Antioxidants

20 pages, 8843 KiB

Open AccessArticle

Paeoniflorin Alleviates Lipopolysaccharide-Induced Neuroinflammation and Depression Through the Keap1/Nrf2/HO-1 Signaling Pathway

by Zhuoyue Hu, Xing Wang, Tian Shi, Lei Yang, Boxi Zhang, Bo Shang, Ruizhi He, Shichen Yi, Jiao He, Jing Hu and Yanjun Cao

Antioxidants 2025, 14(5), 585; https://doi.org/10.3390/antiox14050585 - 13 May 2025

Abstract

Depression is associated with bidirectional interactions between inflammatory responses and behavioral dysfunction. Paeoniflorin (PF), a monoterpene glycoside derived from Paeonia lactiflora, exhibits potent anti-inflammatory properties. This study investigates the therapeutic effects of PF on lipopolysaccharide (LPS)-induced depression-like behaviors in mice and neuroinflammation [...] Read more.

Depression is associated with bidirectional interactions between inflammatory responses and behavioral dysfunction. Paeoniflorin (PF), a monoterpene glycoside derived from Paeonia lactiflora, exhibits potent anti-inflammatory properties. This study investigates the therapeutic effects of PF on lipopolysaccharide (LPS)-induced depression-like behaviors in mice and neuroinflammation in BV2 microglial cells. Mice were co-administered PF (20, 40, or 80 mg/kg/day) and LPS (2 mg/kg) for 7 days. Behavioral tests; Nissl staining; and Golgi, Iba1, DLG4, and cytokine assays were conducted. Additionally, hippocampal NF-κB, Nrf2, and BDNF signaling pathways were analyzed using Western blots. In BV2 cells, oxidative stress and the Nrf2/HO-1 pathway were assessed using CCK-8, flow cytometry, and Western blotting after 24 h of LPS and PF treatment. PF significantly alleviated LPS-induced depression-like behaviors, increased hippocampal neuron and dendritic spine density, and upregulated synaptic proteins (PSD95, SNAP25, and BDNF). Mechanistically, PF suppressed NLRP3 inflammasome activation via the Akt/GSK3β pathway, reduced pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and enhanced the Nrf2/HO-1 antioxidant axis. In BV2 cells, PF restored mitochondrial membrane potential, inhibited apoptosis, and decreased cytokine levels (TNF-α, IL-1β, and IL-6) by inhibiting TLR4/NF-κB signaling. In conclusion, PF significantly improved LPS-induced depression-like behaviors and attenuated neuroinflammation in BV2 microglial cells, highlighting its potential as a therapeutic agent for inflammation-associated depression. Full article

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13 pages, 1094 KiB

Open AccessArticle

Association Between Creatinine and Lung Cancer Risk in Men Smokers: A Comparative Analysis with Antioxidant Biomarkers from the KCPS-II Cohort

by Jong-Won Shin, Thien-Minh Nguyen and Sun-Ha Jee

Antioxidants 2025, 14(5), 584; https://doi.org/10.3390/antiox14050584 - 12 May 2025

Abstract

Bilirubin, albumin, and uric acid are established endogenous antioxidant biomarkers, whereas the antioxidant role of creatinine has not yet been fully clarified. As a byproduct of creatine metabolism, creatinine may reflect underlying metabolic activity and redox balance, particularly under conditions of oxidative stress [...] Read more.

Bilirubin, albumin, and uric acid are established endogenous antioxidant biomarkers, whereas the antioxidant role of creatinine has not yet been fully clarified. As a byproduct of creatine metabolism, creatinine may reflect underlying metabolic activity and redox balance, particularly under conditions of oxidative stress such as cigarette smoking. This study aimed to evaluate the associations between serum creatinine and other antioxidant biomarkers and lung cancer risk, stratified by smoking status. We analyzed 83,371 cancer-free men from the Korean Cancer Prevention Study II (KCPS II) cohort. During a mean follow-up of 13.5 years, 533 incident lung cancer cases were identified. Serum creatinine, total bilirubin, albumin, and uric acid were measured. Smoking status classified participants as never-, former, and ever-smokers, with ever-smokers including both current and former smokers. Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), stratified by smoking status. Biomarkers were also analyzed by quartiles and linear trends. A single standard deviation increase in serum creatinine was significantly and inversely associated with lung cancer risk among former smokers (HR: 0.774, 95% CI: 0.620 to 0.967) and ever-smokers (HR: 0.823, 95% CI: 0.716 to 0.945). Total bilirubin also showed significant inverse associations in former smokers (HR: 0.826, 95% CI: 0.705 to 0.967) and ever-smokers (HR: 0.785, 95% CI: 0.708 to 0.870). Albumin was inversely associated only with ever-smokers (HR: 0.878, 95% CI: 0.807 to 0.955), while uric acid showed inverse associations with both former smokers (HR: 0.832, 95% CI: 0.699 to 0.989) and ever-smokers (HR: 0.847, 95% CI: 0.760 to 0.944). None of the biomarkers showed significant associations among never-smokers. Serum creatinine and other endogenous antioxidant biomarkers were inversely associated with lung cancer risk, particularly in individuals with a history of smoking exposure. Full article

(This article belongs to the Special Issue Oxidative Stress in Lung Diseases)

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17 pages, 3505 KiB

Open AccessArticle

A Novel Hybrid Peptide VLP-Aβ Exhibits Antioxidant Activity In Vitro and In Vivo via KEAP1-NRF2-ARE Signaling Pathway

by Junyong Wang, Wenxiu Zhang, Rijun Zhang, Xuelian Zhao, Jing Zhang, Yichen Zhou, Yucui Tong, Zaheer Abbas, Zhenzhen Li, Haosen Zhang, Di Yang, Sichao Chen, Cong Hu, Dayong Si and Xubiao Wei

Antioxidants 2025, 14(5), 583; https://doi.org/10.3390/antiox14050583 - 12 May 2025

Abstract

Oxidative stress plays a crucial role in the development and progression of various diseases. Antioxidant peptides have attracted great attention in agricultural, food, and clinical fields due to their low toxicity, high efficacy, and easy absorption, but the development of antioxidant peptides and [...] Read more.

Oxidative stress plays a crucial role in the development and progression of various diseases. Antioxidant peptides have attracted great attention in agricultural, food, and clinical fields due to their low toxicity, high efficacy, and easy absorption, but the development of antioxidant peptides and their in-depth molecular mechanisms are still lacking. The previous study established a platform for the high-throughput design and screening of multifunctional peptides and successfully identified a novel hybrid peptide, VLP-Aβ (VA), which exhibits both antioxidant and immunomodulatory properties. This study aimed to evaluate the antioxidant activity of VA and investigate the underlying molecular mechanisms. The antioxidant effects of VA were evaluated using both in vitro (H₂O₂-induced oxidative damage in HepG2 cells) and in vivo (CCl₄-induced liver damage in mice) models. VA exhibited significant antioxidant activity both in vitro and in vivo, significantly improving the cell viability and increasing the levels of antioxidant enzymes (SOD, CAT, GSH-Px) to alleviate oxidative stress. These findings indicated that the antioxidant effect of VA is dependent on NRF2, as evidenced by NRF2 knockdown experiments. Further investigation revealed that VA alleviates oxidative stress by modulating the KEAP1-NRF2-ARE signaling pathway. These findings provide insights into the properties of the antioxidant peptide VA, expand the understanding of its molecular mechanisms, and suggest new opportunities for developing VA as a novel functional agent in the agricultural, food, and clinical industries. Full article

(This article belongs to the Special Issue Cellular ROS and Antioxidants: Physiological and Pathological Role—2nd Edition)

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6 pages, 186 KiB

Open AccessEditorial

Advances in the Astonishing World of Phytochemicals: State-of-the-Art for Antioxidants—2nd Edition

by Marianna Lauricella and Antonella D’Anneo

Antioxidants 2025, 14(5), 582; https://doi.org/10.3390/antiox14050582 - 12 May 2025

Abstract

This Editorial refers to the Special Issue titled “Advances in the Astonishing World of Phytochemicals: State-of-the-Art for Antioxidants—2nd Edition”, which highlights the multifaceted properties of natural compounds containing antioxidants and describes the need to understand how active compounds, solvents, and complex formations interact, [...] Read more.

This Editorial refers to the Special Issue titled “Advances in the Astonishing World of Phytochemicals: State-of-the-Art for Antioxidants—2nd Edition”, which highlights the multifaceted properties of natural compounds containing antioxidants and describes the need to understand how active compounds, solvents, and complex formations interact, in order to better establish their potential in applied sciences [...] Full article

(This article belongs to the Special Issue Advances in the Astonishing World of Phytochemicals: State-of-the-Art for Antioxidants—2nd Edition)

21 pages, 1403 KiB

Open AccessReview

The Role of Antioxidant Compounds from Citrus Waste in Modulating Neuroinflammation: A Sustainable Solution

by Alessia Silla, Angela Punzo, Cristiana Caliceti, Maria Cristina Barbalace, Silvana Hrelia and Marco Malaguti

Antioxidants 2025, 14(5), 581; https://doi.org/10.3390/antiox14050581 - 11 May 2025

Abstract

In normal conditions, neuroinflammation induces microglia and astrocyte activation to maintain brain homeostasis. However, excessive or prolonged neuroinflammation can inflict harmful damage on brain tissue. Numerous factors can trigger chronic neuroinflammation, ultimately leading to neurodegeneration. In this context, considering the pressing need for [...] Read more.

In normal conditions, neuroinflammation induces microglia and astrocyte activation to maintain brain homeostasis. However, excessive or prolonged neuroinflammation can inflict harmful damage on brain tissue. Numerous factors can trigger chronic neuroinflammation, ultimately leading to neurodegeneration. In this context, considering the pressing need for novel, natural approaches to mitigate neuroinflammatory damage, attention has turned to unconventional sources such as agricultural by-products. Citrus fruits are widely consumed globally, producing substantial waste, including peels, seeds, and pulp. Traditionally regarded as agricultural waste, these by-products are now recognized as valuable reservoirs of bioactive compounds, including flavonoids, carotenoids, terpenoids, and limonoids. Among these, citrus polyphenols—particularly flavanones like hesperidin, naringenin, and eriocitrin—have emerged as potent modulators of neuroinflammatory pathways through their multifaceted interactions with cellular antioxidant systems, pro-inflammatory signaling cascades, neurovascular integrity, and gut–brain axis dynamics. This review aims to characterize the key molecules present in citrus waste and synthesizes preclinical and clinical evidence to elucidate the biochemical mechanisms underlying neuroinflammation in neurodegenerative disorders. Full article

(This article belongs to the Special Issue Natural Products: Biological, Antioxidant Properties and Health Effects—4th Edition)

22 pages, 12976 KiB

Open AccessArticle

Tea Polyphenols Mitigate Radiation-Induced Ferroptosis and Intestinal Injury by Targeting the Nrf2/HO-1/GPX4 Signaling Pathway

by Runtian Li, Lintao Li, Haiyang Wu, Hui Gan, Zhuona Wu, Ruolan Gu, Xiaoxia Zhu, Shuchen Liu, Zhiyun Meng and Guifang Dou

Antioxidants 2025, 14(5), 580; https://doi.org/10.3390/antiox14050580 - 11 May 2025

Abstract

Radiation-induced intestinal injury (RIII) is a significant concern for cancer patients receiving radiation therapy, as it can lead to complications such as radiation enteropathy. Presently, there are limited options for preventing or treating RIII. Tea polyphenols (TP), found in tea, provide various health [...] Read more.

Radiation-induced intestinal injury (RIII) is a significant concern for cancer patients receiving radiation therapy, as it can lead to complications such as radiation enteropathy. Presently, there are limited options for preventing or treating RIII. Tea polyphenols (TP), found in tea, provide various health benefits, but their antiradiation mechanisms are not fully understood. C57BL/6 mice pre-treated with TP for five days showed a significant improvement in survival rates after being exposed to 10 Gy of ⁶⁰Co radiation. In the same way, abdominal exposure to 15 Gy of ⁶⁰Co radiation effectively mitigated radiation-induced colon shortening, damage to intestinal tissues, oxidative stress, the release of inflammatory factors, and disruptions in intestinal microbial balance. In addition, TP treatment lowered the elevation of reactive oxygen species (ROS), iron imbalance, mitochondrial damage, and ferroptosis in IEC-6 cells post-irradiation. Utilizing network pharmacology, molecular docking, and affinity testing, we identified that TP has the capability to target the Nrf2/HO-1/GPX4 signaling pathway, while EGCG, a principal constituent of TP, interacts with HSP90 and mitigates radiation-induced ferroptosis. These findings suggest that TP may serve as a promising therapeutic agent to alleviate radiation-induced intestinal injury (RII). Full article

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21 pages, 4965 KiB

Open AccessArticle

Isorhamnetin Attenuates Isoproterenol-Induced Myocardial Injury by Reducing ENO1 (Alpha-Enolase) in Cardiomyocytes

by Zhenli Guo, Shizhong Liu, Xianghong Hou, Xin Zhou, Yan Wang, Yi Rong, Xinzhi Li, Rui Yang and Ketao Ma

Antioxidants 2025, 14(5), 579; https://doi.org/10.3390/antiox14050579 - 11 May 2025

Abstract

The protective effect of isorhamnetin on myocardial injury induced by isoproterenol (ISO) was investigated to identify the key targets and pathways involved, offering potential therapeutic insights for cardiovascular diseases. A myocardial injury model was established through intraperitoneal ISO injection, and the effects of [...] Read more.

The protective effect of isorhamnetin on myocardial injury induced by isoproterenol (ISO) was investigated to identify the key targets and pathways involved, offering potential therapeutic insights for cardiovascular diseases. A myocardial injury model was established through intraperitoneal ISO injection, and the effects of isorhamnetin on apoptosis and oxidative stress in ISO-induced myocardial injury rats were assessed. Additionally, an ISO-induced H9c2 cell injury model was established to evaluate the impact of isorhamnetin on cellular damage. The transcriptomic sequencing of H9c2 cells was conducted to identify differentially expressed genes, followed by gene enrichment analysis. Intracellular glucose, lactate, and ATP levels were quantified, and the protein expression of key pathway targets ENO1, PPARα, and PGC-1α was analyzed via immunoblotting. Isorhamnetin improved cardiac function and morphological damage, reduced serum markers of cardiac injury, and exerted cardioprotective effects by regulating oxidative stress and inhibiting apoptosis. Compared to the ISO group, the glycolytic process—with ENO1 as a key target and the PPAR signaling pathway as the core regulator—was significantly suppressed in the isorhamnetin-pretreated group. Furthermore, isorhamnetin pretreatment reduced intracellular glucose and lactate levels while increasing ATP content in a concentration-dependent manner. These findings suggest that isorhamnetin protects the heart by inhibiting ENO1, activating the PPARα/PGC-1α signaling axis, reversing isoprenaline-induced metabolic shifts in H9c2 cells, suppressing glycolysis, and enhancing ATP release, thereby mitigating apoptosis and oxidative stress. Full article

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

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24 pages, 3218 KiB

Open AccessReview

Biological Models of Oxidative Purine DNA Damage in Neurodegenerative Disorders

by Chryssostomos Chatgilialoglu

Antioxidants 2025, 14(5), 578; https://doi.org/10.3390/antiox14050578 - 11 May 2025

Abstract

Most DNA damage caused by oxidative metabolism consists of single lesions that can accumulate in tissues. This review focuses on two classes of lesions: the two 8-oxopurine (8-oxo-Pu) lesions that are repaired by the base excision repair (BER) enzyme and the four 5′,8-cyclopurine [...] Read more.

Most DNA damage caused by oxidative metabolism consists of single lesions that can accumulate in tissues. This review focuses on two classes of lesions: the two 8-oxopurine (8-oxo-Pu) lesions that are repaired by the base excision repair (BER) enzyme and the four 5′,8-cyclopurine (cPu) lesions that are repaired exclusively by the nucleotide excision repair (NER) enzyme. The aim is to correlate the simultaneous quantification of these two classes of lesions in the context of neurological disorders. The first half is a summary of reactive oxygen species (ROS) with particular attention to the pathways of hydroxyl radical (HO^•) formation, followed by a summary of protocols for the quantification of six lesions and the biomimetic chemistry of the HO^• radical with double-stranded oligonucleotides (ds-ODN) and calf thymus DNA (ct-DNA). The second half addresses two neurodegenerative diseases: xeroderma pigmentosum (XP) and Cockayne syndrome (CS). The quantitative data on the six lesions obtained from genomic and/or mitochondrial DNA extracts across several XP and CS cell lines are discussed. Oxidative stress contributes to oxidative DNA damage by resulting in the accumulation of cPu and 8-oxo-Pu in DNA. The formation of cPu is the postulated culprit inducing neurological symptoms associated with XP and CS. Full article

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

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Graphical abstract

28 pages, 2269 KiB

Open AccessReview

Carotenoids in Skin Photoaging: Unveiling Protective Effects, Molecular Insights, and Safety and Bioavailability Frontiers

by Yingchao Ma, Chengxiang Li, Wanping Su, Zhongshi Sun, Shuo Gao, Wei Xie, Bo Zhang and Liying Sui

Antioxidants 2025, 14(5), 577; https://doi.org/10.3390/antiox14050577 - 11 May 2025

Abstract

Skin photoaging, driven primarily by ultraviolet radiation, remains a critical dermatological concern. Carotenoids, a class of natural pigments with potent antioxidant properties, have emerged as promising agents for preventing and mitigating photoaging. This review comprehensively integrates current understanding regarding the triggers of skin [...] Read more.

Skin photoaging, driven primarily by ultraviolet radiation, remains a critical dermatological concern. Carotenoids, a class of natural pigments with potent antioxidant properties, have emerged as promising agents for preventing and mitigating photoaging. This review comprehensively integrates current understanding regarding the triggers of skin photoaging, oxidative stress and their associated signal pathways, the photoprotective roles and mechanisms of carotenoids, as well as their bioavailability. Common C₄₀ carotenoids, such as β-carotene, lycopene, astaxanthin, lutein, and zeaxanthin demonstrate remarkable antioxidant activity, primarily attributed to their conjugated double bond structures. Many studies have demonstrated that both oral and topical administration of these C₄₀ carotenoids can effectively alleviate skin photoaging. Specifically, they play a crucial role in promoting the formation of a new skin barrier and enhancing the production of collagen and elastin, key structural proteins essential for maintaining skin integrity and elasticity. Mechanistically, these carotenoids combat photoaging by effectively scavenging reactive oxygen species and modulating oxidative stress responsive signal pathways, including MAPK, Nrf2, and NF-κB. Notably, we also anticipate the anti-photoaging potential of novel carotenoids, with a particular emphasis on bacterioruberin, a C₅₀ carotenoid derived from halophilic archaea. Bacterioruberin exhibits a superior radical scavenging capacity, outperforming the conventional C₄₀ carotenoids. Furthermore, when considering the application of carotenoids, aspects such as safe dosage, bioavailability, and possible long term usage issues, including allergies and pigmentation disorders, must be taken into account. This review underscores the anti-photoaging mechanism of carotenoids, providing strategies and theoretical basis for the prevention and treatment of photoaging. Full article

(This article belongs to the Special Issue Free Radicals, Antioxidants, and Oxidative Stress in Aging and Age-Related Diseases—2nd Edition)

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22 pages, 6229 KiB

Open AccessArticle

Vitamin C Inhibits Scale Drop Disease Virus Infectivity by Targeting Nrf2 to Reduce Ferroptosis

by Jiaming Chen, Yuting Fu, Shaoping Weng, Jianguo He and Chuanfu Dong

Antioxidants 2025, 14(5), 576; https://doi.org/10.3390/antiox14050576 - 10 May 2025

Abstract

Scale drop disease virus (SDDV) poses an escalating threat to global aquaculture, prompting an urgent need for research. Our study found that SDDV infection upregulates genes related to iron, oxidative stress, and lipid metabolism, causing iron overload, reactive oxygen species (ROS) accumulation, and [...] Read more.

Scale drop disease virus (SDDV) poses an escalating threat to global aquaculture, prompting an urgent need for research. Our study found that SDDV infection upregulates genes related to iron, oxidative stress, and lipid metabolism, causing iron overload, reactive oxygen species (ROS) accumulation, and ultimately ferroptosis. Among the tested antioxidants, vitamin C (VC) demonstrated the most potent inhibitory effect in mandarin fish, reducing SDDV-induced mortality by 37.5%. qPCR and IFA results showed that VC effectively suppressed SDDV infection; decreased ROS, lipid peroxidation (LPO), and iron levels; and enhanced glutathione peroxidase 4 (GPX4) expression in infected cells. Mechanistically, VC’s inhibitory effect was reversed by the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML-385, indicating an Nrf2-dependent pathway. VC promoted Nrf2 nuclear translocation and activated downstream antioxidant genes. Moreover, VC modulated inflammation by regulating pro- and anti-inflammatory factors. These findings suggest VC as a promising therapeutic for SDDV infection. Full article

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

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19 pages, 2797 KiB

Open AccessArticle

Aster-B Modulates Oxidative Stress Responses and Carotenoid Distribution in ARPE-19 Cells

by Vidya Gopakumar and Johannes von Lintig

Antioxidants 2025, 14(5), 575; https://doi.org/10.3390/antiox14050575 - 10 May 2025

Abstract

Lipid metabolism and oxidative stress are major contributors to ocular diseases, including drusen formation and photoreceptor damage. Aster-B, encoded by GRAMD1B, mediates the non-vesicular transport of cholesterol and carotenoids and is highly expressed in the human eye, though its specific ocular functions [...] Read more.

Lipid metabolism and oxidative stress are major contributors to ocular diseases, including drusen formation and photoreceptor damage. Aster-B, encoded by GRAMD1B, mediates the non-vesicular transport of cholesterol and carotenoids and is highly expressed in the human eye, though its specific ocular functions remain unknown. We investigated Aster-B’s role in ARPE-19 cells, a model of the retinal pigment epithelium (RPE), using CRISPR/dCas9 to generate an Aster-B-expressing cell line. Aster-B expression significantly improved cell survival under oxidative stress induced by hydrogen peroxide (H₂O₂) and was associated with the activation of the p53 and TGFβ signaling pathways, indicating a role in modulating stress responses. To confirm its lipid transport activity, we treated cholesterol-depleted cells with carotenoids and tracked their localization. In Aster-B-expressing cells, carotenoids accumulated in mitochondria, while in control cells, they remained in other cellular compartments. Under oxidative stress, mitochondrial carotenoid levels declined in Aster-B-expressing cells but not in control cells. Interestingly, carotenoids enhanced survival in control cells exposed to H₂O₂ but had a detrimental effect in Aster-B-expressing cells, suggesting that carotenoid function is context and location dependent. These findings highlight Aster-B’s role in coordinating lipid transport and stress responses in the RPE, with implications for oxidative stress-related eye diseases. Full article

(This article belongs to the Special Issue Carotenoids in Health and Disease)

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16 pages, 4821 KiB

Open AccessArticle

Red Wine Grape Pomace Restores Gut Barrier Function and Improves Survival in Diet-Induced Ischemic Heart Disease

by Katherine Rivera, Leticia González, Laura Parra, Juan E. Oyarzún, Alina Concepción-Alvarez, Adriano Costa de Camargo, Raquel Bridi, Attilio Rigotti and Marcelo E. Andia

Antioxidants 2025, 14(5), 574; https://doi.org/10.3390/antiox14050574 - 10 May 2025

Abstract

Red wine grape pomace (RWGP), a winemaking by-product rich in phenolics, flavonoids, and dietary fiber, has shown promise in mitigating cardiovascular disease (CVD), however, its mechanisms of action remain incompletely understood. This study comprehensively profiled the phenolic composition of RWGP—including free, esterified, etherified, [...] Read more.

Red wine grape pomace (RWGP), a winemaking by-product rich in phenolics, flavonoids, and dietary fiber, has shown promise in mitigating cardiovascular disease (CVD), however, its mechanisms of action remain incompletely understood. This study comprehensively profiled the phenolic composition of RWGP—including free, esterified, etherified, and insoluble-bound fractions—and evaluated the effects of RWGP dietary supplementation on gut barrier integrity, inflammation, oxidative stress, and survival in SR-B1^−/−ApoE-R61^h/h mice, a model of diet-induced lethal ischemic heart disease. RWGP supplementation significantly improved survival rates and restored gut barrier function, as evidenced by lower plasma FITC-dextran and LPS levels, increased circulating ZO-1 levels, and reduced histopathological colon damage. In addition, RWGP reduced pro-inflammatory cytokines (IL-1

β

) and showed a trend toward attenuating systemic oxidative stress (TBARS). Analysis of phenolic compounds indicated a significant presence of insoluble-bound phenolics. Nevertheless, the beneficial effects observed are likely attributable to the synergistic actions of RWGP’s complex phytochemical and fiber composition. These results highlight RWGP’s potential as a sustainable, gut-targeted functional food ingredient for CVD prevention and management. Full article

(This article belongs to the Special Issue Phenolic Compounds in Foods, Plants and Related By-Products—2nd Edition)

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29 pages, 6701 KiB

Open AccessArticle

Therapeutic Potential of Lythrum salicaria L. Ethanol Extract in Experimental Rat Models of Streptozotocin-Induced Diabetes Mellitus and Letrozole-Induced Polycystic Ovary Syndrome

by Lia Oxana Usatiuc, Marcel Pârvu, Raluca Maria Pop, Ana Uifălean, Dan Vălean, Adrian Surd, Mădălina Țicolea, Ana Hîruța, Floricuța Ranga, Florinela Adriana Cătoi, Corina Cătană and Alina Elena Pârvu

Antioxidants 2025, 14(5), 573; https://doi.org/10.3390/antiox14050573 - 10 May 2025

Abstract

Polycystic ovary syndrome (PCOS) and diabetes mellitus (DM) are prevalent endocrine disorders with overlapping pathophysiological mechanisms. Type 2 diabetes mellitus (T2DM) is commonly associated with PCOS, with both conditions strongly linked to insulin resistance (IR), while recent studies have also reported an increased [...] Read more.

Polycystic ovary syndrome (PCOS) and diabetes mellitus (DM) are prevalent endocrine disorders with overlapping pathophysiological mechanisms. Type 2 diabetes mellitus (T2DM) is commonly associated with PCOS, with both conditions strongly linked to insulin resistance (IR), while recent studies have also reported an increased prevalence of PCOS among women with type 1 diabetes mellitus (T1DM). This study evaluated the potential of Lythrum salicaria L. ethanol extract (LSEE) to mitigate oxidative stress (OS), inflammation, and metabolic and hormonal imbalances in separate experimental models of Streptozotocin (STZ)-induced DM and Letrozole (LET)-induced PCOS. LSEE underwent phytochemical analysis to quantify total phenolic and flavonoid content and HPLC-MS for polyphenols identification. In vitro, antioxidant capacity was investigated through FRAP, DPPH, NO, and H₂O₂ scavenging assays. Subsequently, in vivo, studies utilized STZ-induced DM and LET-induced PCOS rat models, with 10-day treatments of LSEE, metformin, or trolox (TX) administered by gavage. Dysregulation of hormonal profiles, ultrasound, and histological examinations confirmed PCOS development. At the end of the treatment period, serum samples were collected to assess OS markers (TOS, OSI, MDA, AOPP, 8-OHdG, NO, 3-NT, AGEs, TAR, SH) in both models. Inflammatory markers were also measured (IL-1β, NF-κB, IL-18, and Gasdermin D in DM and IL-1β, NF-κB, IL-18, and IL-10 in PCOS). Additionally, metabolic markers (glucose, lipids, TG-glucose index, liver enzymes) were assessed in DM rats, and hormones (LH, FSH, estrogen, testosterone, insulin, HOMA-IR) were determined in PCOS rats. LSEE demonstrated a high polyphenolic content and notable in vitro antioxidant activity. In vivo, it effectively reduced OS by lowering oxidant levels and enhancing antioxidant defenses, reduced inflammatory markers and blood glucose levels, and improved lipid profiles along with the TyG index and liver injury markers in diabetic rats. In PCOS rats, LSEE lowered the total oxidants, increased antioxidants, reduced LH, FSH, testosterone, and insulin, and increased estrogen levels. The effects exhibited a dose-dependent pattern, with higher doses producing more pronounced benefits comparable to those observed with metformin and TX. In conclusion, LSEE may be a promising complementary treatment for DM and PCOS. Full article

(This article belongs to the Special Issue Plant Antioxidants, Inflammation, and Chronic Disease)

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39 pages, 1431 KiB

Open AccessReview

The Dark Triad of Particulate Matter, Oxidative Stress and Coronary Artery Disease: What About the Antioxidant Therapeutic Potential

by Daniele Grifoni, Elisa Bustaffa, Laura Sabatino, Francesca Calastrini, Fabrizio Minichilli, Melania Gaggini, Sergio Berti and Cristina Vassalle

Antioxidants 2025, 14(5), 572; https://doi.org/10.3390/antiox14050572 - 9 May 2025

Abstract

Particulate matter (PM) is a complex mixture of particles with different adverse effects on health, especially on the cardiovascular (CV) risk and disease (e.g., increased risk of total and CV mortality, ischemic heart disease, heart failure, stroke, hypertension, dyslipidemia and type 2 diabetes). [...] Read more.

Particulate matter (PM) is a complex mixture of particles with different adverse effects on health, especially on the cardiovascular (CV) risk and disease (e.g., increased risk of total and CV mortality, ischemic heart disease, heart failure, stroke, hypertension, dyslipidemia and type 2 diabetes). Since oxidative stress (OS) and inflammation are the main key mechanisms by which PM exerted its biological effects on health, several oxidative and inflammatory-related biomarkers have been measured and associated with PM; abnormalities in these parameters in relation to PM highlight the key role of this relationship in terms of adverse health effects, including CV conditions. Antioxidant strategies might prevent/reverse, almost partly, CV effects related to PM exposure, by addressing OS and inflammation, although the clinical gain of these interventional tools is not yet clearly demonstrated. This review aims to summarize PM source and composition, discussing OS and inflammatory events associated with environmental PM exposure as key mechanistic determinants of CV risk and acute event precipitation. Moreover, the modifying potential of antioxidants, especially in subjects more susceptible to the adverse effects of air pollution and/or more highly exposed, will be discussed as a promising research area beyond conventional strategies actually available to prevent the harmful effects of PM (e.g., reduction of pollution sources and population exposure, assessment of air quality standards) in order to better face this dark triad composed of PM, OS and CV disease. Full article

(This article belongs to the Special Issue Oxidative Stress Induced by Air Pollution, 2nd Edition)

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25 pages, 4637 KiB

Open AccessArticle

Deepening the Modulatory Activity of Bioactive Compounds Against AFB1- and OTA-Induced Neuronal Toxicity Through a Proteomic Approach

by Alessandra Cimbalo, Massimo Frangiamone and Lara Manyes

Antioxidants 2025, 14(5), 571; https://doi.org/10.3390/antiox14050571 - 9 May 2025

Abstract

The aim of this work is to highlight the beneficial effects of bioactive peptides present in fermented whey (FW) and carotenoids from pumpkin (P) against the pro-oxidant effects of aflatoxin B1 and ochratoxin A at the neuronal level. For this purpose, SH-SY5Y human [...] Read more.

The aim of this work is to highlight the beneficial effects of bioactive peptides present in fermented whey (FW) and carotenoids from pumpkin (P) against the pro-oxidant effects of aflatoxin B1 and ochratoxin A at the neuronal level. For this purpose, SH-SY5Y human neuroblastoma differentiated cells were exposed to (A) mycotoxins, (B) the digesta of mycotoxin-contaminated bread formulated with P, or (C) bread enriched with FW + P. A proteomic approach using HPLC-MS/MS-QTOF was then employed to characterize the metabolic pathways affected by the presence of these components, as well as their ability to modulate the toxic effects exacerbated by mycotoxins. Gene ontology functional analysis revealed proteins primarily associated with nucleosome structure, such as the H3-H4 tetramer, H2A-H2B dimer, and HIRA, which were overexpressed in the presence of mycotoxins and, interestingly, downregulated with the addition of the functional ingredients. Additionally, important metabolic pathways associated with the RHO GTPase family, estrogen-dependent gene expression, and androgen receptor transcription stimulated by PKN1 activation were discovered. Network interaction analysis highlighted the modulation of cytoskeletal dynamics, cell migration, and stress responses. These findings provide novel insights into the neuroprotective potential of functional food components, supporting their use in mitigating mycotoxin-induced neuronal damage and opening new avenues for dietary-based neuroprotection strategies. 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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21 pages, 1383 KiB

Open AccessReview

Redox-Driven Epigenetic Modifications in Sperm: Unraveling Paternal Influences on Embryo Development and Transgenerational Health

by Aron Moazamian, Fabrice Saez, Joël R. Drevet, Robert John Aitken and Parviz Gharagozloo

Antioxidants 2025, 14(5), 570; https://doi.org/10.3390/antiox14050570 - 9 May 2025

Abstract

Male-factor infertility accounts for nearly half of all infertility cases, and mounting evidence points to oxidative stress as a pivotal driver of sperm dysfunction, genetic instability, and epigenetic dysregulation. In particular, the oxidative DNA lesion 8-hydroxy-2′-deoxyguanosine (8-OHdG) has emerged as a central mediator [...] Read more.

Male-factor infertility accounts for nearly half of all infertility cases, and mounting evidence points to oxidative stress as a pivotal driver of sperm dysfunction, genetic instability, and epigenetic dysregulation. In particular, the oxidative DNA lesion 8-hydroxy-2′-deoxyguanosine (8-OHdG) has emerged as a central mediator at the interface of DNA damage and epigenetic regulation. We discuss how this lesion can disrupt key epigenetic mechanisms such as DNA methylation, histone modifications, and small non-coding RNAs, thereby influencing fertilization outcomes, embryo development, and offspring health. We propose that the interplay between oxidative DNA damage and epigenetic reprogramming is further exacerbated by aging in both the paternal and maternal germlines, creating a “perfect storm” that increases the risk of heritable (epi)mutations. The consequences of unresolved oxidative lesions can thus persist beyond fertilization, contributing to transgenerational health risks. Finally, we explore the promise and potential pitfalls of antioxidant therapy as a strategy to mitigate sperm oxidative damage. While antioxidant supplementation may hold significant therapeutic value for men with subfertility experiencing elevated oxidative stress, a careful, personalized approach is essential to avoid reductive stress and unintended epigenetic disruptions. Recognizing the dual role of oxidative stress in shaping both the genome and the epigenome underscores the need for integrating redox biology into reproductive medicine, with the aim of improving fertility treatments and safeguarding the health of future generations. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Male Infertility)

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24 pages, 2853 KiB

Open AccessArticle

TEMPO-Oxidized Spruce Galactoglucomannan–Biopolymer with Enhanced Antioxidant Activity and Selective Heavy-Metal Sorption

by Vladislav A. Ionin, Yuriy N. Malyar, Valentina S. Borovkova, Dmitriy V. Zimonin and Aleksandr S. Kazachenko

Antioxidants 2025, 14(5), 569; https://doi.org/10.3390/antiox14050569 - 9 May 2025

Abstract

This study examines galactoglucomannan, a well-studied biopolymer isolated from Siberian spruce (Picea obovata Ledeb). Due to its structure, abundant with hydroxyl groups, galactoglucomannan’s properties, such as heavy-metal ion affinity, are considered to be mediocre. Nevertheless, there are various ways to enhance its [...] Read more.

This study examines galactoglucomannan, a well-studied biopolymer isolated from Siberian spruce (Picea obovata Ledeb). Due to its structure, abundant with hydroxyl groups, galactoglucomannan’s properties, such as heavy-metal ion affinity, are considered to be mediocre. Nevertheless, there are various ways to enhance its functionality via oxidative TEMPO/NaBr/NaOCl processing. This work is concerned with the determination of the oxidation effect on the structure and performance properties, such as thermal decomposition behavior, antioxidant activity, and selective heavy-metal sorption. In the results, TEMPO-oxidized galactoglucomannan yields vary in the range of 78.3 ± 6.4 wt.%. The carboxylate group in the oxidized derivative represents up to 0.084 g/1 g of the sample. According to antioxidant activity tests, the oxidized galactoglucomannan exceeds the initial sample in terms of hydroxyl radical scavenging ability. The spectral characteristics of the initial and oxidized galactoglucomannan samples reveal the differences in absorption units (1725, 1610, and 1371 cm⁻¹). The preservation of the polymeric structure was confirmed by the gel permeation chromatography analysis results. The heavy-metal ion capacity of galactoglucomannan is higher for the oxidized derivative, which demonstrated Cd²⁺, Fe²⁺, Cu²⁺, and Pb²⁺ adsorption values of 166.8 mg/g, 142.8 mg/g, 150.0 mg/g, and 199.2 mg/g, accordingly. The obtained result of the competitive heavy-metal ion adsorption of oxidized galactoglucomannan also exceeds its initial form, as characterized by its summary 143.1 mg/g capacity. Full article

(This article belongs to the Special Issue Methodologies for Improving Antioxidant Properties and Absorption)

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20 pages, 2577 KiB

Open AccessReview

The Potential Role of Oxidative Stress in Modulating Airway Defensive Reflexes

by Yuki Sato, Yoichiro Sugiyama, Tomoya Ishida, Haruhiko Inufusa, Fukka You, Davis Joseph and Shigeru Hirano

Antioxidants 2025, 14(5), 568; https://doi.org/10.3390/antiox14050568 - 9 May 2025

Abstract

Airway defensive reflexes, such as pharyngeal swallowing, coughing, and sneezing, play a pivotal role in maintaining airway homeostasis. These reflexes are controlled by complex mechanisms primarily governed by specific neuronal circuitry in the brainstem, referred to as central pattern generators. These behaviors also [...] Read more.

Airway defensive reflexes, such as pharyngeal swallowing, coughing, and sneezing, play a pivotal role in maintaining airway homeostasis. These reflexes are controlled by complex mechanisms primarily governed by specific neuronal circuitry in the brainstem, referred to as central pattern generators. These behaviors also require optimal conditions for the peripheral organs within the airway and alimentary tracts, including the nose, pharynx, larynx, and trachea, which are vital for ensuring appropriate responsiveness and motor outputs. Oxidative stress is linked to the development and progress of impaired functions of those behaviors. Dysphagia caused by central or peripheral impairments, such as neurodegeneration of related neuronal networks and laryngeal desensitization, is likely associated with an increased level of oxidative stress. Chronic inflammation and allergic airway sensitization in the lower airways, including asthma, elevate oxidative stress levels and diminish the activity of antioxidant defense enzymes, which exacerbate the severity of respiratory conditions. Antioxidant supplements offer promising therapeutic benefits by facilitating the recovery of distorted airway defensive reflexes, although limited information has been provided concerning therapeutic strategies. Further studies are necessary to enhance our understanding of the pathophysiology of dysphagia and airway diseases related to oxidative stress, as well as to develop new treatment strategies for these disorders. Full article

(This article belongs to the Special Issue Oxidative Stress in Human Diseases—4th Edition)

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21 pages, 1875 KiB

Open AccessArticle

Effect of Heat-Assisted and Ultrasound-Assisted Extraction Methods on the Phenolic Profile and Biological Activity of Thymus vulgaris L. Extracts

by Rafael Mascoloti Spréa, Cristina Caleja, Eliana Pereira, Márcio Carocho, José Pinela, Tiane C. Finimundy, Ricardo C. Calhelha, Marina Kostić, Marina Soković, Miguel A. Prieto, Joana S. Amaral and Lillian Barros

Antioxidants 2025, 14(5), 567; https://doi.org/10.3390/antiox14050567 - 9 May 2025

Abstract

This study compares the phenolic composition and antioxidant activity of extracts obtained using heat-assisted extraction (HAE) and ultrasound-assisted extraction (UAE), both optimized through response surface methodology (RSM), with the primary goal of maximizing the extraction of bioactive compounds from Thymus vulgaris L. Eight [...] Read more.

This study compares the phenolic composition and antioxidant activity of extracts obtained using heat-assisted extraction (HAE) and ultrasound-assisted extraction (UAE), both optimized through response surface methodology (RSM), with the primary goal of maximizing the extraction of bioactive compounds from Thymus vulgaris L. Eight phenolic compounds were identified in the extracts, with rosmarinic acid being the most abundant. Depending on the selected conditions in each optimization, the concentration of this compound varied from 2.04 to 72.6 mg/g of extract for HAE and 0.73 to 73.5 mg/g of extract for UAE. The optimal conditions for each method that yielded the highest rosmarinic acid levels were as follows: for HAE, 27% ethanol at 91 °C for 121 min; and for UAE, 60 min at 500 W using 50% ethanol. The UAE-produced extract demonstrated superior antioxidant performance, particularly in inhibiting the formation of thiobarbituric acid reactive substances and oxidative haemolysis. Additionally, the extracts obtained using both optimized methodologies exhibited cytotoxic activity against five tumor cell lines and showed significant bactericidal and fungicidal effects against six bacterial and fungal strains. Overall, UAE proved more efficient as it enables the production of rosmarinic-acid-enriched extracts in less time, making them suitable as natural ingredients for industrial applications. Full article

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

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