Antioxidants

25 pages, 3929 KB

Open AccessArticle

Targeting Skin Aging Hallmarks In Vitro: Antioxidant, Anti-Inflammatory, and Anti-Senescence Effects of Phenolic-Rich Extracts from Cistus L. Species

by Mário Pedro Marques, Euclides Landim, Carla Varela, Ricardo M. F. da Costa, Joana Marques, Luís A. E. Batista de Carvalho, Ana Silva, Maria Teresa Cruz, Rebeca André, Patrícia Rijo, Maria Inês Dias, Aida Carvalho, Paulo J. Oliveira and Célia Cabral

Antioxidants 2026, 15(1), 149; https://doi.org/10.3390/antiox15010149 - 22 Jan 2026

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Abstract

Plant-based extracts are rich sources of phenolic compounds, which may act as skin antiaging mediators. Herein, Cistus albidus L. (Ca), Cistus ladanifer L. subsp. ladanifer (Cl) and Cistus salviifolius L. (Cs) were selected to test whether their phytochemical profile and bioactive potential align [...] Read more.

Plant-based extracts are rich sources of phenolic compounds, which may act as skin antiaging mediators. Herein, Cistus albidus L. (Ca), Cistus ladanifer L. subsp. ladanifer (Cl) and Cistus salviifolius L. (Cs) were selected to test whether their phytochemical profile and bioactive potential align to target human skin aging. Hydroethanolic extracts (HEs) were prepared and characterized using infrared vibrational spectroscopy (FTIR-ATR) and liquid chromatography–mass spectrometry (LC-MS). Non-toxic concentrations were screened, and cytoprotective and antioxidant effects were studied in tert-butyl hydroperoxide-stimulated normal human dermal fibroblasts (NHDFs). Lipopolysaccharide-stimulated RAW 264.7 macrophages were used to assess anti-inflammatory activity, the Organization for Economic Co-operation and Development (OECD) Test Guideline No. 439 was used to assess irritant effects, and the anti-senescence potential was assessed in etoposide-stimulated NHDFs. A series of enzymatic inhibition assays was performed. All extracts comprised ellagic acid derivatives, as well as myricetin and quercetin derivatives in Cs and Ca. The HE of Cs was also markedly composed of ligstroside. At non-toxic concentrations, cytoprotective effects were observed in NHDFs. However, only Cs and Cl exhibited significant antioxidant activity in these cells (p < 0.001 and p < 0.0001, respectively). In addition to that, Cl demonstrated highly significant anti-inflammatory (p < 0.0001) and anti-senescence (p < 0.0001) effects. Cs and Cl showed a remarkable potential to inhibit elastase; in addition, Cs also showed anti-hyaluronidase and anti-tyrosinase activities. Meaningfully, Cs and Cl extracts did not exhibit skin irritant effects. The unveiled potential of Cl in skin aging offset highlights the need to elucidate the detailed mechanisms of action, paving the way for the development of skin anti-aging formulations. Full article

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

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17 pages, 1991 KB

Open AccessArticle

Role of Glutathione in Alleviating Chilling Injury in Bovine Blastocysts: Mitochondrial Restoration and Apoptosis Inhibition

by Jingyu Ren, Fuhan Liu, Gang Liu, Biao Wang, Jie Zhu, Yongbin Liu and Yanfeng Dai

Antioxidants 2026, 15(1), 148; https://doi.org/10.3390/antiox15010148 - 22 Jan 2026

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Abstract

Short-term hypothermic storage at 4 °C represents a promising non-freezing alternative for transporting bovine embryos and synchronizing assisted reproductive procedures. However, chilling induces oxidative stress, mitochondrial dysfunction, and apoptosis, which markedly impair post-preservation embryonic viability. Glutathione (GSH), a key intracellular antioxidant, may mitigate [...] Read more.

Short-term hypothermic storage at 4 °C represents a promising non-freezing alternative for transporting bovine embryos and synchronizing assisted reproductive procedures. However, chilling induces oxidative stress, mitochondrial dysfunction, and apoptosis, which markedly impair post-preservation embryonic viability. Glutathione (GSH), a key intracellular antioxidant, may mitigate these damaging effects, yet its protective mechanisms during bovine blastocyst hypothermic preservation remain unclear. Here, we investigated the impact of exogenous GSH supplementation on the survival, hatching ability, cellular integrity, mitochondrial function, and developmental potential of bovine blastocysts preserved at 4 °C for seven days. Optimization experiments revealed that 4 mM GSH provided the highest post-chilling survival and hatching rates. Using DCFH-DA, TUNEL, and γ-H2AX staining, we demonstrated that 4 °C preservation significantly increased intracellular reactive oxygen species (ROS), DNA fragmentation, and apoptosis. GSH supplementation markedly alleviated oxidative injury, reduced apoptotic cell ratio, and decreased DNA double-strand breaks. MitoTracker and JC-1 staining indicated severe chilling-induced mitochondrial suppression, including decreased mitochondrial activity and membrane potential (ΔΨm), which were largely restored by GSH. Gene expression analyses further revealed that chilling downregulated antioxidant genes (SOD2, GPX1, TFAM, NRF2), pluripotency markers (POU5F1, NANOG), and IFNT, while upregulating apoptotic genes (BAX, CASP3). GSH effectively reversed these alterations and normalized the BAX/BCL2 ratio. Moreover, SOX2/CDX2 immunostaining, total cell number, and ICM/TE ratio confirmed improved embryonic structural integrity and developmental competence. Collectively, our findings demonstrate that exogenous GSH protects bovine blastocysts from chilling injury by suppressing ROS accumulation, stabilizing mitochondrial function, reducing apoptosis, and restoring developmental potential. This study provides a mechanistic foundation for improving 4 °C embryo storage strategies in bovine reproductive biotechnology. Full article

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28 pages, 9454 KB

Open AccessArticle

Integrative Transcriptomic and Network Analysis of Hemocyte Volume Plasticity and Redox Regulation Under Osmotic Stress in Penaeus monodon

by Sheng Huang, Falin Zhou, Qibin Yang, Song Jiang, Jilin Chen, Jie Xiong, Erchao Li and Yundong Li

Antioxidants 2026, 15(1), 147; https://doi.org/10.3390/antiox15010147 - 22 Jan 2026

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Abstract

Osmotic stress affects ion transport and cell hydration, potentially disrupting redox homeostasis through altered proteostasis and mitochondrial metabolism. However, how immune hemocytes coordinate volume regulation with these stress-linked processes, particularly oxidative stress and antioxidant responses, remains unclear in crustaceans. This study integrated quantitative [...] Read more.

Osmotic stress affects ion transport and cell hydration, potentially disrupting redox homeostasis through altered proteostasis and mitochondrial metabolism. However, how immune hemocytes coordinate volume regulation with these stress-linked processes, particularly oxidative stress and antioxidant responses, remains unclear in crustaceans. This study integrated quantitative cytology, RNA sequencing, and network analysis to profile hemocyte volume plasticity in the euryhaline shrimp Penaeus monodon across a salinity gradient. Hemocytes were incubated for 24 h in hypoosmotic, isosmotic, and hyperosmotic media, with significant volume shifts observed while maintaining membrane integrity and morphology. The permeability of solutes (urea and sorbitol) suggested that volume adjustment is coupled with solute transport. Transcriptomic analyses identified key salinity-responsive pathways, including oxidative phosphorylation, MAPK signaling, ribosome biogenesis, and antioxidant defense mechanisms, underscoring the activation of redox-regulatory systems under osmotic stress. Weighted gene co-expression network analysis highlighted ribosomal proteins as central hubs in a salinity-responsive module, with qRT-PCR confirming the co-regulation of these hubs alongside representative osmoregulatory and antioxidant genes (AQP4, Na⁺/K⁺-ATPase, HSP70, CHOP, and antioxidant enzymes). These findings reveal how hemocyte volume dynamics are coupled to redox regulation, providing a mechanistic framework for understanding osmotic stress–redox coupling in crustacean immune cells. Full article

(This article belongs to the Special Issue Antioxidant Defenses Against Stress Caused by Physical or Chemical Environmental Changes)

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22 pages, 3984 KB

Open AccessArticle

Olive Leaf Extract Added to Losartan Treatment Improved Klotho/Wnt/β-Catenin Signaling in Hypertensive Rats with Focal Segmental Glomerulosclerosis

by Danijela Karanović, Nevena Mihailović-Stanojević, Milan Ivanov, Una-Jovana Vujačić, Jelica Grujić-Milanović, Maja Životić, Dragana Dekanski, Djurdjica Jovović and Zoran Miloradović

Antioxidants 2026, 15(1), 146; https://doi.org/10.3390/antiox15010146 - 22 Jan 2026

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Abstract

The downregulation of Klotho in renal injury predicts the progression of chronic kidney disease (CKD). Klotho acts as an antagonist of the Wnt/β-catenin pathway, which is involved in the pathogenesis of proteinuria, glomerulosclerosis and tubulointerstitial fibrosis. We investigated whether losartan (L, angiotensin II [...] Read more.

The downregulation of Klotho in renal injury predicts the progression of chronic kidney disease (CKD). Klotho acts as an antagonist of the Wnt/β-catenin pathway, which is involved in the pathogenesis of proteinuria, glomerulosclerosis and tubulointerstitial fibrosis. We investigated whether losartan (L, angiotensin II type-1 receptor blocker) alone or combined with synthetic (tempol, T) or natural antioxidants (olive leaf extract, O) could alter Klotho/Wnt4/β-catenin signaling, thus reducing fibrosis and slowing the progression of focal segmental glomerulosclerosis (FSGS) in spontaneously hypertensive rats (SHR). The rats were divided into five groups. The control rats received a vehicle. The other groups received adriamycin (2 mg/kg, i.v., twice in a 3-week interval) for FSGS induction. Treatments with L, L+T and L+O (10, 10 + 100 and 10 + 80 mg/kg/day, respectively) were administered by gavage during six weeks. In the kidneys of model rats, Klotho and Wnt4 were downregulated, whereas β-catenin and fibronectin levels were increased compared with the control group. L+T did not alter Klotho, Wnt4 or fibronectin levels, while it further increased β-catenin. In contrast, L+O improved Klotho, and reduced β-catenin and fibronectin levels, although it increased PAI-1. The L+O combination reduced proteinuria more efficiently than L and decreased renal injury close to control levels. Although these findings indicate that combined treatment of losartan and olive leaf extract is promising in slowing the progression of the experimental FSGS, further clinical studies are needed to confirm its favorable outcomes and safety in CKD patients. Full article

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

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22 pages, 3121 KB

Open AccessArticle

Metal-Chelating Macroalgal Extract as a Marine Antioxidant for Stabilizing DHA Nanoemulsions

by Sakhi Ghelichi, Behdad Shokrollahi Yancheshmeh, Mona Hajfathalian, Seyed Hossein Helalat, Arpan Shrestha, Saroj Katwal and Charlotte Jacobsen

Antioxidants 2026, 15(1), 145; https://doi.org/10.3390/antiox15010145 - 22 Jan 2026

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Abstract

Docosahexaenoic acid (DHA), an omega-3 fatty acid essential for human health, is highly prone to oxidation in nanoemulsions due to their large interfacial area and presence of transition metal ions. This study investigated macroalgal chelators for stabilizing DHA-rich nanoemulsions. Sequential enzymatic–alkaline extraction using [...] Read more.

Docosahexaenoic acid (DHA), an omega-3 fatty acid essential for human health, is highly prone to oxidation in nanoemulsions due to their large interfacial area and presence of transition metal ions. This study investigated macroalgal chelators for stabilizing DHA-rich nanoemulsions. Sequential enzymatic–alkaline extraction using Alcalase^® produced an extract with the strongest Fe²⁺-chelating activity (IC₅₀ = 1.22 mg/mL), protein content of 10.11 ± 0.15%, and total phenolics ≈ 17 µg GAE/mL. This extract was incorporated into nanoemulsions (5 wt% DHA oil, 1 wt% Tween^® 20) at 0.61, 1.22, and 2.44 mg/mL and compared with controls containing EDTA (0.025 mg/mL) or no antioxidant. Droplet size remained stable (D_3,2 ≈ 77–80 nm; D_4,3 ≈ 199–215 nm) and zeta potential averaged −17 to −19 mV, confirming physical stability. Confocal microscopy revealed concentration-dependent interfacial adsorption of extract components. During iron-accelerated storage, extract-treated nanoemulsions slowed hydroperoxide formation and delayed tocopherol depletion compared to the control, while reducing volatile oxidation markers such as 1-penten-3-ol by up to 40%. However, EDTA consistently provided superior protection against oxidation. These findings highlight the potential of macroalgal extracts as clean-label, natural chelators for mitigating metal-driven oxidation in DHA nanoemulsions, though synthetic chelators remain more effective under severe prooxidant conditions. Full article

(This article belongs to the Special Issue Antioxidants from the Sea and Their Application)

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21 pages, 4173 KB

Open AccessReview

OPA1 as a Cancer Target: Molecular Mechanisms, Structural Insights, and Strategies for Drug Development

by Antonio Curcio, Ludovica Ganino, Ilenia Valentino, Massimo Gentile, Stefano Alcaro, Roberta Rocca, Anna Artese and Nicola Amodio

Antioxidants 2026, 15(1), 144; https://doi.org/10.3390/antiox15010144 - 22 Jan 2026

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Abstract

Mitochondria are highly dynamic organelles that integrate metabolic regulation, signal transduction, and programmed cell death with their canonical role in adenosine triphosphate (ATP) production. Their ability to undergo continuous remodeling through the opposing processes of fusion and fission is essential for maintaining cellular [...] Read more.

Mitochondria are highly dynamic organelles that integrate metabolic regulation, signal transduction, and programmed cell death with their canonical role in adenosine triphosphate (ATP) production. Their ability to undergo continuous remodeling through the opposing processes of fusion and fission is essential for maintaining cellular homeostasis, preserving organelle quality control, and enabling adaptive responses to metabolic and oxidative stress. Among the core regulators of mitochondrial dynamics, the dynamin-related guanosine triphosphatase (GTPase) OPA1 plays a central role in inner membrane fusion, cristae architecture maintenance, bioenergetic efficiency, and the modulation of redox balance and apoptotic signaling. Accumulating evidence indicates that dysregulation of OPA1 expression or activity contributes to the initiation and progression of multiple malignancies, underscoring its importance in tumor cell survival, proliferation, metabolic adaptation, and resistance to stress. Here, we summarize current knowledge on OPA1 dysregulation in cancer and, based on preliminary, unpublished in silico analyses, we highlight the growing relevance of OPA1 as a therapeutic target, particularly through its GTPase domain and the still understudied Interface 7. Overall, these findings outline how integrated computational approaches could potentially guide the identification of novel OPA1 modulators, offering a conceptual framework that highlights OPA1 as a promising, yet still largely underexplored, target in oncology. Full article

(This article belongs to the Special Issue Redox Regulation of Cancer Metabolism)

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19 pages, 1887 KB

Open AccessArticle

Phytochemical Composition, Antioxidant and Anti-Inflammatory Activities, and Protective Effect Against LPS-Induced Liver Injury in Mice of Gerbera delavayi Franch

by Hongmei Yin, Yinrong Zhao, Rouxian Hu, Jing Yang, Yuanhang Chen, Huaqiao Tang, Xiaoyan Li, Gang Ye, Fei Shi, Cheng Lv and Ling Zhao

Antioxidants 2026, 15(1), 143; https://doi.org/10.3390/antiox15010143 - 22 Jan 2026

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Abstract

The main objective of this study was to preliminarily analyze the major flavonoid and phenolic acid components of the ethanolic extract of Gerbera delavayi Franch (E-GDF), and to evaluate its anti-inflammatory and antioxidant properties in lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7 cells and systemic [...] Read more.

The main objective of this study was to preliminarily analyze the major flavonoid and phenolic acid components of the ethanolic extract of Gerbera delavayi Franch (E-GDF), and to evaluate its anti-inflammatory and antioxidant properties in lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7 cells and systemic inflammation mouse models. Results indicated that E-GDF was rich in flavonoids (16.35 ± 0.19 mg RT/g d.w. Plant Material) and polyphenolic compounds (36.15 ± 0.20 mg GAE/g d.w. Plant Material). LC-MS analysis of E-GDF revealed that its major flavonoid components included kaempferol glycosides, luteolin, and their glycosylated derivatives, while its phenolic acids were predominantly chlorogenic acid, caffeic acid, ferulic acid, and their corresponding glycosides. E-GDF exhibited good antioxidant activities, including the scavenging of DPPH, ABTS, ^•OH, and O₂^•− radicals. E-GDF treatment significantly inhibited the production of ROS and inflammatory mediators (NO, IL-6, TNF-α) in LPS-stimulated macrophages (RAW 264.7), while concurrently down-regulating the mRNA expression of COX-2, IL-1β, Casp1, and GSDMD-1. In addition, in vivo experiments revealed that E-GDF treatment effectively reduced the serum LPS, AST levels, as well as hepatic TNF-α, IL-6 levels in mice with LPS-induced acute liver injury. Furthermore, E-GDF significantly ameliorated LPS-induced liver pathological damage. These results provide a basis for G. delavayi as a potential antioxidant, anti-inflammatory, and hepatoprotective herbal medicine. Full article

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20 pages, 1623 KB

Open AccessReview

The Mechanism of Oxidative Stress in Pulmonary Fibrosis and Research Progress

by Duo Xu, Qian Wang, Meng Lyu, Chunyu Huang, Xianglin Yuan, Xinyi Chen and Yongbiao Huang

Antioxidants 2026, 15(1), 142; https://doi.org/10.3390/antiox15010142 - 22 Jan 2026

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Abstract

Pulmonary fibrosis (PF) is a group of chronic progressive lung diseases characterized by irreversible remodeling of lung tissue structure, abnormal proliferation of fibroblasts, and excessive deposition of extracellular matrix (ECM), among which idiopathic pulmonary fibrosis (IPF) is the most typical subtype. Currently, the [...] Read more.

Pulmonary fibrosis (PF) is a group of chronic progressive lung diseases characterized by irreversible remodeling of lung tissue structure, abnormal proliferation of fibroblasts, and excessive deposition of extracellular matrix (ECM), among which idiopathic pulmonary fibrosis (IPF) is the most typical subtype. Currently, the only two clinically approved therapeutic drugs (nintedanib and pirfenidone) can only partially slow disease progression without reversing fibrotic lesions, and are associated with varying degrees of adverse effects. Oxidative stress, defined as a pathological imbalance between systemic oxidant and antioxidant systems, has been substantiated by extensive research as a pivotal mechanism driving the pathogenesis and progression of pulmonary fibrosis. This review summarizes the regulatory mechanisms of oxidative stress in pulmonary fibrosis, with a focus on its critical role in inducing and promoting fibrosis through relevant target cells and signaling pathways. We also specifically highlight the latest progress and challenges in therapeutic strategies targeting oxidative stress, and discuss next-generation therapies, including the modulation of endogenous antioxidant pathways, supplementation of exogenous antioxidants, as well as nanomaterials, exosomes, and combination therapies. We hope this review will deepen the understanding of oxidative stress and pulmonary fibrosis, and provide new directions for improving the clinical efficacy of oxidative stress-targeted therapies. Full article

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

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20 pages, 1625 KB

Open AccessArticle

European Teas (Camellia sinensis) as a New Frontier in the Specialty Tea Market: Characterizing the Antioxidant, Polyphenolic, and Sensory Profiles Through a Systematic, Comparative Approach

by Patricia Carloni, Benedetta Fanesi, Paolo Lucci, Cristina Truzzi, Federico Girolametti and Elisabetta Damiani

Antioxidants 2026, 15(1), 141; https://doi.org/10.3390/antiox15010141 - 22 Jan 2026

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Abstract

Tea production in Europe represents an emerging segment of the specialty tea market, but a structured comparative analysis remains unexplored. This study employs a standardized approach to systematically characterize hot brews from black and green teas across five European gardens. Antioxidant capacity, total [...] Read more.

Tea production in Europe represents an emerging segment of the specialty tea market, but a structured comparative analysis remains unexplored. This study employs a standardized approach to systematically characterize hot brews from black and green teas across five European gardens. Antioxidant capacity, total polyphenolic content (TPC), total flavonoid content (TFC), and metabolomic profiling by ultra-high performance liquid chromatography–mass spectrometry were evaluated, and for the first time, sensory profiling of these teas was conducted. Green teas consistently exhibited higher TPC, TFC, and antioxidant capacity compared to black teas, confirming the influence of processing methods. Metabolomic analysis revealed variability in caffeine linked to geographical origin and propagation method (cuttings vs. seeds). Importantly, sensory evaluation suggested a negative correlation between high TPC and overall consumer appreciation. The two most highly appreciated teas often showed lower TPC. These reliable findings advance knowledge in European tea research, providing valuable data for growers to enhance cultivar selection and marketing strategies in alignment with consumer preferences. Full article

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

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26 pages, 4478 KB

Open AccessArticle

Integration of Serum and Liver Metabolomics with Antioxidant Biomarkers Elucidates Dietary Energy Modulation of the Fatty Acid Profile in Donkey Meat

by Li Li, Yanli Zhao, Yongmei Guo, Binlin Shi, Jing Zhang, Fanzhu Meng, Fang Hui, Qingyue Zhang, Xiaoyu Guo and Sumei Yan

Antioxidants 2026, 15(1), 140; https://doi.org/10.3390/antiox15010140 - 21 Jan 2026

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Abstract

Donkey meat is valued for its high protein, unsaturated fats, and low cholesterol. Fatty acid (FA) composition critically influences meat quality and is modulated by dietary energy levels. Twenty-four meat donkeys (male) were randomly divided into three groups: a low-energy group (LEG), a [...] Read more.

Donkey meat is valued for its high protein, unsaturated fats, and low cholesterol. Fatty acid (FA) composition critically influences meat quality and is modulated by dietary energy levels. Twenty-four meat donkeys (male) were randomly divided into three groups: a low-energy group (LEG), a medium-energy group (MEG), and a high-energy group (HEG). The trial lasted for 135 days, with dietary digestible energy levels adjusted during the pre-fattening, mid-fattening, and late-fattening phases according to the experimental design. The results showed that MEG and HEG interventions significantly upregulated tissue polyunsaturated fatty acid (PUFA) and n-3 PUFA content while reducing n-6/n-3 ratios, concomitant with enhanced activity and gene expression of most lipid-metabolizing enzymes. Notably, MEG further elevated antioxidant enzyme activities and anti-inflammatory mediators while suppressing pro-inflammatory factors. MEG and HEG significantly upregulated serum cholestane-3,7,12,25-tetrol-3-glucuronide and cortisol, along with hepatic choline, lysoPC(20:2(11Z,14Z)), glycocholic acid, and cholestane-3,7,12,25-tetrol-3-glucuronide. These modified metabolites were predominantly enriched in key metabolic pathways: pentose and glucuronate interconversions, primary bile acid biosynthesis, steroid hormone biosynthesis, glycerophospholipid metabolism, purine metabolism, and glutathione metabolism. Additionally, compared to HEG, MEG improved the antioxidant activities and immune signaling molecule levels with elevated pyroglutamic acid, glutathione, choline, inosine, adenine, and uric acid. Thus, moderately elevated dietary energy levels may enhance FA profiles in muscular and adipose tissues through coordinated regulation of lipid-metabolizing enzymes and associated gene expression, with serum and hepatic metabolites actively participating in these regulatory pathways. However, excessive energy intake could induce oxidative stress in donkeys. Full article

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18 pages, 2652 KB

Open AccessArticle

Baicalin Alleviates Chronic Restraint Stress-Induced Depression-like Behavior by Suppressing ROS/H₂O₂ Generation via a BDNF-Associated Mechanism in Mice

by Yu-Ning Teng, Tien-Wei Hsu, Wei-Hao Peng, Cheng-Chun Wu, Tian-Huei Chu, Yung-Kuo Lee, Ming Tatt Lee and Yu-Cheng Ho

Antioxidants 2026, 15(1), 139; https://doi.org/10.3390/antiox15010139 - 21 Jan 2026

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Abstract

Major depressive disorder (MDD) is a leading cause of global morbidity and mortality. Although pharmacological treatments are widely used, their effects are often limited, and nearly half of patients show resistance to current antidepressants, including those unresponsive to all available therapies. These challenges [...] Read more.

Major depressive disorder (MDD) is a leading cause of global morbidity and mortality. Although pharmacological treatments are widely used, their effects are often limited, and nearly half of patients show resistance to current antidepressants, including those unresponsive to all available therapies. These challenges highlight the need to better understand the neurobiological mechanisms driving MDD and to develop novel therapeutic strategies, especially those involving natural compounds with multitarget actions. Baicalin, a bioactive flavonoid from Scutellaria baicalensis, exhibits antioxidant, anti-inflammatory, and neuroprotective properties and has recently gained attention for its potential to improve cognitive deficits and mood disorders. In this study, we investigated baicalin’s antidepressant potential and its underlying mechanisms across multiple experimental levels. We found that oral administration of baicalin produced antidepressant-like effects in both naïve mice and those subjected to chronic restraint stress (CRS). CRS impaired hippocampal long-term potentiation (LTP), whereas baicalin restored these synaptic deficits. Importantly, intra-dorsal hippocampal microinjection of the TrkB receptor antagonist ANA-12 abolished baicalin’s antidepressant effects, indicating the involvement of BDNF–TrkB signaling. Baicalin also reduced reactive oxygen species (ROS)/H₂O₂ production in a BDNF-associated manner, demonstrating clear antioxidant activity. Molecular docking further suggested that baicalin binds more effectively to the TrkB receptor than ANA-12, supporting its capacity to activate TrkB-mediated signaling. By integrating in vivo, ex vivo, in vitro, and in silico approaches, our study shows that baicalin exerts robust antioxidant in vitro and antidepressant effects in vivo. These benefits are primarily mediated through activation of BDNF–TrkB signaling, leading to reduced ROS/H₂O₂ accumulation and alleviation of CRS-induced depression-like behaviors. Full article

(This article belongs to the Special Issue Oxidative Stress in Brain Function—2nd Edition)

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18 pages, 6743 KB

Open AccessArticle

Differential Toxicity of Water-Soluble Versus Water-Insoluble Components of Cowshed PM2.5 on Ovarian Granulosa Cells and the Regulatory Role of Txnip in Overall Toxicity

by Zhenhua Ma, Xiqing Zhang, Xiaohui Du, Cuizhu Zhao, Yunna Jia, Ye Wang, Xintian Li, Xiuzhen Yu and Yunhang Gao

Antioxidants 2026, 15(1), 138; https://doi.org/10.3390/antiox15010138 - 21 Jan 2026

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Abstract

Fine particulate matter (PM2.5)-induced ovarian damage has attracted widespread attention, but differences in cytotoxicity and underlying mechanisms of water-soluble (WS-PM2.5) and water-insoluble (WIS-PM2.5) fractions are unclear. To investigate potential effects of PM2.5 from livestock farming environments on animal ovaries, PM2.5 samples were collected [...] Read more.

Fine particulate matter (PM2.5)-induced ovarian damage has attracted widespread attention, but differences in cytotoxicity and underlying mechanisms of water-soluble (WS-PM2.5) and water-insoluble (WIS-PM2.5) fractions are unclear. To investigate potential effects of PM2.5 from livestock farming environments on animal ovaries, PM2.5 samples were collected from large-scale cattle barns. There were significant differences between fractions regarding elemental composition, proportion of water-soluble ions, polycyclic aromatic hydrocarbon content, and endotoxin concentrations. Based on transcriptome sequencing results, in a cowshed PM2.5 exposure model (rats), differentially expressed ovarian mRNAs were significantly enriched in signaling pathways such as cytokine interaction and the Hippo pathway, with the expression of thioredoxin-interacting protein (Txnip) significantly increased. In vitro (primary rat ovarian granulosa cells), short-term exposure to WS-PM2.5 (12 h) significantly induced inflammatory factor release, acute oxidative stress, mitochondrial dysfunction, and intracellular Ca²⁺ overload, with characteristics of rapid acute injury. However, extended (24 h) WIS-PM2.5 exposure had greater disruptive effects on estrogen homeostasis, intracellular enzyme release (LDH), and mitochondrial structure (subacute characteristics). Furthermore, downregulating Txnip expression via inhibitors effectively mitigated cowshed PM2.5-induced ovarian granulosa cell toxicity, oxidative stress, and mitochondrial and hormonal dysfunction. In summary, solubility of cowshed PM2.5 components affected cytotoxic characteristics, and Txnip was a key factor linking oxidative stress to granulosa cell damage. The study provided a mechanistic basis and potential targets for preventing and controlling PM2.5-induced ovarian damage in livestock environments. Full article

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21 pages, 3615 KB

Open AccessArticle

Eicosapentaenoic Acid Improves Porcine Oocyte Cytoplasmic Maturation and Developmental Competence via Antioxidant and Mitochondrial Regulatory Mechanisms

by Yibo Sun, Xinyu Li, Chunyu Jiang, Guian Huang, Junjie Wang, Yu Tian, Lin Jiang, Xueping Shi, Jianguo Zhao and Jiaojiao Huang

Antioxidants 2026, 15(1), 137; https://doi.org/10.3390/antiox15010137 - 21 Jan 2026

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Abstract

Oocytes cultured in vitro are exposed to high oxygen tension and lack follicular antioxidants, leading to redox imbalance. Eicosapentaenoic acid (EPA), a marine long-chain n-3 polyunsaturated fatty acid, possesses strong antioxidant activity. Here, using pigs as a model, we examined the effects of [...] Read more.

Oocytes cultured in vitro are exposed to high oxygen tension and lack follicular antioxidants, leading to redox imbalance. Eicosapentaenoic acid (EPA), a marine long-chain n-3 polyunsaturated fatty acid, possesses strong antioxidant activity. Here, using pigs as a model, we examined the effects of EPA on oocyte in vitro maturation (IVM) and subsequent developmental competence. Cumulus–oocyte complexes were cultured with EPA, followed by assessment of nuclear and cytoplasmic maturation and embryonic development; transcriptomic and proteomic analyses were conducted to explore underlying mechanisms. Supplementation with 10 µM EPA significantly improved maturation and blastocyst rates by reducing spindle defects, facilitating a more uniform organization of cortical granules and mitochondria. EPA increased resolvin E1 accumulation and reduced cumulus-cell apoptosis through downregulation of TNF-α and BAX and upregulation of BCL2. In MII oocytes, EPA lowered apoptosis, DNA damage, and ROS levels while enhancing SOD2 and GPX4 expression. Mitochondrial quality and turnover were improved via upregulation of PPARGC1A, NDUFS2, PINK1, LC3, FIS1, MUL1, and OPA1, alongside strengthened ER–mitochondria contacts. These findings demonstrate that EPA alleviates oxidative stress, optimizes mitochondrial function, and enhances porcine oocyte maturation and developmental competence in a parthenogenetic model, highlighting its potential as a marine-derived functional additive for reproductive biotechnology. Future studies will be required to validate these effects under fertilization-based embryo production systems and to further refine dose–response relationships using expanded embryo-quality endpoints. Full article

(This article belongs to the Topic Redox Modulation, Antioxidants, and Metabolites in Animals Through the One Health Concept)

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26 pages, 2015 KB

Open AccessArticle

Shaping Lycopene Nanoparticles Performance: How Surfactants Influence Stability, Antioxidant Activity, and Uptake in Human Skin Spheroids

by Francesca Baldassarre, Chiara Boncristiani, Michela Ottolini, Concetta Nobile, Maryam Shahzad Shirazi, Giuseppe E. De Benedetto, Gianpiero Colangelo, Viviana Vergaro, Ludovico Valli and Giuseppe Ciccarella

Antioxidants 2026, 15(1), 136; https://doi.org/10.3390/antiox15010136 - 21 Jan 2026

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Abstract

There is a growing demand for plant-derived antioxidants to replace synthetic ones in skincare applications. Phytochemicals are characterized by certain limitations, including poor bioavailability and chemical instability, which affect their industrial exploitation. Tomato peel extract has been used as a source of lycopene, [...] Read more.

There is a growing demand for plant-derived antioxidants to replace synthetic ones in skincare applications. Phytochemicals are characterized by certain limitations, including poor bioavailability and chemical instability, which affect their industrial exploitation. Tomato peel extract has been used as a source of lycopene, which is renowned for its antioxidant properties. To improve the bioavailability of extracted lycopene, polymeric (poly-lactic-co-glycolic acid) nano-carriers were synthesized by comparing two non-ionic surfactants, polyvinyl alcohol (PVA) and Tween 20. The impact of surfactants has been studied by evaluating: (i) colloidal stability determined by dynamic light scattering; (ii) lycopene retention and bioactivity over time, as measured by spectrophotometric assays; (iii) biological interactions on 2D and 3D keratinocyte and melanocyte cell cultures. It was found that both surfactants enable the formation of stable lycopene-loaded nanoparticles suspensions; however, greater colloidal stability was exhibited by nanoparticles prepared with Tween 20. PVA, on the other hand, provided greater nanoparticle stability in terms of loaded lycopene retention and antioxidant activity. Tween 20 surfactant improves the internalization of lycopene-loaded nanoparticles in human skin spheroids. It was demonstrated that both surfactants provided excellent intracellular antioxidant activity of lycopene. This was observed in keratinocytes, melanocytes, adherent cells, and spheroids, suggesting potential skincare applications. Full article

(This article belongs to the Special Issue Applications of Antioxidant Nanoparticles, 2nd Edition)

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21 pages, 7230 KB

Open AccessArticle

Betaine Inhibits Ferroptosis After Intracerebral Hemorrhage by Activating the Nrf2/HO-1 Pathway

by Jie Chen, Xurui Lu, Sunqian Liu, Weiliang Hu, Xiaorong Zhou and Zhifeng Wang

Antioxidants 2026, 15(1), 135; https://doi.org/10.3390/antiox15010135 - 21 Jan 2026

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Abstract

Intracerebral hemorrhage (ICH) is a type of stroke with high mortality and disability rates. The hemoglobin and iron ions released by ruptured red blood cells after ICH can induce programmed cell death characterized by lipid peroxide accumulation—a defining feature of ferroptosis—which is one [...] Read more.

Intracerebral hemorrhage (ICH) is a type of stroke with high mortality and disability rates. The hemoglobin and iron ions released by ruptured red blood cells after ICH can induce programmed cell death characterized by lipid peroxide accumulation—a defining feature of ferroptosis—which is one of the key mechanisms for the occurrence and progression of secondary brain injury after ICH. Betaine (BET), a natural amino acid derivative, is known to be an antioxidant, but its protective effect and molecular mechanisms in ICH-induced ferroptosis have not been studied yet. In this study, we investigated the effect of BET intervention on ICH-induced ferroptosis and possible mechanisms in vitro and in vivo, and we evaluated the expression of ferroptosis and oxidative stress molecules through in vivo and in vitro experiments. We analyzed the distribution of nuclear factor E2-related factor 2 (Nrf2) and assessed neurobehavioral function, hematoma volume, and iron content in the brain tissue of mice with ICH. BET upregulates nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling, reducing long-chain acyl-CoA synthetase 4 (ACSL4), reactive oxygen species (ROS), and malondialdehyde (MDA) while increasing glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels. It also decreases brain iron accumulation, aids hematoma clearance, and protects against ferroptosis and oxidative damage post ICH. Inhibition of Nrf2 with ML385 diminishes BET’s neuroprotective effects, highlighting the pathway’s importance in BET’s mechanism of action. BET boosts antioxidant capacity via the Nrf2/HO-1 pathway; inhibits ferroptosis; reduces oxidative stress, brain edema, and iron accumulation post ICH; and aids hematoma clearance, offering neuroprotection. Full article

(This article belongs to the Special Issue Oxidative Stress and NRF2 in Health and Disease—2nd Edition)

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14 pages, 4363 KB

Open AccessArticle

Drosophila Keap1 Proteins Assemble Nuclear Condensates in Response to Oxidative Stress

by Guangye Ji, Bethany Cross, Thomas Killmer, Bee Enders, Emma Neidviecky, Hayden Huber, Grace Lynch and Huai Deng

Antioxidants 2026, 15(1), 134; https://doi.org/10.3390/antiox15010134 - 21 Jan 2026

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Abstract

The Keap1-Nrf2 signaling pathway is a central regulator of transcriptional responses to oxidative stress and is strongly linked to diverse pathologies, particularly cancer. In the cytoplasm, Keap1 (Kelch-like ECH-associated protein 1) promotes proteasomal degradation of Nrf2 (NF-E2–related factor 2). Oxidative stimuli disrupt the [...] Read more.

The Keap1-Nrf2 signaling pathway is a central regulator of transcriptional responses to oxidative stress and is strongly linked to diverse pathologies, particularly cancer. In the cytoplasm, Keap1 (Kelch-like ECH-associated protein 1) promotes proteasomal degradation of Nrf2 (NF-E2–related factor 2). Oxidative stimuli disrupt the Keap1-Nrf2 interaction, facilitating Nrf2 nuclear accumulation and activation of antioxidant and detoxifying genes. Recent evidence suggests that Keap1 family proteins also enter the nucleus, bind chromatin, and regulate transcription, but the underlying mechanisms remain less understood. Here, we show that the Drosophila Keap1 ortholog, dKeap1, accumulates in the nucleus and gradually assembles stable nuclear foci in cells following oxidative treatment. FRAP analyses revealed reduced mobility of dKeap1 within these foci. Both the N-terminal (NTD) and C-terminal (CTD) domains of dKeap1 were required for foci formation. Two intrinsically disordered regions (IDRs) were identified within the CTD, and CTD-YFP fusion proteins readily formed condensates in vitro. Conversely, deletion of the Kelch domain resulted in robust cytoplasmic foci even under basal conditions, and in vitro assays also indicated that the Kelch domain suppresses dKeap1 condensate formation. Together, these findings reveal a novel molecular mechanism for the nuclear function of dKeap1, providing new insight into the broader roles of Keap1 factors in oxidative response, development, and disease. Full article

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15 pages, 1310 KB

Open AccessArticle

Effects of Caffeic Acid Supplementation on Human Sperm Against In Vitro-Induced Oxidative Stress: Nrf2 Molecular Pathway

by Laura Liguori, Cinzia Signorini, Giulia Collodel, Caterina Marcucci and Elena Moretti

Antioxidants 2026, 15(1), 133; https://doi.org/10.3390/antiox15010133 - 20 Jan 2026

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Abstract

Oxidative stress (OS) is a major cause of defective sperm function. During laboratory handling, gametes are exposed to OS, potentially mitigated by in vitro antioxidant supplementation. This study evaluates the protective role of caffeic acid (CAF) on basal human semen and under induced [...] Read more.

Oxidative stress (OS) is a major cause of defective sperm function. During laboratory handling, gametes are exposed to OS, potentially mitigated by in vitro antioxidant supplementation. This study evaluates the protective role of caffeic acid (CAF) on basal human semen and under induced OS. First, six semen samples from normozoospermic donors were incubated with CAF concentrations ranging from 50 to 500 µM at 37 °C for 2 h. Sperm motility and DNA integrity (acridine orange) were evaluated. Then, ten semen samples were divided into four aliquots and incubated, respectively, with CAF at 100 µM, H₂O₂ at 2 mM, or H₂O₂ at 2 mM + CAF at 100 µM, or untreated. Motility, DNA integrity, acrosome status (Pisum sativum agglutinin), OS quantified by F₂-isoprostanes (ELISA), and expression of Nrf2, Keap1, and HO-1 (qRT-PCR) were assessed. CAF at 100 µM improved progressive motility without damaging DNA and was selected for subsequent experiments. CAF showed protective effects on sperm damage induced by H₂O₂ treatment, restoring motility, DNA integrity, and acrosome status and reducing F₂-isoprostane levels. Nrf2 and HO-1 expression were upregulated by CAF, downregulated by H₂O₂, and restored by the co-treatment. CAF supplementation may protect human spermatozoa during in vitro handling by reducing OS, improving several sperm parameters, with a possible mechanism of action involving the Nrf2 pathway. Full article

(This article belongs to the Special Issue Oxidative Stress and NRF2 in Health and Disease—2nd Edition)

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23 pages, 3627 KB

Open AccessArticle

Probiotic Combination of Lactiplantibacillus plantarum M1 and Limosilactobacillus reuteri K4 Alleviates Early Weaning-Induced Intestinal Injury in Lambs via Modulation of Oxidative and Inflammatory Pathways

by Qicheng Lu, Peng Zhang, Yujie Niu, Chuying Wang, Fengshuo Zhang, Junli Niu, Weibin Zeng, Cheng Chen and Wenju Zhang

Antioxidants 2026, 15(1), 132; https://doi.org/10.3390/antiox15010132 - 20 Jan 2026

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Abstract

Early weaning in intensive lamb production improves reproductive efficiency but predisposes lambs to diarrhea, oxidative stress, and intestinal barrier dysfunction, highlighting the need for non-antibiotic strategies to protect gut health. This study evaluated whether a sheep-derived mixed probiotic could alleviate early weaning–induced intestinal [...] Read more.

Early weaning in intensive lamb production improves reproductive efficiency but predisposes lambs to diarrhea, oxidative stress, and intestinal barrier dysfunction, highlighting the need for non-antibiotic strategies to protect gut health. This study evaluated whether a sheep-derived mixed probiotic could alleviate early weaning–induced intestinal injury and clarified its potential molecular mechanisms. Early weaning reduced body weight, average daily gain and feed efficiency, increased diarrhea, decreased plasma and colonic catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) activities, increased malondialdehyde (MDA), elevated interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), reduced interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), increased plasma and mucosal immunoglobulin A, M, and G (IgA, IgM, IgG), and increased colonic lipopolysaccharide (LPS) with reduced diamine oxidase (DAO). Intestinally, EW induced villus atrophy, deeper crypts, lower villus height-to-crypt depth ratios, goblet cell loss, higher histopathological scores, and decreased colonic mucin 2, zonula occludens-1, claudin-1, and occludin. Probiotic supplementation partially reversed these alterations, restoring antioxidant enzyme activities, improving villus architecture and barrier protein expression, and rebalancing cytokine and immunoglobulin profiles. Transcriptomic and network analyses showed that early weaning activated Cytokine–cytokine receptor, NF-κB, TNF and Th17 pathways, whereas probiotics suppressed a weaning-responsive inflammatory gene module, downregulated key hub genes, and enhanced peroxisome proliferator-activated receptor (PPAR) signaling. These results show that supplementing early-weaned lambs with a mixed probiotic generated from sheep is an efficient nutritional strategy to reduce intestinal oxidative and inflammatory damage associated with weaning and to enhance their health and performance. Full article

(This article belongs to the Special Issue The Role of Dietary Antioxidants in Alleviating Oxidative Stress and Inflammation for Enhanced Immunity in Animals)

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19 pages, 3828 KB

Open AccessArticle

Norisoboldine Induces Endothelium-Dependent Vasorelaxation and Attenuates Hypertension by Modulating Ca²⁺-eNOS Signaling, Oxidative Stress, and Inflammation

by Jiaze Li, Shurui Wang, Enyi Jin, Ziyi Zhao, Jinyue Liang, Yun Jung Lee and Lihua Cao

Antioxidants 2026, 15(1), 131; https://doi.org/10.3390/antiox15010131 - 20 Jan 2026

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Abstract

Vascular function is a direct factor affecting blood pressure, and it is a primary strategy for clinically controlling hypertension by regulating the constriction/relaxation of blood vessels. This study evaluates the vasodilatory and anti-hypertensive effects of norisoboldine (NOR), an isoquinoline alkaloid in Ayurvedic medicine. [...] Read more.

Vascular function is a direct factor affecting blood pressure, and it is a primary strategy for clinically controlling hypertension by regulating the constriction/relaxation of blood vessels. This study evaluates the vasodilatory and anti-hypertensive effects of norisoboldine (NOR), an isoquinoline alkaloid in Ayurvedic medicine. The rat thoracic aorta was isolated to investigate the vasodilatory effect, and L-NAME-induced hypertensive rats were established, respectively. In the isolated vascular ring, removal of the endothelium resulted in a significant decrease in the vasodilatory effect. Pretreatment with L-NAME, ODQ, KT5823, WT, Tri, Dilt, calcium-free solution, TG, Gd³⁺, 2-APB, Indo, 4-AP, Gli, and BaCl₂ inhibited the vasodilatory effect of NOR. In vascular endothelial cells, NOR promoted eNOS phosphorylation and inhibited TNF-α-induced expression of ICAM-1 and VCAM-1. SBP and DBP were significantly decreased after administration of different doses of NOR in the femoral vein of rats. In addition, NOR significantly reduced the blood pressure of L-NAME-induced hypertensive rats, up-regulated the serum levels of NO, cGMP, and CAT, and down-regulated MDA, IL-6, and TNF-α in hypertensive rats. NOR administration improved pathological changes in the thoracic aorta by regulating the arrangement of thoracic aortic smooth muscle cells, decreasing the thickness of the thoracic aortic wall, and reducing the degree of collagen deposition and fibrosis. In conclusion, the vasodilatory mechanisms of NOR were related to the Ca²⁺-eNOS signaling pathway, including the PGI₂ and various K⁺/Ca²⁺ channels, the inositol triphosphate receptor (IP₃R) calcium release, and the α-adrenergic receptor pathway. The anti-hypertensive mechanism of NOR may be related to increased NO and cGMP bioavailability, inhibition of oxidative stress and inflammatory responses, and improved vascular remodeling. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Sources with Antioxidant and Anti-Inflammatory Potential)

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15 pages, 929 KB

Open AccessArticle

Myeloperoxidase (MPO) Enzymatic Activity, but Not Its Protein Concentration, Is Associated with the Risk of Type 2 Diabetes in Females, Regardless of Obesity Status

by Alessandro Trentini, Raffaella Riccetti, Domenico Sergi, Juana Maria Sanz, Riccardo Spaggiari, Valentina Rosta, Gianmarco Mola, Angelina Passaro and Carlo Cervellati

Antioxidants 2026, 15(1), 130; https://doi.org/10.3390/antiox15010130 - 19 Jan 2026

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Abstract

To date, neutrophil-derived myeloperoxidase (MPO), a key mediator of inflammation and oxidative stress, has predominantly been assessed in peripheral fluids by protein concentration rather than enzymatic activity, mainly due to methodological limitations. However, MPO activity directly reflects the enzyme’s cytotoxic potential and pathogenic [...] Read more.

To date, neutrophil-derived myeloperoxidase (MPO), a key mediator of inflammation and oxidative stress, has predominantly been assessed in peripheral fluids by protein concentration rather than enzymatic activity, mainly due to methodological limitations. However, MPO activity directly reflects the enzyme’s cytotoxic potential and pathogenic role in inflammatory diseases. To address this gap, we employed an optimized immunocapture assay to evaluate MPO activity, specific activity, and protein concentration in females with type 2 diabetes mellitus (T2DM), a condition tightly linked to chronic low-grade inflammation and obesity. Our findings revealed that females with T2DM exhibited nearly three-fold higher serum MPO activity and more than two-fold greater specific activity compared to controls with no differences in MPO protein concentration. Notably, MPO-specific activity remained significantly associated with T2DM (p < 0.01 to p < 0.001 across multivariate models), even after adjusting for age and dual-energy X-ray absorptiometry-derived measures of total and regional fat mass. Only android/gynoid fat distribution retained marginal significance in these models. This study is the first demonstration that MPO enzymatic activity, rather than protein concentration, is independently linked to T2DM in females. These findings underscore the importance of assessing functional MPO activity in the context of metabolic disease and support its potential role as a pathophysiological marker. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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16 pages, 8045 KB

Open AccessArticle

Effect of Dietary Capsaicinoids Supplementation on Growth Performance, Intestinal Morphology, and Colon Microbiota in Weaned Piglets

by Kangwei Hou, Zhixiang Ni, Jiangdi Mao and Haifeng Wang

Antioxidants 2026, 15(1), 129; https://doi.org/10.3390/antiox15010129 - 19 Jan 2026

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Abstract

This study investigated the effects of encapsulated capsaicinoids (CAPs), containing 0.47% capsaicin and 0.22% dihydrocapsaicin, on growth, serum parameters, nutrient digestibility, and intestinal health in weaned piglets. A total of 168 piglets were randomly assigned to four groups: a basal diet or the [...] Read more.

This study investigated the effects of encapsulated capsaicinoids (CAPs), containing 0.47% capsaicin and 0.22% dihydrocapsaicin, on growth, serum parameters, nutrient digestibility, and intestinal health in weaned piglets. A total of 168 piglets were randomly assigned to four groups: a basal diet or the same diet supplemented with 200 (LDC), 400 (MDC), or 600 (HDC) mg/kg of CAPs. The results indicated that CAPs improved lipid metabolism, evidenced by higher crude fat digestibility in the LDC and MDC groups and reduced serum low-density lipoprotein cholesterol in all CAP groups compared to the control. Glutathione peroxidase activity was significantly higher in the MDC and HDC groups. Histological analysis showed reduced hepatic vacuolation, enlarged fungiform papillae with shallower taste pores in the tongue epithelium, and deeper ileal crypts in the LDC group. At the molecular level, ZO-1 expression in the ileum was significantly upregulated in LDC piglets. Colonic microbiota analysis revealed decreased relative abundances of Lachnospiraceae_AC2044_group, Lachnospiraceae_XPB1014_group, and Rikenellaceae_RC9_gut, while Butyricicoccus was significantly enriched in the LDC group. In conclusion, CAPs supplementation enhanced fat digestibility, lipid metabolism, antioxidant capacity, intestinal development, and colonic microbiota composition, with the 200 mg/kg dose showing the most pronounced effects. Full article

(This article belongs to the Special Issue Oxidative Stress in Animal Reproduction and Nutrition)

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25 pages, 9226 KB

Open AccessArticle

Insights into Bioactive Constituents from Pericarp of Garcinia mangostana: Anti-Inflammatory Effects via NF-κB/MAPK Modulation and M1/M2 Macrophage Polarization

by Cheng-Shin Yang, Sin-Min Li and Jih-Jung Chen

Antioxidants 2026, 15(1), 128; https://doi.org/10.3390/antiox15010128 - 19 Jan 2026

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Abstract

Mangosteen (Garcinia mangostana L.) has long been used in traditional Southeast Asian medicine to treat inflammatory-related conditions. In this study, three new compounds, including garcimangone A (1), garcimangone B (2), and the S-form of garcimangone C ( [...] Read more.

Mangosteen (Garcinia mangostana L.) has long been used in traditional Southeast Asian medicine to treat inflammatory-related conditions. In this study, three new compounds, including garcimangone A (1), garcimangone B (2), and the S-form of garcimangone C (3), and 18 known compounds were isolated and investigated for their anti-inflammatory properties and effects on M1- and M2-associated markers. Among the isolated components, γ-mangostin (5), garcinone D (6), morusignin J (15), and fuscaxanthone C (16) showed the most potent NO-inhibitory effects in LPS-stimulated RAW264.7 cells. SAR study revealed that chromeno moiety at C-3,4, oxygen substituents at C-1,3,6,7, and isoprenyl groups at C-2,8 are key structural features that promoted anti-inflammatory activity. Cytokine analysis results indicated that morusignin J (15) and fuscaxanthone C (16) could modulate the production of pro-inflammatory cytokines, such as TNF-α and IL-6, while modulating the anti-inflammatory cytokine IL-10. Western blot results demonstrated that morusignin J (15) modulated the inflammatory response through NF-κB and MAPK signaling and increased the expression of M2-associated markers KLF4 and arginase-1 in LPS-induced RAW264.7 macrophages. Further molecular docking analysis confirmed the high binding affinity of morusignin J (15) with key iNOS residues, such as Gln257, Pro344, Glu371, and Hem901, and the in silico prediction supported its potent oral bioavailability and drug-likeness. These in vitro and in silico findings highlight that pericarps of G. mangostana possess potential as promising natural sources for functional extracts and bioactive constituents for the development of antioxidative and anti-inflammatory candidates, and warrant further in vivo investigation in the future. Full article

(This article belongs to the Special Issue Agri-Food Wastes as Natural Source of Bioactive Antioxidants: Fourth Edition)

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16 pages, 5147 KB

Open AccessArticle

5G RF-EMFs Mitigate UV-Induced Genotoxic Stress Through Redox Balance and p38 Pathway Regulation in Skin Cells

by Ju Hwan Kim, Hee Jin, Kyu Min Jang, Ji Eun Lee, Sanga Na, Sangbong Jeon, Hyung-Do Choi, Jung Ick Moon, Nam Kim, Kyung-Min Lim, Hak Rim Kim and Yun-Sil Lee

Antioxidants 2026, 15(1), 127; https://doi.org/10.3390/antiox15010127 - 19 Jan 2026

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Abstract

The biological effects of radiofrequency electromagnetic fields (RF-EMFs) remain an unresolved scientific issue with important societal relevance, particularly in the context of the global deployment of fifth-generation (5G) wireless technologies. The skin is continuously exposed to both RF-EMFs and ultraviolet (UV) radiation, a [...] Read more.

The biological effects of radiofrequency electromagnetic fields (RF-EMFs) remain an unresolved scientific issue with important societal relevance, particularly in the context of the global deployment of fifth-generation (5G) wireless technologies. The skin is continuously exposed to both RF-EMFs and ultraviolet (UV) radiation, a well-established inducer of oxidative stress and DNA damage, making it a relevant model for assessing combined environmental exposures. In this study, we investigated whether post-exposure to 5G RF-EMFs (3.5 and 28 GHz) modulates ultraviolet A (UVA)-induced genotoxic stress in human keratinocytes (HaCaT) and murine melanoma (B16) cells. Post-UV RF-EMF exposure significantly reduced DNA damage markers, including phosphorylated histone H2AX (γH2AX) foci formation (by approximately 30–50%) and comet tail moments (by 60–80%), and suppressed intracellular reactive oxygen species (ROS) accumulation (by 56–93%). These effects were accompanied by selective attenuation of p38 mitogen-activated protein kinase (MAPK) phosphorylation (reduced by 55–85%). The magnitude of molecular protection was comparable to that observed with N-acetylcysteine treatment or pharmacological inhibition of p38 MAPK. In contrast, RF-EMF exposure did not reverse UV-induced reductions in cell viability or alterations in cell cycle distribution, indicating that its protective effects are confined to early molecular stress-response pathways rather than downstream survival outcomes. Together, these findings demonstrate that 5G RF-EMFs can facilitate recovery from UVA-induced molecular damage via redox-sensitive and p38-dependent mechanisms, providing mechanistic insight into the interaction between modern telecommunication frequencies and UV-induced skin stress. Full article

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

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15 pages, 5988 KB

Open AccessArticle

Evaluation of the Effects of the Anti-Inflammatory and Antioxidant Properties of Aloperine on Recovery in an Experimental Sciatic Nerve Injury Model

by Mehmet Ertanıdır, Erkan Sabri Ertaş, Ali Güleç, Bahadır Öztürk, Nejat Ünlükal and Sadettin Çiftci

Antioxidants 2026, 15(1), 126; https://doi.org/10.3390/antiox15010126 - 19 Jan 2026

Viewed by 349

Abstract

Peripheral nerve injuries affect 13–23 out of 100,000 people annually, with Wallerian degeneration and subsequent inflammatory/oxidative responses critically impacting recovery. Aloperine, a natural alkaloid from Sophora alopecuroides L., exhibits potent anti-inflammatory and antioxidant properties but has never been studied for nerve repair. In [...] Read more.

Peripheral nerve injuries affect 13–23 out of 100,000 people annually, with Wallerian degeneration and subsequent inflammatory/oxidative responses critically impacting recovery. Aloperine, a natural alkaloid from Sophora alopecuroides L., exhibits potent anti-inflammatory and antioxidant properties but has never been studied for nerve repair. In this study, we aimed to investigate whether aloperine could enhance peripheral nerve regeneration by modulating inflammation and oxidative stress in a rat sciatic nerve injury model. Thirty male Wistar rats underwent sciatic nerve neurotmesis with epineural repair. Animals were divided into surgical controls (Group A), aloperine-treated rats (Group B; single 100 mg/kg intraperitoneal dose), and intact controls (Group C). After 8 weeks, outcomes were assessed via functional tests (pinprick, hot plate, extensor postural thrust), biochemical analyses (TNF-α, IL-6, IL-10, TOS/TAS), and histomorphometric evaluations (axon counts, diameter indices, immunohistochemistry). Aloperine treatment significantly improved functional recovery, with near-normal hot plate latency and motor performance. Biochemically, it reduced pro-inflammatory markers (TNF-α) while elevating IL-10. Oxidative stress was attenuated. Histologically, treated nerves showed better-preserved axonal architecture (reduced inflammation). This first investigation of aloperine for nerve repair demonstrates its therapeutic potential through dual anti-inflammatory and antioxidant mechanisms, significantly improving functional and structural outcomes. These findings support its development as a novel treatment for peripheral nerve injuries. Full article

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21 pages, 30469 KB

Open AccessArticle

Transcriptome and Gene Family Analyses Reveal the Physiological and Immune Regulatory Mechanisms of Channa maculata Larvae in Response to Nanoplastic-Induced Oxidative Stress

by Ziwen Yang, Dandan Gao, Yuntao Lu, Yang Zou, Yueying Deng, Luping Liu, Qing Luo, Haiyang Liu, Shuzhan Fei, Kunci Chen, Jian Zhao and Mi Ou

Antioxidants 2026, 15(1), 125; https://doi.org/10.3390/antiox15010125 - 19 Jan 2026

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Abstract

The increasing accumulation of plastic debris in aquatic environments has raised concerns about the ecotoxicological effects of polystyrene nanoplastics (PSNPs). This study examined PSNPs toxicity during a critical developmental stage by exposing 15 days post-fertilization (dpf) larvae of blotched snakehead (Channa maculata [...] Read more.

The increasing accumulation of plastic debris in aquatic environments has raised concerns about the ecotoxicological effects of polystyrene nanoplastics (PSNPs). This study examined PSNPs toxicity during a critical developmental stage by exposing 15 days post-fertilization (dpf) larvae of blotched snakehead (Channa maculata), an economically important freshwater fish, to PSNPs concentrations of 0.05–20 mg/L for 15 days. Histopathological analysis showed concentration-dependent damage, including hepatocellular vacuolization (5–10 mg/L) and hepatic sinusoidal dilation (20 mg/L) in the liver, alongside intestinal injuries ranging from villus erosion to rupture (5–20 mg/L). Biochemically, PSNPs triggered a biphasic oxidative response, where superoxide dismutase (SOD) and catalase (CAT) activities peaked at 5 mg/L before declining, while malondialdehyde (MDA) levels exhibited an opposite trend. Transcriptomic analysis and Quantitative real-time PCR (qRT-PCR) indicated that PSNPs disrupted growth, energy metabolism, and immune regulation in C. maculata larvae, evidenced by the dysregulation of growth hormone/insulin-like growth factor (GH/IGF) axis genes and up-regulation of immune-related genes. Furthermore, Weighted Gene Co-expression Network Analysis (WGCNA) identified the heterogeneous nuclear ribonucleoproteins (HNRNP) gene family as hub genes from the key turquoise module, suggesting that PSNPs interfere with RNA processing and post-transcriptional control. In summary, PSNPs caused multi-level toxicity in C. maculata larvae, providing new insights into their ecotoxicological hazards in freshwater ecosystems. Full article

(This article belongs to the Special Issue Antioxidant Defenses and Oxidative Stress Management in Aquaculture)

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20 pages, 1179 KB

Open AccessSystematic Review

Oxidative Stress, Micronutrient Deficiencies and Coagulation Disorders After Bariatric Surgery: A Systematic Review

by Katarzyna Giedzicz, Przemysław Zubrzycki, Aleksander Łukaszewicz, Paulina Głuszyńska and Hady Razak Hady

Antioxidants 2026, 15(1), 124; https://doi.org/10.3390/antiox15010124 - 18 Jan 2026

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Abstract

Metabolic bariatric surgery (MBS) induces substantial metabolic, inflammatory, and nutritional changes that can alter hemostatic balance through redox-dependent mechanisms. This systematic review evaluated coagulation disturbances after MBS with emphasis on oxidative stress and micronutrient deficiencies. A structured search of PubMed, Scopus, and Web [...] Read more.

Metabolic bariatric surgery (MBS) induces substantial metabolic, inflammatory, and nutritional changes that can alter hemostatic balance through redox-dependent mechanisms. This systematic review evaluated coagulation disturbances after MBS with emphasis on oxidative stress and micronutrient deficiencies. A structured search of PubMed, Scopus, and Web of Science (2000–2025) identified 1707 records; 21 studies met inclusion criteria. Available evidence suggests that although MBS reduces obesity-related inflammation and oxidative burden in many patients, a proportion of individuals may present with persistent redox imbalance, elevated D-dimer or vWF (von Willebrand Factor), and delayed normalization of fibrinolysis. Micronutrient deficiencies—particularly vitamins K, B12, folate, selenium, zinc, and copper—are common after malabsorptive procedures and contribute to both thrombotic and hemorrhagic complications by impairing antioxidant defenses, endothelial function, and vitamin K-dependent coagulation pathways. Postoperative venous thromboembolism (VTE) incidence ranges from 0.3 to 0.5%, with higher risk after Roux-en-Y gastric bypass than sleeve gastrectomy, while bleeding is primarily associated with vitamin K deficiency, marginal ulcers, and anticoagulant exposure. The findings underscore the interdependence of oxidative stress, nutritional status, and hemostasis after MBS. Individualized thromboprophylaxis, routine detection of micronutrient deficiencies, and long-term biochemical monitoring are essential to maintain hemostatic stability. Standardized redox–hemostasis biomarker panels are needed to clarify mechanistic pathways and improve postoperative preventive strategies. Full article

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

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23 pages, 1460 KB

Open AccessArticle

Potent Nrf2-Inducing C6-Isothiocyanate Glucose Derivatives with Dual Antioxidant and Antitumor Activity

by Luis Alberto Prieto, Nora Khiar-Fernández, Rocío Calderón-Ruiz, Emelyne Giraud, José Manuel Calderón-Montaño, Jesús Lucia-Tamudo, Rafael León, José Antonio Pérez-Simón, Miguel López-Lázaro, Rocío Recio, Elena de la Torre, Victoria Valdivia and Inmaculada Fernández

Antioxidants 2026, 15(1), 123; https://doi.org/10.3390/antiox15010123 - 18 Jan 2026

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Abstract

Isothiocyanates (ITCs) are well-known electrophilic agents with antioxidant and anticancer properties, largely attributed to their ability to activate the Nrf2/ARE pathway. Building on previous work with C1-ITC glycosyl derivatives, we designed and synthesized a new series of S-glycosyl isothiocyanates in which the ITC [...] Read more.

Isothiocyanates (ITCs) are well-known electrophilic agents with antioxidant and anticancer properties, largely attributed to their ability to activate the Nrf2/ARE pathway. Building on previous work with C1-ITC glycosyl derivatives, we designed and synthesized a new series of S-glycosyl isothiocyanates in which the ITC group was repositioned to the C6 carbon of the glucose scaffold. This structural rearrangement yielded stable and synthetically accessible derivatives with markedly enhanced biological profiles. Several compounds showed potent Nrf2 activation at non-cytotoxic concentrations, with CD values comparable to or exceeding those of natural ITCs. In parallel, the new C6-ITC derivatives displayed significant antiproliferative activity against leukemia and solid tumor cell lines. Among them, the phenylsulfone derivative 13 emerged as a particularly promising dual-action molecule, combining strong Nrf2 induction with low-micromolar cytotoxicity. Molecular docking was used as a hypothesis-generating approach and suggested a possible interaction with the STAT3 SH2 domain, although further studies are needed to validate this target. Overall, these results support glucose-based ITCs as a versatile platform for the development of multifunctional antioxidants with complementary anticancer properties. Full article

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

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16 pages, 2923 KB

Open AccessArticle

Functional and Molecular Characterization of Melamine-Induced Disruption of Human Spermatozoa via Oxidative Stress and Apoptotic Pathways: An In Vitro Study

by Francesca Paola Luongo, Eugenia Annunzi, Rosetta Ponchia, Francesca Girolamo, Giuseppe Morgante, Paola Piomboni and Alice Luddi

Antioxidants 2026, 15(1), 122; https://doi.org/10.3390/antiox15010122 - 17 Jan 2026

Viewed by 312

Abstract

Melamine, a nitrogen-rich industrial chemical, has raised increasing concern as an emerging environmental contaminant with potential reproductive toxicity. While its nephrotoxic effects are well established, the direct impact of melamine on human sperm remains poorly defined. In this study, we investigated the in [...] Read more.

Melamine, a nitrogen-rich industrial chemical, has raised increasing concern as an emerging environmental contaminant with potential reproductive toxicity. While its nephrotoxic effects are well established, the direct impact of melamine on human sperm remains poorly defined. In this study, we investigated the in vitro effects of melamine on human sperm, under both capacitating and non-capacitating conditions. Functional analyses revealed that the exposure to 0.8 mM melamine, the highest non-cytotoxic concentration in vitro, significantly compromised sperm motility and disrupted key capacitation processes, including tyrosine phosphorylation patterns, cholesterol efflux, and the acrosome reaction. Molecular assessments demonstrated melamine-induced mitochondrial dysfunction, characterized by COX4I1 downregulation, reduced mitochondrial membrane potential, and altered reactive oxygen species production. In parallel, gene expression analyses revealed the activation of apoptotic pathways, with the upregulation of BAX and downregulation of BCL2, changes that were more pronounced during capacitation. Furthermore, melamine exposure significantly increased sperm DNA fragmentation and denaturation, indicating genotoxic stress. Collectively, these findings demonstrate that even low, non-cytotoxic concentrations of melamine compromise sperm function by disrupting capacitation, mitochondrial activity, and genomic integrity. This study identifies capacitation as a critical window of vulnerability and underscores the need to consider melamine as a potential environmental risk factor for male reproductive health. Full article

(This article belongs to the Special Issue Oxidative Stress and Sperm: Technical, Biological and Clinical Aspects—2nd Edition)

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19 pages, 4673 KB

Open AccessArticle

Reactive Oxygen Species Drive Cell Migration and PD-L1 Expression via YB-1 Phosphorylation in Pleural Mesothelioma

by Muhammad Hashim, Gerald Timelthaler, Dominik Kirchhofer, Beatrice Irina Kudlacek, Berta Mosleh, Katharina Sinn, Ezzat Mohamed Awad, Mir Alireza Hoda, Bettina Grasl-Kraupp, Balazs Dome, Walter Berger, Georg Krupitza, Karin Schelch and Michael Grusch

Antioxidants 2026, 15(1), 121; https://doi.org/10.3390/antiox15010121 - 17 Jan 2026

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Abstract

Reactive oxygen species (ROS)-induced aberrant oncogenic signalling has been proposed to mediate the progression and development of pleural mesothelioma (PM). In this study, we demonstrate how ROS promote oncogenic signalling, especially in the context of cell migration and immune evasion via YB-1 phosphorylation [...] Read more.

Reactive oxygen species (ROS)-induced aberrant oncogenic signalling has been proposed to mediate the progression and development of pleural mesothelioma (PM). In this study, we demonstrate how ROS promote oncogenic signalling, especially in the context of cell migration and immune evasion via YB-1 phosphorylation in mesothelial and PM cell models. Xanthine (X)- and xanthine oxidase (XO)-generated ROS exposure led to increased migration and a more elongated cell shape in mesothelial and PM cells in live-cell videomicroscopy analyses. These effects were associated with the enhanced phosphorylation of ERK, AKT, and YB-1 and the elevated gene expression of PD-L1 and PD-L2, which were analysed with immunoblotting and quantitative real-time RT-PCR, respectively. The pharmacological inhibition of AKT (ipatasertib), MEK (trametinib), and RSK (BI-D1870) resulted in the reversal of ROS-induced effects, with the strongest effects observed upon the inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS-responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune-evasive effects in PM. Full article

(This article belongs to the Special Issue Redox Signaling in Cancer: Mechanisms and Therapeutic Opportunities)

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11 pages, 716 KB

Open AccessPerspective

Microbial Metabolism of Levodopa as an Adjunct Therapeutic Target in Parkinson’s Disease

by Jimmy B. Feix, Gang Cheng, Micael Hardy and Balaraman Kalyanaraman

Antioxidants 2026, 15(1), 120; https://doi.org/10.3390/antiox15010120 - 17 Jan 2026

Viewed by 374

Abstract

Parkinson’s disease is the second leading neurodegenerative disease of aging. For over five decades, oral levodopa has been used to manage the progressive motor deficits that are the hallmark of the disease. However, individual dose requirements are highly variable, and patients typically require [...] Read more.

Parkinson’s disease is the second leading neurodegenerative disease of aging. For over five decades, oral levodopa has been used to manage the progressive motor deficits that are the hallmark of the disease. However, individual dose requirements are highly variable, and patients typically require increased levodopa dosage as the disease progresses, which can cause undesirable side effects. It has become increasingly apparent that the gut microbiome can have a major impact on the metabolism and efficacy of therapeutic drugs. In this Perspective, we examine recent studies highlighting the impact of metabolism by Enterococcus faecalis, a common commensal gut bacterium, on levodopa bioavailability. E. faecalis expresses a highly conserved tyrosine decarboxylase that promiscuously converts levodopa to dopamine in the gut, resulting in decreased neuronal uptake of levodopa and reduced dopamine formation in the brain. Mitochondria-targeted antioxidants conjugated to a triphenylphosphonium moiety have shown promise in transiently suppressing the growth of E. faecalis and decreasing microbial levodopa metabolism, providing an approach to modulating the microbiome that is less perturbing than conventional antibiotics. Thus, mitigating metabolism by the gut microbiota is an attractive therapeutic target to preserve and potentiate the efficacy of oral levodopa therapy in Parkinson’s disease. Full article

(This article belongs to the Special Issue Oxidative Stress and Its Mitigation in Neurodegenerative Disorders)

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