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Antioxidants

Antioxidants is an international, peer-reviewed, open access journal, published monthly online by MDPI. The International Coenzyme Q10 Association (ICQ10A), Israel Society for Oxygen and Free Radical Research (ISOFRR) and European Academy for Molecular Hydrogen Research (EAMHR) are affiliated with Antioxidants and their members receive discounts on the article processing charge.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, FSTA, PubAg, CAPlus / SciFinder, and other databases.
Journal Rank: JCR - Q1 (Chemistry, Medicinal) / CiteScore - Q1 (Food Science)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.4 days after submission; acceptance to publication is undertaken in 2.4 days (median values for papers published in this journal in the first half of 2025).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Testimonials: See what our editors and authors say about Antioxidants.
Companion journal: Oxygen.

Impact Factor: 6.6 (2024); 5-Year Impact Factor: 7.3 (2024)

Imprint Information Journal Flyer Open Access ISSN: 2076-3921

Latest Articles

32 pages, 5594 KB

Open AccessArticle

In Vitro Antioxidant Activity and In Vivo Neuroprotective Effect of Parastrephia quadrangularis in a Drosophila Parkinson’s Disease Model

by Branco Cárdenas, Ayza Cuevas, Duxan Arancibia, Lucas Urrutia, Pedro Zamorano, Adrián Paredes and Rafaella V. Zárate

Antioxidants 2025, 14(10), 1226; https://doi.org/10.3390/antiox14101226 (registering DOI) - 12 Oct 2025

Oxidative stress (OxS) is a central factor in neurodegenerative diseases (NDs), including Parkinson’s disease (PD). Phenolic compounds, including flavonoids and coumarins, counteract reactive species and modulate key intracellular survival pathways, highlighting their therapeutic potential. Parastrephia quadrangularis (Pq), a plant from the [...] Read more.

Oxidative stress (OxS) is a central factor in neurodegenerative diseases (NDs), including Parkinson’s disease (PD). Phenolic compounds, including flavonoids and coumarins, counteract reactive species and modulate key intracellular survival pathways, highlighting their therapeutic potential. Parastrephia quadrangularis (Pq), a plant from the Atacama Desert traditionally used by Andean communities, contains phenolic compounds with antioxidant, antifungal, and anti-inflammatory activities. However, its neuroprotective potential remains unexplored. Here, a hydroalcoholic extract (HAE) of Pq and four subfractions (MeOH, EtOAc, DCM, and n-hex) were obtained and assessed for in vitro antioxidant activity, with HAE selected for its consistent activity. In SH-SY5Y cells, HAE-Pq lowered basal reactive oxygen species and attenuated hydrogen peroxide-induced OxS. The UHPLC-MS analysis of HAE-Pq unveiled a high abundance of flavonoids, followed by coumarins and phenolic acids, and identified 16 additional metabolites, including jaceidin as the most abundant. In vivo assays using a Drosophila genetic PD model induced by overexpression of human α-synuclein, showed that HAE-Pq was non-toxic and non-aversive and that it delayed the onset of motor defects by one week in female flies. This study provides the first evidence of the neuroprotective potential of Pq, supporting its value as a source of bioactive metabolites relevant to NDs and reinforcing its ethnopharmacological validation. Full article

(This article belongs to the Special Issue Antioxidant Research in Chile—2nd Edition)

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21 pages, 6661 KB

Open AccessArticle

Bioactive Antioxidants from Avocado By-Products: Mechanistic Study and Laboratory-Scale Extraction Optimization

by Ziyao Xin, Yicheng Gao, Leiyu He, Zhilong Xiu and Lihui Sun

Antioxidants 2025, 14(10), 1225; https://doi.org/10.3390/antiox14101225 (registering DOI) - 11 Oct 2025

This study aimed to develop an environmentally friendly and relatively efficient method for extracting natural antioxidants from avocado by-products while investigating the antioxidant mechanisms of their core bioactive components on multiple dimensions. In vitro antioxidant assays (ABTS, FRAP, SAFR, SFR, ORAC, DPPH) demonstrated [...] Read more.

This study aimed to develop an environmentally friendly and relatively efficient method for extracting natural antioxidants from avocado by-products while investigating the antioxidant mechanisms of their core bioactive components on multiple dimensions. In vitro antioxidant assays (ABTS, FRAP, SAFR, SFR, ORAC, DPPH) demonstrated that flavonoid procyanidin was the primary antioxidant component in avocado seeds, exhibiting the strongest activity (DPPH EC₅₀ = 3.6 µg/mL). The Hill model indicated a positive synergistic effect (n = 3.1). Chemical and molecular mechanism analyses revealed that avocado seeds exert antioxidant activity predominantly through hydrogen atom transfer (HAT) and electron transfer (ET) pathways. The model predictions suggested procyanidins may stably bind to protein targets in the Keap1-Nrf2 pathway and NOX2 via hydrogen bonding, hydrophobic interactions, and π-cation interactions. Furthermore, response surface methodology (RSM) was employed to optimize the extraction process of avocado seed antioxidants in an ethanol-water system. This study underscores the considerable health benefits and antioxidant capacity of avocado by-products, supporting their promising application in functional foods formulations. Full article

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20 pages, 737 KB

Open AccessArticle

Comprehensive Characterization of Bioactive Properties in Extracts from Different Chilean Hop Ecotypes (Humulus lupulus L.): Antioxidant, Antimicrobial and Antitumor Activities

by María C. Betancur, Fernando Salazar, Michael Araya, Anita Behn, Jéssica López, Ana Quesille-Villalobos, José M. Villatoro, Jacqueline Poblete and Angara Zambrano

Antioxidants 2025, 14(10), 1224; https://doi.org/10.3390/antiox14101224 (registering DOI) - 11 Oct 2025

Chilean hop (Humulus lupulus L.) ecotypes are an under-explored resource with high bioactive potential, offering promising applications in food preservation and health promotion. This study aimed to characterize the chemical composition and evaluate the antioxidant, antimicrobial, and cytotoxic properties of methanolic extracts [...] Read more.

Chilean hop (Humulus lupulus L.) ecotypes are an under-explored resource with high bioactive potential, offering promising applications in food preservation and health promotion. This study aimed to characterize the chemical composition and evaluate the antioxidant, antimicrobial, and cytotoxic properties of methanolic extracts from three native ecotypes—Ranco, La Unión, and Valdivia—to identify their potential as sources of multifunctional bioactive compounds. Each ecotype exhibited a distinct composition of bioactive compounds; Valdivia stood out for its pronounced levels of α- and β-acids and xanthohumol. Antioxidant capacity, assessed by DPPH, FRAP, and ABTS, was strong across extracts, with Valdivia showing the highest values in all the tests carried out. The extracts inhibited multidrug-resistant clinical isolates, notably Enterococcus faecalis and Pseudomonas aeruginosa, and showed dose-dependent cytotoxic effects in H1299 and MCF-7 cell lines, with the La Unión extract particularly active against H1299. Overall, these findings position Chilean hop ecotypes as promising sources of natural antioxidants and antimicrobial agents for functional food and nutraceutical applications. Full article

(This article belongs to the Special Issue Antioxidant Research in Chile—2nd Edition)

23 pages, 2884 KB

Open AccessArticle

The Role of miR-144/Nrf2 Pathway in Muscle Oxidative Stress Induced by Oxidized Fish Oil in Megalobrama amblycephala, with an Emphasis on Protein Oxidation

by Jie Yang, Xiaochuan Zheng, Qunlan Zhou, Changyou Song, Hongyan Tian, Aimin Wang, Xiangfei Li, Bo Liu and Cunxin Sun

Antioxidants 2025, 14(10), 1223; https://doi.org/10.3390/antiox14101223 (registering DOI) - 11 Oct 2025

This study investigated the role of miR-144 in mitigating oxidized fish oil (OFO)-induced muscle oxidative stress and quality deterioration in Megalobrama amblycephala. The feeding trial was conducted for 5 weeks, and four experimental diets were formulated, namely NC (fresh fish oil), OF [...] Read more.

This study investigated the role of miR-144 in mitigating oxidized fish oil (OFO)-induced muscle oxidative stress and quality deterioration in Megalobrama amblycephala. The feeding trial was conducted for 5 weeks, and four experimental diets were formulated, namely NC (fresh fish oil), OF (OFO), OF + ago (OFO and miR-144 agomir), and OF + anta (OFO and miR-144 antagomir). Histological results showed that OFO significantly reduced myofiber density (from 758.00 ± 13.69 to 636.57 ± 13.44 N/mm²) and decreased the percentage of myofibers with diameters > 50 μm (from 53.45% to 38.52%). OFO intake significantly increased the content of malondialdehyde (MDA), protein carbonyl (PC), advanced oxidation protein product (AOPP), and 3-nitrotyrosine (3-NT), and significantly decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in muscle. OFO treatment significantly up-regulated the expression of inflammatory factors (NF-κB, TNF-α, HO-1, and IL-6), significantly down-regulated NQO1. Moreover, OFO reduced muscle differentiation and maturation by down-regulating the expression of MyoG, MYHC1, and protein synthesis genes (AKT3, TOR, and S6K1), and up-regulating the expression of protein hydrolysis genes (FoxO3a, MuRF1, HSP70, Beclin-1, P62, and ATG8). Moreover, miR-144 agomir exacerbated OFO-induced muscle damage by suppressing Nrf2, whereas miR-144 antagomir mitigated these effects. Silencing miR-144 re-activates Nrf2, alleviating oxidative damage, enhancing protein deposition, and improving muscle quality. These findings suggest that targeting the miR-144/Nrf2 axis could counteract OFO-induced muscle deterioration. Full article

(This article belongs to the Special Issue Natural Antioxidants and Aquatic Animal Health—2nd Edition)

16 pages, 2871 KB

Open AccessArticle

PK11007 Covalently Inhibits Thioredoxin Reductase 1 to Induce Oxidative Stress and Autophagy Impairment in NSCLC Cells

by Hanziyi Zhou, Shibo Sun, Haowen Liu, Tong Li, Yiran Xu, Rui Yang, Haiyan Liu, Leiyu He, Weiping Xu, Shui Guan and Jianqiang Xu

Antioxidants 2025, 14(10), 1222; https://doi.org/10.3390/antiox14101222 (registering DOI) - 11 Oct 2025

Selenoprotein thioredoxin reductase 1 (TXNRD1) is frequently upregulated in various cancer cells to sustain cellular redox homeostasis, and its inhibition has emerged as a promising anti-cancer strategy. In this study, we identified PK11007, a thiol-modifying compound previously characterized as a p53 reactivator, as [...] Read more.

Selenoprotein thioredoxin reductase 1 (TXNRD1) is frequently upregulated in various cancer cells to sustain cellular redox homeostasis, and its inhibition has emerged as a promising anti-cancer strategy. In this study, we identified PK11007, a thiol-modifying compound previously characterized as a p53 reactivator, as a potent inhibitor of TXNRD1. PK11007 irreversibly inhibited recombinant TXNRD1 in a time- and dose-dependent manner. Using differential scanning fluorimetry (DSF) and LC–MS/MS analysis, we confirmed that PK11007 covalently modifies the C-terminal redox motif (Cys⁴⁹⁷-Sec⁴⁹⁸) of TXNRD1. In non-small cell lung cancer (NSCLC) H1299 cells, PK11007-induced TXNRD1 inhibition disrupted cellular redox balance, leading to impaired autophagy flux and cell death. Similar autophagy suppression was observed in TXNRD1-knockdown cells, as well as pharmacological inhibition of TXNRD1 by Auranofin (AF) and TXNRD1 inhibitor 1 (TRi-1). Taken together, these findings highlight that oxidative stress contributes to the cytotoxic effects of PK11007 and uncover autophagy disorder as a downstream consequence of TXNRD1 inhibition. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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20 pages, 605 KB

Open AccessArticle

Effect of Dietary PUFAs and Antioxidants on Antioxidant and Anti-Inflammatory Functions of HDL in a Cohort of Women

by Gianmarco Mola, Raffaella Riccetti, Domenico Sergi, Alessandro Trentini, Valentina Rosta, Angela Passaro, Juana M. Sanz and Carlo Cervellati

Antioxidants 2025, 14(10), 1221; https://doi.org/10.3390/antiox14101221 - 10 Oct 2025

High-density lipoproteins (HDLs) protect against atherosclerosis through their antioxidant, anti-inflammatory, and other beneficial properties. Although interest is increasing in uncovering both physiological and external factors that influence these functions, definitive evidence remains lacking in this area. To fill this gap, we assessed for [...] Read more.

High-density lipoproteins (HDLs) protect against atherosclerosis through their antioxidant, anti-inflammatory, and other beneficial properties. Although interest is increasing in uncovering both physiological and external factors that influence these functions, definitive evidence remains lacking in this area. To fill this gap, we assessed for the first time how intake of saturated and unsaturated fatty acids and dietary antioxidants affects key HDL-associated proteins. We observed that myeloperoxidase (MPO) activity, a marker of HDL oxidation, was inversely correlated with total polyunsaturated fatty acids (PUFAs), omega-3 and omega-6 intake (p < 0.05), polyphenols (p < 0.001), and overall antioxidant capacity (p < 0.05). Levels of lipoprotein-associated phospholipase A2 also decreased with higher antioxidant consumption (p < 0.05). By contrast, glutathione peroxidase 3 (Gpx3) activity, a protective HDL enzyme, increased in tandem with omega-3 and antioxidant intake. Finally, a composite HDL-antioxidant/anti-inflammatory score integrating all measured proteins rose in association with total PUFAs (p < 0.001), omega-6 (p < 0.001), omega-3 (p < 0.01), polyphenols, and total antioxidants (p < 0.05). These findings suggest that higher dietary PUFA, especially omega-6, and antioxidant intake may enhance HDL’s atheroprotective properties. Full article

(This article belongs to the Special Issue Impact of Antioxidant and Anti-Inflammatory Functions of HDL in Diseases—3rd Edition)

29 pages, 51386 KB

Open AccessArticle

Aspirin Eugenol Ester Alleviates Vascular Endothelial Ferroptosis by Enhancing Antioxidant Ability and Inhibiting the JNK/c-Jun/NCOA4/FTH Signaling Pathway

by Ji Feng, Qi Tao, Zhi-Jie Zhang, Qin-Fang Yu, Ya-Jun Yang and Jian-Yong Li

Antioxidants 2025, 14(10), 1220; https://doi.org/10.3390/antiox14101220 - 10 Oct 2025

Oxidative stress occurs within bovine when exposed to harmful stimuli, accompanied by substantial accumulation of reactive oxygen species. Without timely clearance, these reactive oxygen species attack vascular endothelial cells, concurrently inducing extensive production of lipid peroxides within the vascular endothelium, and thereby triggering [...] Read more.

Oxidative stress occurs within bovine when exposed to harmful stimuli, accompanied by substantial accumulation of reactive oxygen species. Without timely clearance, these reactive oxygen species attack vascular endothelial cells, concurrently inducing extensive production of lipid peroxides within the vascular endothelium, and thereby triggering ferroptosis. Aspirin eugenol ester (AEE) showed pharmacological activity against oxidative stress-induced vascular endothelial damage. However, whether it could alleviate vascular endothelial damage by inhibiting ferroptosis remains unclear. This study aimed to evaluate the effects of AEE on vascular endothelial ferroptosis and elucidate its underlying molecular mechanisms. This study established vascular endothelial damage models in vitro and in vivo to explore the ability of AEE to inhibit ferroptosis and oxidative stress by measuring ferroptosis- and oxidative stress-related biomarkers. Transcriptomic and network pharmacology analyses were performed to identify AEE-regulated pathways and key targets. Validation of the pathways were conducted using molecular docking, cellular thermal shift assay, and specific protein agonists/inhibitors. AEE inhibited oxidative stress and ferroptosis in bovine aortic endothelial cells induced by hydrogen peroxide (H₂O₂) or RSL3 via suppressing the upregulation of ferroptosis-related genes and enhancing the expression of antioxidant genes. Transcriptomic and network pharmacology analyses identified JNK as a core target of AEE in regulating ferroptosis. JNK agonists enhanced H₂O₂-induced ferritinophagy; on the contrary, JNK inhibitors alleviated it. AEE suppressed H₂O₂-induced phosphorylation of JNK/c-Jun and ferritinophagy. In a carrageenan-induced rat aortic vascular endothelial damage model, AEE alleviated vascular endothelial damage and ferroptosis-related gene changes, promoted antioxidant gene expression, and inhibited JNK/c-Jun phosphorylation and ferritinophagy. AEE inhibited vascular endothelial ferroptosis by enhancing antioxidant ability, blocking downstream ferritinophagy, and reducing ferrous ion release. Full article

(This article belongs to the Section Aberrant Oxidation of Biomolecules)

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19 pages, 4771 KB

Open AccessArticle

Comparative Analysis of the Tolerance of Young and Old Kidneys to Injury in a Rat Model of Reversible Ureteral Obstruction

by Polina A. Abramicheva, Ilya A. Sokolov, Vasily N. Manskikh, Nadezda V. Andrianova, Dmitry S. Semenovich, Ljubava D. Zorova, Irina B. Pevzner and Egor Y. Plotnikov

Antioxidants 2025, 14(10), 1219; https://doi.org/10.3390/antiox14101219 - 10 Oct 2025

Obstructive nephropathy is a common clinical condition caused by urinary retention. After urine flow is restored, kidney function is recovered. However, the effectiveness of this process can be influenced by many factors, including the age of the patient. In this study, we analyzed [...] Read more.

Obstructive nephropathy is a common clinical condition caused by urinary retention. After urine flow is restored, kidney function is recovered. However, the effectiveness of this process can be influenced by many factors, including the age of the patient. In this study, we analyzed the following parameters in young and old rats subjected to a 3-day reversible unilateral ureteral obstruction (R-UUO): AKI severity, renal tissue proliferation and histology, inflammatory and fibrosis marker expression, as well as autophagosomal-lysosomal and mitochondrial function. Compared to old rats, young animals exhibited more pronounced renal tissue proliferation and higher expression of profibrotic markers (Col1a1, Fn1, Tgfb1, MMP2), but diminished expression of pro-inflammatory markers (Il1b, Tnfa, Cd32) in response to R-UUO. Additionally, young rats showed more pronounced activity of autophagy, as indicated by increased beclin-1 levels. R-UUO induced severe damage to the mitochondrial respiratory chain in old animals, as indicated by reduced complex I, IV, cytochrome c, VDAC protein levels, and impaired mitochondrial biogenesis (associated with decreased Pgc1a mRNA expression). Thus, we demonstrated that despite restored urine outflow, kidneys exhibited autophagy activation, inflammatory response, and mitochondrial dysfunction after R-UUO. Negative alterations in the kidney were age-dependent indicating necessity for therapeutic strategies optimization for patients of different ages. Full article

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16 pages, 7410 KB

Open AccessArticle

Exogenous Melatonin Attenuates Sleep Restriction-Induced Kidney Injury via Gut Microbiota-Derived Propionate in Mice

by An Cui, Qingyun Guan, Zixu Wang, Jing Cao, Yulan Dong and Yaoxing Chen

Antioxidants 2025, 14(10), 1218; https://doi.org/10.3390/antiox14101218 - 9 Oct 2025

Chronic sleep restriction (SR) impairs multiple organs. Although exogenous melatonin counteracts SR-induced gut microbiota disruption, its role in protecting renal function and the involvement of gut microbiota remain unclear. To this end, we subjected mice to a 28-day SR paradigm with exogenous melatonin [...] Read more.

Chronic sleep restriction (SR) impairs multiple organs. Although exogenous melatonin counteracts SR-induced gut microbiota disruption, its role in protecting renal function and the involvement of gut microbiota remain unclear. To this end, we subjected mice to a 28-day SR paradigm with exogenous melatonin treatment or antibiotic-induced microbiota depletion. SR mice demonstrated significant renal dysfunction evidenced by elevated serum creatinine, blood urea nitrogen, and uric acid levels compared to controls. Histopathological analysis revealed characteristic tubular abnormalities in SR mice, including epithelial degeneration and lumen dilation, with reduced expression of key renal filtration markers (Nephrin, Podocin, CD2-associated protein, and α-Actinin-4). All of these could be mitigated by melatonin treatment, and all changes were statistically significant (p < 0.05 or p < 0.01). Intriguingly, microbiota depletion significantly reversed the protective effect of exogenous melatonin on kidney injury in SR mice, while propionic acid supplementation mitigated SR-induced kidney injury. Furthermore, we found that gut microbiota and the metabolite propionic acid mediated the role of exogenous melatonin probably through attenuating SR-induced renal oxidative damage, including regulating renal superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) level. These findings collectively indicated that melatonin may ameliorate SR-associated kidney injury through gut microbiota-derived propionic acid. Our finding highlights a novel gut–kidney axis in SR-related pathophysiology. Full article

(This article belongs to the Special Issue Redox Resilience Signaling of Functional Nutrients and Neurotoxicant Pollutants for Human Health)

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15 pages, 2165 KB

Open AccessArticle

Screening of Mediterranean Plant-Derived Extracts for Antioxidant Effect in Cell-Free and Human Cell Line Models

by Giuseppe Argentino, Edoardo Giuseppe Di Leo, Chiara Stranieri, Stefano Negri, Mauro Commisso, Flavia Guzzo, Anna Maria Fratta Pasini, Annalisa Castagna and Simonetta Friso

Antioxidants 2025, 14(10), 1217; https://doi.org/10.3390/antiox14101217 - 9 Oct 2025

Oxidative stress plays a critical role in the development of various chronic diseases, leading to major health problems worldwide. There has been increasing interest in using natural antioxidants as complementary agents for maintaining redox homeostasis and assuring a healthy lifestyle. This study aimed [...] Read more.

Oxidative stress plays a critical role in the development of various chronic diseases, leading to major health problems worldwide. There has been increasing interest in using natural antioxidants as complementary agents for maintaining redox homeostasis and assuring a healthy lifestyle. This study aimed to systematically screen the antioxidant potential and cytotoxicity profiles of 19 plant-derived extracts using both a cell-free Fenton reaction-based assay and human monocytic THP-1 cells in vitro. The radical-scavenging capacity varied markedly among the extracts, with Acalypha virginica Linnaeus (ACALYPHA), Acorus calamus Linnaeus (ACORUS), Actinidia deliciosa (A.Chev.) C.F. Liang & A.R. Ferguson (ACTINIDIA), and Heuchera sanguinea Pursh (HEUCHERA) demonstrating strong activity in the chemical assay. In the cellular model, 15 extracts significantly reduced intracellular reactive oxygen species (ROS) levels without inducing cytotoxicity at effective concentrations. Notably, Acalypha virginica Linnaeus (ACALYPHA), Actinidia deliciosa (A.Chev.) C.F. Liang & A.R. Ferguson (ACTINIDIA), Dianthus superbus Linnaeus subsp. superbus (DIANTHUS), Succisa pratensis Moench (SUCCISA), and Typha laxmannii Lepech (TYPHA) exhibited consistent antioxidant efficacy across multiple doses. At higher concentrations, all extracts triggered apoptosis and/or necrosis, emphasizing the importance of defining safe ranges. These findings provide a comprehensive comparative analysis of Mediterranean plant-based natural antioxidants obtained by an in vitro approach. The selected plant extracts could be considered as promising candidates for the development of strategies targeting oxidative stress-related disorders. Further investigations considering the specific phytochemical composition of each extract and in vivo validation are needed to confirm their efficacy and safety. Full article

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

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22 pages, 2908 KB

Open AccessArticle

Proteomic Changes in the Cytoplasmatic Fraction of Weaned Piglets’ Liver and Kidney Under Antioxidant and Mycotoxin Diets

by Roua Gabriela Popescu, Anca Dinischiotu, Andreea-Angelica Stroe, Sergiu Emil Georgescu and George Cătălin Marinescu

Antioxidants 2025, 14(10), 1216; https://doi.org/10.3390/antiox14101216 - 9 Oct 2025

Mycotoxin contamination represents a major risk to both human and animal health. Antioxidants can mitigate some of these effects through free radical scavenging, reduction in oxidative stress, and anti-inflammatory and immunomodulatory actions. This work investigated the potential of antioxidants derived from grapeseed and [...] Read more.

Mycotoxin contamination represents a major risk to both human and animal health. Antioxidants can mitigate some of these effects through free radical scavenging, reduction in oxidative stress, and anti-inflammatory and immunomodulatory actions. This work investigated the potential of antioxidants derived from grapeseed and sea buckthorn to mitigate the adverse effects of aflatoxin B1 (AFB1) and ochratoxin A (OTA) in weaned piglets. An unbiased Data-Independent Acquisition (DIA) proteomic approach was used to analyse the impact of OTA- and AFB1-contaminated diets on liver and kidney cytoplasmic metabolism, particularly focusing on the conjugation phase. Our results indicate that several toxic effects of these mycotoxins were partially alleviated by dietary antioxidant supplementation. Additionally, in kidneys, some of the effects are synergistically amplified, such as proteins involved in fatty acid degradation, peroxisome, PPAR signalling, translation, the TCA cycle, and excretion pathways. Inclusion of antioxidants in the animal diet can have beneficial effects. Nevertheless, caution is advised; synergistic effects can occur with potentially more serious consequences than the effects of mycotoxins alone. Full article

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

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17 pages, 9922 KB

Open AccessArticle

Edaravone Mitigates Postovulatory Aging by Preserving Oocyte and Embryo Quality in Mice

by Kyeoung-Hwa Kim, Eun-Young Kim, Ah-Reum Lee, Mi-Kyoung Koong and Kyung-Ah Lee

Antioxidants 2025, 14(10), 1215; https://doi.org/10.3390/antiox14101215 - 9 Oct 2025

Postovulatory aging (POA) significantly contributes to fertility decline, primarily through oxidative stress, which impairs oocyte quality, reduces embryonic developmental competence, and may adversely affect offspring health. Edaravone (EDA), a potent free radical scavenger, is known for its cytoprotective effects in various disease models. [...] Read more.

Postovulatory aging (POA) significantly contributes to fertility decline, primarily through oxidative stress, which impairs oocyte quality, reduces embryonic developmental competence, and may adversely affect offspring health. Edaravone (EDA), a potent free radical scavenger, is known for its cytoprotective effects in various disease models. This study aimed to evaluate whether EDA can mitigate the detrimental effects of POA on mouse oocyte and embryo quality and confirm its reproductive safety. Supplementation with 10 nM EDA significantly reduced meiotic abnormalities, restored mitochondrial distribution, enhanced mitochondrial membrane potential and ATP production, and decreased intracellular reactive oxygen species (ROS) in aged oocytes. Although EDA did not markedly improve fertilization or blastocyst formation rates, it enhanced embryo quality, with morphokinetic parameters comparable to those of young oocytes. Moreover, F₁ offspring derived from embryos produced by EDA-treated POA oocytes were healthy, and female progeny exhibited normal reproductive competence. These findings demonstrate that EDA safely improves oocyte quality by alleviating POA-induced oxidative damage, offering a potential antioxidant strategy to enhance assisted reproductive technology (ART) outcomes when applied to IVF clinics. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—3rd Edition)

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22 pages, 2773 KB

Open AccessArticle

Antioxidant, Neuroprotective, and Antinociceptive Effects of Peruvian Black Maca (Lepidium meyenii Walp.)

by Iván M. Quispe-Díaz, Roberto O. Ybañez-Julca, Daniel Asunción-Alvarez, Cinthya Enriquez-Lara, José L. Polo-Bardales, Rafael Jara-Aguilar, Edmundo A. Venegas-Casanova, Ricardo D. D. G. de Albuquerque, Noé Costilla-Sánchez, Edison Vásquez-Corales, Pedro Buc Calderon and Julio Benites

Antioxidants 2025, 14(10), 1214; https://doi.org/10.3390/antiox14101214 - 8 Oct 2025

Lepidium meyenii Walp. (black maca, BM) is a traditional Andean crop increasingly studied for its bioactive potential. This work characterized the phytochemical profile and evaluated the antioxidant, antinociceptive, and neuroprotective properties of a lyophilized aqueous extract of BM hypocotyls. UHPLC-ESI-QTOF-MS/MS identified twelve major [...] Read more.

Lepidium meyenii Walp. (black maca, BM) is a traditional Andean crop increasingly studied for its bioactive potential. This work characterized the phytochemical profile and evaluated the antioxidant, antinociceptive, and neuroprotective properties of a lyophilized aqueous extract of BM hypocotyls. UHPLC-ESI-QTOF-MS/MS identified twelve major compounds, including macamides, imidazole alkaloids, sterols, and fatty acid amides. BM showed a moderate total phenolic content but strong electron transfer-based antioxidant activity in CUPRAC and FRAP assays, together with moderate radical scavenging capacity in ABTS and DPPH systems. In ovariectomized rats, BM significantly reduced brain malondialdehyde levels, mitigated oxidative stress, and improved spatial learning during acquisition in the Morris water maze, confirming its neuroprotective effect. Antinociceptive assays (hot plate, cold plate, and tail immersion) further revealed a rapid but transient increase in nociceptive thresholds. This study provides experimental evidence supporting the analgesic effect of black maca. Molecular docking highlighted lepidiline B and campesterol as key metabolites with strong interactions with redox enzymes, the μ-opioid receptor, and the FAAH enzyme, supporting their role in the observed bioactivities. ADMET predictions indicated favorable oral bioavailability, CNS penetration, systemic clearance, and acceptable safety profiles. These results substantiate the role of black maca as a neuroprotective nutraceutical and highlight its promise as a novel source of rapidly acting natural analgesic compounds. Full article

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

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14 pages, 1168 KB

Open AccessReview

Resveratrol and Its Nitric Oxide–Donor Hybrid as an Emerging Therapy for Oxidative-Stress-Driven Priapism in Sickle Cell Disease

by Carolina Oliveira Splendore, Mariana G. de Oliveira, Fernando Ferreira Costa and Fábio Henrique Silva

Antioxidants 2025, 14(10), 1213; https://doi.org/10.3390/antiox14101213 - 8 Oct 2025

Priapism is a frequent and debilitating complication in patients with sickle cell disease (SCD), characterized by recurrent ischemic episodes that can culminate in fibrosis of the erectile tissue and irreversible erectile dysfunction. Despite significant advancements in the management of acute episodes, current therapies [...] Read more.

Priapism is a frequent and debilitating complication in patients with sickle cell disease (SCD), characterized by recurrent ischemic episodes that can culminate in fibrosis of the erectile tissue and irreversible erectile dysfunction. Despite significant advancements in the management of acute episodes, current therapies remain largely ineffective in preventing recurrences, emphasizing the need for novel strategies that target the underlying pathophysiology. This narrative review describes the mechanistic links between oxidative stress and nitric oxide (NO) dysregulation in the pathogenesis of SCD-associated priapism, with a particular focus on the NO–cyclic guanosine monophosphate (cGMP)–phosphodiesterase type 5 (PDE5) signaling axis. We analyze preclinical evidence supporting resveratrol, a natural polyphenolic compound, as well as its NO-donor hybrid derivatives, as emerging therapeutic candidates. Additionally, we discuss the potential of combining resveratrol with current treatment approaches, and address the translational challenges that must be overcome to move from preclinical data to clinical application. Taken together, the evidence presented in this review supports resveratrol-based therapies as a promising approach for oxidative-stress-driven priapism in SCD and delineates critical perspectives for their further investigation. Full article

(This article belongs to the Special Issue Oxidative Stress and Male Reproductive Health)

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23 pages, 6082 KB

Open AccessArticle

A Bibenzyl from Dendrobium pachyglossum Exhibits Potent Anti-Cancer Activity Against Glioblastoma Multiforme

by Hnin Mon Aung, Onsurang Wattanathamsan, Kittipong Sanookpan, Aphinan Hongprasit, Chawanphat Muangnoi, Rianthong Phumsuay, Thanawan Rojpitikul, Boonchoo Sritularak, Tankun Bunlue, Naphat Chantaravisoot, Claudia R. Oliva, Corinne E. Griguer and Visarut Buranasudja

Antioxidants 2025, 14(10), 1212; https://doi.org/10.3390/antiox14101212 - 7 Oct 2025

Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options and a poor prognosis. Natural phytochemicals from Dendrobium species, particularly bibenzyl derivatives, possess diverse pharmacological activities, yet their potential against GBM remains largely unexplored. Here, we investigated the anticancer activity of [...] Read more.

Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options and a poor prognosis. Natural phytochemicals from Dendrobium species, particularly bibenzyl derivatives, possess diverse pharmacological activities, yet their potential against GBM remains largely unexplored. Here, we investigated the anticancer activity of 4,5,4′-trihydroxy-3,3′-dimethoxybibenzyl (TDB), a potent antioxidant bibenzyl derivative isolated from Dendrobium pachyglossum. In U87MG cells, TDB reduced viability in a dose- and time-dependent manner, suppressed clonogenic growth, induced apoptosis via Bax upregulation and Bcl-xL/Mcl-1 downregulation, and inhibited both mTORC1 and mTORC2 signaling. TDB also impaired cell migration and downregulated epithelial–mesenchymal transition (EMT)-associated proteins. Notably, TDB enhanced the cytotoxicity of temozolomide (TMZ), the current standard of care for GBM. These TMZ-sensitizing properties were further confirmed in patient-derived xenograft (PDX) Jx22 cells. To assess its potential for central nervous system delivery, blood–brain barrier (BBB) permeability was predicted using four independent in silico platforms—ADMETlab 3.0, LogBB_Pred, LightBBB, and BBB Predictor (Tree2C)—all of which consistently classified TDB as BBB-permeable. This predicted CNS accessibility, together with its potent anticancer profile, underscores TDB’s translational promise. Collectively, our findings identify TDB as a plant-derived antioxidant with multifaceted anti-GBM activity and favorable BBB penetration potential, warranting further in vivo validation and preclinical development as a novel therapeutic candidate for GBM. Full article

(This article belongs to the Special Issue Anti-Cancer Potential of Plant-Based Antioxidants)

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Effect of Microparticle Crystallinity and Food Matrix on the Release Profile and Antioxidant Activity of Encapsulated Gallic and Ellagic Acids During Simulated In Vitro Intestinal Digestion

by Yesica Vilcanqui, Alejandra Quintriqueo-Cid, Patricio Romero-Hasler, Begoña Giménez, Eduardo Soto-Bustamante and Paz Robert

Antioxidants 2025, 14(10), 1211; https://doi.org/10.3390/antiox14101211 - 7 Oct 2025

The development of phenolic-based functional food ingredients is of growing interest due to their beneficial effects on human health. This study investigated the combined influence of microparticle physical state, phenolic compound type (gallic acid, GA; and ellagic acid, EA), and model food matrix [...] Read more.

The development of phenolic-based functional food ingredients is of growing interest due to their beneficial effects on human health. This study investigated the combined influence of microparticle physical state, phenolic compound type (gallic acid, GA; and ellagic acid, EA), and model food matrix on the release profile, bioaccessibility, and antioxidant activity of GA and EA during in vitro gastrointestinal digestion. GA and EA were encapsulated with inulin (In) by spray-drying. By varying formulation and operational conditions, both semicrystalline (GA-InSc, EA-InSc) and amorphous (GA-InA, EA-InA) microparticles were obtained. Microparticles were characterized for crystallinity, encapsulation efficiency, particle size, morphology, and release profile during in vitro simulated gastrointestinal digestion following the INFOGEST method. The physical state of microparticles and type of phenolic compound critically influenced release profile, bioaccessibility, and antioxidant activity during digestion. GA, being more water-soluble, was rapidly released, reaching nearly 100% in the gastric phase, whereas EA exhibited limited gastric release and higher intestinal release, particularly in EA-InSc. Incorporation into different food matrices further modulated these effects; carbohydrate- and blend-based matrices improved phenolic release and antioxidant activity for both compounds. These findings highlight the importance of microparticle formulation, phenolic characteristics, and matrix interactions in designing functional food ingredients with optimized health benefits. Full article

(This article belongs to the Special Issue Phenolic Antioxidants—2nd Edition)

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6-O-trans-feruloyl Catalpol, a Natural Antioxidant from the Stem Bark of Catalpa ovata, Accelerates Liver Regeneration In Vivo via Activation of Hepatocyte Proliferation Signaling Pathways

by Jiyoung Park, Yun-Seo Kil, Ho Jin Yi, Eun Kyoung Seo and Hyun Ae Woo

Antioxidants 2025, 14(10), 1210; https://doi.org/10.3390/antiox14101210 - 6 Oct 2025

Background: Liver regeneration is a complex process involving multiple signaling pathways that coordinate hepatocyte proliferation, survival, and tissue repair. Natural compounds like silymarin, ursolic acid, quercetin, and resveratrol have shown regenerative potential, though their precise molecular mechanisms remain unclear. 6-O-trans-feruloyl catalpol [...] Read more.

Background: Liver regeneration is a complex process involving multiple signaling pathways that coordinate hepatocyte proliferation, survival, and tissue repair. Natural compounds like silymarin, ursolic acid, quercetin, and resveratrol have shown regenerative potential, though their precise molecular mechanisms remain unclear. 6-O-trans-feruloyl catalpol (6FC), a major bioactive compound from Catalpa ovata, exhibits anti-inflammatory and potential antioxidant effects via regulation of NF-κB signaling and redox-sensitive pathways such as Akt and MAPK, which are critical for cell survival and proliferation. Moreover, 6FC exhibits peroxynitrite-scavenging activity, suggesting its potential antioxidant properties that may protect hepatocytes from oxidative damage during regeneration. However, the role of 6FC in liver regeneration has not been elucidated, positioning it as a promising natural therapeutic candidate for hepatic repair. Purpose: This study aimed to determine whether 6FC promotes hepatocyte proliferation and liver regeneration in vivo using a 2/3 PHx mouse model, and to validate its proliferative effects in vitro with HGF-stimulated Hep3B cells. Methods: A 2/3 PHx liver regeneration model was used to evaluate 6FC-mediated liver regeneration. Histological and molecular analyses assessed hepatocyte proliferation and signaling activation. HGF-stimulated Hep3B cells were also used to examine 6FC proliferative effects in vitro. Results: 6FC significantly promoted liver regeneration by restoring the liver-to-body weight ratio and reducing serum ALT and AST levels without inducing excessive immune responses. Mechanistic studies revealed that 6FC activates Akt and MAPK pathways, increases the expression of critical growth factors, and upregulates cell cycle regulators. These effects were also observed in HGF-stimulated Hep3B cells, suggesting that 6FC may enhance hepatocyte proliferation without triggering excessive immune responses. Conclusions: 6FC accelerates hepatocyte proliferation and promotes liver regeneration by activating key redox-sensitive signaling pathways, highlighting its potential as a natural antioxidant-based therapeutic agent. Full article

(This article belongs to the Special Issue Antioxidant and Protective Effects of Plant Extracts—2nd Edition)

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28 pages, 6651 KB

Open AccessArticle

Effects of Lysolecithin on Growth Performance, Antioxidant Capacity, and Lipid Metabolism of Litopenaeus vannamei

by Yun Wang, Hailiang Yan, Hong Liang, Yafei Duan, Jun Wang, Chuanpeng Zhou and Zhong Huang

Antioxidants 2025, 14(10), 1209; https://doi.org/10.3390/antiox14101209 - 6 Oct 2025

Lysolecithin, characterized by its superior emulsifying and stabilizing properties, facilitates nutrient absorption and is extensively utilized in aquatic feed formulation. Nevertheless, its precise function in shrimp nutrition and physiology remains inadequately understood. This study aimed to evaluate the feasibility and optimal dosage of [...] Read more.

Lysolecithin, characterized by its superior emulsifying and stabilizing properties, facilitates nutrient absorption and is extensively utilized in aquatic feed formulation. Nevertheless, its precise function in shrimp nutrition and physiology remains inadequately understood. This study aimed to evaluate the feasibility and optimal dosage of replacing 2% soybean lecithin with varying levels of soybean lysolecithin (0–2%) in the diet of Litopenaeus vannamei. Growth performance, antioxidant indices, and lipid metabolism were assessed. The results demonstrated that dietary supplementation with 0.1% lysolecithin had the best growth performance, significantly improved lipid retention and apparent crude fat digestibility, while reducing malondialdehyde (MDA) levels in the hepatopancreas and alleviating endoplasmic reticulum (ER) stress. The 0.1% group also exhibited better hepatopancreatic tissue structure and lipid metabolic homeostasis. In contrast, higher inclusion levels (≥1.5%) led to increased lipid accumulation and enhanced activities of lipid metabolic enzymes but were associated with a risk of oxidative stress and less favorable tissue morphology. No significant differences in antioxidant enzyme activities were observed among groups. It is hypothesized that lysolecithin may regulate lipid metabolism and homeostasis via the Ca²⁺/CaMKKβ/AMPK signaling pathway; further studies are required to confirm this mechanism. In conclusion, 0.1% soybean lysolecithin is recommended as the optimal dietary level for L. vannamei, supporting its feasibility as a substitute for 2% soybean lecithin in shrimp feed. Full article

(This article belongs to the Special Issue Use of Antioxidant Supplementation in Aquaculture: Impact on Growth, Health, and Product Quality)

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24 pages, 2679 KB

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Schizochytrium Supplementation in Compound Feed: Effects on Growth, Metamorphosis, Intermediate Metabolism, and Intestinal Health of Bullfrogs (Lithobates catesbeianus)

by Hao Ding, Yinglin He, Yujian Song, Jingjing Liang, Woxing Li, Chao Xu and Huirong Yang

Antioxidants 2025, 14(10), 1208; https://doi.org/10.3390/antiox14101208 - 5 Oct 2025

Schizochytrium is often added to feed to enhance the growth and health of farmed animals, yet research on its effects on amphibians remains relatively scarce. Here, this study investigated the effects of dietary Schizochytrium meal on growth, metamorphosis, intermediate metabolism, and intestinal health [...] Read more.

Schizochytrium is often added to feed to enhance the growth and health of farmed animals, yet research on its effects on amphibians remains relatively scarce. Here, this study investigated the effects of dietary Schizochytrium meal on growth, metamorphosis, intermediate metabolism, and intestinal health of bullfrogs. Six compound feeds (S0–S5) containing different gradients of Schizochytrium meal (0.00, 2.00, 5.00, 10.00, 15.00, and 20.00 g/kg diets) were formulated. After 90 days, the S4 group (15.00 g/kg) exhibited significantly superior growth performance, with the weight gain rate (WGR) increasing by up to 23.78% compared to the control (S0). Metamorphosis rate (MR) peaked at 23.33% in the S4 group. The enzyme activities of digestion (amylase (AMS), lipase (LPS), protease), brush border membrane (Na⁺, K⁺-ATPase, alkaline phosphatase (AKP), γ-glutamyl transferase (γ-GT), creatine kinase (CK), and antioxidation (superoxide dismutase (SOD), catalase (CAT)), as well as microvilli length and mucosal epithelial cell height in the intestine were the highest in the S4 group. Intestinal microbial diversity (Ace index) significantly increased by 41.28% in the S4 group, which also promoted beneficial bacteria. Key genes related to the GH-IGF-1 axis, metabolism, and intestinal barrier function were significantly upregulated with increasing Schizochytrium levels up to 15.00 g/kg, whereas pro-inflammatory genes showed an opposite trend. Overall, dietary supplementation with Schizochytrium meal at 15.00 g/kg promotes growth, metamorphosis, and intestinal health in bullfrog tadpoles by modulating the GH-IGF-1 axis, enhancing digestion and absorption, and improving intestinal integrity. Optimal Schizochytrium meal levels were identified as 13.27 g/kg. Full article

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25 pages, 2327 KB

Open AccessArticle

Extraction Methods Shape the Phenolic Composition and Bioactivities of Defatted Moroccan Pistacia lentiscus L. Resin

by Abdessamad Beraich, Daniela Batovska, Krastena Nikolova, Burak Dikici, Göksen Gören, Yousra Belbachir, Mohamed Taibi, Amine Elbouzidi, Irena Mincheva, Natalina Panova, Abdesselam Tahani, Abdeslam Asehraou and Abdelmonaem Talhaoui

Antioxidants 2025, 14(10), 1207; https://doi.org/10.3390/antiox14101207 - 5 Oct 2025

Mastic gum from Pistacia lentiscus L. has long been valued in Mediterranean medicine and food preservation, yet its bioactive potential remains underexplored in specific geographic contexts. In Morocco, the resin—locally known as Meska Horra—is abundant but insufficiently characterized. This study compared three extraction [...] Read more.

Mastic gum from Pistacia lentiscus L. has long been valued in Mediterranean medicine and food preservation, yet its bioactive potential remains underexplored in specific geographic contexts. In Morocco, the resin—locally known as Meska Horra—is abundant but insufficiently characterized. This study compared three extraction methods—cold maceration (CM), Soxhlet extraction (SE), and ultrasound-assisted extraction (UAE)—using sequential acetone and 70% ethanol to recover complementary phenolic compounds from defatted resin. Targeted UHPLC–ESI–MS/MS profiling identified and quantified 30 phenolics, mainly flavonoids and phenolic acids, providing the first systematic dataset for Moroccan mastic gum. UAE–EtOH extract displayed the strongest antioxidant activity (DPPH IC₅₀ = 0.029 mg/mL; ABTS•⁺ IC₅₀ = 0.026 mg/mL). SE–acetone and SE–EtOH extracts showed potent antifungal activity, particularly against Geotrichum candidum, Rhodotorula glutinis, and Aspergillus niger (MBC = 1.7%). The SE–acetone extract exhibited cytotoxicity toward MIA PaCa-2 pancreatic cancer cells (IC₅₀ = 19 µg/mL). These findings demonstrate that extraction method and solvent choice strongly influence phenolic recovery and associated bioactivities, supporting the valorization of Moroccan mastic gum as a promising source for nutraceutical and pharmaceutical applications. Full article

(This article belongs to the Special Issue Green Extraction of Antioxidant from Natural Source)

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