Antioxidants

21 pages, 2776 KB

Open AccessArticle

Sustainable Extraction of Antioxidant Phytocompounds from Yellow Onion Wastes for Value-Added Product Development

by Anca M. Rosca, Adina I. Gavrila, Ioan Calinescu, Christina Zalaru, Mihaela D. Popescu, Alexandra Ene-Manea and Justinian A. Tomescu

Antioxidants 2026, 15(5), 632; https://doi.org/10.3390/antiox15050632 (registering DOI) - 15 May 2026

Abstract

Yellow onion (Allium cepa L.) outer skins are a high-volume agricultural waste that can be converted into commercially valuable bioproducts using various extraction techniques. This research focused on optimizing a green ultrasound-assisted extraction (UAE) method which allows for the isolation of [...] Read more.

Yellow onion (Allium cepa L.) outer skins are a high-volume agricultural waste that can be converted into commercially valuable bioproducts using various extraction techniques. This research focused on optimizing a green ultrasound-assisted extraction (UAE) method which allows for the isolation of several phytochemicals valued for their health benefits, such as polyphenols and flavonoids. HPLC/UV analysis of the extracts showed that the main component was quercetin. A one-factor-at-a-time (OFAT) design was used to identify the extraction parameters needed in order to maximize the amount of extracted target phytochemicals. The polyphenols, flavonoids and quercetin contents, along with the antioxidant activity of the extracts, were optimized by response surface methodology using a Box–Behnken design. Ultrasound amplitude, ethanol concentration, and time were selected as the most appropriate variables. The final results showed that TPC ranged from 78.16 to 97.16 mg GAE/g DM, TFC ranged from 22.77 to 26.46 mg QE/g DM, while CUPRAC values varied between 145.24 and 163.75 mg TE/g DM. The optimal extraction conditions were determined using a Box–Behnken model as 30% ultrasound amplitude, 53% ethanol concentration, and an extraction time of 13 min. The use of these conditions allowed the TPC, TFC and CUPRAC to show predicted values of 97.8 mg GAE/g DM, 27.2 mg QE/g DM, and 159.8 mg TE/g DM, respectively. These findings indicate that onion skin extracts could represent a green and promising source of antioxidant phytochemicals. Full article

24 pages, 2286 KB

Open AccessReview

Antioxidant Protein Hydrolysates and Peptides from Catfish: Enzymatic Production, In Vitro Bioactivity, and Translational Gaps for Functional Foods

by Fai-Chu Wong, Ai-Lin Ooi, Wen-Jie Ng, Fazilah Abd Manan and Tsun-Thai Chai

Antioxidants 2026, 15(5), 631; https://doi.org/10.3390/antiox15050631 (registering DOI) - 15 May 2026

Abstract

Over the past decade, an increasing demand for natural antioxidants has driven research into antioxidant peptides and protein hydrolysates from fish and their processing by-products. Catfishes, especially species like Pangasius and Clarias, generate large amounts of protein-rich by-products, which represent a valuable [...] Read more.

Over the past decade, an increasing demand for natural antioxidants has driven research into antioxidant peptides and protein hydrolysates from fish and their processing by-products. Catfishes, especially species like Pangasius and Clarias, generate large amounts of protein-rich by-products, which represent a valuable bioresource for valorization. This review discusses advances from the past decade in the production, characterization, and antioxidant capacity of protein hydrolysates and peptides that have been discovered from catfish muscle and by-products. This review emphasizes enzymatic hydrolysis strategies, using Alcalase and other commercial and by-product-derived proteases. Potent antioxidant fractions, particularly those with low molecular weight (<3 kDa) and rich in hydrophobic/aromatic amino acids, have been obtained from the hydrolysates. Mechanisms of antioxidant action, which include hydrogen atom transfer and electron transfer, are discussed in this review, along with the efficacy of catfish-derived antioxidant peptides and protein hydrolysates as demonstrated in chemical and in vivo models. Applications in food systems, such as emulsion-type sausages, have shown potential for shelf-life extension. Nevertheless, knowledge gaps remain, which include an over-dependence on in vitro assays, limited identification of antioxidant peptide sequences, and insufficient data on sensory properties, intestinal permeability, bioavailability, and stability under food processing conditions. Future work should prioritize proteomic characterization, cellular validation, flavor-masking strategies, and scalable production protocols to accelerate the application of catfish protein hydrolysates as viable natural antioxidants for the functional food industry. Full article

(This article belongs to the Special Issue Antioxidant Properties and Applications of Food By-Products—2nd Edition)

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15 pages, 1468 KB

Open AccessArticle

Septic Cardiac Remodeling: A New Concept in Cardiac Dysfunction Induced by Experimental Sepsis

by Nayane Maria Vieira, Letycia Netto de Paula Cunha, Carolina Rodrigues Tonon, Marina Gaiato Monte, Paola da Silva Ballin, Natália Fernanda Ferreira, Dijon Henrique Salomé de Campos, Camila Renata Correa, Gilson Masahiro Murata, Paulo Eduardo Martins Ribolla, Diego Peres Alonso, Taline Lazzarin, Paula Schmidt Azevedo, Bertha Furlan Polegato, Sergio Alberto Rupp de Paiva, Marina Politi Okoshi, Katashi Okoshi, Camila Molina Soares, Maria Cláudia Irigoyen, Marcos Ferreira Minicucci and Leonardo Zornoff Show full author list Hide full author list

Antioxidants 2026, 15(5), 630; https://doi.org/10.3390/antiox15050630 (registering DOI) - 15 May 2026

Abstract

Septic cardiomyopathy is recognized as an acute, transient, and reversible condition. However, septic insult may induce latent changes characteristic of cardiac remodeling, with future consequences. Therefore, the present study aimed to evaluate the morphological and functional cardiac changes in the acute and subacute [...] Read more.

Septic cardiomyopathy is recognized as an acute, transient, and reversible condition. However, septic insult may induce latent changes characteristic of cardiac remodeling, with future consequences. Therefore, the present study aimed to evaluate the morphological and functional cardiac changes in the acute and subacute phases (with 7-day follow-up) in male Wistar rats subjected to experimental sepsis using a cecal ligation and puncture (CLP) model. In the acute phase, the animals underwent echocardiographic assessment at baseline and 48 h after the induction of sepsis. In the subacute 7 days follow-up, animals were allocated in control and sepsis groups. After this period, the animals underwent echocardiographic assessment, followed by euthanasia, papillary muscle testing, and subsequent morphometric and biochemical analyses. Fecal samples from six animals per group were collected at baseline and after 7 days for microbiota analysis. In the acute phase, echocardiographic assessment revealed that, following sepsis, animals exhibited reduced systolic function. In the subacute 7 days follow-up, both echocardiogram and papillary muscles revealed cardiac dysfunction in the sepsis group. Cardiomyocyte cross-sectional area and collagen content were significantly greater in the sepsis group compared with that in the control group. Analysis of maximal enzymatic activities involved in cardiac energy metabolism and oxidative stress biomarkers revealed no significant differences between groups. Considering microbiota assessment, beta diversity analysis revealed significant differences between septic animals and controls. In conclusion, sepsis was associated with persistent systolic/diastolic dysfunction, cardiomyocyte hypertrophy, and fibrosis after 7 days. These data suggest that septic cardiomyopathy should not be considered merely an acute, transient, and reversible condition in this experimental context. Full article

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19 pages, 1201 KB

Open AccessReview

Phyllobilins: Emerging Bioactive Chlorophyll Metabolites and Their Potential Impact on Human Health

by María del Rosario Serra, Antonio Pérez-Gálvez and María Roca

Antioxidants 2026, 15(5), 629; https://doi.org/10.3390/antiox15050629 (registering DOI) - 15 May 2026

Abstract

Phyllobilins are chlorophyll metabolites that belong to bilin-type linear tetrapyrroles. Chlorophyll, the omnipresent green pigment from algae to higher plants, is essential for life on Earth, underscoring the significance of its metabolites among phytochemicals. Once largely overlooked, phyllobilins are now gaining recognition for [...] Read more.

Phyllobilins are chlorophyll metabolites that belong to bilin-type linear tetrapyrroles. Chlorophyll, the omnipresent green pigment from algae to higher plants, is essential for life on Earth, underscoring the significance of its metabolites among phytochemicals. Once largely overlooked, phyllobilins are now gaining recognition for their widespread presence in the human diet through the consumption of fruits and vegetables. This, together with their favorable bioavailability, has heightened the importance of elucidating their bioactive properties. Numerous studies have demonstrated their antioxidant and anticancer activities in vitro, as well as their ability to target actin. The anti-inflammatory effects of phyllobilins have also been demonstrated by evaluating their ability to inhibit the COX-2 pathway or attenuate the activation of the tryptophan–kynurenine pathway. The objective of this review is to highlight the value of phyllobilins by compiling current knowledge, with a particular emphasis on their bioactivity and potential impact on human health. Full article

(This article belongs to the Special Issue Next-Generation Insights into Anthocyanins and Phytopigments: Bioactivity, Bioavailability, and Health Impacts)

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16 pages, 2169 KB

Open AccessArticle

Thiourea-Based H₂S-Releasing Pramipexole Hybrids as Neuroprotective Agents

by Angela Corvino, Valentina Citi, Antonia Scognamiglio, Alma Martelli, Vincenzo Calderone, Giulia Neggiani, Carmela Fimognari, Ferdinando Fiorino, Elisa Magli, Rosa Sparaco, Vincenzo Santagada, Giuseppe Caliendo and Beatrice Severino

Antioxidants 2026, 15(5), 628; https://doi.org/10.3390/antiox15050628 (registering DOI) - 15 May 2026

Abstract

Multitarget hybrid molecules are a promising strategy for treating complex neurodegenerative disorders such as Parkinson’s disease (PD), where dopaminergic dysfunction, oxidative stress, neuroinflammation, and cellular senescence coexist and drive disease progression. Here, we developed pramipexole-derived hydrogen sulfide (H₂S)-releasing hybrids using, for [...] Read more.

Multitarget hybrid molecules are a promising strategy for treating complex neurodegenerative disorders such as Parkinson’s disease (PD), where dopaminergic dysfunction, oxidative stress, neuroinflammation, and cellular senescence coexist and drive disease progression. Here, we developed pramipexole-derived hydrogen sulfide (H₂S)-releasing hybrids using, for the first time, a thiourea moiety as an H₂S-donating linker to extend the therapeutic profile of pramipexole beyond dopamine receptor agonism. The hybrids were synthesized and characterized, and their H₂S-releasing properties were assessed by amperometric and intracellular detection assays. Among the series, compound 2e (PRAM-ADA) showed the most efficient and sustained H₂S release, indicating a favorable thiol-dependent release profile. PRAM-ADA was further evaluated for antioxidant and anti-senescent activities in BV2 microglial cells, as well as for chemical and enzymatic stability under simulated physiological conditions. The hybrid significantly reduced LPS-induced reactive oxygen species accumulation and attenuated oxidative stress–induced cellular senescence, demonstrating a superior cytoprotective profile compared with pramipexole. These findings support the concept that combining dopaminergic activity with controlled H₂S donation enhances antioxidant and anti-senescent responses, indicating their potential as multitarget agents with neuroprotective properties relevant to neurodegenerative disorders, including PD. Full article

(This article belongs to the Special Issue Hydrogen Sulfide, Reactive Sulfur Species, and Donor Compounds: Natural and Synthetic Tools for Physiology and Disease)

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37 pages, 2545 KB

Open AccessSystematic Review

Mega-Events, Air Pollution and Health Outcomes: A Systematic Review

by Hiba El Khattaby, Marco Panizzolo, Federica Ghelli, Samar El Sherbiny, Valeria Bellisario, Nicoletta Colombi, Roberto Bono and Giulia Squillacioti

Antioxidants 2026, 15(5), 627; https://doi.org/10.3390/antiox15050627 (registering DOI) - 14 May 2026

Abstract

Air pollution represents a public health threat; it is co-responsible for millions of premature deaths annually and economic losses. Mega-events create abrupt changes in air pollution providing quasi-experimental settings to investigate related health impacts. This systematic review synthesizes the evidence on air pollution [...] Read more.

Air pollution represents a public health threat; it is co-responsible for millions of premature deaths annually and economic losses. Mega-events create abrupt changes in air pollution providing quasi-experimental settings to investigate related health impacts. This systematic review synthesizes the evidence on air pollution level changes during mega-events and associated short-term health effects, including mortality, hospitalizations and early biological responses. A literature search was conducted in PubMed, Embase, Scopus and Web of Science up to 7 April 2025. Study quality was evaluated using the EPHPP Quality Assessment Tool for Quantitative Studies. Thirty-one studies met the inclusion criteria. Mega-events without effective air pollution control measures were associated with increased pollutant levels and higher risks of respiratory and cardiovascular morbidity. Biomarker studies demonstrated rapid and reversible changes in oxidative stress and inflammatory biomarkers in response to short-term variations in air pollution. Instead, significant reductions in air pollution during mega-events were observed upon emission control measures. The evidence is predominantly from Asian countries, no Europe/Africa studies and only one from North America, limiting generalizability. Findings indicate that mega-events may influence air quality which affects human health, reinforcing the value of temporary emission control measures strategies for future mega-events. The systematic review was registered with Prospero (CRD420251032553). Full article

(This article belongs to the Special Issue Oxidative Stress from Environmental Exposures)

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16 pages, 3892 KB

Open AccessReview

Sialic Acids in Kidney Disease: Immune Regulation, Complement Activation and Glomerular Injury

by Agnese Spennacchio, Gianluca Caridi, Carolina Bigatti, Gabriele Gaggero, Katia Mazzocco, Maria Teresa Gambaudo, Roberta Musso, Valerio Gaetano Vellone, Andrea Angeletti and Xhuliana Kajana

Antioxidants 2026, 15(5), 626; https://doi.org/10.3390/antiox15050626 (registering DOI) - 14 May 2026

Abstract

Oxidative stress and inflammation are key drivers of kidney injury and disease progression. In this context, the role of sialic acids emerged as a critical regulatory layer linking redox imbalance, immune activation, and tissue damage. Sialic acids are terminal negatively charged residues that [...] Read more.

Oxidative stress and inflammation are key drivers of kidney injury and disease progression. In this context, the role of sialic acids emerged as a critical regulatory layer linking redox imbalance, immune activation, and tissue damage. Sialic acids are terminal negatively charged residues that regulate complement activity, immune cell signaling, and the structural integrity of the glomerular filtration barrier. Alterations in sialylation, resulting from impaired biosynthesis or increased sialidase activity, disrupt immune homeostasis, enhance inflammatory responses, and promote complement-mediated injury. In the kidney, these mechanisms contribute to podocyte dysfunction, glomerular inflammation, and fibrosis and are implicated in glomerulopathies, transplantation, and plasma cell dyscrasias. Emerging evidence also highlights the therapeutic potential of targeting sialic acid metabolism through inhibition of desialylation or restoration of sialylation pathways. Overall, sialic acids represent dynamic modulators at the intersection of oxidative stress and immunity, offering novel opportunities for biomarker development and mechanism-based therapies in kidney disease. Full article

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

15 pages, 2085 KB

Open AccessArticle

Reevaluation of Physical and Chemical Singlet Oxygen Quenching Efficiency of Antioxidants via a Specific Methanol-Soluble Trap

by Dongkun Zhao, Xin Wang, Lijuan Wang, Qing Ma, Jingwen Li, Baocheng Xu, Xinjing Dou and Lili Liu

Antioxidants 2026, 15(5), 625; https://doi.org/10.3390/antiox15050625 (registering DOI) - 14 May 2026

Abstract

Furfuryl alcohol (FFA), a methanol-soluble and highly specific compound for singlet oxygen (¹O₂), was used as a ¹O₂ trapping agent to reevaluate physical and chemical ¹O₂ quenching efficiency of five antioxidants, namely α-tocopherol, butylated hydroxyanisole [...] Read more.

Furfuryl alcohol (FFA), a methanol-soluble and highly specific compound for singlet oxygen (¹O₂), was used as a ¹O₂ trapping agent to reevaluate physical and chemical ¹O₂ quenching efficiency of five antioxidants, namely α-tocopherol, butylated hydroxyanisole (BHA), tert-butylhydroquinone (TBHQ), epigallocatechin gallate (EGCG), and quercetin. The total ¹O₂ quenching rate constants of α-tocopherol, BHA, TBHQ, EGCG, and quercetin were 2.0 (±0.1) × 10⁹, 1.1 (±0.1) × 10⁸, 5.6 (±0.3) × 10⁸, 4.1 (±0.1) × 10⁸, and 2.2 (±0.1) × 10⁸ M⁻¹s⁻¹, respectively. The chemical quenching rate constants of α-tocopherol, BHA, TBHQ, EGCG, and quercetin were 1.4 × 10⁷, 2.0 × 10⁶, 7.7 × 10⁶, 2.0 × 10⁷, and 7.9 × 10⁶ M⁻¹s⁻¹, respectively. The percentages of chemical quenching in total ¹O₂ quenching were 0.7%, 1.8%, 1.4%, 4.8%, and 3.6% for α-tocopherol, BHA, TBHQ, EGCG, and quercetin, respectively, indicating that the five antioxidants quenched ¹O₂ almost exclusively by a physical quenching mechanism. This is the first report on the ¹O₂ quenching mechanism of quercetin in methanol solvent. The results of this study will provide theoretical guidance for the application of antioxidants to inhibit edible oil or fat-containing food from photooxidation. Full article

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

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30 pages, 2299 KB

Open AccessArticle

Integrated Structural, Physiological, and Molecular Assessment of Sugar Beet Infested by Scrobipalpa ocellatella Under Field Conditions

by Ildikó Jócsák, Ádám Csóka, Tamás Donkó, György Végvári, Bálint Gerbovits, Ferenc Csima and Sándor Keszthelyi

Antioxidants 2026, 15(5), 624; https://doi.org/10.3390/antiox15050624 (registering DOI) - 14 May 2026

Abstract

Background: The beet moth, Scrobipalpa ocellatella Boyd, 1858 (Lep.: Gelechiidae), is an increasingly important pest whose climate-driven expansion threatens sugar beet (Beta vulgaris L.) production in Europe. This study aimed to characterize the structural, physiological, biochemical, and molecular responses of sugar beet [...] Read more.

Background: The beet moth, Scrobipalpa ocellatella Boyd, 1858 (Lep.: Gelechiidae), is an increasingly important pest whose climate-driven expansion threatens sugar beet (Beta vulgaris L.) production in Europe. This study aimed to characterize the structural, physiological, biochemical, and molecular responses of sugar beet to infestation. Methods: Plants were analysed using computed tomography (CT), SPAD and NDVI measurements, HPLC-based sugar analysis, FRAP and MDA assays, and RT-qPCR of antioxidant-related genes. Results: CT imaging enabled non-destructive detection of larvae (mean length: 7.32 ± 0.73 mm) and pest-induced cavities (982.20 ± 316.04 mm³). SPAD did not differ significantly among treatments, whereas NDVI was consistently reduced in infested plants, declining from 0.648 ± 0.031 in non-infested plants to 0.593 ± 0.038 in infested-treated plants and 0.611 ± 0.021 in infested-untreated plants at the first sampling. Infestation induced pronounced oxidative stress, with FRAP increasing from 14.102 ± 0.943 to 25.471 ± 0.922 µg AA eq g⁻¹ FW and MDA from 558.065 ± 21.819 to 1325.806 ± 16.762 nmol g⁻¹ FW in untreated infested plants. Antioxidant gene expression was significantly upregulated, particularly for SOD, CAT, APX, DHAR, MDAR, and GPX. Conclusions: S. ocellatella infestation triggered coordinated oxidative stress responses in sugar beet, while CT and NDVI proved useful for early damage detection. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defense in Crop Plants, 3rd Edition)

19 pages, 2169 KB

Open AccessArticle

Combined Supplementation of Live Yeast and Yeast Postbiotics Enhances Antioxidant Capacity and Intestinal Health in Weaned Piglets

by Xiangshi Luo, Pingping Xu, Shukai Cao, Zhengcheng Zeng, Shupeng Wang, Hao Zhang, Tadele Kiros and Shuai Zhang

Antioxidants 2026, 15(5), 623; https://doi.org/10.3390/antiox15050623 (registering DOI) - 14 May 2026

Abstract

Weanling piglets, with immature immune system and physiological functions, often experience post-weaning diarrhea. This study investigated the effects of combined supplementation of live yeast and yeast postbiotics on the growth performance, antioxidant capacity and intestinal health of weaned piglets. A total of 224 [...] Read more.

Weanling piglets, with immature immune system and physiological functions, often experience post-weaning diarrhea. This study investigated the effects of combined supplementation of live yeast and yeast postbiotics on the growth performance, antioxidant capacity and intestinal health of weaned piglets. A total of 224 weaned piglets (22 days old) were randomly assigned to four groups: a basal diet (CON) or the same diet supplemented with 1600 ppm zinc oxide (ZnO), high-dose live yeast and yeast postbiotics (LYYP-H), or low-dose live yeast and yeast postbiotics (LYYP-L). The trial lasted 28 days, with diets divided into 2 phases. The results showed that dietary combined supplementation with live yeast and yeast postbiotics did not significantly affect the average daily gain (ADG), average daily feed intake (ADFI), or the diarrhea rate (p > 0.05). However, dietary combined supplementation with live yeast and yeast postbiotics significantly enhanced fecal consistency in piglets (p < 0.05). Moreover, dietary combined supplementation with live yeast and yeast postbiotics significantly improved representative antioxidant indices, notably superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and strengthened immune capabilities; additionally, a marked improvement in intestinal morphology was observed (p < 0.05). In conclusion, the combination of live yeast and yeast postbiotics can improve antioxidant capacity and intestinal health and show the potential to replace high doses of ZnO during the first two weeks post-weaning. Full article

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

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25 pages, 4451 KB

Open AccessReview

Exercise Improves Mitochondrial Homeostasis: A Potential Neuroprotective Strategy for Ischemic Stroke

by Wenyan Bo, Qingxiang Guo, Wanyu Zhu and Yixuan Ma

Antioxidants 2026, 15(5), 622; https://doi.org/10.3390/antiox15050622 (registering DOI) - 14 May 2026

Abstract

Regular exercise and physical activity are beneficial in reducing the risk and progression of ischemic stroke. However, the underlying physiological mechanisms by which exercise confers these protective effects remain incompletely understood. Disruption of mitochondrial homeostasis is key contributors to the pathophysiology of ischemic [...] Read more.

Regular exercise and physical activity are beneficial in reducing the risk and progression of ischemic stroke. However, the underlying physiological mechanisms by which exercise confers these protective effects remain incompletely understood. Disruption of mitochondrial homeostasis is key contributors to the pathophysiology of ischemic stroke. Exercise training effectively attenuates the onset and progression of ischemic stroke by significantly maintaining mitochondrial homeostasis, including improving mitochondrial biogenesis, balancing mitochondrial dynamics, maintaining mitochondrial redox, promoting mitophagy and mitochondrial transport. This review systematically summarizes the beneficial effects of exercise in the context of ischemic stroke and highlights the critical link between mitochondrial homeostasis disruption and stroke pathology. By providing a detailed analysis of the underlying molecular mechanisms, this study offers novel insights into exercise-based therapeutic strategies for ischemic stroke. Full article

(This article belongs to the Special Issue Redox Signaling in Chronic Diseases)

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39 pages, 3111 KB

Open AccessReview

Natural Small Molecules Targeting Oxidative Stress and Redox Homeostasis in Aging: Mechanisms and Therapeutic Potential

by Yu Li, Haodong Wu, Zeyi Zhang, Mingshan Wang, Yue Zhao and Huimin Sun

Antioxidants 2026, 15(5), 621; https://doi.org/10.3390/antiox15050621 (registering DOI) - 14 May 2026

Abstract

The global population is ageing rapidly; adults aged ≥ 60 years are projected to exceed 2 billion by 2050. Ageing is a major risk factor for chronic and degenerative disorders and is increasingly viewed as a modifiable biological program. Oxidative stress is a [...] Read more.

The global population is ageing rapidly; adults aged ≥ 60 years are projected to exceed 2 billion by 2050. Ageing is a major risk factor for chronic and degenerative disorders and is increasingly viewed as a modifiable biological program. Oxidative stress is a central driver: sustained ROS/RNS accumulation damages lipids, proteins and nucleic acids and amplifies mitochondrial dysfunction, inflammaging, cellular senescence, impaired autophagy and telomere instability. Targeting these shared mechanisms may therefore deliver multi-disease benefits beyond single-disease therapy. Medicinal plants provide chemically defined monomers that can act as direct antioxidants and, more importantly, restore redox homeostasis by modulating conserved signaling axes, including Nrf2/FOXO/SIRT1, AMPK/mTOR and NF-κB. However, the current evidence base remains highly heterogeneous, and reliable clinical validation is still limited. In this review, we summarize studies published over the last decade on medicinal plant-derived monomers with reported anti-ageing relevance in the context of oxidative stress and redox homeostasis. We compare major redox-centered pathways, molecular targets, model systems, and outcome measures, and evaluate the evidence with attention to its strength, consistency, and translational relevance. Particular emphasis is placed on current limitations, including model dependence, variable bioavailability, uncertain dose–exposure relationships, and the lack of well-designed clinical studies. These considerations are intended to provide a more cautious and evidence-based framework for future mechanistic and translational research. Full article

(This article belongs to the Collection Advances in Antioxidant Ingredients from Natural Products)

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2 pages, 135 KB

Open AccessCorrection

Correction: Gao et al. Camellia japonica Flower Extract and the Active Constituent Hyperoside Repair DNA Damage Through FUNDC1-Mediated Mitophagy Pathway for Skin Anti-Aging. Antioxidants 2025, 14, 968

by Hongqi Gao, Jiahui Shi, Guangtao Li, Zhifang Lai, Yan Liu, Chanling Yuan and Wenjie Mei

Antioxidants 2026, 15(5), 620; https://doi.org/10.3390/antiox15050620 (registering DOI) - 14 May 2026

Abstract

In the original publication [...] Full article

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

26 pages, 19554 KB

Open AccessReview

Regulation of Amino Acid Transporters by Cell Surface Receptors

by Chiara Brignola, Myrhiam Cassese, Stefano Marrone, Teresa Esposito, Vincenza Barresi, Gabriella Esposito, Daniele Filippo Condorelli, Rosario Ammendola and Fabio Cattaneo

Antioxidants 2026, 15(5), 619; https://doi.org/10.3390/antiox15050619 (registering DOI) - 14 May 2026

Abstract

Cancer progression is closely linked to the enhanced uptake of extracellular amino acids, mediated by specific transporters that support biosynthesis, metabolic activity, and energy production through the tricarboxylic acid cycle. By increasing the expression of these transporters, tumor cells secure a continuous amino [...] Read more.

Cancer progression is closely linked to the enhanced uptake of extracellular amino acids, mediated by specific transporters that support biosynthesis, metabolic activity, and energy production through the tricarboxylic acid cycle. By increasing the expression of these transporters, tumor cells secure a continuous amino acid supply that sustains the proliferation, metabolic balance, and activation of major signaling pathways. While most studies have emphasized post-translational control of amino acid transporters, such as phosphorylation, ubiquitination, glycosylation, and palmitoylation, emerging evidence highlights regulatory crosstalk between these transporters and other membrane proteins, including G protein-coupled receptors and receptor tyrosine kinases. This review summarizes the current literature on the receptor-mediated mechanisms governing amino acid uptake and explores how interactions among families of membrane proteins contribute to the regulation of transporter activity. Full article

(This article belongs to the Special Issue Roles of NADPH Oxidase in Modulation of Signal Transduction and Cellular Metabolism—2nd Edition)

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22 pages, 2332 KB

Open AccessArticle

Regulation of Ferroptosis Sensitivity in Hepatocellular Carcinoma Cells by Lysosomal Ion Channels TPC2 and TRPML1

by Franz Geisslinger, Victoria Gell, Finja Witt, Dawid Jaślan, Christian Grimm, Andreas Koeberle and Karin Bartel

Antioxidants 2026, 15(5), 618; https://doi.org/10.3390/antiox15050618 (registering DOI) - 13 May 2026

Abstract

Ferroptosis is an iron-dependent, lipid peroxidation–driven form of regulated cell death that has emerged as a therapeutic vulnerability in hepatocellular carcinoma (HCC), yet the contribution of lysosomes to this process remains incompletely understood. In this study, we investigated whether lysosomal ion channels regulate [...] Read more.

Ferroptosis is an iron-dependent, lipid peroxidation–driven form of regulated cell death that has emerged as a therapeutic vulnerability in hepatocellular carcinoma (HCC), yet the contribution of lysosomes to this process remains incompletely understood. In this study, we investigated whether lysosomal ion channels regulate ferroptosis sensitivity in HCC cells, focusing on the two-pore channel 2 (TPC2) and the transient receptor potential mucolipin 1 (TRPML1). Using pharmacological modulation, genetic knockout models, flow cytometry-based cell death and lipid peroxidation assays, lipidomics, calcium measurements, and molecular analyses across multiple HCC cell lines, we examined how these channels influence ferroptotic signaling. We show that NAADP-dependent TPC2 activity is required for efficient ferroptosis induction, whereas TPC2 loss renders HCC cells resistant to ferroptosis triggered by system Xc⁻ inhibition or glutathione peroxidase 4 (GPX4)blockade. This resistance is associated with reduced lipid peroxidation, altered calcium signaling, and selective depletion of polyunsaturated phosphatidylethanolamine species linked to decreased Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) expression. In contrast, TRPML1 deficiency sensitizes cells to ferroptosis and correlates with enhanced endoplasmic reticulum stress and oxidative imbalance rather than major lipid remodeling. Collectively, these findings identify lysosomal ion channels as key modulators of ferroptosis in HCC and highlight distinct mechanisms by which TPC2 and TRPML1 regulate cellular redox balance and death susceptibility. Full article

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

19 pages, 305 KB

Open AccessReview

Recent Advances in Exosome-Based Therapeutic Strategies for Acute Lung Injury: Mechanisms and Translational Advances

by Joon-Ha Song, Hye-Ryun Kim, Dong-Ha Song, Su-Min Jin, Won-Jae Ko, Jinbong Park, Ki-Eun Hwang and Yohan Han

Antioxidants 2026, 15(5), 617; https://doi.org/10.3390/antiox15050617 (registering DOI) - 13 May 2026

Abstract

Inflammatory lung diseases are characterized by complex immune dysregulation and structural tissue damage, demanding the development of novel therapeutic and diagnostic strategies. Exosomes (Exos) have emerged as promising alternatives to address these challenges by serving as key mediators and effective therapeutic nanocarriers. This [...] Read more.

Inflammatory lung diseases are characterized by complex immune dysregulation and structural tissue damage, demanding the development of novel therapeutic and diagnostic strategies. Exosomes (Exos) have emerged as promising alternatives to address these challenges by serving as key mediators and effective therapeutic nanocarriers. This review systematically analyzes the multifunctional roles of Exos derived from various sources, including immune cells, mesenchymal stem cells (MSCs), lung structural cells, and non-mammalian sources such as plants and milk, in the context of inflammatory lung diseases. These vesicles modulate critical pathological processes, such as macrophage polarization, oxidative stress, and programmed cell death, by delivering functional cargos, including miRNAs and proteins. Studies demonstrating the antioxidant properties of Exos are classified, and their roles in attenuating oxidative stress-mediated lung injury are discussed. Furthermore, engineering and priming strategies, as well as airway-directed delivery methods such as nebulization, are reported to enhance therapeutic efficacy and targeting. Evidence also indicates that plant-derived Exos could be scalable and safer alternatives to mammalian cell-derived Exos. Collectively, Exos represent a next-generation platform for precision medicine, functioning as potent therapeutic agents and efficient drug-delivery systems for the treatment of complex inflammatory lung diseases. Full article

(This article belongs to the Special Issue Therapeutic Potential of Natural Antioxidants in Respiratory Diseases and Airway Inflammation)

20 pages, 4137 KB

Open AccessArticle

3D Reactive Oxygen Species Dosimetry in Pleural Photodynamic Therapy: Integration of Macroscopic Kinetic Modeling and Deformable Registration

by Hongjing Sun, Michele M. Kim, Andreea Dimofte, Sunil Singhal, Keith A. Cengel and Timothy C. Zhu

Antioxidants 2026, 15(5), 616; https://doi.org/10.3390/antiox15050616 (registering DOI) - 13 May 2026

Abstract

Photodynamic therapy (PDT) is a promising treatment for pleural malignancies, yet accurate dosimetry remains challenging due to complex cavity geometries and the need to protect surrounding critical structures. The reactive oxygen species ([ROS]_rx) generated during treatment serve as a direct predictor [...] Read more.

Photodynamic therapy (PDT) is a promising treatment for pleural malignancies, yet accurate dosimetry remains challenging due to complex cavity geometries and the need to protect surrounding critical structures. The reactive oxygen species ([ROS]_rx) generated during treatment serve as a direct predictor of therapeutic efficacy. We developed a finite element model using COMSOL Multiphysics to simulate macroscopic photophysical kinetics, using clinical data inputs, including light fluence derived from a navigation system and patient-specific photosensitizer concentrations. Crucially, we integrated a deformable image registration framework to align intra-operative navigation data with pre-treatment CT scans, enabling the calculation of [ROS]_rx dose accumulation in critical Organs at Risk (OARs), such as the lung, heart, and esophagus. The model successfully reconstructed 3D [ROS]_rx distributions for multiple clinical cases. Point-to-point comparison at 32 detector locations across ten patients showed strong agreement between COMSOL-simulated and clinically calculated [ROS]_rx (mean percentage difference 0.6 ± 5.8%), while volume-averaged values differed by −6.0%, reflecting the enhanced spatial coverage of the 3D model relative to discrete sampling. The two-stage deformable registration improved CT-to-navigation surface alignment from HD95 = 4.08 mm to 1.78 mm (56.4% reduction) and MSD = 1.77 mm to 0.68 mm (61.5% reduction), enabling the first patient-specific mapping of [ROS]_rx onto OAR structures. This study demonstrates the feasibility of a comprehensive 3D dosimetry system for pleural PDT. By integrating kinetic modeling with deformable registration, we provide a robust platform for evaluating treatment efficacy and ensuring OAR safety, paving the way for eventual integration into treatment planning and real-time feedback. Full article

(This article belongs to the Special Issue Reactive Oxygen Species and Growth Factors in Photodynamic Therapy (PDT), Photobiomodulation (PBM), and Radiation Therapy (RT)—2nd Edition)

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38 pages, 491 KB

Open AccessReview

Antioxidant, Anti-Inflammatory and Anticancer Peptides from Extreme Marine Environments

by Muhammad Zakariya, Eleonora Montuori, Gwendoline Kopp, Alessandro Coppola, Daniela Giordano, Stefano Bruno and Chiara Lauritano

Antioxidants 2026, 15(5), 615; https://doi.org/10.3390/antiox15050615 (registering DOI) - 13 May 2026

Abstract

Marine organisms have proven to be excellent sources of bioactive natural products with potential therapeutic applications. To date, seventeen marine-derived molecules are on the market for the treatment of human diseases, mainly cancer. While multiple bioactivities of marine compounds have been consecutively reported, [...] Read more.

Marine organisms have proven to be excellent sources of bioactive natural products with potential therapeutic applications. To date, seventeen marine-derived molecules are on the market for the treatment of human diseases, mainly cancer. While multiple bioactivities of marine compounds have been consecutively reported, peptides represent promising candidates for these applications. This review focuses on peptides from marine organisms living in extreme marine environments, such as the deep ocean, polar regions, and tropical ecosystems. These are particularly promising for further bioprospecting, since their distinctive conditions have driven the evolution of unique biomolecules, as well as unique stability profile that can improve efficacy, shelf life, and performance under a wide range of industrial conditions. Ziconotide (Prialt), a neurotoxic peptide derived from the venom of a marine snail (Conus sp.) found at depths greater than 1000 m, is already commercially available for the treatment of severe pain. Recent technologies and computational tools are speeding up the discovery of new peptides and enzymes (very few from extreme environments). Overall, the review reports about eight peptides with anticancer properties from deep environments, nine, two and seven from polar habitats with antioxidants, anti-inflammatory and anticancer properties, respectively, and approximately ninety peptides from tropical waters (five antioxidant, thirty-five anti-inflammatory and fifty-four anticancer peptides). However, future studies in extreme environments will need to develop and apply sampling technologies, cultivation systems, as well as methods to assess efficacy, side effects and mechanisms of action, in vitro and in vivo. Full article

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

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28 pages, 7388 KB

Open AccessArticle

Isoliquiritigenin, a Bioactive Blood Component Derived from Licorice, Activates Nrf2 Enzymes to Confer Protection Against Radiation-Induced Nerve Injury

by Juan Yao, Jiaqi Ma, Huanhuan Lin, Changxin Shao, Xuefeng Liu and Xiaojie Jin

Antioxidants 2026, 15(5), 614; https://doi.org/10.3390/antiox15050614 (registering DOI) - 13 May 2026

Abstract

Licorice is a traditional Chinese medicine; however, its bioactive constituents and specific molecular mechanisms responsible for protecting against radiation-induced brain injury remain poorly elucidated. Oxidative stress overactivation acts as the core pathological mechanism underlying radiation-triggered neuronal injury. This study aimed to investigate the [...] Read more.

Licorice is a traditional Chinese medicine; however, its bioactive constituents and specific molecular mechanisms responsible for protecting against radiation-induced brain injury remain poorly elucidated. Oxidative stress overactivation acts as the core pathological mechanism underlying radiation-triggered neuronal injury. This study aimed to investigate the neuroprotective effect and underlying mechanism of isoliquiritigenin (ISL), a major blood-absorbed component of licorice, against radiation-induced neural injury in C57BL/6J mice via the Keap1-Nrf2 signaling pathway. Molecular docking and MST analysis verified the strong binding affinity of ISL to Keap1. In vitro, ISL restored the viability of X-ray-irradiated PC12 cells; reduced LDH release and intracellular ROS accumulation; and enhanced SOD1 activity, GSH content, and T-AOC levels. Moreover, ISL upregulated the expression of antioxidant-related genes and induced Nrf2 nuclear translocation. In vivo, oral ISL administration ameliorated radiation-induced cognitive impairment, improved spatial learning and memory, alleviated hippocampal neuronal loss, and increased cerebral cortical Nrf2 expression in C57BL/6J mice. In conclusion, ISL alleviates radiation-induced neuronal injury by suppressing oxidative stress and activating the Keap1-Nrf2 signaling pathway, thus representing a promising therapeutic agent for the prevention and treatment of radiation brain injury. Full article

(This article belongs to the Special Issue Inhibition of Oxidative Stress and Related Signaling Pathways in Neuroprotection—3rd Edition)

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