Antioxidants

18 pages, 938 KB

Open AccessArticle

Phenolic Characterization and Comparative Antioxidant Profiling of Australian Asparagopsis armata and A. taxiformis Across Their Developmental Stages

by Kethabile Sonno, Faezeh Ebrahimi, Ziqi Lou, Hoang Chinh Nguyen, Colin J. Barrow and Hafiz A. R. Suleria

Antioxidants 2026, 15(2), 273; https://doi.org/10.3390/antiox15020273 - 23 Feb 2026

Viewed by 568

Abstract

Asparagopsis has gained global attention for its chemical properties and environmental applications. However, its two main species, Asparagopsis armata and Asparagopsis taxiformis, remain understudied, with limited information available regarding their bioactive potential, especially across their development. In this study, we examined the [...] Read more.

Asparagopsis has gained global attention for its chemical properties and environmental applications. However, its two main species, Asparagopsis armata and Asparagopsis taxiformis, remain understudied, with limited information available regarding their bioactive potential, especially across their development. In this study, we examined the phenolic profiles and antioxidant potentials of gametophyte and tetrasporophyte life stages and compared differences between conventional solvent extraction (CSE) and ultrasound-assisted extraction (UAE), including total phenol content, total flavonoid content, determination of condensed tannins, and seven types of antioxidant activity detections such as DPPH and ABTS. In general, the phenolic compounds and antioxidant potential of the Asparagopsis species vary significantly at different life stages and under different extraction techniques. Among them, the phenolic profile and antioxidant capacity of A. armata were recorded as significantly higher than those of A. taxiformis, as reflected by its greater relative antioxidant capacity index scores. In our study, while UAE did not universally outperform CSE, species- and life stage-specific improvements were recorded. Moreover, LC-ESI-QTOF-MS/MS tentatively identified 24 phenolic compounds (17 in A. armata and 14 in A. taxiformis), pointing to a diverse bioactive profile. Overall, Asparagopsis species demonstrated marked variability in phenolic and antioxidant potentials across life stages and extraction techniques. Full article

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

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31 pages, 2153 KB

Open AccessReview

Phytochemicals and REDOX Modulation: Molecular Mechanisms, Clinical Relevance, and Therapeutic Perspectives

by Desh Deepak Singh, Dharmendra Kumar Yadav and Dongyun Shin

Antioxidants 2026, 15(2), 272; https://doi.org/10.3390/antiox15020272 - 22 Feb 2026

Cited by 2 | Viewed by 867

Abstract

Oxidative stress and redox (REDOX) imbalance play a key role in the development of many chronic and degenerative disorders, including cardiovascular diseases, neurodegenerative conditions, cancer, and age-related illnesses. Beyond causing direct damage to macromolecules, disrupted REDOX signaling affects cellular homeostasis, alters inflammatory responses, [...] Read more.

Oxidative stress and redox (REDOX) imbalance play a key role in the development of many chronic and degenerative disorders, including cardiovascular diseases, neurodegenerative conditions, cancer, and age-related illnesses. Beyond causing direct damage to macromolecules, disrupted REDOX signaling affects cellular homeostasis, alters inflammatory responses, and modifies metabolic control, leading to disease onset and progression. Therefore, targeting oxidative pathways offers a promising therapeutic approach for managing chronic diseases. Naturally derived antioxidants, especially phytochemicals such as polyphenols, flavonoids, and carotenoids, have been identified as novel REDOX modulators with diverse biological effects that extend beyond simple free-radical scavenging. This review provides a detailed overview of the molecular mechanisms through which these phytochemicals influence oxidative pathways and exert protective effects on cells. We discuss their relevance in oxidative stress–related diseases, evaluate current clinical evidence regarding their efficacy, and highlight key challenges that limit their clinical application. Special attention is given to the roles of bioavailability, metabolism, and gut microbiota in shaping health outcomes associated with phytochemical consumption. Additionally, we outline emerging strategies to enhance phytochemical efficacy, including synergistic combinations and advanced delivery systems. Overall, this article underscores the potential of phytochemicals as active modulators of REDOX biology, supporting their role in precision nutrition and modern therapeutic approaches. Full article

(This article belongs to the Special Issue Antioxidant Activity of Polyphenolic Extracts)

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17 pages, 14638 KB

Open AccessArticle

Astragaloside IV Alleviates Trueperella pyogenes-Induced Endometritis via the Nrf2/HO-1 Signaling Pathway

by Chunyang Gou, Hetian Mu, Yueting Wang, Yanan Liu, Ziqi Peng, Yun Li, Mingwei Xing and Maozhen Qi

Antioxidants 2026, 15(2), 271; https://doi.org/10.3390/antiox15020271 - 22 Feb 2026

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Abstract

The increasing antimicrobial resistance of T. pyogenes, one of the principal pathogens associated with endometritis, presents a formidable challenge in veterinary medicine. Astragaloside IV (AS-IV) is a triterpene saponin compound isolated from the traditional Chinese medicine Astragalus membranaceus. While recognized as the [...] Read more.

The increasing antimicrobial resistance of T. pyogenes, one of the principal pathogens associated with endometritis, presents a formidable challenge in veterinary medicine. Astragaloside IV (AS-IV) is a triterpene saponin compound isolated from the traditional Chinese medicine Astragalus membranaceus. While recognized as the primary bioactive constituent of Astragalus membranaceus with diverse pharmacological properties, its potential to counteract T. pyogenes-induced endometritis has yet to be elucidated. In the current study, T. pyogenes infection models were successfully established in both mouse uteri and cultured goat endometrial epithelial cells (gEECs). Integrating histopathology, molecular biology and transcriptomic technology, this study characterized the multifaceted biological effects of AS-IV. Transcriptomic analysis indicates that the regulatory effects of AS-IV on T. pyogenes-induced infection are primarily associated with the enrichment of signaling pathways related to inflammation, apoptosis, and oxidative stress. Subsequent validation demonstrated that AS-IV treatment effectively alleviated T. pyogenes-induced endometrial damage by suppressing inflammation, apoptosis, and oxidative stress. These effects were mediated through Nrf2 and its downstream target HO-1, a mechanism further confirmed by the loss of protection upon Nrf2 inhibition. In summary, AS-IV protects the endometrium against T. pyogenes-induced inflammatory and oxidative damage by activating the Nrf2/HO-1 signaling pathway. Full article

(This article belongs to the Special Issue Bioactive Compounds: Antioxidant, Antibacterial, and Anti-Inflammatory Modulation—2nd Edition)

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20 pages, 100075 KB

Open AccessArticle

Exploring the Beneficial Effects of Se-Methylselenocysteine on GC-1/GC-2 Cells: From Cellular Uptake to Metabolic Pathway Regulation in Male Reproduction

by Yiqing Lu, Xiaofei Duan, Huatao Che, Tong Li, Xiaoling Dun, Xinfa Wang, Lixi Jiang, Zhenna Chen and Hanzhong Wang

Antioxidants 2026, 15(2), 270; https://doi.org/10.3390/antiox15020270 - 22 Feb 2026

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Abstract

Male infertility, a global health issue marked by spermatogenic failure, hinges on selenium (Se) as a key element for normal spermatogenesis. Among different Se species, Se-methylselenocysteine (MeSeCys) has been developed as a natural organic Se supplement with potent antioxidant and anti-inflammatory properties, but [...] Read more.

Male infertility, a global health issue marked by spermatogenic failure, hinges on selenium (Se) as a key element for normal spermatogenesis. Among different Se species, Se-methylselenocysteine (MeSeCys) has been developed as a natural organic Se supplement with potent antioxidant and anti-inflammatory properties, but its direct effects on male reproduction need to be further explored. This study investigated the effect of MeSeCys on GC-1 spg (GC-1) and GC-2 spd (ts) (GC-2) cell lines, which mimic early stages. Treatment with 75 μmol/L MeSeCys for 24 h markedly enhanced the viability of both cell lines, with a more pronounced effect observed in GC-1 than in GC-2 cells. Moreover, this study demonstrated that MeSeCys enters cells through SLC7A11 or LRP8 channels and elevates intracellular Se levels in both GC-1 and GC-2 cells, with higher levels observed in GC-1 cells. RNA sequencing (RNA-seq) and bioinformatics analysis revealed that MeSeCys may regulate selenocompound metabolism and the glutathione metabolism pathway in both cell lines, increasing their intracellular glutathione (GSH) levels. Importantly, in GC-1 cells, MeSeCys specifically modulates the mTOR pathway, which further modulates glutathione metabolism and intracellular redox balance. This finding provides novel insights into the beneficial effects of MeSeCys on male reproductive cells, highlighting its potential as a nutritional supplement for male reproductive health. Full article

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

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6 pages, 592 KB

Open AccessBrief Report

Increased Blood Plasma Levels of Methionine-Oxidized Clusterin Correlate with a Shift from Normal to Mild Cognitive Impairment and Alzheimer’s Disease Stages

by Amina H. Tbaba, Adam S. Smith and Jackob Moskovitz

Antioxidants 2026, 15(2), 269; https://doi.org/10.3390/antiox15020269 - 21 Feb 2026

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Abstract

Clusterin is a chaperon protein that is involved in many physiological processes, including binding to beta-amyloid (Aβ). Recently, we showed that in Alzheimer’s disease (AD) model mice and human postmortem brains, there are elevated levels of methionine-oxidized clusterin in the disease state versus [...] Read more.

Clusterin is a chaperon protein that is involved in many physiological processes, including binding to beta-amyloid (Aβ). Recently, we showed that in Alzheimer’s disease (AD) model mice and human postmortem brains, there are elevated levels of methionine-oxidized clusterin in the disease state versus controls. These observations prompted us to investigate the possibility that elevated methionine-oxidized levels of clusterin in human blood plasma correlate with clinical diagnosis of both mild cognitive impairment (MCI) and AD stages. To achieve this goal, we have used a combination of Elisa kits for determining the total level of clusterin and methionine-oxidized clusterin in human blood plasma, enabling the quantification of a methionine-oxidized clusterin to total clusterin ratio. This ratio was correlated with the diagnostics of three groups of patients (normal controls (NL), MCI, and AD; with n = 44 per group). Accordingly, it was determined that there was a significant increase in the relative methionine-oxidized clusterin level in the MCI and AD groups compared to the controls. In conclusion, it is suggested that increased levels of methionine-oxidized clusterin in human blood plasma may serve as a potential marker for MCI and AD diagnosis. Full article

(This article belongs to the Special Issue Oxidative Stress as a Therapeutic Target of Alzheimer’s Disease—2nd Edition)

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15 pages, 2561 KB

Open AccessArticle

Evaluation of Intratympanic Alpha-Lipoic Acid and Diltiazem as Alternatives to Dexamethasone in Noise-Induced Hearing Loss in a Murine Model

by Jae Sang Han, Kyusun Park, Ye Lin Kim, Ji Hyung Lim, So Young Park and Shi Nae Park

Antioxidants 2026, 15(2), 268; https://doi.org/10.3390/antiox15020268 - 21 Feb 2026

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Abstract

This study evaluates the protective effects of alpha-lipoic acid (ALA), diltiazem (DIL), and N-acetylcysteine (NAC) as potential adjunctive agents to enhance intratympanic dexamethasone (IT-DEX) therapy in noise-induced hearing loss. A two-phase experiment using C57BL/6J mice was conducted. In phase 1, candidate drugs [...] Read more.

This study evaluates the protective effects of alpha-lipoic acid (ALA), diltiazem (DIL), and N-acetylcysteine (NAC) as potential adjunctive agents to enhance intratympanic dexamethasone (IT-DEX) therapy in noise-induced hearing loss. A two-phase experiment using C57BL/6J mice was conducted. In phase 1, candidate drugs were screened by perilymph concentration analysis using ultra-high-performance liquid chromatography, auditory brainstem response (ABR) threshold, and organ of Corti (OC) morphology. Western blot analysis evaluated inflammatory markers. Phase 2 investigated the synergistic effects of co-administration of the most promising candidates with DEX. All drugs successfully penetrated the inner ear via IT injection. In the noise-induced hearing loss model, ALA and DIL individually demonstrated significant improvements in ABR thresholds and OC morphology compared to DEX alone, while NAC showed no therapeutic benefit. Western blot analysis revealed that ALA and DIL suppressed inflammatory markers through distinct antioxidant-mediated mechanisms, contrasting with DEX’s anti-inflammatory pathway. However, combination therapy with DEX + ALA or DEX + DIL increased middle ear inflammation and failed to produce synergistic therapeutic effects. While ALA and DIL showed individual therapeutic promise through complementary mechanisms, combination with DEX did not enhance efficacy, suggesting that simple drug combinations may not translate to improved IT therapy outcomes. Full article

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

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19 pages, 4205 KB

Open AccessArticle

Three Polyphenolic Compounds from Inonotus obliquus: Antioxidant Activity, Xanthine Oxidase Inhibition, and Regulatory Effects on MyD88/TLR4/NF-κB Pathway in MSU-Induced RAW 264.7 Macrophages

by Yuting Shu, Jiahui Chen, Shuyue Pang, Hongfei Liu, Helong Bai, Lina Chen, Jing Wang and Fanlei Meng

Antioxidants 2026, 15(2), 267; https://doi.org/10.3390/antiox15020267 - 21 Feb 2026

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Abstract

Background: Inonotus obliquus (Chaga), a medicinal and edible macrofungus abundant in bioactive polyphenols, is a potential source of natural antioxidants and anti-inflammatory agents for functional foods. This study aimed to evaluate the antioxidant capacity of three key polyphenols (osmundacetone [OS], protocatechuic aldehyde [PAH], [...] Read more.

Background: Inonotus obliquus (Chaga), a medicinal and edible macrofungus abundant in bioactive polyphenols, is a potential source of natural antioxidants and anti-inflammatory agents for functional foods. This study aimed to evaluate the antioxidant capacity of three key polyphenols (osmundacetone [OS], protocatechuic aldehyde [PAH], protocatechuic acid [PA]) from I. obliquus and decipher their anti-inflammatory mechanisms via the MyD88/TLR4/NF-κB pathway in a gout-related model. Methods: Antioxidant activity was assessed by xanthine oxidase (XO) inhibition (IC₅₀), superoxide anion (O₂⁻) scavenging, and structure–activity relationship (SAR) analysis; in a monosodium urate (MSU)-induced acute gout cell model, reactive oxygen species (ROS), nitric oxide (NO), lactate dehydrogenase (LDH), superoxide dismutase (SOD), pro-inflammatory cytokines (TNF-α, IL-1β) were quantified, and MyD88/TLR4/NF-κB pathway proteins were analyzed by Western blot. Results: OS showed the strongest XO inhibition (IC₅₀ = 4.91 mM), followed by PAH (IC₅₀ = 5.92 mM) and PA (IC₅₀ = 26.53 mM); OS exerted dual redox effects by scavenging O₂⁻ and suppressing XO-mediated O₂⁻ generation, with its conjugated C=C-carbonyl system and PAH’s aldehyde group enhancing XO binding. All polyphenols and I. obliquus crude extract significantly reduced ROS, NO, LDH, and cytokines (p < 0.05), increased SOD, and downregulated TLR4, MyD88, and NF-κB expression. Conclusions: I. obliquus-derived polyphenols exhibit obvious antioxidant and xanthine oxidase inhibitory effects, and regulate oxidative stress, pro-inflammatory mediators, and the MyD88/TLR4/NF-κB signaling pathway in monosodium urate-stimulated RAW 264.7 inflammatory macrophages, supporting their development as natural functional food ingredients and potential candidates for gout-related and oxidative stress-associated inflammatory cellular disorders. Full article

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

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17 pages, 2144 KB

Open AccessArticle

by Francisco J. Blanco, Natividad Oreiro, Jorge Vázquez-García, Antonio Morano-Torres, Sara Relaño, Laura Martínez-Sotodosos, Diana M. Noriega-Cobo, Fátima Otero-Fariña, Alejandro Mosquera, Jose L. Fernández and Ignacio Rego-Pérez

Antioxidants 2026, 15(2), 266; https://doi.org/10.3390/antiox15020266 - 21 Feb 2026

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Abstract

Rapid pain progression in knee osteoarthritis (OA) is heterogeneous and may reflect redox-related mechanisms. We performed an exploratory analysis in Osteoarthritis Initiative (OAI) participants, combining nuclear genome-wide association, mitochondrial DNA (mtDNA) haplogroups, and leukocyte telomere length. Rapid pain progression was defined using the [...] Read more.

Rapid pain progression in knee osteoarthritis (OA) is heterogeneous and may reflect redox-related mechanisms. We performed an exploratory analysis in Osteoarthritis Initiative (OAI) participants, combining nuclear genome-wide association, mitochondrial DNA (mtDNA) haplogroups, and leukocyte telomere length. Rapid pain progression was defined using the rescaled Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain (0–100) within 24-month windows. An additive genome-wide association study (GWAS) in 2946 participants tested 7,762,204 imputed variants, adjusting for age, sex, body mass index (BMI) and three principal components. Haplogroups were analysed in 3357 participants, and telomere length (telomere-to-single-copy gene, T/S, ratio) was analysed in 301 participants. No variant reached genome-wide significance (p < 5 × 10⁻⁸), but six loci were suggestive (p < 5 × 10⁻⁶), with minimal inflation (λ = 0.995). mtDNA haplogroup H was nominally associated with rapid pain progression (odds ratio, OR = 1.179, p = 0.023). Rapid pain progressors had shorter baseline telomeres (0.825 ± 0.268 vs. 0.985 ± 0.375; p < 0.001), and telomere length was inversely associated with progression (OR per 1-unit T/S = 0.260, p = 0.007). These preliminary, hypothesis-generating findings are compatible with a redox-related interpretation of rapid pain progression and require external validation in independent cohorts, while providing candidates for future mechanistic studies. Full article

(This article belongs to the Special Issue Exploring New Frontiers in Oxidative Stress and Antioxidant Research: From Model Organisms to Human Disease)

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13 pages, 654 KB

Open AccessArticle

Integrative Analysis of 4-Hydroxynonenal-Modified Proteins and Plasma Metabolome in Breast Cancer Patients

by Morana Jaganjac, Matea Nikolac Perkovic, Tea Horvat, David Rojo, Marija Krizic, Natalija Dedic Plavetic, Damir Vrbanec, Biserka Orehovec, Kamelija Zarkovic and Neven Zarkovic

Antioxidants 2026, 15(2), 265; https://doi.org/10.3390/antiox15020265 - 21 Feb 2026

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Abstract

Breast cancer is a highly heterogeneous malignancy, characterized by diverse genetic, epigenetic, and phenotypic variations, as well as by metabolic reprogramming and oxidative stress. Lipid peroxidation bioactive product 4-hydroxynonenal (4-HNE) plays a significant role in the development and progression of cancer. In this [...] Read more.

Breast cancer is a highly heterogeneous malignancy, characterized by diverse genetic, epigenetic, and phenotypic variations, as well as by metabolic reprogramming and oxidative stress. Lipid peroxidation bioactive product 4-hydroxynonenal (4-HNE) plays a significant role in the development and progression of cancer. In this study, we quantified circulating 4-HNE-modified proteins and performed comprehensive untargeted metabolomic profiling of the patients’ plasma using LC-ESI-QTOF-MS and GC-EI-QMS, aiming to investigate systemic metabolic pathways associated with oxidative damage in breast cancer. Significantly elevated levels of 4-HNE-modified proteins were detected in breast cancer patients compared to healthy controls, accompanied by distinct metabolomic signatures enriched in lipid metabolism. Several metabolites, including specific long-chain fatty acids, exhibited significant correlations with circulating 4-HNE-modified proteins, suggesting an interaction between lipid peroxidation-driven protein modification and breast cancer-associated metabolic reprogramming. Overall, this study provides evidence of associations between systemic 4-HNE-mediated protein modification and altered metabolic profiles in breast cancer, highlighting oxidative stress–related metabolites as potential biomarkers and pointing to redox-metabolic crosstalk in breast cancer patients. Full article

(This article belongs to the Special Issue Oxidative Stress in Cell Senescence)

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25 pages, 2474 KB

Open AccessArticle

Thermal Processing Effects on Bioactive Composition and Physicochemical Parameters of Citrus grandis Juices: A Cultivar-Specific Study

by Lucia Francesca Vuono, Roberta Pino, Natale Badalamenti, Antonio Gattuso, Rosa Tundis, Maurizio Bruno, Rosario Schicchi, Anna Geraci, Monica Rosa Loizzo and Vincenzo Sicari

Antioxidants 2026, 15(2), 264; https://doi.org/10.3390/antiox15020264 - 20 Feb 2026

Viewed by 529

Abstract

Conventional thermal pasteurization is widely applied to ensure the safety of fruit juices, although its impact on bioactive compounds and functional properties may vary according to cultivar. This study evaluated the effects of conventional pasteurization on physicochemical parameters, bioactive composition, antioxidant capacity, and [...] Read more.

Conventional thermal pasteurization is widely applied to ensure the safety of fruit juices, although its impact on bioactive compounds and functional properties may vary according to cultivar. This study evaluated the effects of conventional pasteurization on physicochemical parameters, bioactive composition, antioxidant capacity, and enzyme inhibitory activities of juices obtained from five Sicilian Citrus grandis cultivars (Todarii, Maxima, Pyriformis, Chadock, and Terracciani). Total polyphenols, flavonoids, and carotenoids were quantified, while flavanone profiles were characterized by means of HPLC analysis. Antioxidant activity was assessed using DPPH, ABTS, FRAP, and β-carotene bleaching assays, and in vitro inhibitory activities against α-amylase, α-glucosidase, and pancreatic lipase were determined. Pasteurization led to cultivar-dependent reductions in total polyphenols (up to ~40%), flavonoids (up to ~45%), and carotenoids (up to ~25%), accompanied by decreased radical scavenging capacity and reducing power. Naringin was identified as the predominant flavanone, with thermal processing inducing both degradation and release phenomena depending on the cultivar. Fresh juices exhibited stronger enzyme inhibitory activities, particularly against α-amylase and α-glucosidase. Multivariate analysis discriminated against fresh and pasteurized juices, identifying phenolics as the main contributors to antioxidant capacity. Despite bioactive reductions, functional quality was partially preserved, supporting targeted cultivar selection for optimized industrial processing. Full article

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19 pages, 2513 KB

Open AccessArticle

Antimetastatic Effects of a Griffonia simplicifolia Seed Extract in Osteosarcoma Cell Lines

by Daniele Bellavia, Flores Naselli, Graziella Serio, Paola Miriam Russo, Viviana Costa, Angela De Luca, Lavinia Raimondi, Carla Gentile, Fabio Caradonna and Gianluca Giavaresi

Antioxidants 2026, 15(2), 263; https://doi.org/10.3390/antiox15020263 - 19 Feb 2026

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Abstract

Osteosarcoma is one of the most common malignant tumors that develop in the bone. Currently, surgery is often the best and most used approach, often preceded and followed by chemotherapy, which, however, carries serious short- and long-term side effects. Recently, much attention has [...] Read more.

Osteosarcoma is one of the most common malignant tumors that develop in the bone. Currently, surgery is often the best and most used approach, often preceded and followed by chemotherapy, which, however, carries serious short- and long-term side effects. Recently, much attention has been paid to natural compounds capable of inducing tumor cell death, reducing tumor and metastatic activity, and interacting with selective chemotherapy targeting tumor cells. Griffonia simplicifolia, a tropical African plant, has attracted attention because its extracts with bioactive chemicals have demonstrated multiple therapeutic uses. We show the antitumor properties of a Griffonia seed extract, obtained by maceration in a hydroalcoholic mixture (ethanol/water, 70/30, v/v, Gri70), on osteosarcoma cell lines, evaluating cytotoxicity, interaction with a pro-inflammatory signal (interleukin-1β), epigenetic activity of this signal on interleukin-6 gene expression, and interactions with an elective chemotherapeutic agent, doxorubicin. Although the extract did not have strong antiproliferative activity in the cell lines analyzed, we nevertheless observed that it was able to block proliferative and migration signals induced by interleukin-1β, as well as acting epigenetically by blocking the de-methylation of the interleukin-6 promoter and its expression. Furthermore, the extract did not appear to interfere with the antitumor activity of doxorubicin, and the interaction potentiated antimetastatic effects. These results indicate that Gri-70 extract may be useful as adjuvants to enhance the effect of doxorubicin, reducing the adverse effects associated with the increased EMT process of osteosarcoma cells that manage to overcome cell death induction. Indeed, metastasis represents the main cause of poor prognosis. Full article

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

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17 pages, 668 KB

Open AccessArticle

Multilevel Assessment of the Antioxidant Potential of Two Edible Insects Following In Vitro Simulated Gastrointestinal Digestion

by Eleni Dalaka, Demeter Lorentha S. Gidari, Constantin S. Filintas, Violetta Bantola, Nickolas G. Kavallieratos and Georgios Theodorou

Antioxidants 2026, 15(2), 262; https://doi.org/10.3390/antiox15020262 - 19 Feb 2026

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Abstract

In recent years, insect-derived peptides have attracted attention for their potential biological activities, particularly antioxidant properties. This study assessed the antioxidant activity of two widely consumed edible insects, T. molitor and A. diaperinus larvae, using cell-free and cell-based approaches. Whole lyophilized larvae, digestion [...] Read more.

In recent years, insect-derived peptides have attracted attention for their potential biological activities, particularly antioxidant properties. This study assessed the antioxidant activity of two widely consumed edible insects, T. molitor and A. diaperinus larvae, using cell-free and cell-based approaches. Whole lyophilized larvae, digestion products from the oral, gastric, and intestinal phases, as well as the <3 kDa permeate fraction (D-P3) derived from the intestinal digestion phase, were evaluated using biochemical antioxidant assays. Overall, digested samples exhibited higher antioxidant capacity than their undigested counterparts. At the cellular level, treatment of LPS-stimulated, PMA-differentiated THP-1 macrophages with A. diaperinus D-P3 was associated with increased mRNA expression of genes related to antioxidant defense, including NFE2-like bZIP transcription factor 2 (NFE2L2, also known as Nrf2), glutathione-disulfide reductase (GSR), superoxide dismutase 1 (SOD1), and catalase (CAT), whereas T. molitor D-P3 preferentially modulated nuclear factor kappa B p50 subunit (NFKB1) and nuclear factor kappa B p65 subunit (RELA). Overall, these findings indicate that gastrointestinal digestion enhances the bioaccessibility of antioxidant components in both edible insect species while revealing species-specific transcriptional responses under in vitro inflammatory conditions. This multilevel assessment provides mechanistic insight into the antioxidant-related biological activity of digestion-derived insect peptides and supports their further investigation as functional ingredients in food and feed systems. Full article

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58 pages, 3432 KB

Open AccessReview

Receptor–Mitochondria Crosstalk in the Kynurenine Metabolic Pathway: Integrating Metabolomics and Clinical Mass Spectrometry

by László Juhász, Zsolt Galla, Masaru Tanaka and László Vécsei

Antioxidants 2026, 15(2), 261; https://doi.org/10.3390/antiox15020261 - 19 Feb 2026

Cited by 1 | Viewed by 1032

Abstract

Mitochondria govern energy transfer, redox balance, and cell fate. Tryptophan catabolism generates kynurenines (KYNs) that can tune mitochondrial function, with growing evidence that G protein-coupled receptor 35 (GPR35), aryl hydrocarbon receptor (AhR), and N-methyl-D-aspartate receptors (NMDA receptors) link extracellular cues to adenosine 5 [...] Read more.

Mitochondria govern energy transfer, redox balance, and cell fate. Tryptophan catabolism generates kynurenines (KYNs) that can tune mitochondrial function, with growing evidence that G protein-coupled receptor 35 (GPR35), aryl hydrocarbon receptor (AhR), and N-methyl-D-aspartate receptors (NMDA receptors) link extracellular cues to adenosine 5 prime triphosphate (ATP) maintenance, calcium (Ca²⁺) handling, mitophagy, and inflammasome control. In parallel, quinolinic acid (QA)-driven de novo nicotinamide adenine dinucleotide (NAD⁺) synthesis connects KYN flux to tricarboxylic acid (TCA) cycle activity and sirtuin programs across tissues. Key gaps remain: receptor pharmacology is rarely integrated with NAD⁺ economics and respiration, and clinical workflows still lack single-run assays that quantify both kynurenine and TCA nodes. We therefore integrate receptor proximal signaling, QA-driven NAD⁺ supply, and unified liquid chromatography–mass spectrometry (LC-MS) measurement into one translational framework spanning kynurenic acid (KYNA), KYN, 3-hydroxykynurenine (3-HK), and QA, using mitochondrial endpoints as the common readout. We synthesize evidence for mitochondrial GPR35 signaling that preserves ATP, AhR programs that tune oxidative defenses and mitophagy, and NMDA receptor antagonism that limits excitotoxic stress. These mechanisms are linked to QA-dependent NAD⁺ biogenesis and alpha ketoglutarate control points, then aligned with chromatography and ionization choices suited to routine LC-MS workflows. This receptor to organelle framework couples KYN flux to respiratory control and provides a practical roadmap for standardized single-run LC-MS panels. It can strengthen target validation in ischemia, neurodegeneration, psychiatry, and oncology while improving biomarker qualification through harmonized analytics and decision-grade readouts. Full article

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

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18 pages, 22873 KB

Open AccessArticle

Long-Term Consumption of Hydrogen-Rich Water Mitigates Oxidative Stress, Hepatic Inflammation, and Apoptosis in Rats with LPS-Induced Chronic Liver Injury

by Luyao Zhang, Hanyu Wang, Yingxuan Mai, Qi He, Tao Liu, Na Zhang and Jiantao Zhang

Antioxidants 2026, 15(2), 260; https://doi.org/10.3390/antiox15020260 - 18 Feb 2026

Viewed by 846

Abstract

(1) Background: Chronic inflammation is considered an important pathological basis underlying the development and progression of multiple metabolic liver diseases; although hydrogen-rich water (HRW) has shown beneficial effects in acute inflammation, its long-term impact on chronic hepatic inflammation remains unclear. (2) Methods [...] Read more.

(1) Background: Chronic inflammation is considered an important pathological basis underlying the development and progression of multiple metabolic liver diseases; although hydrogen-rich water (HRW) has shown beneficial effects in acute inflammation, its long-term impact on chronic hepatic inflammation remains unclear. (2) Methods: Sprague–Dawley rats were pretreated with HRW for 8 months, after which a lipopolysaccharide (LPS)-induced rat model of chronic hepatic inflammation was established, with continuous HRW administration throughout the experimental period. (3) Results: Long-term HRW consumption significantly reduced LPS-induced inflammatory cell infiltration in liver tissue, suppressed the abnormal elevation of pro-inflammatory factors, and maintained relatively stable expression levels of anti-inflammatory factors. In addition, HRW attenuated pro-apoptotic signaling associated with the death receptor pathway, mitochondrial pathway, and endoplasmic reticulum stress (including Bax, Cyt c, Caspase-3, Caspase-8, Caspase-9, Caspase-12, CHOP, and GRP78), while preserving the expression of the anti-apoptotic protein Bcl-2, thereby partially preventing the tendency toward hepatocyte apoptosis induced by chronic inflammation. (4) Conclusions: Long-term consumption of HRW may delay the onset and progression of chronic inflammation-related liver injury by alleviating inflammatory responses, oxidative stress, mitochondrial dysfunction, and apoptotic activity, thus exerting a preventive protective effect on the liver. Full article

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

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28 pages, 4086 KB

Open AccessArticle

Targeted Reduction of Excessive Mitochondrial Superoxide by Mitoquinone Rescues Cognitive Impairment Without Affecting Spontaneous Recurrent Seizures in a Mouse Model of Temporal Lobe Epilepsy

by Segewkal H. Heruye, Stephanie A. Matthews, Shruthi H. Iyer, Malavika Deodhar, Ted J. Warren, Peter J. West, Kristina A. Simeone and Timothy A. Simeone

Antioxidants 2026, 15(2), 259; https://doi.org/10.3390/antiox15020259 - 18 Feb 2026

Viewed by 868

Abstract

Cognitive impairment is a major comorbidity in temporal lobe epilepsy (TLE), yet its underlying pathophysiology remains poorly understood and current therapies provide minimal benefit. While oxidative stress has traditionally been viewed as a precursor to cell death-mediated cognitive decline, cell death is absent [...] Read more.

Cognitive impairment is a major comorbidity in temporal lobe epilepsy (TLE), yet its underlying pathophysiology remains poorly understood and current therapies provide minimal benefit. While oxidative stress has traditionally been viewed as a precursor to cell death-mediated cognitive decline, cell death is absent in many patients and preclinical models with memory impairment. Here, we tested whether excessive mitochondrial reactive oxygen species (ROS) actively contribute to memory impairment through mechanisms distinct from cell death. Using Kv1.1 knockout (KO) mice, a TLE model with mitochondrial respiratory chain complex I (MRCI) impairment, we found elevated hippocampal mitochondrial superoxide, impaired recognition memory, deficits in synaptic plasticity, and abnormal sharp wave–ripple oscillations. Applying the MRCI inhibitor rotenone to wild-type hippocampal slices caused increased superoxide and mirrored electrophysiology deficits. Both acute and sub-chronic treatment with the mitochondria-targeted antioxidant mitoquinone (MitoQ) reduced superoxide levels, rescued synaptic plasticity, restored network activity, and normalized memory performance in KO mice—without altering seizure frequency, severity, or neuronal excitability. Our results identify mitochondrial superoxide as a reversible driver of hippocampal dysfunction in epilepsy and demonstrate that mitochondria-targeted antioxidant therapy can restore cognition despite persistent seizures. This study provides proof-of-concept for novel treatments improving cognitive comorbidities in TLE beyond seizure control. Full article

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

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23 pages, 5790 KB

Open AccessArticle

Saposhnikovia divaricata Inhibits Inflammation, Oxidative Stress, and Ferroptosis to Alleviate DSS-Induced Ulcerative Colitis

by Lin Liu, Qiting Dou, Xiaoxuan Zhao, Yun Liang, Ziyi Tian, Dantong Su, Lin Zhou and Xuguang Hu

Antioxidants 2026, 15(2), 258; https://doi.org/10.3390/antiox15020258 - 18 Feb 2026

Viewed by 892

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that seriously jeopardizes health. Saposhnikovia divaricata (FF) has anti-inflammatory and antioxidant pharmacological effects. Numerous studies have demonstrated the efficacy of FF in alleviating UC, but the potential mechanism by which inhibiting ferroptosis alleviates UC [...] Read more.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that seriously jeopardizes health. Saposhnikovia divaricata (FF) has anti-inflammatory and antioxidant pharmacological effects. Numerous studies have demonstrated the efficacy of FF in alleviating UC, but the potential mechanism by which inhibiting ferroptosis alleviates UC remains unclear. This research aims to investigate the ways in which FF regulates inflammation, oxidative stress and ferroptosis to attenuate UC. Firstly, the chemical compounds of FF were identified by UPLC-Q-Orbitrap HRMS. FF significantly reduced levels of nitric oxide (NO), proinflammatory cytokines and reactive oxygen species (ROS) in the lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophage cells. We used 3% Dextrose sulfate sodium (DSS) to establish the UC model in C57BL/6 mice. FF (8.4 g/kg) effectively ameliorated the symptoms of weight loss and colon damage, significantly attenuating oxidative stress and modulated the levels of ferroptosis markers in the colon. Moreover, FF can down-regulate the expression of p53 protein and up-regulate the expression of SLC7A11 and GPX4 proteins. The results showed that FF can inhibit inflammation, oxidative stress, and ferroptosis to alleviate DSS-induced UC, by regulating the p53 signaling pathway. Full article

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24 pages, 4096 KB

Open AccessArticle

Impacts of Long-Term High-Temperature and Low-Salinity Stress on the Circadian Rhythms of Antioxidant, Immune, and Endocrine Systems in Turbot (Scophthalmus maximus)

by Zhifeng Liu, Mingchao Yang, Yuelei Shi, Yilin Wang, Junlian Zhong, Yunyi Gao and Aijun Ma

Antioxidants 2026, 15(2), 257; https://doi.org/10.3390/antiox15020257 - 17 Feb 2026

Viewed by 679

Abstract

Turbot (Scophthalmus maximus) is an economically vital cold-water fish frequently challenged by summer heat and low salinity. However, the temporal response of physiological circadian rhythms to such long-term stress remains underexplored. This study investigated antioxidant, immune, and endocrine rhythms in turbot [...] Read more.

Turbot (Scophthalmus maximus) is an economically vital cold-water fish frequently challenged by summer heat and low salinity. However, the temporal response of physiological circadian rhythms to such long-term stress remains underexplored. This study investigated antioxidant, immune, and endocrine rhythms in turbot acclimated to control (16 °C, 30 ppt), high-temperature (23 °C), and low-salinity (10 ppt) conditions for 30 days. Subsequently, time-series sampling was performed every 4 h for 72 consecutive hours. Under optimal conditions, hepatic superoxide dismutase (SOD), serum alanine aminotransferase (ALT), and melatonin exhibited robust 24 h rhythms. Long-term stress disrupted this homeostasis through divergent mechanisms. Low-salinity stress induced “rhythmic remodeling,” maintaining balance via phase shifts or novel infradian (48–72 h) oscillations in thyroid hormones (T3, T4) and ALT, without oxidative damage. Conversely, high-temperature stress triggered “rhythmic collapse,” characterized by a loss of daily rhythms in SOD and ALT, sustained inflammation indicated by elevated acid phosphatase (ACP), metabolic depression (suppressed T3), and malondialdehyde accumulation. These findings demonstrate that heat stress poses a more destructive threat to circadian integrity than hyposmotic stress. Consequently, the rhythmic dynamics of ACP, ALT, T3, and T4 are identified as critical indicators of stress status, serving as potential biomarkers for screening stress-tolerant strains for selective breeding. Full article

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

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19 pages, 1461 KB

Open AccessArticle

Structural Descriptors and Antioxidant Activity Markers of 4-[4-(2-Aminoethoxy)benzyl]aniline

by Dmitry A. Filimonov, Alexander B. Eresko, Nadezhda N. Trubnikova, Irina A. Kisilenko, Margarita A. Belotserkovskaya, Elena V. Raksha, Roman V. Ishchenko and Dorota M. Chudoba

Antioxidants 2026, 15(2), 256; https://doi.org/10.3390/antiox15020256 - 17 Feb 2026

Viewed by 1212

Abstract

The release of reactive oxygen species accompanying oxidative stress is one of the most significant damaging mechanisms during brain ischemia. Some aspects of the neuroprotective activity of the thyronamine T0AM synthetic analogue, 4-[4-(2-aminoethoxy)benzyl]aniline (ABA), were studied and discussed in two independent experiments using [...] Read more.

The release of reactive oxygen species accompanying oxidative stress is one of the most significant damaging mechanisms during brain ischemia. Some aspects of the neuroprotective activity of the thyronamine T0AM synthetic analogue, 4-[4-(2-aminoethoxy)benzyl]aniline (ABA), were studied and discussed in two independent experiments using a model of acute cerebral ischemia. Antioxidant effects were evaluated in adult male and female Wistar rats (Rattus norvegicus), while neurological outcomes were assessed in adult male outbred white rats. Administration of the ABA in a rat brain hemisphere ischemia model was associated with significant changes in redox markers: malondialdehyde, glutathione peroxidase and superoxide dismutase levels in the ischemic hemisphere. Also, the introduction of ABA into the model of acute cerebral ischemia contributed to a reduction in neurological deficit compared to untreated controls. It was revealed that the considered thyronamine T0AM analogue could control redox status in acute brain ischemia. Mono protonated form of ABA (ABA-H⁺) is considered to be the main species at pH 6.9–7.2. Structural models of the neutral (ABA), protonated (ABA-H⁺) thyronamine and its solvate (DMSO…ABA-H⁺) were used in DFT calculations, followed by estimation of molecular and supramolecular level descriptors. Full article

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

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18 pages, 727 KB

Open AccessArticle

Protective Effects of Curcumin and Sulforaphane Against Ionising Radiation–Induced Oxidative Stress and Inflammatory Responses in Rat Lung Tissue

by Katarina Baralić, Jovana Živanović, Predrag Božović, Nikola Kržanović, Neda Šćepanović, Jelena Petrović and Danijela Đukić-Ćosić

Antioxidants 2026, 15(2), 255; https://doi.org/10.3390/antiox15020255 - 15 Feb 2026

Viewed by 782

Abstract

Ionising radiation-induced lung injury is a major complication of thoracic radiotherapy, primarily driven by oxidative stress and inflammation. The current study evaluates and compares the protective effects of sulforaphane (SFN) and curcumin (CUR) pretreatment against radiation-induced oxidative damage and inflammation in rat lung [...] Read more.

Ionising radiation-induced lung injury is a major complication of thoracic radiotherapy, primarily driven by oxidative stress and inflammation. The current study evaluates and compares the protective effects of sulforaphane (SFN) and curcumin (CUR) pretreatment against radiation-induced oxidative damage and inflammation in rat lung tissue. Female Wistar rats were pretreated in vivo with SFN (2 mg/kg b.w./day) or CUR (4.13 mg/kg b.w./day) for 28 days per os. Isolated lung tissues were exposed ex vivo to γ-radiation (absorbed dose: 2 Gy). Oxidative stress markers—malondialdehyde (MDA), ischemia-modified albumin (IMA), total sulfhydryl (SH) groups, reduced glutathione (GSH), and superoxide dismutase (SOD)—and inflammatory markers—tumour necrosis factor alpha (TNF-α), prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β)—were measured to evaluate irradiation and protective effects. Radiation significantly increased MDA, TNF-α, PTGS2/COX-2, and IL-6 levels while decreasing SH groups. Pretreatment with SFN or CUR attenuated these changes. CUR showed a more pronounced effect on oxidative stress-related parameters, whereas SFN more strongly influenced inflammatory markers. These findings suggest that SFN and CUR differentially modulate radiation-induced oxidative and inflammatory responses in lung tissue under the applied experimental conditions and warrant further investigation of their potential as protective agents in radiotherapy. Full article

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29 pages, 3255 KB

Open AccessArticle

Fermented and Unfermented Rooibos (Aspalathus linearis) Exhibit Selective Protection Against Hepatic Stress in Rats Exposed to Fumonisin B1

by Jeanine L. Marnewick, Omeralfaroug Ali, Naeem Sheik Abdul, Taskeen Fathima Docrat, Elias Chipofya, Paolo Bristow, András Szabó, Tamás Schieszl, Krisztián Balogh, Brigitta Bóta, Janka Turbók, Viktória Varga-Szatmári, Edward Agyarko and Melinda Kovács

Antioxidants 2026, 15(2), 254; https://doi.org/10.3390/antiox15020254 - 14 Feb 2026

Viewed by 765

Abstract

The exploration of natural redox-modulating agents to mitigate/reduce oxidative damage triggered by toxins is a major area of interest in nutritional and pharmacological fields. Aspalathus linearis (rooibos), traditionally consumed in South Africa for health benefits, was assessed for hepatoprotective effects against fumonisin B1 [...] Read more.

The exploration of natural redox-modulating agents to mitigate/reduce oxidative damage triggered by toxins is a major area of interest in nutritional and pharmacological fields. Aspalathus linearis (rooibos), traditionally consumed in South Africa for health benefits, was assessed for hepatoprotective effects against fumonisin B1 (FB1)-induced damage. This study involved 24 male rats (n = 6/group) that received FB1 (50 mg/kg diet equivalent, i.p. for 5 days) with or without oral exposure to unfermented (GR) or fermented (FR) rooibos extracts. Alongside somatic records, we assessed blood biochemicals, as well as liver histology, antioxidative stress markers (GSH, GPx, MDA, and carbonylation), regulatory proteins (Nrf2, Sirt3, PGC-α, TRX1, HSP70, and LONp1), inflammation (cytokines), and phospholipid fatty acid profile. Based on results, FB1 suppressed growth, compromised liver function, altered redox status, and elevated stress markers. Both rooibos extracts decreased oxidative damage (↓MDA, ↓carbonylation) and modulated stress regulators (↑Nrf2, ↓HSP70). FR uniquely increased GPx and TRX1 while decreasing IL-1β and PGC-α concentrations, whereas GR strongly increased Nrf2 and Sirt3, reflecting distinct bioactivities linked to their differing polyphenolic profiles. Neither extract compensated for FB1-induced alterations in the liver total phospholipid fatty acid profile or serum cholesterol. In conclusion, GR and FR improved redox potential and inflammatory/stress response; however, this effect was selective, as it did not translate into comprehensive hepatoprotection. These findings support the potential role of rooibos as a dietary modulator of endogenous antioxidant defenses, although clinical translational trials are needed. Full article

(This article belongs to the Special Issue Antioxidant Phytochemicals for Promoting Human Health and Well-Being)

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30 pages, 9155 KB

Open AccessArticle

Multi-Target Cardioprotection from Berberis kaschgarica Extract in Zebrafish via AMPK Pathway Activation

by Alhar Baishan, Dilihuma Dilimulati, Alifeiye Aikebaier, Yipaerguli Paerhati, Xiaoxiao Qiu, Nazhakaiti Yusufujiang, Yilixiati Wusiman, Adili Abudoureheman and Wenting Zhou

Antioxidants 2026, 15(2), 253; https://doi.org/10.3390/antiox15020253 - 14 Feb 2026

Viewed by 629

Abstract

Background: Heart failure (HF) has a complex pathogenesis involving oxidative stress, inflammation, and energy metabolism disorders, and requires multi-target agents. Berberis kaschgarica Rupr. (BKR) is used in Uyghur folk medicine to improve cardiovascular health, but its cardioprotective mechanisms against HF remain unclear. Methods: [...] Read more.

Background: Heart failure (HF) has a complex pathogenesis involving oxidative stress, inflammation, and energy metabolism disorders, and requires multi-target agents. Berberis kaschgarica Rupr. (BKR) is used in Uyghur folk medicine to improve cardiovascular health, but its cardioprotective mechanisms against HF remain unclear. Methods: UPLC-MS/MS was used to identify BKRE components; DPPH/ABTS assays evaluated antioxidant activity. The MTC of BKRE was determined in zebrafish, and its effects on ISO-induced HF zebrafish were assessed via cardiac function, apoptosis, oxidative stress, and inflammation indicators. Network pharmacology, molecular docking, transcriptomics, and qRT-PCR clarified targets and pathways. Results: BKRE contained 14 bioactive flavonoids/alkaloids with favorable drug-likeness, showing concentration-dependent DPPH and ABTS scavenging. In HF zebrafish, BKRE (5/10/20 μg/mL) dose-dependently improved cardiac function, inhibited apoptosis, reduced ROS and TNF-α/IL-6, restored GSH/T-SOD, activated the AMPK-PPARα-PGC-1α pathway by binding ALOX5/NQO1, etc. Conclusions: BKRE exerts multi-mechanistic cardioprotective effects, validating BKR’s ethnopharmacological value and highlighting it as a promising HF agent/functional food. Full article

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

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22 pages, 12109 KB

Open AccessArticle

Potential Involvement of PI3K/AKT Signaling Pathway in the Protective Effects of Rhinacanthus nasutus Against Diabetic Nephropathy-Induced Oxidative Stress

by Junyu Liu, Yehao Lin, Xudong Yi, Min Zhang, Pharkphoom Panichayupakaranant, Joseph Buhagiar and Haixia Chen

Antioxidants 2026, 15(2), 252; https://doi.org/10.3390/antiox15020252 - 14 Feb 2026

Viewed by 686

Abstract

Oxidative stress is a primary driver of diabetic nephropathy (DN), highlighting the urgent need for potent natural antioxidants. This study explored the reno-protective potential and associated mechanisms of Rhinacanthus nasutus aqueous extract (AE). Phytochemical profiling via Q Exactive HF Orbitrap LC–MS/MS and serum [...] Read more.

Oxidative stress is a primary driver of diabetic nephropathy (DN), highlighting the urgent need for potent natural antioxidants. This study explored the reno-protective potential and associated mechanisms of Rhinacanthus nasutus aqueous extract (AE). Phytochemical profiling via Q Exactive HF Orbitrap LC–MS/MS and serum pharmacochemistry analysis identified 38 constituents, among which 25 bioavailable constituents (e.g., caffeic acid and naringenin) might be the key bioactive ones. In the L6 myotubes in vitro assays, AE (75 μg/mL) was observed to upregulate the PI3K/AKT and GLUT4 signaling cytokines, coinciding with enhanced glucose uptake, as confirmed by Western blot with insulin as a positive control. Furthermore, in STZ-induced DN rats, AE could reduce MDA levels (0.58 vs. 1.44 nmol/mgprot) and restore T-SOD, CAT, and GSH-Px levels (170.57, 51.93, 63.68 vs. 114.93, 40.84, 50.99 mgprot). The protective effects were accompanied by the modulation of PI3K/AKT/mTOR signaling axis. These findings suggest that AE exerts dual efficacy involving glucose uptake regulation and oxidative stress inhibition. Consequently, Rhinacanthus nasutus represents a promising natural antioxidant resource with potential for the management of DN. Full article

(This article belongs to the Special Issue Phytochemical Profiling, Antioxidant Activity and Therapeutic Properties of Medicinal Plants)

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31 pages, 1774 KB

Open AccessReview

A Narrative Review of Ginkgo Biloba Extract: Biological Function, Molecular Mechanisms, and Applications in Animal Production

by Mengfan Yao, Lu Liu, Zhihui Hao, Jianzhong Shen and Chongshan Dai

Antioxidants 2026, 15(2), 251; https://doi.org/10.3390/antiox15020251 - 14 Feb 2026

Viewed by 890

Abstract

Ginkgo biloba extract (GBE), obtained from dried Ginkgo biloba leaves, provides a natural option. GBE supplementation can increase livestock’s productivity through various biological functions, such as combating oxidative stress, reducing inflammation, optimizing gut microbiota, detoxifying intestinal toxins, and regulating immune responses. In this [...] Read more.

Ginkgo biloba extract (GBE), obtained from dried Ginkgo biloba leaves, provides a natural option. GBE supplementation can increase livestock’s productivity through various biological functions, such as combating oxidative stress, reducing inflammation, optimizing gut microbiota, detoxifying intestinal toxins, and regulating immune responses. In this review, we utilized keywords such as “Ginkgo biloba extract” or “Ginkgo biloba extract” and “animal production” or “animal nutrition” to gather research on its various biological functions and the underlying mechanisms from databases such as Web of Science and PubMed, up to December 2025. Then, we systematically summarize the main bioactive components of GBE, its beneficial effects in livestock at different life stages and during different production cycles, and the related molecular pathways. Additionally, safety assessments and the potential applications were also discussed. This review highlights that GBE may be an effective plant-derived feed additive with multiple functions and strong potential to improve animal health, production efficiency, and product quality under intensive farming conditions. We hope that this review can stimulate broader discussions and better develop and utilize GBE as a feed additive in animal production. Full article

(This article belongs to the Topic Recent Advances in Veterinary Pharmacology and Toxicology, 2nd Edition)

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17 pages, 1273 KB

Open AccessArticle

Short-Term Consumption of Low-Molecular Weight Polyphenols (Oligonol) Is Associated with Improved Post-Exercise Recovery in Healthy Young Men: A Randomized Single-Blind Crossover Study

by Hyojin Kim, Jihyun Park, Su Min Hwang, Sumin Oh, Byounghyeon Kim, Jin-Hee Woo and Oh Yoen Kim

Antioxidants 2026, 15(2), 250; https://doi.org/10.3390/antiox15020250 - 14 Feb 2026

Viewed by 618

Abstract

Polyphenols have been suggested to aid exercise recovery through antioxidant properties, but their efficacy remains controversial, partly due to limited bioavailability. This study investigated whether low-molecular weight polyphenols (LMWPs, oligonol) influence metabolic responses related to fatigue and oxidative stress during and after a [...] Read more.

Polyphenols have been suggested to aid exercise recovery through antioxidant properties, but their efficacy remains controversial, partly due to limited bioavailability. This study investigated whether low-molecular weight polyphenols (LMWPs, oligonol) influence metabolic responses related to fatigue and oxidative stress during and after a maximal exercise test in healthy young men. A randomized, single-blind crossover design includes a placebo, a single dose of LMWP (S-LMWP), and 5-day LMWP (5-LMWP) intervention with ≥2-week washouts. Ten eligible participants completed all conditions. Exercise performance, fatigue-related metabolic parameters, and oxidative stress markers were measured before, immediately after, and 30 min after exercise. Heart rate and lactate were additionally assessed for 5 min post-exercise. Exercise performance and anthropometrics did not differ among conditions. However, both LMWP groups showed significantly lower blood lactate at 30 min recovery compared with the placebo group (placebo: 17.09 ± 1.29; S-LMWP: 8.36 ± 0.73; 5-LMWP: 9.18 ± 0.60; p = 0.005). Malondialdehyde (MDA), elevated immediately post-exercise, returned closer to baseline at 30 min in the LMWP groups, particularly S-LMWP. Percent MDA change was significantly lower in the S-LMWP group than in the placebo group (placebo: 26.80 ± 3.01; S-LMWP: −8.41 ± 4.86; p = 0.007). Short-term LMWP supplementation did not affect performance or immediate responses but was associated with a more favorable recovery profile, including lower lactate and faster normalization of oxidative stress markers. Larger controlled studies are needed to confirm these findings. Full article

(This article belongs to the Special Issue The Effects of Antioxidants as Supplements on Exercise Performance and Recovery)

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24 pages, 1905 KB

Open AccessReview

Extracellular Superoxide Dismutase in Acute Respiratory Distress Syndrome: Pathogenic Mechanisms and Therapeutic Implications

by William Osier, Eva S. Nozik and Christina Sul

Antioxidants 2026, 15(2), 249; https://doi.org/10.3390/antiox15020249 - 13 Feb 2026

Viewed by 751

Abstract

The lung is highly susceptible to oxidative stress because of its exposure to high oxygen tension and environmental stressors, making tight regulation of the redox environment essential for homeostasis and disease pathogenesis. Extracellular superoxide dismutase (EC-SOD, sod3) is an important antioxidant enzyme [...] Read more.

The lung is highly susceptible to oxidative stress because of its exposure to high oxygen tension and environmental stressors, making tight regulation of the redox environment essential for homeostasis and disease pathogenesis. Extracellular superoxide dismutase (EC-SOD, sod3) is an important antioxidant enzyme in the lung that catalyzes the dismutation of superoxide into hydrogen peroxide and oxygen, thereby regulating the redox environment of the extracellular matrix, cell surfaces, and lining fluids of the lung. This review summarizes the structural features, post-translational regulation, genetic variations, and cellular sources of EC-SOD, with a particular focus on its role in acute respiratory distress syndrome (ARDS). We highlight evidence demonstrating that loss of EC-SOD exacerbates dysregulated immune responses, whereas enhanced EC-SOD activity confers protection in multiple experimental models of acute lung injury. We also discuss how inflammatory signaling, epigenetic regulation, aging, and genetic polymorphisms in the sod3 gene influence EC-SOD expression and function. Finally, we review emerging therapeutic strategies, including SOD mimetics and mRNA-based approaches, and address the challenges associated with non-specific antioxidant therapies in ARDS. Collectively, the data position EC-SOD as a central regulator of extracellular redox signaling and a promising, mechanism-driven therapeutic target in acute lung injury and ARDS. Full article

(This article belongs to the Special Issue Super Oxide Dismutase (SOD) Isoenzymes and Reactive Oxygen Species (ROS) in Immuno-Pathophysiology)

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29 pages, 11052 KB

Open AccessArticle

Integrative Proteomic and Bioenergetic Profiling Reveals Diet- and Strain-Specific Mitochondrial Dysfunction in Cohen Diabetic Rat Hearts

by Lauren Pavelich, Tasnim Arroum, Lucynda Pham, Dragana Komnenov, Paul M. Stemmer, Rachel Lax, Ann Saada, Sarah Weksler-Zangen and Maik Hüttemann

Antioxidants 2026, 15(2), 248; https://doi.org/10.3390/antiox15020248 - 13 Feb 2026

Viewed by 652

Abstract

Mitochondrial dysfunction contributes to diabetic cardiomyopathy, yet how genetic predisposition and diet interact to reshape cardiac metabolism in diabetic and prediabetic states remains unclear. The Cohen diabetic rat model, comprising diabetes-resistant (CDr) and diabetes-sensitive (CDs) strains, provides a unique platform to dissect this [...] Read more.

Mitochondrial dysfunction contributes to diabetic cardiomyopathy, yet how genetic predisposition and diet interact to reshape cardiac metabolism in diabetic and prediabetic states remains unclear. The Cohen diabetic rat model, comprising diabetes-resistant (CDr) and diabetes-sensitive (CDs) strains, provides a unique platform to dissect this interplay. Here, we present an integrative global proteomic and bioenergetic characterization of cardiac tissue from CDr and CDs rats fed either a regular or a diabetogenic diet. Proteomic pathway mapping revealed downregulation of cytochrome c oxidase (CcO) subunits, strain-dependent rewiring of fatty-acid oxidation pathways, and CcO subunits switch from “heart-type” to “liver-type” isoforms in the sensitive strain. These changes were accompanied by impaired mitochondrial respiration, ATP depletion, and disruption of mitochondrial quality-control mechanisms, together with increased accumulation of tyrosine 304 phosphorylation of cytochrome c oxidase subunit I, indicative of inflammation-driven regulatory inhibition in a diet-specific manner. These findings establish an understanding of how genetic susceptibility and diet contribute to cardiac mitochondrial dysfunction in the Cohen diabetic rat model. Full article

(This article belongs to the Special Issue Mitochondria, Redox and Pancreatic β-Cells: Maturation, Function and Inflammatory Stress)

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31 pages, 2597 KB

Open AccessReview

Functional Benefits of Brewer’s Spent Grain and the Challenge of Developing Food Ingredients for Human Health

by Carmen Soto-Maldonado, Alejandra Espinosa, José Luis Bucarey and Lida Fuentes

Antioxidants 2026, 15(2), 247; https://doi.org/10.3390/antiox15020247 - 13 Feb 2026

Viewed by 875

Abstract

Recent developments have highlighted the importance of using by-products such as brewer’s spent grain (BSG) as functional food ingredients. BSG is a source of polyphenols, antioxidants, dietary fiber, and protein, all of which are crucial for preventing metabolic syndrome and cardiovascular disease. This [...] Read more.

Recent developments have highlighted the importance of using by-products such as brewer’s spent grain (BSG) as functional food ingredients. BSG is a source of polyphenols, antioxidants, dietary fiber, and protein, all of which are crucial for preventing metabolic syndrome and cardiovascular disease. This review focuses on bioactive compounds in BSG, such as ferulic and p-coumaric acids, which are distinguished for their antioxidant and anti-inflammatory properties. These compounds play a vital role in liver protection by boosting antioxidant enzyme activity and reducing inflammation and oxidative stress. Additionally, arabinoxylans (AX) in BSG enhance gut health by promoting the growth of beneficial microbiota. The review also identifies gaps in understanding how processing affects bioactive compound bioavailability in foods, emphasizing the need for innovative food technologies to enhance nutrient release and absorption, including the recent studies that show the role of gut microbiota in fermenting BSG components, leading to the release of beneficial compounds, such as ferulic and butyric, which positively influence health and metabolism. Despite these advancements, further research is essential to explore the interactions within the gut, liver effects, and the overall health benefits of BSG, aiming to optimize processing techniques to preserve its nutritional value and promote sustainable food innovation. Full article

(This article belongs to the Special Issue Natural Antioxidants from Plant-Based By-Products: Mechanisms and Applications in Food Systems)

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21 pages, 6717 KB

Open AccessArticle

The FBXL Gene Family in Tobacco (Nicotiana tabacum L.): Identification and Expression Response to TMV and Abiotic Stresses

by Jiaxin Li, Jia Shen, Fang Wang, Wei Wang, Yifeng Yan, Xiaolu Pan, Chaoqiang Jiang, Huaying Yang and Qing Dong

Antioxidants 2026, 15(2), 246; https://doi.org/10.3390/antiox15020246 - 13 Feb 2026

Viewed by 463

Abstract

F-box-LRR (FBXL) proteins are crucial components of the SCF ubiquitin ligase complex, regulating diverse processes such as development and stress responses in plants. However, the FBXL family in tobacco (Nicotiana tabacum L.) remains poorly characterized. This study performed the first genome-wide analysis [...] Read more.

F-box-LRR (FBXL) proteins are crucial components of the SCF ubiquitin ligase complex, regulating diverse processes such as development and stress responses in plants. However, the FBXL family in tobacco (Nicotiana tabacum L.) remains poorly characterized. This study performed the first genome-wide analysis of the FBXL gene family in tobacco and identified 47 NtaFBXL genes. Phylogenetic analysis classified them into five clades, among which Clade III exhibited notable expansion. Promoter analysis revealed abundant stress- and hormone-related cis-elements. Expression profiling demonstrated tissue-specific patterns and strong responses to drought, ABA, IAA, and TMV infection. Importantly, six genes exhibited a significant negative correlation with TMV accumulation, suggesting their potential roles in antiviral defense. Moreover, both drought and TMV stress triggered a disturbance of redox homeostasis, a dynamic process that was closely associated with the expression of specific NtaFBXL genes, characterized by upregulated antioxidant enzymes (SOD, POD, CAT) and accumulated oxidative markers (H₂O₂, MDA). Collectively, this study provided a foundational resource for understanding the function of NtaFBXLs and identified key candidate genes for the genetic improvement of stress resistance in tobacco. Full article

(This article belongs to the Special Issue Advances in Plant Redox Biology Research)

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23 pages, 15760 KB

Open AccessArticle

Dietary Lycopene Mitigates Reproductive Impairment in Heat-Stressed Rongchang Boars: Roles of Antioxidant, Anti-Inflammatory and Nrf2 Pathway

by Ying Lei, Hanxin Liu, Qiujin Xiang, Ying Liu, De Wu, Junjie Zhang and Yan Lin

Antioxidants 2026, 15(2), 245; https://doi.org/10.3390/antiox15020245 - 13 Feb 2026

Viewed by 665

Abstract

Heat stress (HS) severely impairs boar reproductive function by inducing oxidative stress and inflammatory responses, while lycopene (LYC), as a potent antioxidant, exerts a potential protective effect on the male reproductive system. This study aimed to clarify the mechanism underlying LYC-mediated alleviation of [...] Read more.

Heat stress (HS) severely impairs boar reproductive function by inducing oxidative stress and inflammatory responses, while lycopene (LYC), as a potent antioxidant, exerts a potential protective effect on the male reproductive system. This study aimed to clarify the mechanism underlying LYC-mediated alleviation of HS-induced decline in semen quality in Rongchang boars, identify the most affected tissues, and explore its regulatory role in the Nrf2 (Nuclear factor E2-related factor 2) pathway. A total of 18 Rongchang boars with an initial body weight of 15.81 ± 1.07 kg were randomly assigned to three groups (6 boars per group): the control group (CON, 26 ± 1 °C), the heat stress group (HS, exposed to 35 ± 1 °C for 8 h daily), and the heat stress + 100 mg/kg lycopene group (HS + LYC). After 28 days of adaptive feeding and 14 days of HS treatment, samples were collected for semen quality analysis, testicular histological analysis, antioxidant index detection, transcriptome analysis, Nrf2 pathway detection, and inflammatory index detection. The results showed that HS significantly increased the sperm abnormality rate (p < 0.05), damaged the testicular structure, and induced oxidative stress in serum, lung, liver, left ventricle, testis, and epididymis (caput epididymis, corpus epididymis, cauda epididymis), with varying degrees of oxidative stress observed in these samples. Among these tissues, the testis and cauda epididymis exhibited the most significant responses to HS and LYC, with the comprehensive impact magnitudes of 317% and 514%, respectively. Enrichment analysis of differentially expressed genes (DEGs) in these two tissues revealed that the pathways mediating oxidative stress response displayed distinct tissue specificity, and all of them were closely associated with the Nrf2 antioxidant signaling pathway. HS significantly downregulated the mRNA expressions of Nrf2, Quinone Oxidoreductase (NQO1), Heme Oxygenase 1 (HMOX1) and Glutamate-Cysteine Ligase Catalytic Subunit (GCLC) genes as well as the protein level of Nrf2 in the testis and cauda epididymis, increased the protein level of Keap1, and significantly elevated the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in these two tissues (p < 0.05). Compared with the HS group, dietary supplementation of LYC significantly improved sperm motility and the proportion of rapidly progressive sperm, reduced the proportion of immotile sperm and sperm abnormality rate (p < 0.05), alleviated testicular damage and oxidative stress in various tissues, upregulated the mRNA expressions of Nrf2 and HMOX1 genes in the testis as well as the mRNA expressions of Nrf2, NQO1, HMOX1 and GCLC genes in cauda epididymis (p < 0.05), significantly increased the Nrf2 protein level and decreased the Keap1 protein level in these two tissues, and simultaneously decreased the levels of the aforementioned inflammatory factors (p < 0.05). In conclusion, dietary supplementation with 100 mg/kg LYC can alleviate HS-induced decline in semen quality and testicular damage by regulating the oxidative status and inflammatory level of relevant tissues (e.g., testis and cauda epididymis) in boars, and this protective effect may be associated with the regulation of the Nrf2 signaling pathway. Full article

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

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Open AccessReview

Exploring the Dermatological Benefits of Coffee Extracts and Their Derivatives

by Hsiao-Fang Liao, Po-Yuan Wu, Kuo-Ching Wen, Tsen-Jung Lin, Hung-Lung Chiang and Hsiu-Mei Chiang

Antioxidants 2026, 15(2), 244; https://doi.org/10.3390/antiox15020244 - 12 Feb 2026

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Abstract

Coffee-derived materials from diverse botanical sources (beans, leaves, fruit and spent grounds) contain bioactive polyphenolic compounds, alkaloids, and diterpenes with potential dermatological applications. This review critically evaluates evidence quality across study designs. In vitro studies demonstrate antioxidant, anti-aging, anti-inflammatory, photoprotective, wound-healing, and antimicrobial [...] Read more.

Coffee-derived materials from diverse botanical sources (beans, leaves, fruit and spent grounds) contain bioactive polyphenolic compounds, alkaloids, and diterpenes with potential dermatological applications. This review critically evaluates evidence quality across study designs. In vitro studies demonstrate antioxidant, anti-aging, anti-inflammatory, photoprotective, wound-healing, and antimicrobial activities. Animal models show photoprotection and wound-healing effects. These studies highlight the multifunctional dermatological value of coffee-derived materials as ingredients for cosmetic and therapeutic formulations aimed at combating skin aging, inflammation, and barrier dysfunction. Limited human trials (typically small sample sizes and short duration) report modest improvements in skin hydration, elasticity, barrier function, and reductions in erythema, transepidermal water loss, and ultraviolet-induced damage, though methodological limitations constrain interpretation. Observational epidemiological studies report inverse associations between coffee consumption and melanoma/basal cell carcinoma risk, but residual confounding by sun exposure, lifestyle factors, and genetic susceptibility precludes causal inference. Critical translational barriers include insufficient pharmacokinetic characterization, inadequate extract standardization across sources and processing methods, formulation challenges, bioavailability uncertainties, and limited independent validation. While preclinical evidence supports diverse biological activities and suggests multifunctional potential for cosmetic and therapeutic applications, current evidence remains insufficient to recommend coffee-derived products as a primary evidence-based dermatological intervention. Overall, large-scale, independent clinical trials with adequate duration and clinically meaningful endpoints are essential for translating laboratory findings into validated clinical applications. Full article

(This article belongs to the Special Issue Natural Antioxidants: Multiple Mechanisms for Skin Protection and Skin Disease)

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Antioxidants, Volume 15, Issue 2 (February 2026) – 124 articles

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