics, and mitophagy. The cardiovascular system illustrates this framework, as myocardial inflammation runs mainly through mtDNA–cGAS–STING signaling and vascular inflammation through oxidized mtDNA–NLRP3 signaling, while cardiovascular aging engages both axes at once. Throughout, exercise refers to repeated training rather than to a single bout, and the framework targets middle-aged and older adults with, or at risk of, cardiovascular disease. The upstream half of the sequence, in which training raises mitochondrial content and antioxidant capacity, rests on human muscle biopsy data; the downstream half remains largely preclinical. MQC is therefore proposed as a testable target rather than an established one. Full article

22 pages, 994 KB

Open AccessArticle

Clinical Relevance of Oxidative Imbalance in Patients with Temporomandibular Disorder—Myofascial Pain with Referral: An Exploratory Case–Control Study

by Joanna Kuć, Mateusz Maciejczyk, Krzysztof Dariusz Szarejko, Małgorzata Żendzian-Piotrowska, Walery Tarnawski, Sara Zięba and Anna Zalewska

Antioxidants 2026, 15(9), 1133; https://doi.org/10.3390/antiox15091133 - 7 Sep 2026

Abstract

Background: Temporomandibular disorders constitute multifaced systemic impairments capable of compromising overall physiological homeostasis. This study compares oxidative and nitrosative stress biomarkers between patients with temporomandibular myofascial pain with referral and healthy controls. Methods: We enrolled 44 individuals with temporomandibular myofascial pain with referrals [...] Read more.

Background: Temporomandibular disorders constitute multifaced systemic impairments capable of compromising overall physiological homeostasis. This study compares oxidative and nitrosative stress biomarkers between patients with temporomandibular myofascial pain with referral and healthy controls. Methods: We enrolled 44 individuals with temporomandibular myofascial pain with referrals and 44 controls. The procedure involved clinical examination based on the Diagnostic Criteria for Temporomandibular Disorders and saliva collection. Biochemical determination involved advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), thiobarbituric-acid-reactive substances (TBARS), and total nitric oxide (NO). Results: Median concentrations of TBARS and total NO were significantly elevated in the study group relative to the controls (TBARS: 6.078 vs. 1.486; total NO: 138.6 vs. 23.82), whereas the concentration of AOPPs was significantly lower (151.1 vs. 505.3). Multiple regression revealed that myofascial pain was an independent predictor of the observed differences, even after we adjusted for age and salivary flow rate (TBARS: β = 4.78 [95% CI: 2.020, 7.541], _adjp = 0.0018; total NO β = 128.4 [95% CI: 82.70, 174.1] _adjp = 0.0004; AOPP β = −755.7 [95% CI: −1228, −283.5] _adjp-value = 0.0028. Conclusions: Myofascial pain with referral is independently associated with oxidative imbalance, highlighting the relevance of TBARS and total NO as promising severity biomarkers. The unexpected decrease in AGE and AOPP levels requires standardized studies to confirm diagnostic utility. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Chronic Pain and Inflammation)

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21 pages, 11129 KB

Open AccessArticle

LDHC Hyperacetylation Disrupts the Guanidinoacetic Acid–Creatine Axis Underlying Cryoinjury in Boar Sperm: Rescue by GAA Supplementation

by Shan Dou, Bo Liu, Malik Ahsan Ali, Anqi Huang and Changjun Zeng

Antioxidants 2026, 15(9), 1132; https://doi.org/10.3390/antiox15091132 - 7 Sep 2026

Abstract

Boar sperm are highly sensitive to cryopreservation, limiting the use of frozen semen in pig breeding. We previously reported that cryopreservation alters lysine acetylation of metabolism-related proteins, including the sperm-specific isoform LDHC. Here we show that cryopreservation reduces LDH activity, and that the [...] Read more.

Boar sperm are highly sensitive to cryopreservation, limiting the use of frozen semen in pig breeding. We previously reported that cryopreservation alters lysine acetylation of metabolism-related proteins, including the sperm-specific isoform LDHC. Here we show that cryopreservation reduces LDH activity, and that the LDH inhibitor galloflavin recapitulates this loss, confirming that LDHC is required for boar sperm motility, acrosome integrity, and mitochondrial membrane potential. Treatment with the SIRT inhibitor nicotinamide increased LDHC acetylation and simultaneously suppressed LDH activity, indicating that hyperacetylation negatively regulates LDHC function. Untargeted metabolomics of LDH-inhibited sperm revealed a notable decrease in guanidinoacetic acid (GAA), the sole precursor of creatine. Supplementing the freezing extender with 600 μM GAA significantly improved post-thaw motility, preserved mitochondrial membrane potential and ATP levels, reduced oxidative stress, and protected acrosome integrity. These improvements were accompanied by elevated intracellular creatine content, enhanced antioxidant capacity (increased T-AOC, CAT, and SOD activities, decreased MDA), and reduced apoptosis. Our findings demonstrate that cryopreservation-induced LDHC hyperacetylation impairs enzyme activity and sperm quality, and that GAA replenishment effectively counteracts this injury through creatine-dependent and antioxidant mechanisms. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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8 pages, 848 KB

Open AccessEditorial

Beyond Combustion: Oxidative Stress as a Shared Pathway of Harm Across Conventional Cigarettes, Heated Tobacco Products, E-Cigarettes, and Waterpipe Smoking

by Lorenzo Loffredo

Antioxidants 2026, 15(9), 1131; https://doi.org/10.3390/antiox15091131 - 7 Sep 2026

Abstract

Tobacco smoking is an established cardiovascular risk factor and is closely associated with the development and progression of atherosclerosis, as well as complications such as myocardial infarction and stroke [...] Full article

(This article belongs to the Special Issue Cigarette Smoke and Oxidative Stress)

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26 pages, 23688 KB

Open AccessArticle

Sphallerocarpus gracilis Polyphenols Alleviate DSS-Induced Colitis by Remodeling Gut Microbiota and Inhibiting the AGE-RAGE/HMGB1 Pathway

by Xuanjun Wang, Jun Zhang, Saizhen Guo, Wenbo Zhang, Ziyan Yang, Dengyou Nie, Zemin Xiang and Yongkai Xi

Antioxidants 2026, 15(9), 1130; https://doi.org/10.3390/antiox15091130 - 7 Sep 2026

Abstract

As a traditional Tibetan medicine and health food, the fleshy roots of Sphallerocarpus gracilis were adopted to extract polyphenol powder(PP) in this research. Using a DSS-induced colitis mouse model combined with multi-omics analysis and experimental validation, we explored the protective effects and molecular [...] Read more.

As a traditional Tibetan medicine and health food, the fleshy roots of Sphallerocarpus gracilis were adopted to extract polyphenol powder(PP) in this research. Using a DSS-induced colitis mouse model combined with multi-omics analysis and experimental validation, we explored the protective effects and molecular mechanisms of PP against intestinal inflammation. PP mitigated colitis-related symptoms in a dose-dependent manner, inhibited pro-inflammatory cytokines and dose-dependently reversed elevated IL-10 levels to BC group. Multi-omics data revealed that PP intervention was associated with gut microbiota remodeling, enrichment of Akkermansia muciniphila, restoration of bacterial–fungal homeostasis, and improvement of tryptophan and biotin metabolism. By suppressing HMGB1 and RAGE expression, PP blocked the AGE-RAGE-mediated inflammatory cascade. In addition, PP maintained intestinal mucosal integrity through goblet cell protection, MDA reduction, and the regulation of BAX/Bcl-2, MMP3 and MMP9. Overall, PP relieves UC by regulating gut microecology, host metabolism and the AGE-RAGE pathway, which supports the translational potential of natural polyphenols for inflammatory bowel disease treatment as a gut microecological modulator. Full article

(This article belongs to the Special Issue Antioxidants as Adjuvants for Inflammatory Bowel Disease Treatment)

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30 pages, 4692 KB

Open AccessReview

Nobiletin as a Geroprotective Flavonoid: Mechanisms of Action, Therapeutic Potential, and Challenges of Bioavailability

by Szymon Sip, Anna Gościniak, Niklas Hoede, Min Hein Htike, Hnin Yuzana Khin, Wei-Wei Lai, Hein Htet Naing, Agnieszka Szopa and Judyta Cielecka-Piontek

Antioxidants 2026, 15(9), 1129; https://doi.org/10.3390/antiox15091129 - 7 Sep 2026

Abstract

Flavonoids are a diverse group of naturally occurring polyphenolic compounds found in plant-based foods and are known for their broad-spectrum biological activities. Among them, nobiletin, a polymethoxylated flavone derived from citrus peels, has gained attention for its multifaceted role in promoting healthy ageing [...] Read more.

Flavonoids are a diverse group of naturally occurring polyphenolic compounds found in plant-based foods and are known for their broad-spectrum biological activities. Among them, nobiletin, a polymethoxylated flavone derived from citrus peels, has gained attention for its multifaceted role in promoting healthy ageing and mitigating age-related diseases. This review explores the chemical properties, mechanisms of action, therapeutic potential, and challenges related to nobiletin. The focus is placed on its antioxidant, anti-inflammatory, neuroprotective, cardioprotective, and metabolic regulatory effects, as well as its capacity to enhance mitophagy, modulate circadian rhythms, and prevent ferroptosis. Despite promising preclinical results across various models, including in vitro cell lines, C. elegans, and mice, the clinical translation of nobiletin is hindered by poor oral bioavailability, complex extraction, and limited human data. Novel delivery systems, such as nanoemulsions and phospholipid-based carriers, offer potential solutions to enhance its bioavailability. As research advances, nobiletin emerges as a promising candidate for geroprotective therapy, warranting further investigation through well-designed clinical trials to extend healthspan and prevent age-associated pathologies. Full article

(This article belongs to the Special Issue Bioactivity Mechanisms of Antioxidant Compounds from Natural Products)

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17 pages, 6877 KB

Open AccessArticle

Effects of Moringa oleifera Oil on Adipokine Responses, Inflammation, Oxidative Stress, Bacterial Burden, and Early Survival in CLP-Induced Septic Rats

by Ufuk Ülker, Bülent Bayraktar, Mehmet Eray Alçığır, Sibel Kızıl, Tünay Karan, Gökşad Cemil Kotan and Mustafa Yeni

Antioxidants 2026, 15(9), 1128; https://doi.org/10.3390/antiox15091128 - 7 Sep 2026

Abstract

Moringa oleifera has anti-inflammatory and antioxidant properties, but its effects in polymicrobial sepsis are incompletely defined. We evaluated M. oleifera oil (MOO) in female Wistar rats subjected to cecal ligation and puncture (CLP). Forty rats were randomized to Control, Sham, CLP, CLP + [...] Read more.

Moringa oleifera has anti-inflammatory and antioxidant properties, but its effects in polymicrobial sepsis are incompletely defined. We evaluated M. oleifera oil (MOO) in female Wistar rats subjected to cecal ligation and puncture (CLP). Forty rats were randomized to Control, Sham, CLP, CLP + MOO 100 mg/kg, or CLP + MOO 200 mg/kg (n = 8/group). At 24 h, survival, clinical scores, serum apelin, omentin-1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), recoverable bacterial burden, and histopathology were assessed. CLP decreased omentin-1 and increased IL-6, TNF-α, MDA, recoverable Staphylococcus aureus and Escherichia coli, clinical severity, and multi-organ injury. At 200 mg/kg, apelin and omentin-1 were 1.15 ± 0.12 and 28.4 ± 3.1 ng/mL, while IL-6, TNF-α, and MDA decreased to 18.4 ± 1.8 pg/mL, 24.1 ± 2.8 pg/mL, and 2.5 ± 0.3 nmol/mL, respectively. Neither organism was recovered above the detection limit. Survival was 62.5% in CLP, 87.5% with 100 mg/kg, and 100% with 200 mg/kg MOO. Within this 24 h model, a single post-CLP oral dose of MOO was associated with lower inflammatory cytokine concentrations and MDA, reduced recoverable bacterial burden, improved clinical and histopathological findings, and higher descriptive survival. Because MDA was the sole oxidative endpoint and no non-septic MOO-only group or molecular redox assays were included, these findings support the attenuation of sepsis-associated lipid peroxidation but do not establish a direct antioxidant mechanism. Full article

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

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25 pages, 3806 KB

Open AccessArticle

Astrocyte Senescence Disrupts the Extracellular Mitochondrial Compartment and Compromises Bioenergetic Support to Human Neurons

by Pedro Amorim, Lívia de Sá Hayashide, Vitor Emanuel Leocadio, Mariana Marques, Isabelle Navarra, Cherley Borba Vieira Andrade, Jorge José de Carvalho, Rafael Serafim Pinto and Luan Pereira Diniz

Antioxidants 2026, 15(9), 1127; https://doi.org/10.3390/antiox15091127 - 6 Sep 2026

Abstract

Astrocyte senescence is a recognized feature of brain aging, but its impact on neuronal mitochondrial homeostasis remains poorly defined, particularly in human cells. Here we show that doxorubicin-induced senescence disrupts mitochondrial function in primary human astrocytes and compromises their capacity to sustain neuronal [...] Read more.

Astrocyte senescence is a recognized feature of brain aging, but its impact on neuronal mitochondrial homeostasis remains poorly defined, particularly in human cells. Here we show that doxorubicin-induced senescence disrupts mitochondrial function in primary human astrocytes and compromises their capacity to sustain neuronal bioenergetics. Senescent astrocytes accumulated a denser population of smaller, ultrastructurally damaged mitochondria together with increased levels of fission, fusion and biogenesis-associated proteins. Despite this apparent expansion of the mitochondrial compartment, these cells displayed reduced mitochondrial membrane potential, intracellular ATP and cellular metabolic activity, indicating accumulation of a functionally impaired mitochondrial population. Senescence also remodeled the extracellular mitochondrial compartment: conditioned medium from senescent astrocytes contained fewer mitochondrial particles with lower membrane potential and reduced ATP. Functionally, conditioned medium from control astrocytes increased TOMM20 and PGC-1α levels in human postmitotic neurons, whereas medium from senescent astrocytes failed to elicit this response and instead promoted hydrogen peroxide accumulation, ATP depletion and reduced cellular metabolic activity in the absence of overt cytotoxicity. Neurons acquired an astrocyte-derived MitoTracker signal from both conditions. Our data indicate that factors released by senescent human astrocytes are sufficient to induce neuronal mitochondrial and redox dysfunction. Full article

(This article belongs to the Special Issue Mitochondrial Dysfunction and Oxidative Stress in Aging and Age-Related Disorders)

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21 pages, 335 KB

Open AccessArticle

NADES-Extracted SunGold Kiwifruit Polyphenols as Functional Ingredients in Antioxidant-Enriched Yoghurt

by Rifqah Azzahra Naulidia and Michelle Ji Yeon Yoo

Antioxidants 2026, 15(9), 1126; https://doi.org/10.3390/antiox15091126 - 5 Sep 2026

Abstract

Natural deep eutectic solvents (NADES) offer a potentially food-compatible alternative for extracting plant polyphenols, although their direct application in yoghurt remains limited. This study evaluated the antioxidant and physicochemical properties of yoghurt fortified with SunGold kiwifruit extracts obtained using a selected choline chloride [...] Read more.

Natural deep eutectic solvents (NADES) offer a potentially food-compatible alternative for extracting plant polyphenols, although their direct application in yoghurt remains limited. This study evaluated the antioxidant and physicochemical properties of yoghurt fortified with SunGold kiwifruit extracts obtained using a selected choline chloride and glycerol NADES, with water extraction used for comparison. The phenolic profile of the NADES extract was characterised using LC-MS/MS. Both extracts were incorporated before (PRE) or after (POS) fermentation at concentrations of 10%, 20%, and 30% (v/v). The extracts and fortified yoghurts were analysed for total phenolic content (TPC), total flavonoid content (TFC), DPPH radical scavenging activity, FRAP, CUPRAC, and physicochemical properties. LC-MS/MS tentatively annotated several phenolic compounds in the NADES extract, with catechin showing the largest peak area among the annotated compounds. The water extract showed higher TPC and DPPH activity, whereas the NADES extract showed higher TFC, FRAP, and CUPRAC values. Increasing extract concentration generally increased the measured bioactive properties of the yoghurts, although the magnitude of change varied among assays and treatments. Water extract-fortified yoghurts generally showed higher TPC and DPPH values, while NADES extract-fortified yoghurts showed higher TFC, FRAP, and CUPRAC values. Extract type, fortification stage, and concentration also influenced pH, °Brix, viscosity, colour, and syneresis. Higher fortification concentrations reduced viscosity and increased syneresis, while low-concentration NADES extract-fortified yoghurts retained physicochemical properties closer to those of the control. Overall, the NADES extract showed potential as an ingredient for yoghurt fortification. Further studies are required to evaluate sensory acceptability, storage stability, starter culture viability, and gastrointestinal bioaccessibility. Full article

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

14 pages, 1906 KB

Open AccessArticle

Succinate Dehydrogenase Subunit D as a Redox-Responsive Mitochondrial Component Linked to Aquaporin-Associated Hydrogen Peroxide Signaling in Glioblastoma Cells

by Kuen-Jang Tsai, Kuan-Tso Chen, Chin-Chuan Tsai, Zi-Xuan Hong, Li-Ying Qiu, Chan-Chuan Liu, Kwang-Yu Chang, Pin-Yuan Chen and Chia-Hung Chien

Antioxidants 2026, 15(9), 1125; https://doi.org/10.3390/antiox15091125 (registering DOI) - 5 Sep 2026

Abstract

Glioblastoma (GBM) frequently recurs after temozolomide (TMZ) therapy and exhibits substantial redox plasticity. Our previous work showed that the effects of hydrogen peroxide (H₂O₂) vary with its level and between parental and TMZ-resistant GBM cells. Succinate dehydrogenase subunit D [...] Read more.

Glioblastoma (GBM) frequently recurs after temozolomide (TMZ) therapy and exhibits substantial redox plasticity. Our previous work showed that the effects of hydrogen peroxide (H₂O₂) vary with its level and between parental and TMZ-resistant GBM cells. Succinate dehydrogenase subunit D (SDHD), a membrane-anchoring component of mitochondrial complex II, is positioned at the interface of electron transport and redox homeostasis, but its regulation in GBM remains unclear. We therefore examined whether SDHD expression changes across distinct H₂O₂-responsive contexts involving aquaporins (AQPs) and AKT. TCGA transcriptomic analysis showed higher SDHD mRNA expression in WHO grade IV than in grade II/III gliomas, whereas paired primary/recurrent high-grade glioma samples showed heterogeneous SDHD changes at recurrence. TMZ reduced SDHD, and SDHD knockdown decreased intracellular reactive oxygen species. Combined redox perturbation reduced SDHD, whereas AKT inhibition restored SDHD expression. Under receptor-associated signaling conditions, EGFRvIII expression or CXCL12 stimulation increased measured H₂O₂ together with AQP3, AKT Ser473 phosphorylation, and SDHD. In TMZ-resistant cells, pharmacological perturbation of aquaporin-associated signaling decreased AQP9 together with AKT Ser473 phosphorylation and SDHD. An AQP3-targeting compound further reduced cell density when combined with TMZ. Together, these findings suggest that changes in SDHD expression are consistent with a compensatory redox response in GBM cells and that its regulation varies with the nature of H₂O₂-associated signaling during TMZ-related stress. Full article

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

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13 pages, 1522 KB

Open AccessArticle

Low-Grade Endotoxemia Is Associated with NOX2-Mediated Oxidative Stress and Endothelial Dysfunction in Takotsubo Syndrome: A Cross-Sectional Study

by Lorenzo Loffredo, Enrico Maggio, Simona Bartimoccia, Vito Cantisani, Antonio Angeloni, Aurora Paraninfi, Paolo Ciacci, Simona Battaglia, Federica Armeli, Ilaria Maria Palumbo, Mariaelena Malvasi, Giancarlo D’Ambrosio, Pasquale Pignatelli, Roberto Carnevale, Francesco Violi, Francesco Barillà and Gaetano Tanzilli

Antioxidants 2026, 15(9), 1124; https://doi.org/10.3390/antiox15091124 - 5 Sep 2026

Abstract

Takotsubo syndrome (TTS) is an acute and reversible heart failure condition characterized by transitional left ventricular systolic dysfunction without obstructive coronary artery disease. Although sympathetic hyperactivation is considered a key pathogenic mechanism, the contribution of gut-derived endotoxemia and oxidative stress is still unclear. [...] Read more.

Takotsubo syndrome (TTS) is an acute and reversible heart failure condition characterized by transitional left ventricular systolic dysfunction without obstructive coronary artery disease. Although sympathetic hyperactivation is considered a key pathogenic mechanism, the contribution of gut-derived endotoxemia and oxidative stress is still unclear. Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria, may translocate from the gut into the bloodstream and increase oxidative stress through activation of NADPH oxidase 2 (NOX2), nitric oxide (NO) depletion and endothelial dysfunction. This study aimed to evaluate circulating LPS levels in TTS and investigate their association with NOX2 activation, oxidative stress, and endothelial dysfunction. Twenty consecutive patients with TTS and 20 age- and sex-matched healthy controls were included. Within 48 h of admission, fasting blood samples were collected to assess soluble NOX2-derived peptide (sNOX2-dp), hydrogen peroxide (H₂O₂), NO metabolites (NOx), LPS, and zonulin. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Compared with controls, TTS patients had significantly higher serum levels of sNOX2-dp, H₂O₂, LPS, and zonulin, lower NOx and impaired FMD. sNOX2-dp was positively correlated with LPS (Rs = 0.539, p < 0.001) and zonulin (Rs = 0.331, p = 0.037) and inversely correlated with FMD (Rs = −0.462, p = 0.003). NOx correlated negatively with H₂O₂, zonulin and LPS. In multivariable analysis, LPS was the only independent predictor of FMD (β = 0.498, SE = 0.126, p = 0.001) and sNOX2-dp (β = −0.572, SE = 0.034 p < 0.001); FMD (β = −0.347, SE = 0.455, p = 0.005), H₂O₂ (β = 0.445, SE = 0.155, p < 0.001), and zonulin (β = 0.298, SE = 2.309, p = 0.016) emerged as independent predictors of LPS (adjusted R² = 0.585). TTS is associated with low-grade endotoxemia, NOX2-driven oxidative stress, reduced NO bioavailability, and endothelial dysfunction. The independent association between LPS and NOX2 activation supports a potential gut–vascular axis in TTS pathophysiology. Full article

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19 pages, 1113 KB

Open AccessArticle

Vaginal Infection in Pregnancy Is Associated with Amniotic Oxidative Stress: Insights from AOPP and MDA on Neonatal Outcomes

by Meryem Kececi Oguzhanoglu, Icten Olgu Bafali, Kursat Oguzhanoglu, Senem Karacabey Cakmak, Busra Seker Atas, Muhammed Oguz Yildiz and Ali Cetin

Antioxidants 2026, 15(9), 1123; https://doi.org/10.3390/antiox15091123 - 4 Sep 2026

Abstract

Amniotic oxidative stress in women with vaginal infection but no documented intra-amniotic infection has received little attention. In this prospective cohort study of 90 women undergoing elective cesarean delivery, 45 had symptomatic, culture- or Nugent-confirmed vaginal infection and 45 were asymptomatic controls. Amniotic [...] Read more.

Amniotic oxidative stress in women with vaginal infection but no documented intra-amniotic infection has received little attention. In this prospective cohort study of 90 women undergoing elective cesarean delivery, 45 had symptomatic, culture- or Nugent-confirmed vaginal infection and 45 were asymptomatic controls. Amniotic fluid advanced oxidation protein products (AOPP) and malondialdehyde (MDA) were measured by commercial ELISA. Both were higher in the infection group (median 7.96 versus 5.77 ng/mL and 12.49 versus 7.73 nmol/mL, both p < 0.001), with lower cord blood pH (p = 0.003) and more frequent neonatal intensive care unit (NICU) admission (26.7% versus 4.4%, p = 0.007). AOPP was associated with NICU admission (area under the curve 0.917, 95% CI 0.777 to 0.999), although this rests on 14 events with thresholds derived and evaluated in the same sample. Elevations were largest in the bacterial vaginosis and aerobic bacterial subgroups, but the etiologies did not differ. Both kits were designed for serum and are not validated for amniotic fluid, and 16.7% of MDA measurements fell outside the calibration range, so the MDA results are semi-quantitative. Vaginal infection at cesarean delivery is associated with higher amniotic oxidative stress markers; these findings are exploratory and require external validation. Full article

(This article belongs to the Special Issue Oxidative Stress in Pregnant Women and Fetuses)

27 pages, 7480 KB

Open AccessArticle

Targeting SQLE-Mediated Cholesterol Metabolism to Promote Oxidative Stress and Attenuate Drug Resistance in Osteosarcoma

by Amonnat Sukhamwang, Dumnoensun Pruksakorn, Pornngarm Dejkriengkraikul, Michael A. Dengler and Supachai Yodkeeree

Antioxidants 2026, 15(9), 1122; https://doi.org/10.3390/antiox15091122 - 4 Sep 2026

Abstract

High-grade osteosarcoma presents a significant clinical challenge due to unpredictable therapeutic responses and aggressive progression. This study aimed to identify the critical molecular pathways driving chemotherapy resistance and aggressive phenotypes in osteosarcoma patients. Through transcriptomic and bioinformatic analyses, we identified cholesterol biosynthesis as [...] Read more.

High-grade osteosarcoma presents a significant clinical challenge due to unpredictable therapeutic responses and aggressive progression. This study aimed to identify the critical molecular pathways driving chemotherapy resistance and aggressive phenotypes in osteosarcoma patients. Through transcriptomic and bioinformatic analyses, we identified cholesterol biosynthesis as a key upregulated metabolic pathway in poor chemotherapy responders, where squalene epoxidase (SQLE) emerged as an exploratory candidate hub gene whose elevated expression significantly correlates with shortened survival in the TCGA cohort. We validated these findings by administering terbinafine, a known SQLE inhibitor. In highly chemoresistant SaOS-2 cells exhibiting the highest baseline SQLE expression, terbinafine synergistically sensitized cells to doxorubicin by driving cell death partly through apoptosis, as confirmed by caspase inhibition. The combination also promoted ferroptosis, indicated by elevated ROS and MDA along with decreased FSP1 and GPX4 expression. Furthermore, the co-treatment effectively suppressed clonogenic potential, induced G2/M phase cell cycle arrest, and inhibited metastatic progression. These effects were mediated by the modulation of cell proliferation, metastasis, and survival genes through the coordinated regulation of the PI3K/AKT/mTOR, ERK, and JNK signaling cascades. Together, these results highlight the therapeutic potential of targeting the SQLE pathway to overcome doxorubicin resistance and suppress aggressive progression in high-grade osteosarcoma. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Carcinogenesis: A Multifaceted Approach—2nd Edition)

17 pages, 752 KB

Open AccessArticle

Antioxidant, Antibacterial, and Antivirulence Activities of a Bioactive Fraction from Lycopus lucidus Against Porphyromonas gingivalis

by Jung Min Park, Sohae Park, Dae Youn Hwang, Heeseob Lee and Jumin Park

Antioxidants 2026, 15(9), 1121; https://doi.org/10.3390/antiox15091121 - 4 Sep 2026

Abstract

Porphyromonas gingivalis (Pg) is a keystone periodontal pathogen associated with biofilm formation and gingipain-mediated virulence. This study evaluated the antioxidant, antibacterial, antibiofilm, and antivirulence activities of a hexane extract of Lycopus lucidus (LLH) and its eight chromatographic fractions (H1–H8). Antioxidant activity was assessed [...] Read more.

Porphyromonas gingivalis (Pg) is a keystone periodontal pathogen associated with biofilm formation and gingipain-mediated virulence. This study evaluated the antioxidant, antibacterial, antibiofilm, and antivirulence activities of a hexane extract of Lycopus lucidus (LLH) and its eight chromatographic fractions (H1–H8). Antioxidant activity was assessed using DPPH and ABTS radical-scavenging assays, whereas antibacterial activity, biofilm formation, and virulence-associated gene expression were evaluated using corresponding in vitro assays. LLH exhibited antioxidant and antibacterial activities, while H4 showed the strongest overall biological activity among the fractions. The DPPH IC₅₀ values of LLH and H4 were 98.33 ± 2.05 and 60.67 ± 3.09 µg/mL, respectively, and the corresponding ABTS IC₅₀ values were 89.24 ± 1.67 and 28.15 ± 1.21 µg/mL, respectively. H4 also showed greater inhibition of biofilm formation than LLH and more pronounced downregulation of several virulence-associated genes. LC–MS/MS analysis tentatively identified α-cyperone as a constituent of H4. Overall, chromatographic fractionation of LLH yielded H4 with enhanced biological activity across several measured endpoints, including radical-scavenging, antibacterial, and antibiofilm effects, together with more pronounced suppression of several virulence-associated genes. However, the contribution of α-cyperone or other individual constituents to these effects remains to be established. Full article

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

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34 pages, 31728 KB

Open AccessArticle

Mitochondrial Transplantation Suppresses mtDNA-cGAS/STING-Mediated Innate Immunity by Enhancing PINK1/Parkin-Dependent Mitophagy to Attenuate Keloid Fibrosis

by Wenjing Wang, Yuanbo Liu, Jipeng Song, Zouzou Yu, Zixiang Chen and Hu Jiao

Antioxidants 2026, 15(9), 1120; https://doi.org/10.3390/antiox15091120 - 4 Sep 2026

Abstract

Keloids are characterized by fibrosis and chronic inflammation, but links between mitochondrial dysfunction and keloid pathogenesis remain unclear. This study examined whether impaired PINK1/Parkin-dependent mitophagy is associated with mitochondrial DNA (mtDNA)-mediated innate immune activation and fibrosis in keloids, and evaluated mitochondrial transplantation as [...] Read more.

Keloids are characterized by fibrosis and chronic inflammation, but links between mitochondrial dysfunction and keloid pathogenesis remain unclear. This study examined whether impaired PINK1/Parkin-dependent mitophagy is associated with mitochondrial DNA (mtDNA)-mediated innate immune activation and fibrosis in keloids, and evaluated mitochondrial transplantation as a potential therapeutic strategy. Primary keloid fibroblasts (KFs), normal skin fibroblasts (NFs), adipose-derived stem cells (ADSCs), human keloid tissues, and human keloid xenografts in immunodeficient BALB/c nude mice were analyzed using ultrastructural, molecular, and functional approaches. Freshly isolated NF-derived mitochondria (nMito) and ADSC-derived mitochondria (aMito) were compared at protein-equivalent doses. KFs exhibited mitochondrial abnormalities, impaired oxidative phosphorylation, increased reactive oxygen species, mtDNA leakage, and cGAS/STING pathway activation. Elevated PINK1 expression, reduced Parkin expression and p62 accumulation were consistent with impaired downstream mitophagic clearance. Both nMito and aMito were associated with improved mitochondrial function, changes in mitophagy-related markers, reduced cytosolic mtDNA and cGAS/STING signaling, and attenuated fibroblast activation, with greater aMito-associated changes in selected endpoints. In xenografts, intralesional administration of either mitochondria improved collagen organization and reduced fibrotic and inflammatory signaling. Together, these findings link altered PINK1/Parkin-dependent mitophagy to mtDNA-driven inflammation and fibrosis and support mitochondrial transplantation as a potential organelle-based therapeutic approach. Full article

(This article belongs to the Special Issue Antioxidant Therapies, Mitochondrial Function, and Transplantation Strategies: Mechanisms and Emerging Therapeutics)

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24 pages, 4494 KB

Open AccessArticle

Mung Bean Seed Coat Extract Promotes Diabetic Wound Healing in High-Glucose-Exposed HaCaT Keratinocytes

by Sineenad Teerapatpaisan, Alisa Naladta, Kamonpan Wanichsri, Penpimol Ponchunchoovong, Suthasinee Thapphasaraphong and Natsajee Nualkaew

Antioxidants 2026, 15(9), 1119; https://doi.org/10.3390/antiox15091119 - 4 Sep 2026

Abstract

Mung bean seed coat (MBSC) is a byproduct of commercial vermicelli production that possesses essential activities capable of delaying diabetic wound progression. This study aimed to evaluate the potential of MBSC extracts to promote diabetic wound healing, an effect that has not yet [...] Read more.

Mung bean seed coat (MBSC) is a byproduct of commercial vermicelli production that possesses essential activities capable of delaying diabetic wound progression. This study aimed to evaluate the potential of MBSC extracts to promote diabetic wound healing, an effect that has not yet been reported. The hypoglycemic effect was assessed by glucose uptake stimulation in L6 myotubes and by an α-glucosidase inhibition assay. Antiglycation was determined by BSA-glucose and BSA-methylglyoxal assays. Intracellular reactive oxygen species (ROS) reduction and wound healing were assessed in human keratinocytes (HaCaT) exposed to high glucose (HG), and gene expression in HG-wounded cells was analyzed by qPCR. The results demonstrated that the ethanolic extract (EE) from MBSC exhibited glucose-lowering effects and suppressed glycation reactions at the early and intermediate stages, with IC₅₀ values of 75 and 140 µg/mL, respectively. EE reduced ROS by 70%, stimulated cell proliferation by 57% in the high-glucose (HG)-exposed HaCaT cells, and accelerated cell migration to close the HG-exposed wound. EE increased the gene expression of Nrf2, NQO-1, SOD2, and CAT. It also downregulated TNF-α, upregulated TGF-β1, and downregulated MMP-9. In conclusion, EE has the potential to delay the progression of diabetic wounds by lowering blood glucose levels, inhibiting AGE and ROS formation, and enhancing cell proliferation and migration in HG-exposed HaCaT cells. The gene regulatory effects of EE were demonstrated as an Nrf2 activator that reduced oxidative stress, exerted anti-inflammatory effects, and regulated ECM balance. The preparation of oral and topical products could be further developed. Full article

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

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32 pages, 5564 KB

Open AccessReview

Natural Histidine Derivatives—From Basic Research to Potential Applications in Cosmetics and Nutricosmetics

by Edyta Gołaś and Mateusz Maciejczyk

Antioxidants 2026, 15(9), 1118; https://doi.org/10.3390/antiox15091118 - 4 Sep 2026

Abstract

Skin aging is a complex process influenced by oxidative stress, protein glycation, chronic inflammation, and increased extracellular matrix remodeling. Intensive research is underway on new anti-aging substances with multi-target mechanisms of action while maintaining safety and efficacy. Ergothioneine, selenoneine, and ovothiol A are [...] Read more.

Skin aging is a complex process influenced by oxidative stress, protein glycation, chronic inflammation, and increased extracellular matrix remodeling. Intensive research is underway on new anti-aging substances with multi-target mechanisms of action while maintaining safety and efficacy. Ergothioneine, selenoneine, and ovothiol A are natural histidine derivatives of marine origin, in which the oxygen atom of the hydroxyl group has been replaced with sulphur or selenium. In recent years, a broad spectrum of their biological activity has been demonstrated. Despite the well-documented antioxidant potential of these compounds, their anti-aging effects, particularly in terms of antiglycation and anti-inflammatory activity, remain insufficiently understood. This study presents the current state of knowledge regarding the biological activity of ergothioneine, selenoneine, and ovothiol A, and discusses available cosmetic preparations and dietary supplements containing these compounds. Meanwhile, significant research gaps have been identified regarding their potential use in the prevention and treatment of skin aging. Full article

(This article belongs to the Special Issue Natural Antioxidants for Cosmetic Applications)

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19 pages, 9459 KB

Open AccessArticle

Carnosine Potentiates a Compensatory Mitochondrial–Synaptic Proteomic Response in the ALS Cerebellum

by Hellen P. Valerio, Valeria Oliveira, Stephanie Y. Ferreira, Isabel R. Pereira, Giuseppe Palmisano, Mariana P. Massafera, Vanderson S. Bispo, Fernanda M. Prado, Paolo Di Mascio and Marisa H. G. Medeiros

Antioxidants 2026, 15(9), 1117; https://doi.org/10.3390/antiox15091117 - 4 Sep 2026

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration and chronic neuroinflammation in the brain and spinal cord, involving complex interactions between neurons and immune cells. Carnosine (β-alanyl-L-histidine) has pathophysiological relevance due to its ability to detoxify [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration and chronic neuroinflammation in the brain and spinal cord, involving complex interactions between neurons and immune cells. Carnosine (β-alanyl-L-histidine) has pathophysiological relevance due to its ability to detoxify reactive carbonyl species, including α,β-unsaturated aldehydes, scavenge free radicals, and chelate zinc, and has also been proposed to function in the central nervous system as a histidine reservoir for histamine synthesis. Here, we investigated the effects of carnosine supplementation on the cerebellar proteome of SOD1^G93A ALS rats using quantitative proteomics. Carnosine treatment extensively remodeled mitochondrial, antioxidant, and synaptic vesicle-trafficking protein networks and increased the abundance of glutamatergic and GABAergic receptor subunits relative to untreated ALS animals, with several of these changes exceeding wild-type levels. Pathway enrichment analyses identified significant up-regulation of Rab-mediated vesicle trafficking, synaptic vesicle cycling, and neurotransmitter transport/secretion pathways, alongside a partial reduction in RNA splicing and proteasomal subunits that were elevated in untreated ALS animals. Cross-comparison with the ALS-associated proteomic signature revealed that most carnosine-responsive proteins followed, rather than reversed, the direction of disease-associated change, indicating that carnosine predominantly potentiates an endogenous compensatory program rather than restoring a wild-type-like proteome. Collectively, these findings show that carnosine drives systems-level remodeling of mitochondrial and synaptic networks in the ALS cerebellum, identifying candidate compensatory pathways and supporting further functional validation of carnosine as a component of multimodal therapeutic strategies in ALS. Full article

(This article belongs to the Special Issue Carnosine: A Multifaceted Antioxidant and Anti-Inflammatory Peptide—Molecular Mechanisms and Biological Relevance)

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35 pages, 2797 KB

Open AccessReview

Oxidative Stress and Mitochondrial Dysfunction in Chronic Kidney Disease: From Molecular Mechanisms to Biomarkers and Targeted Therapies

by Federica De Luca, Dario Troise, Valentina Camporeale, Giorgia Leccese, Federica Galloso, Roberto Cuttano, Barbara Infante, Giovanni Stallone, Elena Ranieri and Giuseppe Stefano Netti

Antioxidants 2026, 15(9), 1116; https://doi.org/10.3390/antiox15091116 - 4 Sep 2026

Abstract

Chronic kidney disease (CKD) represents a major global health challenge, affecting more than 10% of the population and contributing substantially to morbidity and premature mortality. Growing evidence identifies oxidative stress and mitochondrial dysfunction as central drivers of renal injury and disease progression across [...] Read more.

Chronic kidney disease (CKD) represents a major global health challenge, affecting more than 10% of the population and contributing substantially to morbidity and premature mortality. Growing evidence identifies oxidative stress and mitochondrial dysfunction as central drivers of renal injury and disease progression across diverse etiologies. The kidney is one of the most mitochondria-rich organs in the body, reflecting the high bioenergetic demands required for tubular reabsorption and metabolic homeostasis. Disruption of mitochondrial oxidative phosphorylation, excessive production of reactive oxygen species (ROS), and impaired mitochondrial quality control mechanisms promote tubular injury, inflammation, and fibrosis. In particular, dysfunction of the electron transport chain, activation of NADPH oxidase isoforms—especially NOX4—and alterations in mitochondrial dynamics create a vicious cycle of oxidative damage and bioenergetic failure. Emerging evidence highlights the importance of mitochondrial quality control pathways, including fusion–fission balance, PINK1/Parkin-mediated mitophagy, and mitochondrial biogenesis regulated by PGC-1α and TFAM. Additional mechanisms include ferroptosis, epigenetic regulation, mitochondrial DNA-mediated innate immune activation, and Na⁺/K⁺-ATPase-linked redox signaling. At the translational level, redox and mitochondrial biomarkers and targeted therapies are biologically compelling, but the evidence is uneven: most candidate biomarkers remain insufficiently standardized, and direct mitochondria-targeted interventions are supported predominantly by preclinical studies or small human proof-of-concept trials. This review therefore emphasizes not only mechanistic advances but also conflicting findings, model limitations, and the barriers that currently separate experimental efficacy from clinically meaningful CKD outcomes. Full article

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

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