Antioxidants

21 pages, 2066 KB

Open AccessArticle

Antioxidants Trolox and Methazolamide Protect Microvascular Endothelial Cells from Oxidative Damage Induced by Sporadic and Familial Forms of Oligomeric Amyloid-β

by Maria Luisa Valle, Bitseat Getaneh, Christopher William, Jorge Ghiso and Agueda Rostagno

Antioxidants 2025, 14(11), 1375; https://doi.org/10.3390/antiox14111375 (registering DOI) - 19 Nov 2025

Abstract

Cerebral amyloid angiopathy (CAA), present in more than 90% of Alzheimer’s disease (AD) cases, associates with focal ischemia and neurovascular dysfunction. Genetic variants at positions 21–23 of amyloid beta (Aβ), among them the Dutch mutation (AβE22Q), are primarily linked to CAA and the [...] Read more.

Cerebral amyloid angiopathy (CAA), present in more than 90% of Alzheimer’s disease (AD) cases, associates with focal ischemia and neurovascular dysfunction. Genetic variants at positions 21–23 of amyloid beta (Aβ), among them the Dutch mutation (AβE22Q), are primarily linked to CAA and the development of cerebral hemorrhages. An important contributor to CAA pathogenesis is the dysregulation of mitochondria-mediated pathways with concomitant induction of oxidative stress. Using biochemical assays and immunofluorescence microscopy, this work demonstrates the exacerbated formation of reactive oxygen species (ROS) in human brain microvascular endothelial cells after short exposure to soluble oligomers of synthetic homologues of Aβ1-42 and the Dutch variant, inducing lipid peroxidation and protein carbonylation, both markers of oxidative stress. The heterogeneity of the soluble oligomeric assemblies inducing this oxidative response was highlighted by their reactivity with two conformational antibodies recognizing specific and mutually exclusive epitopes associated with either soluble prefibrillar oligomers or soluble fibrillar oligomers. Treatment with the multitarget antioxidants Trolox and methazolamide significantly attenuated the Aβ-mediated ROS production and reduced oxidative stress markers to basal levels. Our data highlight the damaging role of heterogeneous Aβ oligomers and the preventing effect of antioxidants, suggesting ROS modulation as a complementary therapeutic strategy to preserve neurovascular unit integrity. 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, 4809 KB

Open AccessSystematic Review

The Nephroprotective Effects of Alpha-Mangostin for Acute Kidney Injury: A Systematic Review and Meta-Analysis

by Moragot Chatatikun, Aman Tedasen, Ratana Netphakdee, Jitbanjong Tangpong, Phichayut Phinyo, Pakpoom Wongyikul, Fumitaka Kawakami, Makoto Kubo, Motoki Imai, Wiyada Kwanhian Klangbud and Atthaphong Phongphithakchai

Antioxidants 2025, 14(11), 1374; https://doi.org/10.3390/antiox14111374 (registering DOI) - 19 Nov 2025

Abstract

Acute kidney injury (AKI) is characterized by rapid loss of renal function due to oxidative stress, inflammation, and apoptosis, with limited targeted therapies. Alpha-mangostin (AM), a natural compound from Garcinia mangostana, exhibits antioxidant and anti-inflammatory properties in preclinical studies, but its efficacy [...] Read more.

Acute kidney injury (AKI) is characterized by rapid loss of renal function due to oxidative stress, inflammation, and apoptosis, with limited targeted therapies. Alpha-mangostin (AM), a natural compound from Garcinia mangostana, exhibits antioxidant and anti-inflammatory properties in preclinical studies, but its efficacy in AKI has not been reviewed. This systematic review and meta-analysis, registered on the Open Science Framework and adhering to PRISMA guidelines, analyzed in vivo and in vitro studies on AM’s effects in AKI models through searches of PubMed, Scopus, Embase, and Web of Science. Primary outcomes included serum creatinine and cell viability, while secondary outcomes encompassed oxidative stress markers (malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS)), inflammatory cytokines, apoptosis indicators, and histopathology. Data were extracted independently and assessed using the Toxicological Data Reliability Assessment Tool (ToxRTool). AM significantly reduced serum creatinine (mean difference (MD) = −0.67 mg/dL; 95% confidence interval (CI): −1.28 to −0.06; p = 0.03) and improved cell viability (MD = 28.26%; 95% CI: 17.25 to 39.26; p < 0.0001). It markedly decreased MDA and ROS, increased GSH, and enhanced antioxidant enzymes (glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD)). In vivo, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were lowered, and histopathology showed reduced tubular necrosis and structural damage. Subgroup analyses indicated dose- and model-dependent effects, with lower doses often yielding greater benefits. Sensitivity analyses confirmed robustness despite heterogeneity. Preclinical evidence supports AM’s nephroprotective potential and underscores the need for dose optimization, mechanistic validation, and clinical translation. Full article

(This article belongs to the Special Issue Potential Health Benefits of Dietary Antioxidants)

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21 pages, 3552 KB

Open AccessArticle

Ferroptosis Enhances T Lymphocyte Infiltration into Glioblastoma Spheroids

by Anna Schwantes, Yara Shadid, Vanesa Maria Guerrero Ruiz, Blerina Aliraj, Anja Wickert, Megan A. Palmer, Sofie P. Meyer, Andreas Weigert, Bernhard Brüne and Dominik C. Fuhrmann

Antioxidants 2025, 14(11), 1373; https://doi.org/10.3390/antiox14111373 - 19 Nov 2025

Abstract

Glioblastoma is one of the most aggressive and therapeutically challenging brain tumors. It is characterized by a highly immunosuppressive tumor microenvironment and poor prognosis, requiring novel treatment strategies. Along this line, ferroptosis has been proposed. To study the impact of ferroptosis on glioblastoma [...] Read more.

Glioblastoma is one of the most aggressive and therapeutically challenging brain tumors. It is characterized by a highly immunosuppressive tumor microenvironment and poor prognosis, requiring novel treatment strategies. Along this line, ferroptosis has been proposed. To study the impact of ferroptosis on glioblastoma cells and immune cell infiltration, we established a spheroid model using LN229 glioblastoma cells and verified ferroptosis by measuring lipid peroxidation and RNA expression of ferroptosis-related genes. We then co-cultured spheroids with human peripheral blood mononuclear cells to follow the infiltration of distinct immune cell subsets by flow cytometry and immunohistochemistry. T lymphocyte infiltration into ferroptotic spheroids compared to control spheroids became apparent with the notion that ferroptotic cells attracted T cells more efficiently compared to apoptotic or necrotic cells. Mechanistically, ferroptotic glioblastoma spheroids released high amounts of ATP, which caused T cell attraction, while ATP deprivation reduced this effect. Ferroptosis appears to be an interesting therapy approach but might need co-treatments to ensure proper T cell activation. Full article

(This article belongs to the Special Issue Lipid Peroxidation and Cancer)

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Graphical abstract

38 pages, 504 KB

Open AccessReview

Factors Influencing the Biological Effects of FLASH Irradiation

by Sergey Igorevich Glukhov, Elena Ananievna Kuznetsova and Sergey Vsevolodovich Akulinichev

Antioxidants 2025, 14(11), 1372; https://doi.org/10.3390/antiox14111372 - 19 Nov 2025

Abstract

Among the methods for increasing the specificity of tumor radiotherapy, FLASH radiotherapy (FLASH-RT) stands out, having recently entered clinical trials. A distinctive feature of this treatment method is the delivery of a therapeutic dose in a fraction of a second with a typical [...] Read more.

Among the methods for increasing the specificity of tumor radiotherapy, FLASH radiotherapy (FLASH-RT) stands out, having recently entered clinical trials. A distinctive feature of this treatment method is the delivery of a therapeutic dose in a fraction of a second with a typical mean dose rate greater than 40 Gy/s. In addition to improved patient comfort and a shorter hospital stay, this therapy potentially carries a lower risk of radiation-related side effects due to reduced damage to normal tissues. Numerous preclinical and in vivo laboratory trials of FLASH-RT have demonstrated that, in addition to reducing the severity of radiation-related complications, FLASH radiotherapy has antitumor efficacy similar to conventional radiotherapy. Partly reduced radiotoxicity after such a dose rate delivery obtained, in a broader radiobiological sense, an eponymous term FLASH effect. Although the first clinical trials aimed to evaluate the safety and efficiency of FLASH-RT against bone metastases (FAST-01/02), melanoma skin metastases (IMPulse, Flash-Skin I), Squamous Cell Carcinoma, or Basal Cell Carcinoma (LANCE) have already started or even finished and showed promising results (FAST-01), the radiobiological basis of the FLASH effect is far from a complete explanation. The fundamental factors explaining the nature of the FLASH effect are mainly considered to be the following: (1) changes in the balance of water radiolysis products and a decrease in the generation of stable reactive oxygen species (ROS), (2) differential oxygen depletion, depending on the initial oxygen concentration in tissues, and (3) physiological and metabolic, gene expression and probably epigenetic shifts in response to irradiation in normal and tumor cells. The main purpose of this review is the systematization of the radiobiological manifestations of the FLASH effect together with a consideration of the elementary processes laying in the basis of the FLASH effect in order to actualize rationale and future application developments of FLASH-RT. Full article

(This article belongs to the Special Issue Oxidative Stress, Antioxidants, and Mechanisms in FLASH Radiotherapy)

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20 pages, 1544 KB

Open AccessArticle

Phenolic Fingerprints of Spanish Olive Mill Wastewaters (Alpechin): A Step Toward Regional Valorization Through Antioxidant Recovery

by Sergio Martínez-Terol, Emilia Ferrer, Pedro V. Martínez-Culebras, Houda Berrada, Noelia Pallarés, Jose Saez-Tovar, Luciano Orden, María R. Martínez-Gallardo, Ana J. Toribio and Francisco J. Barba

Antioxidants 2025, 14(11), 1371; https://doi.org/10.3390/antiox14111371 - 18 Nov 2025

Abstract

Olive mill wastewater (OMW), a by-product of olive oil extraction, poses significant environmental challenges due to its toxicity and heterogeneity. This study evaluates the phenolic and mineral composition of OMW and alpechin sludges from abandoned ponds in Spain, and establishes a standardized conventional [...] Read more.

Olive mill wastewater (OMW), a by-product of olive oil extraction, poses significant environmental challenges due to its toxicity and heterogeneity. This study evaluates the phenolic and mineral composition of OMW and alpechin sludges from abandoned ponds in Spain, and establishes a standardized conventional method to recover phenolic fractions and promote their safe valorization as bioactive ingredients. Phenolic compounds were identified by triple-TOF-LC-MS/MS, and minerals and heavy metals were quantified by ICP-MS. Across thirteen ponds analyzed, samples from Cordoba, Tarragona, Alicante and Toledo showed higher phenolic levels, ranging from 7.2 g GAE/kg to 18.9 g GAE/kg, with methanolic extracts reaching 10.98–15.67 mg GAE/mL. Thirty-one phenolic compounds were identified, predominantly luteolin, apigenin, quercetin, and secoiridoid derivatives, notably hydroxytyrosol and tyrosol, supporting their functional potential as natural antioxidants. The mineral profile was dominated by K and Ca and showed negligible carryover to the phenolic organic fraction (<1%). Heavy metal concentrations in fresh OMW were 0.32–1.06 µg/kg for Cd and Hg and 9–43.9 µg/kg for As and Pb. In OMW sludge, they ranged between 0.033 and 0.19 mg/kg for Cd, 0.01 and 0.12 mg/kg for Hg, 5.45 and 8.06 mg/kg for As, and 4.45 and 23.70 mg/kg for Pb, whereas phenolic extracts contained only 0.15–21.50 µg/kg, remaining below EU food safety limits. This work presents one of the first integrated approaches to risk-benefit mapping of abandoned ponds in Spanish soils and advances extraction standardization by jointly considering functional potential, contaminant profiles, and matrix location. Full article

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

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2 pages, 288 KB

Open AccessCorrection

Correction: Giresha et al. Sinapic Acid Inhibits Group IIA Secretory Phospholipase A₂ and Its Inflammatory Response in Mice. Antioxidants 2022, 11, 1251

by Aladahalli S. Giresha, Deepadarshan Urs, Sophiya Pundalik, Rajkumar S. Meti, Siddanakoppalu N. Pramod, Ballenahalli H. Supreetha, Madhusudana Somegowda, Kattepura K. Dharmappa, Ahmed M. El-Shehawi, Sarah Albogami, Mona M. Elseehy, Abdullah Alaklabi, Hosam O. Elansary, Alanoud Omur A. Mehder and Eman A. Mahmoud

Antioxidants 2025, 14(11), 1370; https://doi.org/10.3390/antiox14111370 - 18 Nov 2025

Abstract

In the published paper [...] Full article

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

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22 pages, 1263 KB

Open AccessSystematic Review

Curcumin in the Treatment of Kidney Disease: A Systematic Review with a Focus on Drug Interactions

by Ebenezer Ofori-Attah, Abigail Aning and Layla Simón

Antioxidants 2025, 14(11), 1369; https://doi.org/10.3390/antiox14111369 - 18 Nov 2025

Abstract

Kidney disease (KD) is a major health challenge, affecting millions of people worldwide, highlighting the need for improved prevention and management strategies. The pathophysiological mechanisms converged on a common pathway characterized by inflammation, oxidative stress, fibrosis, nephron loss and failure. Curcumin, the active [...] Read more.

Kidney disease (KD) is a major health challenge, affecting millions of people worldwide, highlighting the need for improved prevention and management strategies. The pathophysiological mechanisms converged on a common pathway characterized by inflammation, oxidative stress, fibrosis, nephron loss and failure. Curcumin, the active compound derived from turmeric (Curcuma longa), attracts considerable interest as a potential therapy for KD due to its anti-inflammatory, antioxidant and anti-fibrotic properties. Despite the benefits of curcumin, co-administration with kidney medications may cause drug interactions. Here, we systematically reviewed the efficacy of curcumin in alleviating KD and its safety when used with conventional treatments. Search terms included: curcumin AND (“diabetic nephropathy” OR “renal disease” OR “kidney disease”). Data on mechanisms of action, redox status, clinical benefits, side effects, and drug interactions were extracted and analyzed. Curcumin reduces oxidative stress, inflammation, apoptosis, fibrosis, ER stress, and lipid and glucose metabolism. Curcumin has multifaceted nephroprotective effects, while it is safe and well-tolerated. The curcumin–drug interactions reviewed were: -piperine, -epigallocatechin gallate, -losartan, -ginkgolide B, -rosuvastatin, -insulin, -cilostazol, and -ginger. These interactions improve curcumin bioavailability, and synergistic anti-inflammatory/antioxidant/antifibrotic and renoprotective effects. Future research should prioritize large-scale clinical trials to evaluate the efficacy and safety of curcumin in diverse KD populations. Full article

(This article belongs to the Special Issue Selected Papers from the 2nd International Electronic Conference on Antioxidants (IECAN2025))

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17 pages, 1060 KB

Open AccessArticle

Phytochemical Screening and Biological Activity of Female and Male Cones from Pinus nigra subsp. laricio (Poir.) Maire

by Mary Fucile, Carmine Lupia, Martina Armentano, Mariangela Marrelli, Ekaterina Kozuharova, Giancarlo Statti and Filomena Conforti

Antioxidants 2025, 14(11), 1368; https://doi.org/10.3390/antiox14111368 - 18 Nov 2025

Abstract

The Corsican pine (Pinus nigra subsp. laricio (Poir.) Maire), a subspecies of black pine endemic to southern Italy, is widely known for the quality of its valuable timber, and the parts of the plant that are not used for this purpose are [...] Read more.

The Corsican pine (Pinus nigra subsp. laricio (Poir.) Maire), a subspecies of black pine endemic to southern Italy, is widely known for the quality of its valuable timber, and the parts of the plant that are not used for this purpose are considered unusable production waste. In this study, we investigated the phytochemical profile and a series of biological activities of extracts from the female and male pine cones. The extracts were prepared by maceration with ethanol and subsequently fractionated using liquid-liquid separation. The total phenolic and flavonoid content, antioxidant potential (DPPH and β-carotene bleaching tests), anti-inflammatory activity (nitric oxide inhibition in RAW 264.7 cells), and enzymatic inhibition against pancreatic lipase and α-amylase were determined. The female cones showed a higher crude extract yield and total phenolic content (76.4 mg GAE/g) than the male cones, while the latter were richer in flavonoids. The extracts from the female cones showed higher antioxidant and pancreatic lipase inhibitory activities. On the contrary, extracts from male cones showed greater activity against α-amylase, with the dichloromethane fraction proving to be the most potent (IC₅₀ = 35.28 ± 3.08 µg/mL). The hexane fraction of female cones also showed significant anti-inflammatory activity (IC₅₀ = 107.50 ± 15.22 µg/mL). Our results reveal that the pine cones of Pinus nigra subsp. laricio (Poir.) Maire are a rich source of bioactive compounds. These results provide the first scientific evidence of the potential of extracts from this still poorly studied part of the plant for further investigation of their antioxidant and anti-inflammatory capabilities. Full article

(This article belongs to the Special Issue Plants and Plant-Based By-Products as Valuable Sources of Antioxidants: Current Tendencies and Achievements in Their Exploitation)

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17 pages, 1912 KB

Open AccessArticle

Resveratrol–Curcumin Hybrid Selectively Induces Chromosomal Abnormalities and Apoptosis in Colon Adenocarcinoma Cells

by Mariane Minussi Baptistella, Aléxia Polo Siqueira, Dâmaris Lizia Santos Magalhães, Bruno Zavan, Carolina Sales de Oliveira, Matheus de Freitas Silva, Ellen Tardelli Falleiros Lima, Claúdio Viegas, Jr., Bruno Martins Dala-Paula, Ester Siqueira Caixeta, Marisa Ionta and Pollyanna Francielli de Oliveira

Antioxidants 2025, 14(11), 1367; https://doi.org/10.3390/antiox14111367 - 17 Nov 2025

Abstract

Colorectal cancer (CRC) therapy frequently relies on chemotherapeutic agents with high cytotoxicity, low selectivity, and suboptimal efficacy. Thus, the search for alternative therapeutic strategies for CRC continues. In the present work, the antitumor potential of a hybrid compound, which contains fragments derived from [...] Read more.

Colorectal cancer (CRC) therapy frequently relies on chemotherapeutic agents with high cytotoxicity, low selectivity, and suboptimal efficacy. Thus, the search for alternative therapeutic strategies for CRC continues. In the present work, the antitumor potential of a hybrid compound, which contains fragments derived from resveratrol and curcumin, was evaluated. These natural compounds are known by their antioxidant, chemopreventive, and chemotherapeutic properties. Different methodologic approaches were used to investigate cytotoxic, genotoxic, antiproliferative, and antioxidant effects of a hybrid compound, named PQM-162, on HCT-8 colorectal cancer cells. The results showed that PQM-162 displays radical scavenging capacity as demonstrated by DPPH assay. Furthermore, this substance reduced cell viability and inhibited cell cycle progression at G2/M in HCT-8 cells. Antiproliferative activity of PQM-162 was associated with its ability to modulate the expression of critical regulators of G2/M transition and mitosis progression such as PLK1, AURKB, and CDKN1A. Taken together, our data indicate that PQM-162 is a promising antitumor agent due to its disruption of the redox balance in cancer cells and its modulation of the expression of regulators of the cell cycle and mitotic apparatus. Full article

(This article belongs to the Special Issue Therapeutic Potential of Bioactive Substances in Oxidative Stress-Induced Carcinogenesis)

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17 pages, 6186 KB

Open AccessArticle

5-Hydroxymethylfurfural Alleviates Lipopolysaccharide-Induced Depression-like Behaviors by Suppressing Hypothalamic Oxidative Stress and Regulating Neuroinflammation in Mice

by Bailiu Ya, Haiyan Yin, Lili Yuan, Aihong Jing, Yuxuan Li, Fenglian Yan, Hui Zhang, Huabao Xiong and Mingsheng Zhao

Antioxidants 2025, 14(11), 1366; https://doi.org/10.3390/antiox14111366 - 17 Nov 2025

Abstract

5-hydroxymethylfurfural (5-HMF) has been shown to exert neuroprotective effects in a global cerebral ischemia mouse model in our previous study, where it demonstrated antioxidant and anti-inflammatory properties. However, studies on its antidepressant mechanisms remain scarce. Since oxidative stress and neuroinflammation are closely associated [...] Read more.

5-hydroxymethylfurfural (5-HMF) has been shown to exert neuroprotective effects in a global cerebral ischemia mouse model in our previous study, where it demonstrated antioxidant and anti-inflammatory properties. However, studies on its antidepressant mechanisms remain scarce. Since oxidative stress and neuroinflammation are closely associated with depression, this study investigated the antidepressant effects of 5-HMF, focusing on its potential inhibition of oxidative stress via the Nrf2 pathway and its role in microglial M1 polarization-mediated neuroinflammation. An acute depression mouse model induced by intraperitoneal injection of lipopolysaccharide (LPS) was utilized. Mice received 5-HMF (12 mg/kg) or an equal volume of vehicle via intraperitoneal injection 30 min prior to and 5 min after LPS administration. At 24 h post-modeling, behavioral tests (sucrose preference, forced swim, and open field tests) were conducted to evaluate the antidepressant effect of 5-HMF. Histological damage in the hypothalamus was assessed using Nissl staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Immunofluorescence was performed to evaluate M1 polarization of hypothalamic microglia. Oxidative stress damage was assessed by measuring malondialdehyde (MDA), carbonyl groups, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. Nrf2 DNA-binding activity was examined using an ELISA-based assay. The expression of inflammatory cytokines, Nrf2, and downstream antioxidant proteins was analyzed by ELISA kits and Western blotting. 5-HMF significantly alleviated LPS-induced depression-like behaviors, reduced hypothalamic neuronal damage, decreased oxidative stress, and inhibited microglial M1 polarization. It also regulated the expression of inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-4, and IL-10) and activated the Nrf2 signaling pathway, enhancing nuclear translocation efficiency. Notably, these effects were significantly attenuated by the Nrf2 inhibitor brusatol. In conclusion, 5-HMF exerts neuroprotective effects by modulating Nrf2-mediated oxidative stress responses and suppressing microglial M1 polarization-driven neuroinflammation. These findings suggest that 5-HMF may provide therapeutic potential for alleviating depression symptoms induced by acute inflammation. Full article

(This article belongs to the Special Issue Bioactive Compounds: Antioxidant, Antibacterial, Anti-inflammatory Modulation)

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12 pages, 503 KB

Open AccessEditorial

Redox Homeostasis in Poultry/Animal Production

by Peter F. Surai, Anton Surai and Katie Earle-Payne

Antioxidants 2025, 14(11), 1365; https://doi.org/10.3390/antiox14111365 - 17 Nov 2025

Abstract

Commercial animal/poultry production is associated with a range of stresses, including physiological, environmental, technological, nutritional, and internal/immunological stresses [...] Full article

(This article belongs to the Special Issue Redox Homeostasis in Poultry/Animal Production)

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28 pages, 3155 KB

Open AccessReview

Dual-Target Insight into Drug Discovery from Natural Products as Modulators of GLP-1 and the TXNIP–Thioredoxin Antioxidant System in Metabolic Syndrome

by Peter Chinedu Agu, Appolonia Fulgence Yudas and Jun Lu

Antioxidants 2025, 14(11), 1364; https://doi.org/10.3390/antiox14111364 - 17 Nov 2025

Abstract

Metabolic Syndrome (MetS), a cluster of interconnected metabolic abnormalities, poses a growing global health burden. A well-established therapeutic target for the diseases is the incretin hormone glucagon-like peptide-1 (GLP-1); however, synthetic agonists have drawbacks such as expense, injectable administration, and side effects. Concurrently, [...] Read more.

Metabolic Syndrome (MetS), a cluster of interconnected metabolic abnormalities, poses a growing global health burden. A well-established therapeutic target for the diseases is the incretin hormone glucagon-like peptide-1 (GLP-1); however, synthetic agonists have drawbacks such as expense, injectable administration, and side effects. Concurrently, one of the main pathogenic characteristics of MetS is oxidative stress, in which the Thioredoxin-Interacting Protein (TXNIP)/thioredoxin system is a critical player. The strong evidence that natural compounds derived from plant, marine, and microbiological sources can simultaneously target the TXNIP–thioredoxin antioxidant axis and GLP-1 signaling is examined in this study. These substances can limit TXNIP expression and increase thioredoxin activity while also stimulating GLP-1 secretion, inhibiting dipeptidyl peptidase-4 (DPP-4), or acting as GLP-1 receptor agonists. A cycle of reinforcement is created by these two actions: Pancreatic β-cell activity and incretin responsiveness are improved by GLP-1-mediated TXNIP downregulation, which also strengthens antioxidant defense. However, translational development must overcome major pharmacological obstacles, especially those related to bioavailability, metabolic stability, and standardization, despite encouraging preclinical effectiveness. To speed up this translational process, integrative computational techniques (such as molecular docking, network pharmacology, and artificial intelligence) are strong tools for lead optimization and creation of hypothesis. Thus, natural products can provide a special chance to discover multi-target treatments that comprehensively address the oxidative and hormonal causes of MetS. Full article

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

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18 pages, 1059 KB

Open AccessArticle

Enhancing Stallion Semen Cryopreservation: Selected Antioxidant Extracts and Sperm Freezability

by Raffaele Boni, Raffaella Ruggiero, Felisia De Luca, Graziano Preziosi, Maria Antonietta Ferrara, Angela Ostuni, Simone Guerriero, Alessandra Gallo, Carola Murano and Stefano Cecchini Gualandi

Antioxidants 2025, 14(11), 1363; https://doi.org/10.3390/antiox14111363 - 16 Nov 2025

Abstract

Cryopreservation of equine semen remains challenging due to pronounced individual variability in cryotolerance. Because freezing induces oxidative stress and spermatozoa are particularly susceptible to such damage, this study aimed to comparatively evaluate the effects of natural extracts from nutraceutical compounds with high antioxidant [...] Read more.

Cryopreservation of equine semen remains challenging due to pronounced individual variability in cryotolerance. Because freezing induces oxidative stress and spermatozoa are particularly susceptible to such damage, this study aimed to comparatively evaluate the effects of natural extracts from nutraceutical compounds with high antioxidant activity, specifically matcha, spirulina, and horseradish, as well as quercetin, a well-known antioxidant molecule. These compounds were added to the freezing extender, and semen from 12 Salernitano stallions (48 ejaculates in total) was analyzed. Several parameters were assessed, including sperm kinetics, bioenergetics, oxidative and nitrosative stress markers, and the sperm DNA fragmentation index, both before and after cryopreservation. Neither the natural extracts nor quercetin significantly improved sperm freezability, likely due to the high degree of inter-individual variability. Stallion age also had a significant effect on nearly all the parameters evaluated, although no significant interactions were observed between age and treatment for any of the sperm quality traits. In conclusion, supplementation of the freezing extender with matcha, spirulina, horseradish extracts, or quercetin did not significantly enhance stallion semen cryopreservation outcomes. Conversely, stallion age and individual variability had a marked effect on sperm cryotolerance, highlighting the need for customized and holistic strategies to optimize cryotolerance in individual stallions. Full article

(This article belongs to the Special Issue Oxidative and Nitrosative Stress in Male Reproduction)

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17 pages, 3383 KB

Open AccessReview

Dysfunction of the ABCA1 and ABCG1 Transporters and Their Impact on HDL Metabolism

by Kevin David Laguna-Maldonado, Daniel Uribe-Ramírez, Melissa Vázquez-Carrada, Deyamira Matuz-Mares and María Magdalena Vilchis-Landeros

Antioxidants 2025, 14(11), 1362; https://doi.org/10.3390/antiox14111362 - 14 Nov 2025

Abstract

High-density lipoprotein (HDL) metabolism depends on several key factors, including ATP-binding cassette (ABC) transporters such as ABCA1 and ABCG1. These transporters are essential for maintaining cholesterol homeostasis by mediating the efflux of cellular lipids and promoting HDL formation and maturation. Dysfunction in these [...] Read more.

High-density lipoprotein (HDL) metabolism depends on several key factors, including ATP-binding cassette (ABC) transporters such as ABCA1 and ABCG1. These transporters are essential for maintaining cholesterol homeostasis by mediating the efflux of cellular lipids and promoting HDL formation and maturation. Dysfunction in these pathways compromises HDL biogenesis, leading to lipid accumulation in macrophages and peripheral cells. Together with oxidized low-density lipoproteins (LDLs), these alterations promote foam cell formation, atherosclerotic plaque development, and the progression of cardiovascular and metabolic diseases. Oxidative stress plays a central role in disturbing lipid balance and impairing ABC transporter activity. Unlike previous reviews that have mainly summarized mechanisms of oxidative regulation, this work integrates recent molecular findings to propose a unifying framework in which oxidative stress sequentially disrupts ABCA1 and ABCG1 function, thereby altering HDL metabolism. Moreover, it highlights emerging pharmacological strategies aimed at restoring cholesterol homeostasis and mitigating oxidative damage, contributing to the prevention of cardiovascular and metabolic disorders. Full article

(This article belongs to the Special Issue Prevention of Atherosclerosis and of Low-Density Lipoprotein Oxidation: Role of Dietary Antioxidant Compounds and Altered Redox Pathways. A Commemorative Special Issue in Honour of Professor Stanley Omaye)

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22 pages, 5732 KB

Open AccessArticle

Exploring the Cytotoxic and Redox-Modulatory Effects of Nanoceria in MCF7 Breast Cancer Cells Using Integrated Molecular and Proteomic Analyses

by Rukhsana Gul, Hicham Benabdelkamel, Mushtaq Ahmad Dar, Arwa Bazighifan, Afshan Masood, Salini Scaria Joy, Ousman Mahmood Ousman and Assim A. Alfadda

Antioxidants 2025, 14(11), 1361; https://doi.org/10.3390/antiox14111361 - 14 Nov 2025

Abstract

Background: Cerium oxide nanoparticles (nanoceria) have attracted growing attention as promising anticancer agents due to their unique redox properties. Their selective cytotoxicity in cancer cells is thought to be mediated primarily through disruption of redox homeostasis. However, the precise molecular mechanisms underlying their [...] Read more.

Background: Cerium oxide nanoparticles (nanoceria) have attracted growing attention as promising anticancer agents due to their unique redox properties. Their selective cytotoxicity in cancer cells is thought to be mediated primarily through disruption of redox homeostasis. However, the precise molecular mechanisms underlying their action in breast cancer remain unclear. To address this gap, the present study investigates the dose-dependent cytotoxic, oxidative, and mitochondrial effects of nanoceria in MCF7 breast cancer cells, with mechanistic insights gained through gene expression and proteomic analyses. Methods: MCF7 breast cancer cells were treated with nanoceria (200 µg/mL and 400 µg/mL). Cytotoxicity, ROS levels, and mitochondrial membrane potential were assessed via MTT, DCFDA staining, and MitoTracker, respectively. Gene expression and label-free LC-MS/MS proteomics were used to evaluate molecular and pathway-level changes. Results: Nanoceria exhibited dose-dependent cytotoxicity, significantly reducing MCF7 cell viability to 61 ± 1.5% (p < 0.01) and 57 ± 1.8% (p < 0.01) at 200 µg/mL and 400 µg/mL, respectively, compared with the control. ROS levels increased 1.4-fold (p < 0.01) and 1.5-fold (p < 0.0001), accompanied by a decreased mitochondrial membrane potential by 11% (p < 0.01) and 25% (p < 0.05), indicating oxidative stress and mitochondrial dysfunction. Gene expression analysis supported activation of apoptotic pathways demonstrated by upregulation of BNIP3, the BAX/BCL-2 ratio (p < 0.05), and disruption of mitochondrial homeostasis. Proteomic profiling revealed dose-specific alterations in >150 proteins (fold change ≥ 1.5, p < 0.05) related to redox balance, mitochondrial function, apoptosis, and cell cycle regulation. Conclusions: Nanoceria induces dose-dependent oxidative stress and mitochondrial dysfunction in MCF7 breast cancer cells, triggering apoptotic pathways and widespread alterations in protein expression. These results offer valuable mechanistic insights into nanoceria’s selective anticancer activity and highlight its potential as a promising therapeutic agent for breast cancer. Full article

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

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16 pages, 3392 KB

Open AccessArticle

CoQ10-Supported HIIT Modulates Skeletal Muscle and Hippocampal Biomarkers in Rats: A Randomized, Repeated-Measures, Post-Test Controlled Design

by Büşra Yılmaz, Ömer Şenel, Ayşen Çalıkuşu, Elif Gülçiçek Abbasoğlu, Yavuz Yasul, Elvan Anadol, Fatih Sarısoy, Kerem Atalar, Meltem Bahçelioğlu and Canan Yılmaz

Antioxidants 2025, 14(11), 1360; https://doi.org/10.3390/antiox14111360 - 14 Nov 2025

Abstract

This study examined how coenzyme Q10-supported high-intensity interval training (HIIT) influences plasma lactate threshold, skeletal muscle oxidative capacity, circulating irisin and corticosterone, and hippocampal brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) levels in rats. Forty-eight male Sprague Dawley rats (8 [...] Read more.

This study examined how coenzyme Q10-supported high-intensity interval training (HIIT) influences plasma lactate threshold, skeletal muscle oxidative capacity, circulating irisin and corticosterone, and hippocampal brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) levels in rats. Forty-eight male Sprague Dawley rats (8 weeks old; 250.4 ± 11.2 g) were randomized into four groups: control (C), coenzyme Q10 (Supp), HIIT, and HIIT with coenzyme Q10 (HIITsupp). HIIT was performed five days per week on a treadmill following a four-stage familiarization. Coenzyme Q10 (5 mg/kg/day) was given by gavage 30 min before HIIT during weeks II–IV. Plasma lactate threshold, corticosterone, irisin, and citrate synthase (CS) activity were measured by ELISA, while hippocampal BDNF and GFAP were analyzed by both ELISA and immunohistochemistry. The HIITsupp group showed greater muscle mass, CS activity, plasma irisin, and hippocampal BDNF, along with lower GFAP and lactate threshold than the C, Supp, and HIIT groups. The Supp group had the lowest corticosterone, while the HIIT group maintained the highest lactate threshold before supplementation. Principal Component Analysis (PCA) indicated distinct clustering, with the C group closely associated with GFAP and corticosterone, whereas the HIITsupp group aligned with oxidative and neurotrophic markers. Coenzyme Q10-supported HIIT improved muscle oxidative capacity, lowered lactate, and modulated corticosterone, GFAP, and hippocampal BDNF, indicating integrated metabolic and neurobiological adaptations. Full article

(This article belongs to the Special Issue Unveiling the Essential Role of Coenzyme Q in Health)

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19 pages, 9057 KB

Open AccessArticle

Dynamic Characterization of Antioxidant-Related, Non-Volatile, and Volatile Metabolite Profiles of Cherry Tomato During Ripening

by Zhimiao Li, Sihui Guan, Rongqing Wang, Meiying Ruan, Qingjing Ye, Zhuping Yao, Chenxu Liu, Hongjian Wan, Guozhi Zhou and Yuan Cheng

Antioxidants 2025, 14(11), 1359; https://doi.org/10.3390/antiox14111359 - 13 Nov 2025

Abstract

Cherry tomato is a notable dietary source of metabolites associated with antioxidant functions. However, how ripening reshapes primary, specialized, and volatile metabolites remains incompletely resolved. Green-ripe and red-ripe fruits were comparatively analyzed using targeted HPLC assays for quality indices and vitamins, UPLC–MS/MS for [...] Read more.

Cherry tomato is a notable dietary source of metabolites associated with antioxidant functions. However, how ripening reshapes primary, specialized, and volatile metabolites remains incompletely resolved. Green-ripe and red-ripe fruits were comparatively analyzed using targeted HPLC assays for quality indices and vitamins, UPLC–MS/MS for non-volatile metabolites, and HS-SPME–GC–MS for volatiles. Ripening was accompanied by a pronounced accumulation of lycopene and an increase in soluble solids, reflecting a shift of sugars toward glucose and fructose while sucrose remained low. Organic acids declined overall, with citric acid remaining predominant. The free-amino-acid pool expanded, with redistribution from GABA toward glutamate and aspartate. Vitamins exhibited stage-dependent patterns; antioxidant-related vitamins (A, E, and C) were higher at the red-ripe stage, indicating a compositional enhancement relevant to nutritional quality. Non-volatile metabolomics revealed 618 differentially accumulated metabolites, with phenolic acids, flavonoids, alkaloids, amino acids, and lipids as major classes. Phenolic acids and flavonols, dominated by hydroxycinnamoyl-quinic acids and quercetin/kaempferol glycosides, accumulated at the red-ripe stage, whereas steroidal glycoalkaloids decreased, suggesting conversion away from bitter or anti-nutritional constituents. GC–MS profiling identified 788 volatiles, with esters, terpenoids, and ketones contributing more than half of the volatilome. Ripening favored fruity–floral odorants such as β-ionone and (5Z)-octa-1,5-dien-3-one, while reducing green-leaf aldehydes. These stage-specific shifts in metabolite composition jointly define the sensory and nutritional maturation of cherry tomato. The identified metabolite markers provide a foundation for evaluating fruit maturity and guiding breeding toward improved quality attributes. Full article

(This article belongs to the Special Issue Bioactive Compounds in Functional Foods and Their Role in Combating Oxidative Stress)

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17 pages, 11041 KB

Open AccessArticle

In Vivo and In Vitro Antioxidant Effects of Arthrospira platensis Polysaccharide Component 1 (PAP-1)

by Haifeng Yuan, Yuheng Wei, Zhaoyuan He, Xinrui Wang, Xiaoli Yu, Qiuhua Wang, Meiling Yu and Tingjun Hu

Antioxidants 2025, 14(11), 1358; https://doi.org/10.3390/antiox14111358 - 13 Nov 2025

Abstract

Arthrospira platensis polysaccharide component 1 (PAP-1), a purified polysaccharide monomer isolated from Arthrospira platensis, exhibits pronounced antioxidant activity. To investigate the in vivo and in vitro regulatory effects of PAP-1 on antioxidant enzyme activities and inflammatory mediators in mice and RAW264.7 cells, [...] Read more.

Arthrospira platensis polysaccharide component 1 (PAP-1), a purified polysaccharide monomer isolated from Arthrospira platensis, exhibits pronounced antioxidant activity. To investigate the in vivo and in vitro regulatory effects of PAP-1 on antioxidant enzyme activities and inflammatory mediators in mice and RAW264.7 cells, the mice were administered PAP-1 by gavage, and the cells were cultured with PAP-1. Subsequently, serum, lung, spleen, and thymus tissues from mice, as well as the cultured RAW264.7 cells, were collected for analysis using RNA sequencing, commercial assay kits, immunohistochemistry, RT-qPCR, and Western blotting. The results demonstrated that PAP-1 significantly reduced the levels of oxidative stress-related indicators (NO, iNOS, MDA, MPO, and XOD), while markedly enhancing the activities of antioxidant enzymes (SOD, CAT, and GSH-Px) (p < 0.05), a trend consistently observed in both in vivo and in vitro experiments. Furthermore, PAP-1 upregulated the expression of key antioxidant genes and proteins, including HO-1, NQO1, GCLM, p62, Prdx1, and SLC7A11. Collectively, these findings indicate that PAP-1 exerts regulatory antioxidant effects in mice and RAW264.7 cells by enhancing antioxidant enzyme activity and suppressing oxidative stress responses, underscoring its potential as a natural antioxidant agent. Full article

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

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22 pages, 5615 KB

Open AccessArticle

Dietary Antioxidants Influence IER5 Activation and DNA Repair: Implications for Radioprotection and Healthy Aging

by Petr Novotný, Ivana Laknerová, Milan Jakubek and Jana Petrusová

Antioxidants 2025, 14(11), 1357; https://doi.org/10.3390/antiox14111357 - 13 Nov 2025

Abstract

Radioprotective agents derived from natural food sources represent promising candidates for reducing the harmful effects of ionizing radiation and supporting healthy aging. In this study, we investigated the effects of selected micronized bioactive compounds and their mixes on DNA damage response pathways in [...] Read more.

Radioprotective agents derived from natural food sources represent promising candidates for reducing the harmful effects of ionizing radiation and supporting healthy aging. In this study, we investigated the effects of selected micronized bioactive compounds and their mixes on DNA damage response pathways in human retinal epithelial cells (hTERT-RPE1). Individual compounds and their combinations were applied to cultured cells, and the expression of IER5, a radiation-inducible gene associated with DNA repair and cell survival, was evaluated, showing that most potent compound to be lycopene and quercetin. Thus, in the next step, commonly consumed foods available on the Czech market rich in moth—tomato and garlic—were analyzed for their antioxidant capacity. The results revealed marked variability in antioxidant potential among food sources, with specific cultivars exhibiting significantly higher values. Importantly, experimental mixtures of pure and micronized compounds demonstrated distinct and sometimes opposing effects on IER5 expression. These findings indicate that the radioprotective activity of dietary antioxidants depends not only on the properties of individual compounds but also on their specific combinations. Our study provides evidence that phytochemicals such as quercetin, lycopene, but also partially resveratrol and curcumin can modulate DNA-repair-associated pathways and underscores their potential as combinatory agents in strategies aimed at promoting genomic stability and potentially healthy aging. Full article

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

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