Antioxidants

26 pages, 11058 KB

Open AccessArticle

Green Tea Extract Attenuates Oxidative Stress and Prolongs Red Blood Cell Survival in Iron-Overloaded β-Thalassemic Mice

by Yanping Zhong, Sakaewan Ounjaijean, Sirichai Srichairatanakool, Narisara Paradee, Suphatta Yubo, Honghong Xu, Pimpisid Koonyosying, Phatchariya Phannasil, Saovaros Svasti and Somdet Srichairatanakool

Antioxidants 2026, 15(8), 990; https://doi.org/10.3390/antiox15080990 (registering DOI) - 10 Aug 2026

Abstract

Green tea extract (GTE) contains catechin polyphenols with potent antioxidant and iron-chelating activities. This study investigated whether GTE could attenuate oxidative stress and improve red blood cell (RBC) survival in iron-overloaded β-thalassemic mice. Catechin composition and antioxidant activity of GTE and black tea [...] Read more.

Green tea extract (GTE) contains catechin polyphenols with potent antioxidant and iron-chelating activities. This study investigated whether GTE could attenuate oxidative stress and improve red blood cell (RBC) survival in iron-overloaded β-thalassemic mice. Catechin composition and antioxidant activity of GTE and black tea extract (BTE) were evaluated using HPLC-photodiode array detection and ABTS radical scavenging assays. Anti-hemolytic effects were examined in RBC from healthy subjects and transfusion-dependent β-thalassemia patients. In vivo studies were performed using male C57BL/6J wild-type (WT) and heterozygous β-globin knockout (BKO) mice fed a ferrocene-enriched diet to induce iron overload. Mice subsequently received oral GTE (300 mg/kg/day) or deferiprone (DFP, 50 mg/kg/day) for 12 weeks. GTE contained markedly higher levels of catechin derivatives, particularly epigallocatechin-3-gallate, and exhibited stronger antioxidant activity than BTE. GTE significantly reduced RBC hemolysis, reactive oxygen species, malondialdehyde, and plasma non-transferrin-bound iron levels while restoring glutathione concentrations and prolonging RBC survival in iron-overloaded mice. The protective effects of GTE were comparable to DFP treatment. These findings suggest that GTE may serve as a promising natural adjunctive strategy for reducing oxidative injuries in β-thalassemia and iron-overload disorders. Full article

(This article belongs to the Special Issue Oxidative Stress in Hematologic Disease)

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21 pages, 6198 KB

Open AccessArticle

Adipose-Derived Mesenchymal Stem Cells Alleviate ᴅ-Galactose-Induced Testicular Injury by Activating the Keap1/Nrf2 Pathway and Suppressing NLRP3-Associated Pyroptosis

by Mengjia He, Tianhang Yang, Songpo Liu, Dan Zhang, Zhiran Shui, Xianyao Wang, Tao Song, Jun Tan, Qinghong Kong and Jidong Zhang

Antioxidants 2026, 15(8), 989; https://doi.org/10.3390/antiox15080989 (registering DOI) - 10 Aug 2026

Abstract

Objective: To evaluate whether human adipose-derived mesenchymal stem cells (ADSCs) protect against ᴅ-galactose (ᴅ-gal)-induced aging-like testicular injury and to investigate the involvement of the Keap1/Nrf2 pathway and NLRP3-associated pyroptosis. Methods: A mouse model of aging-like testicular injury was established by subcutaneous administration of [...] Read more.

Objective: To evaluate whether human adipose-derived mesenchymal stem cells (ADSCs) protect against ᴅ-galactose (ᴅ-gal)-induced aging-like testicular injury and to investigate the involvement of the Keap1/Nrf2 pathway and NLRP3-associated pyroptosis. Methods: A mouse model of aging-like testicular injury was established by subcutaneous administration of ᴅ-gal for 8 weeks, followed by tail vein injection of ADSCs. Testicular morphology, blood–testis barrier (BTB) integrity, and senescence-associated markers (p16, p21) were assessed. In vitro, TM4 Sertoli cells were used to establish a senescence model and Tranwell co-cultured with ADSCs. Oxidative stress, inflammatory responses, and pyroptosis-related markers were evaluated using biochemical assays, immunofluorescence, Western blotting, and RT-qPCR. The involvement of the Keap1/Nrf2-NLRP3 axis was further examined using pharmacological inhibitors. Results: ADSC treatment significantly alleviated ᴅ-gal-induced testicular atrophy and histopathological injury, accompanied by reduced expression of the senescence markers p16 and p21 and partial restoration of BTB-related structures. ADSCs also attenuated oxidative stress, as evidenced by decreased ROS and MDA levels, increased SOD activity, and enhanced expression of Nrf2 and its downstream antioxidant targets, including HO-1 and NQO1. In parallel, ADSC administration suppressed NLRP3 activation, reduced caspase-1 cleavage, and lowered the expression of pro-inflammatory cytokines. In TM4 cells, inhibition of Nrf2 weakened the protective effects of ADSCs and was accompanied by reactivation of NLRP3-associated signaling, whereas inhibition of NLRP3 attenuated senescence- and inflammation-related changes without restoring Nrf2 activity. Conclusions: ADSCs alleviate ᴅ-gal-induced aging-like testicular injury, at least in part, by restoring redox balance, preserving BTB-associated structure, and suppressing NLRP3-associated pyroptosis through the Keap1/Nrf2 pathway. These findings suggest that ADSC-based therapy may represent a promising strategy for age-related male reproductive dysfunction, while further studies using genetic models and functional fertility endpoints are needed to confirm causality and translational relevance. Full article

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

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21 pages, 3657 KB

Open AccessArticle

Integrated Multi-Omics Analysis Reveals the Mechanism of Haloxyfop-P-methyl Residue Suppressing Seed Germination in Oilseed Rape (Brassica napus L.)

by Chaochao He, Zhongjing Zhou, Kaige Yi, Yupeng Jiang, Xianling Wang, Zhiqi Ma, Yun Ren, Shuang Liang, Lixi Jiang, Yang Zhu and Shuijin Hua

Antioxidants 2026, 15(8), 988; https://doi.org/10.3390/antiox15080988 (registering DOI) - 10 Aug 2026

Abstract

Haloxyfop-P-methyl (HPM) is widely used for grass weed control in oilseed rape production. However, whether its residues affect subsequent seed germination and the underlying mechanisms remains unclear. In this study, seeds harvested from HPM-treated fields exhibited a significantly reduced germination rate of 36.5%, [...] Read more.

Haloxyfop-P-methyl (HPM) is widely used for grass weed control in oilseed rape production. However, whether its residues affect subsequent seed germination and the underlying mechanisms remains unclear. In this study, seeds harvested from HPM-treated fields exhibited a significantly reduced germination rate of 36.5%, compared with 100% in the control group, accompanied by abnormal cell morphology. Residue analysis revealed an HPM concentration of 3.36 mg kg⁻¹ in the treated seeds, exceeding the Chinese maximum residue limit (MRL) of 3 mg kg⁻¹ (GB 2763). Given that herbicides often induce oxidative stress, we measured a range of antioxidant markers (H₂O₂, MDA, SOD, POD, GSH, GSSG, AsA, and DHA) during germination (12 h and 24 h) but detected no significant changes, which did not support oxidative stress as the primary mechanism during this phase. Relative electrical conductivity measurements further indicated that membrane integrity was already compromised in dry seeds, suggesting that oxidative injury—if it occurred—may have taken place during seed development rather than during germination. To elucidate the molecular basis, we performed transcriptomic, metabolomic, and lipidomic analyses, which revealed significant downregulation of fatty acid biosynthesis genes and marked alterations in the lipidome profile. Collectively, our multi-stage investigation demonstrates that HPM residue accumulation is associated with impaired seed germination, primarily through metabolic disruption of lipid reserves rather than oxidative damage during germination, highlighting a non-target phytotoxic effect of this herbicide on the crop itself. These findings provide a theoretical basis for understanding the potential toxicity of persistent HPM residues in rapeseed, with implications for pesticide environmental risk assessment and the safe production of rapeseed. Full article

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

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21 pages, 1600 KB

Open AccessArticle

Integrated Liver Multi-Omics Reveals Beneficial Effects and Potential Mechanisms of Noni Fruit Flavonoids on Antioxidant Status and Anti-Inflammatory Responses in Cashmere Goats

by Shuhui Dong, Qingyue Zhang, Hao Yu, Yanli Zhao, Yu Xin, Yongmei Guo, Xiaoyu Guo, Yuanqing Xu and Sumei Yan

Antioxidants 2026, 15(8), 987; https://doi.org/10.3390/antiox15080987 (registering DOI) - 9 Aug 2026

Abstract

This study investigated the effects of noni fruit flavonoids (NFF) on antioxidant status and anti-inflammatory responses in cashmere goats and explored the underlying mechanisms based on liver transcriptomics and metabolomics. Sixteen male Albas cashmere goats were randomly assigned to two groups: a control [...] Read more.

This study investigated the effects of noni fruit flavonoids (NFF) on antioxidant status and anti-inflammatory responses in cashmere goats and explored the underlying mechanisms based on liver transcriptomics and metabolomics. Sixteen male Albas cashmere goats were randomly assigned to two groups: a control (CON) group and a group supplemented with 0.1% NFF. The adaptation and trial periods were 2 and 12 weeks, respectively. The results showed that NFF significantly enhanced antioxidant capacity, with mean increases of 32.9%, 20.7%, and 35.5% for total antioxidant capacity (T-AOC), glutathione peroxidase (GPx), and catalase (CAT) activities, respectively, across serum, liver, spleen, and thymus (p < 0.05). NFF also modulated the inflammatory profile, with a mean increase of 18.0% for interleukin (IL)-10 and mean reductions of 18.6%, 19.4%, and 16.7% for IL-1β, IL-2, and tumor necrosis factor (TNF)-α, respectively, across the serum, liver, and thymus (p < 0.05). Integrative transcriptomic and metabolomic analyses suggested that the AMPK signaling pathway, glutathione metabolism, and TGF-β signaling pathway may be critically involved in mediating these effects. GPX3, GPX8, GCLM, NFKB1, and IL1B were identified as key candidate genes, while adenosine-5′-monophosphate (AMP), cysteinylglycine, and pyroglutamic acid were key differential metabolites. Dietary supplementation with 0.1% NFF enhanced the antioxidant levels and anti-inflammatory response in cashmere goats. Full article

29 pages, 13077 KB

Open AccessArticle

Optimization of Ultrasonic-Assisted Extraction, Structural Characterization, and Bioactivities of Polysaccharides from Nitraria tangutorum Bobr.

by Baotang Zhao, Faqin Tao, Shengfang Wang and Wendi Jin

Antioxidants 2026, 15(8), 986; https://doi.org/10.3390/antiox15080986 (registering DOI) - 9 Aug 2026

Abstract

Nitraria tangutorum Bobr. fruits are rich in bioactive polysaccharides (QBC) with high nutritional and developmental potential. This study optimized the ultrasonic-assisted extraction QBC via RSM, determining the optimal parameters to be 45 min, 59 °C, 19:1 mL/g, and 50% (150 W eq.), yielding [...] Read more.

Nitraria tangutorum Bobr. fruits are rich in bioactive polysaccharides (QBC) with high nutritional and developmental potential. This study optimized the ultrasonic-assisted extraction QBC via RSM, determining the optimal parameters to be 45 min, 59 °C, 19:1 mL/g, and 50% (150 W eq.), yielding 15.13%. Structurally, QBC exhibited a Mw of 1.997 × 10⁵, Mw/Mn of 3.727, Rz of 15.6, and a monosaccharide molar ratio of rhamnose:arabinose:mannose:glucose:galactose = 1:1.12:1.66:7.3:1.86. In this study, the effects of QBC on oxidative stress markers and pro-inflammatory cytokines were evaluated via in vivo experiments. The results demonstrated that QBC significantly improved the thymic index and restored immune function. Specifically, QBC upregulated the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IFN-γ. The analysis of α/β diversity via 16S rRNA sequencing revealed that the CTX group induced a reduction in microbial richness, a more dispersed community structure, and increased intergroup dissimilarities. KEGG functional prediction indicated that polysaccharides regulated the ‘Infectious disease: parasitic’ and ‘Nitrotoluene degradation’ pathways, potentially by exerting their effects through metabolite-mediated immune regulation. Full article

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

17 pages, 1045 KB

Open AccessArticle

Enhancement of Poly-γ-glutamic Acid Formation and Antioxidant Activity in Cheonggukjang Fermented with Bacillus velezensis CH7P29

by Jong Hyoung Hong, Young Hun Jin, Shuxiang Liu and Jae-Hyung Mah

Antioxidants 2026, 15(8), 985; https://doi.org/10.3390/antiox15080985 (registering DOI) - 9 Aug 2026

Abstract

This study aimed to isolate Bacillus strains producing poly-γ-glutamic acid (γ-PGA), a natural antioxidant biopolymer, from Cheonggukjang, optimize fermentation conditions, improve γ-PGA production in the food by applying the selected strain, and investigate its potential association with antioxidant activity. Among 157 isolates, [...] Read more.

This study aimed to isolate Bacillus strains producing poly-γ-glutamic acid (γ-PGA), a natural antioxidant biopolymer, from Cheonggukjang, optimize fermentation conditions, improve γ-PGA production in the food by applying the selected strain, and investigate its potential association with antioxidant activity. Among 157 isolates, Bacillus velezensis CH7P29 demonstrated the highest γ-PGA production (602.80 ± 6.55 μg/mL) and was selected for fermentation. Optimal in vitro conditions for γ-PGA production were determined as 40 °C and 0–2% NaCl. In Cheonggukjang fermentation under optimal conditions, the CH7P29-inoculated group exhibited a marked increase in γ-PGA content (16.02 mg/g on day 4), which was significantly higher than the uninoculated control (not detected) and reference strain groups (12.25 and 11.38 mg/g, respectively). Simultaneously, its DPPH radical scavenging activity exceeded 60%, and γ-PGA content strongly correlated with antioxidant activity (R = 0.95). Conversely, total polyphenol content remained stable, indicating that γ-PGA and microbial metabolites contributed primarily to antioxidant activity. Further analysis supported this by showing that γ-PGA accounted for 37.40% of the total DPPH radical scavenging activity in the CH7P29-inoculated group at the end of fermentation. These data emphasize that B. velezensis CH7P29 is a promising functional starter culture for enhancing the biofunctional properties of Cheonggukjang and fermented soybean food. Full article

(This article belongs to the Special Issue The Antioxidants in Fermented Foods—2nd Edition)

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26 pages, 11036 KB

Open AccessArticle

Computer-Aided Discovery of EGFR G-Quadruplex Targeting Phenanthroimidazole Derivatives Inducing Concurrent Multi-Organelle Damage in Glioblastoma

by Mengjiao She, Ao Yu, Xiaozhan Qiu, Wanyu Liu, Rui Chen, Renshan Deng, Huan Zeng, Chunling Zhu, Qiong Wu, Jinlan Meng and Wenjie Mei

Antioxidants 2026, 15(8), 984; https://doi.org/10.3390/antiox15080984 (registering DOI) - 8 Aug 2026

Abstract

The urgent need for novel glioblastoma (GBM) therapies has motivated the exploration of EGFR G-quadruplex (G4) targeting, which suppresses oncogene transcription independently of kinase activity. However, existing EGFR G4 ligands lack subtype selectivity. Through computer-aided design and systematic bioisosteric modifications of the 1 [...] Read more.

The urgent need for novel glioblastoma (GBM) therapies has motivated the exploration of EGFR G-quadruplex (G4) targeting, which suppresses oncogene transcription independently of kinase activity. However, existing EGFR G4 ligands lack subtype selectivity. Through computer-aided design and systematic bioisosteric modifications of the 1H-imidazo[4,5-f][1,10]phenanthroline scaffold, we synthesized a series of derivatives. We evaluated their G4 interactions by molecular docking, UV-Vis, FRET, ITC, and CD. Compound 3, bearing a 6-bromopiperonyl group, exhibited nanomolar affinity for EGFR G4 (Kd = 102 nM) with ~146-fold selectivity over K-Ras G4, stabilizing it via end-stacking. It potently inhibited U87-MG glioblastoma cell proliferation (IC₅₀ = 0.49 μM), with a wide safety margin relative to normal HMC3 microglia (safety index = 14.18). Mechanistically, compound 3 triggered DNA damage, mitochondrial oxidative stress, and sequential multi-organelle damage to mitochondria, lysosomes, and the endoplasmic reticulum, while impairing cell migration and invasion. These findings establish compound 3 as a uniquely selective EGFR G4 stabilizer, offering a promising multi-organelle-damage strategy for glioblastoma therapy. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals: Antioxidant Activities and Pharmacological Potential)

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25 pages, 26312 KB

Open AccessArticle

Exogenous Methyl Jasmonate Enhances Heat Tolerance in Herbaceous Peony by Modulating Endogenous Hormone Homeostasis and the ROS Scavenging System

by Xiaohua Shi, Ziyu Zhou, Yan Shen, Xiaoxuan Chen, Qianzi Zhen, Danqing Li, Xiaobin Wang, Yiping Xia, Kaiyuan Zhu, Huichun Liu and Jiaping Zhang

Antioxidants 2026, 15(8), 983; https://doi.org/10.3390/antiox15080983 - 7 Aug 2026

Abstract

High-temperature stress severely limits the cultivation and ornamental quality of herbaceous peony, especially in low-latitude regions. The objective of this study was to reveal the potential mechanism involved in regulation of jasmonates on herbaceous peony heat tolerance through crosstalk between phytohormones and the [...] Read more.

High-temperature stress severely limits the cultivation and ornamental quality of herbaceous peony, especially in low-latitude regions. The objective of this study was to reveal the potential mechanism involved in regulation of jasmonates on herbaceous peony heat tolerance through crosstalk between phytohormones and the reactive oxygen species (ROS) scavenging system. The study found that exogenous methyl jasmonate (MeJA) significantly improved thermotolerance of the low-latitude cultivar ‘Hang Baishao’ by enhancing antioxidase activities and modulating endogenous phytohormone levels. The MeJA-treated group exhibited markedly higher ratios of MeJA to zeatin riboside (ZR), gibberellic acid (GA₃), brassinolide (BR), and indole-3-acetic acid (IAA) compared with the control group; catalase (CAT) and superoxide dismutase (SOD) activities were significantly elevated relative to hydrogen peroxide (H₂O₂) content, with both ratios peaking at 36 h post-heat treatment. Transcriptomic results revealed that MeJA reshaped the expression of genes involved in jasmonic acid (JA) signaling and ROS scavenging, such as FAD4, MED25, and JAZ2 and CSD2/3, FSD1, and CAT3. Four modules including the hub genes CIPK5/6, WRKY19/40 and CYPs were identified from the weighted gene co-expression network analysis (WGCNA), which may be key players in coordinating JA signaling and antioxidant defense. This study demonstrates that MeJA enhanced herbaceous peony thermotolerance by orchestrating a regulatory network involving phytohormonal crosstalk and activation of the ROS scavenging system, and offers candidate genes for future exploration of function and interactions. Full article

(This article belongs to the Special Issue Redox Regulation of Plant Growth and Development)

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24 pages, 21881 KB

Open AccessArticle

Enhancing Hepatic Antioxidant Capacity and Carbohydrate, Lipid, and Bile Acid Metabolism in Largemouth Bass Through Dietary Betaine Supplementation

by Jibin Lin, Manqi Yang, Qingxiang Huang, Liangliang Zhang, Liming Lu, Chunxiao Zhang and Jianchun Jiang

Antioxidants 2026, 15(8), 982; https://doi.org/10.3390/antiox15080982 - 7 Aug 2026

Abstract

This study aimed to investigate the effect of dietary betaine on the growth, glucose and lipid metabolism, and bile acid (BA) metabolism in Micropterus salmoides fed high-cottonseed concentrated protein (CPC) diets. In this study, Micropterus salmoides were fed six experimental diets: the basal [...] Read more.

This study aimed to investigate the effect of dietary betaine on the growth, glucose and lipid metabolism, and bile acid (BA) metabolism in Micropterus salmoides fed high-cottonseed concentrated protein (CPC) diets. In this study, Micropterus salmoides were fed six experimental diets: the basal diet (BD diet; high fish meal), the low-fish meal diet (LF diet; 75% of the fish meal protein in the BD diet was substituted with CPC), and four betaine-supplemented diets (1.0 g/kg, 2.0 g/kg, 4.0 g/kg, and 8.0 g/kg of betaine were added to the LF diet, designated as LFB1.0, LFB2.0, LFB4.0, and LFB8.0, respectively). After an 8-week feeding trial, compared with the BD diet, fish fed the LF diet had decreased weight gain rate, reduced feed utilization efficiency, and poor liver health and impaired metabolic function. Conversely, fish fed the LFB4.0 diet showed an increased weight gain rate and feeding rate, improved liver antioxidant capacity, and decreased hepatic lipid droplets and glycogen content. Non-targeted metabolomics of the liver revealed that betaine regulated carbohydrate and lipid metabolism and was associated with primary bile acid metabolism. Moreover, the hepatic levels of the BA regulatory factors short heterodimer partner and farnesoid-X-receptor, as well as the gene expression of BA transporter bile salt export pump, were increased in fish fed the LFB4.0 diet. Supplementing the LF diet (high CPC levels) with 4.0 g/kg betaine improves fish growth performance and enhances hepatic carbohydrate and lipid metabolism via the positive regulation of BA metabolism by betaine. Full article

(This article belongs to the Special Issue Natural Antioxidants in Animal Nutrition)

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19 pages, 2251 KB

Open AccessArticle

Antioxidant, Anti-Inflammatory, and Bone-Remodeling Modulatory Activities of Thai Pigmented and Non-Pigmented Rice Bran Oils Containing Tocols and γ-Oryzanol

by Thanawat Pattananandecha, Sutasinee Apichai, Jakaphun Julsrigival, Kannika Thiankhanithikun, Fumihiko Ogata, Naohito Kawasaki, Jetsada Ruangsuriya and Chalermpong Saenjum

Antioxidants 2026, 15(8), 981; https://doi.org/10.3390/antiox15080981 - 7 Aug 2026

Abstract

Rice bran oil (RBO) is a rich source of lipophilic bioactive compounds that may contribute to antioxidant, anti-inflammatory, and bone-health-promoting activities. This study investigated the effects of RBOs containing tocopherols, tocotrienols, and γ-oryzanol derived from Thai pigmented and non-pigmented rice cultivars on oxidative [...] Read more.

Rice bran oil (RBO) is a rich source of lipophilic bioactive compounds that may contribute to antioxidant, anti-inflammatory, and bone-health-promoting activities. This study investigated the effects of RBOs containing tocopherols, tocotrienols, and γ-oryzanol derived from Thai pigmented and non-pigmented rice cultivars on oxidative stress, inflammatory responses, and bone-remodeling-related activities. The content of tocopherols, tocotrienols, and γ-oryzanol was determined by high-performance liquid chromatography (HPLC). Reactive oxygen species (ROS) production was determined in human fetal osteoblast (hFOB 1.19) cells where nitric oxide (NO) and inducible nitric oxide synthase (iNOS) production were evaluated in RAW264.7 cells. Following compositional profiling and correlation analyses of antioxidant and anti-inflammatory activities, three representative RBOs were subsequently evaluated for their effects on bone-remodeling-related activities in hFOB 1.19 cells through alkaline phosphatase (ALP) activity and the production of osteocalcin (OC), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL). Additionally, calcification was investigated by Alizarin Red S staining. Pigmented RBOs, particularly Khao’ Hom Nil and RD69, contained higher levels of tocopherols, tocotrienols, and γ-oryzanol than non-pigmented RBOs. These oils significantly suppressed ROS, NO, and iNOS production, which correlated with tocopherol, tocotrienol, and γ-oryzanol content, while enhancing ALP activity, OC and OPG production, reducing RANKL levels and the RANKL/OPG ratio, and promoting matrix mineralization. Overall, pigmented RBOs represent promising natural sources of lipophilic bioactive compounds with potential antioxidant, anti-inflammatory, and bone-remodeling-related activities under in vitro conditions. Full article

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

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22 pages, 2544 KB

Open AccessSystematic Review

Growth Performance and Antioxidant Responses to Dietary Flavonoids in Swine: A Systematic Review and Meta-Analysis with Exploratory Dose–Time Relationships

by Yi Xiao, Qiannan Han, Zhenglin Dong, Xizi Yang, Zhihao Xu, Kaiyu Hu, Zhihao Xuan, Guiping Liang, Weimin Jiang, Yinglin Peng and Yingying Liu

Antioxidants 2026, 15(8), 980; https://doi.org/10.3390/antiox15080980 - 7 Aug 2026

Abstract

Dietary flavonoids are increasingly investigated in swine nutrition, but how supplementation level, intervention duration, and growth stage are associated with growth and antioxidant responses remains unclear. This PRISMA 2020 systematic review and meta-analysis evaluated dietary flavonoid supplementation in pigs. Twenty-eight randomized controlled trials [...] Read more.

Dietary flavonoids are increasingly investigated in swine nutrition, but how supplementation level, intervention duration, and growth stage are associated with growth and antioxidant responses remains unclear. This PRISMA 2020 systematic review and meta-analysis evaluated dietary flavonoid supplementation in pigs. Twenty-eight randomized controlled trials were synthesized using three-level random-effects models to account for dependent effect sizes. Flavonoid supplementation was associated with increased average daily gain (ADG; SMD = 0.719, 95% CI: 0.428 to 1.009;

I^{2} = 51.85 %

) and a lower feed-to-gain ratio (F/G; SMD = −0.708, 95% CI: −0.929 to −0.487;

I^{2} = 32.25 %

), whereas the association with average daily feed intake (ADFI) was not statistically significant (SMD = 0.217, 95% CI: −0.101 to 0.535;

I^{2} = 59.30 %

). Supplementation was also associated with increased superoxide dismutase (SMD = 0.907) and glutathione peroxidase activities (SMD = 0.666) and reduced malondialdehyde concentrations (SMD = −0.989), although heterogeneity was substantial for these outcomes (

I^{2} = 96.47

–

97.83 %

). The certainty of evidence was assessed as low for ADG and moderate for ADFI, F/G, and antioxidant outcomes under the adapted GRADE framework. Exploratory stage-specific dose–time meta-regression identified potential relationships between supplementation intensity and ADG in weaned pigs (35 effect sizes from 14 studies) and finishing pigs (12 effect sizes from four studies). In finishing pigs, intervention duration was associated with growth responses. However, this subgroup contained few independent studies, and intervention duration covaried with age, physiological stage, flavonoid source, dose, health status, and basal diet. This association therefore does not establish an independent causal effect of intervention duration. Full article

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

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18 pages, 3031 KB

Open AccessArticle

Novel Exploratory Transcriptomic Candidates as Biomarkers and Cancer Hallmark Fingerprints for Ovarian Endometroid and Clear Cell Carcinomas in Women

by Pawel Kordowitzki and Kejun Ying

Antioxidants 2026, 15(8), 979; https://doi.org/10.3390/antiox15080979 - 6 Aug 2026

Abstract

Background: Endometriosis-associated ovarian cancers (EAOCs), encompassing clear cell (CC) and endometrioid carcinomas (EC), constitute distinct biological entities yet lack robust biomarkers for precise classification, prognostication, and therapeutic decision-making in women. Therefore, we aimed to describe novel biomarkers. Methods: In this study, we conducted [...] Read more.

Background: Endometriosis-associated ovarian cancers (EAOCs), encompassing clear cell (CC) and endometrioid carcinomas (EC), constitute distinct biological entities yet lack robust biomarkers for precise classification, prognostication, and therapeutic decision-making in women. Therefore, we aimed to describe novel biomarkers. Methods: In this study, we conducted an integrated transcriptomic analysis, powered by machine learning, to discover novel consensus biomarkers and delineate cancer hallmark signatures specific to EC and CC. Drawing on gene expression profiles from EAOC specimens, we merged differential expression analysis with LASSO regression and Random Forest classification to generate a reliable biomarker panel that effectively distinguishes EC from CC. Kaplan–Meier survival analyses and mutation analyses have been performed for selected biomarker genes. Results: Novel biomarkers, among others, the genes RPS28, EPAS1, ALKBH2, and DCLRE1A, uncover extensive transcriptional alterations tied to hypoxia signaling, oxidative stress, DNA repair, and metabolic reprogramming. Gene Ontology and pathway enrichment analyses revealed synchronized upregulation of epithelial–mesenchymal transition, TNF-α/NF-κB signaling, oxidative stress, hypoxia, and KRAS signaling pathways. Conclusions: Our work establishes novel exploratory transcriptomic candidates for innovative consensus biomarkers, yielding novel diagnostic and prognostic insights into EAOC and supporting further study of subtype-associated expression programs. The current study was designed primarily as an integrative computational investigation aimed at identifying candidate genes and molecular pathways distinguishing CC from EC. Full article

(This article belongs to the Special Issue Metabolic Reprogramming and Epigenetic Crosstalk in the Tumor Microenvironment)

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33 pages, 3310 KB

Open AccessArticle

Molecular Characterization of Melatonin Receptors in Perccottus glenii and Its Potential Roles in Melatonin-Mediated Antioxidant and Anti-Inflammatory Responses During Post-Freezing Recovery

by Jiajun Zhou, Tianmei Liu, Zhaoyang Ning, Xiaoyu Zhao, Ye Huang, Kaitong Zhu, Xiangxin Kong and Weijie Mu

Antioxidants 2026, 15(8), 978; https://doi.org/10.3390/antiox15080978 - 6 Aug 2026

Abstract

In this study, we report for the first time the cloning and identification of three melatonin receptors (PgMtnr1a, PgMtnr1b, and PgMtnr1c) from the freeze-resistant fish Perccottus glenii, all of which encode typical GPCR proteins. These receptors are expressed [...] Read more.

In this study, we report for the first time the cloning and identification of three melatonin receptors (PgMtnr1a, PgMtnr1b, and PgMtnr1c) from the freeze-resistant fish Perccottus glenii, all of which encode typical GPCR proteins. These receptors are expressed widely in high-metabolism tissues such as the liver. During the freezing and recovery process at −2 °C, the expression of liver receptors exhibited dynamic changes: PgMtnr1a and PgMtnr1c were significantly upregulated during the middle of resuscitation, while PgMTNR1A reached its peak expression in the later stages, suggesting its involvement in stress repair. In vitro experiments confirmed that melatonin significantly enhances the activity of liver antioxidant enzymes in a receptor-dependent manner, an effect that can be inhibited by the antagonist luzindole. Anti-inflammatory analyses indicate that melatonin primarily inhibits inflammation-related genes through Mtnr1a and Mtnr1b. Furthermore, the overexpression of PgMTNR1A can synergistically activate ERK in the presence of melatonin, inhibit the JNK/p38 MAPK pathway, and downregulate the expression of NF-κB and COX2. Pathway inhibition experiments further validated that the MAPK/NF-κB axis, including ERK, JNK, and p38 pathways, mediates the anti-inflammatory effects of melatonin. This study systematically elucidates the molecular mechanisms by which the melatonin receptors of P. glenii play crucial antioxidant and anti-inflammatory roles during the later stages of freeze–thaw resuscitation, particularly by regulating the MAPK/NF-κB signaling axis through MTNR1A, thereby providing a novel basis for understanding the adaptation of vertebrates to extreme environments. Full article

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

28 pages, 12609 KB

Open AccessArticle

Sexual Dimorphism in Placental mTORC1 Signaling, Amino Acid Transport, and Mitochondrial Respiration at Term

by Hiroshi Shimada, Toshihide Sakuragi, Vincent Zaegel, Anita Kramer, Kristen E. Boyle, Theresa L. Powell, Thomas Jansson and Fredrick J. Rosario

Antioxidants 2026, 15(8), 977; https://doi.org/10.3390/antiox15080977 - 6 Aug 2026

Abstract

Male fetuses generally grow faster in utero and are heavier at birth than females, whereas the rates of perinatal mortality and morbidity are often higher in boys than in girls. Sexual dimorphism in placental function is believed to contribute to these differences. However, [...] Read more.

Male fetuses generally grow faster in utero and are heavier at birth than females, whereas the rates of perinatal mortality and morbidity are often higher in boys than in girls. Sexual dimorphism in placental function is believed to contribute to these differences. However, evidence for sex-specific differences in placental function remains limited. We hypothesized that placental nutrient-sensing signaling activity, amino acid transport capacity, and mitochondrial respiration are higher in male than female placentas. Placentas were collected from 46 women (BMI 18.5–29.9 kg/m²) with uncomplicated pregnancies delivering appropriate-for-gestational-age infants (n = 23 female; n = 23 male). In homogenates of male placentas, the phosphorylation of S6RP (Ser235/236) was increased and total 4E-BP1 protein expression was reduced compared with female placentas, indicating enhanced mTORC1 signaling. In vitro System A amino acid transport activity was also greater in microvillous plasma membranes isolated from male placentas. Placental mitochondrial respiratory capacity was assessed in villous tissue using high-resolution respirometry with carbohydrate and lipid substrate–uncoupler–inhibitor titration (Carb SUIT and Lipid SUIT) protocols on the Oroboros O2k platform. Male placentas exhibited greater maximal oxidative phosphorylation capacity, enhanced complex II-linked respiration, and higher maximal electron transport system capacity compared with female placentas under both carbohydrate- and lipid-supported respiratory conditions. Although placental weight did not differ between sexes, the birth weight-to-placental weight ratio was significantly higher in male pregnancies, consistent with greater placental functional efficiency. In conclusion, placental mTORC1 signaling activity, System A amino acid transport activity, and mitochondrial respiratory capacity are greater in male than female placentas and are associated with greater placental functional efficiency and fetal growth in male pregnancies. Full article

(This article belongs to the Special Issue Oxidative Stress and Human Reproduction)

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23 pages, 5519 KB

Open AccessArticle

Bypassing Androgens: Retina-Targeted 17β-Estradiol Delivery via DHED Eye Drops Ameliorates Orchiectomy-Induced Shifts in the Male Rat Visual Cortex Proteome

by Khadiza Zaman, Ammar Kapic, Vien Nguyen, Laszlo Prokai and Katalin Prokai-Tatrai

Antioxidants 2026, 15(8), 976; https://doi.org/10.3390/antiox15080976 - 6 Aug 2026

Abstract

Mass spectrometry-based proteomics has become instrumental for elucidating the molecular mechanisms of neurodegeneration, enabling the identification of disease-associated proteomic alterations and protein-level responses to therapeutic interventions. Building on our previous proteomic characterization of the orchiectomized (ORX) Brown Norway male rat retina as a [...] Read more.

Mass spectrometry-based proteomics has become instrumental for elucidating the molecular mechanisms of neurodegeneration, enabling the identification of disease-associated proteomic alterations and protein-level responses to therapeutic interventions. Building on our previous proteomic characterization of the orchiectomized (ORX) Brown Norway male rat retina as a model of androgen deprivation, we extend this investigation to the visual cortex (VC), a key node in the visual pathway. Here we report the first comprehensive proteomic characterization of ORX-VC employing nanoflow liquid chromatography–tandem mass spectrometry complemented by bioinformatic pathway analyses and quantitative assessment of selected protein markers of ORX-induced changes. Our discovery-driven proteomics approach revealed over 500 differentially expressed proteins following ORX. Principal component analysis showed complete separation between ORX and naïve groups with no overlap, indicating a profound effect of androgen deprivation on the VC proteome. Ingenuity Pathway Analysis^® predicted that the widespread proteome dysregulation included oxidative stress as a primary contributor, alongside estrogen receptor (ESR) predominance over androgen receptor signaling, consistent with our prior findings in the ORX retina. To explore whether this ESR predominance translates to a benefit of E2 supplementation alone, independent of circulating testosterone, we utilized our DHED (10β,17β-dihydroxyestra-1,4-dien-3-one) prodrug as eye drops to target E2 formation into the retina. Quantitative assessment demonstrated that this approach resulted in attenuation of ORX-induced expression changes in a selected panel of key proteins. These findings warrant future studies to determine whether this effect extends across the full spectrum of ORX-induced proteomic shifts and confers a benefit for vision preservation. Full article

(This article belongs to the Special Issue Role of Oxidative Stress in Eye Diseases)

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15 pages, 2649 KB

Open AccessArticle

The Nephroprotective Efficacy of Omega-3 Fatty Acids Against Streptozotocin-Induced Diabetic Renal Injury: A Biochemical, Histopathological and Ultrastructural Study

by Emrah Zayman, Eda Nur Özsoy, Mehmet Erman Erdemli, Zeynep Erdemli, Nilüfer Bulut, Feyza İnceoğlu and Mehmet Gül

Antioxidants 2026, 15(8), 975; https://doi.org/10.3390/antiox15080975 - 6 Aug 2026

Abstract

The present study was designed to evaluate the structural and biochemical efficacy of Omega-3 fatty acids in preventing renal injury in streptozotocin (STZ)-induced diabetic kidney injury and to correlate systemic oxidative stress parameters with histological and ultrastructural parameters. Twenty-eight male Wistar Albino rats [...] Read more.

The present study was designed to evaluate the structural and biochemical efficacy of Omega-3 fatty acids in preventing renal injury in streptozotocin (STZ)-induced diabetic kidney injury and to correlate systemic oxidative stress parameters with histological and ultrastructural parameters. Twenty-eight male Wistar Albino rats were randomly divided into four groups (n = 7) as follows: Control, Omega-3 (500 mg/kg, orally), Diabetes Mellitus (DM; 50 mg/kg STZ, i.p.), and DM+Omega-3 (STZ, followed by 500 mg/kg Omega-3 for 42 days). Biochemical analysis of renal function (blood urea nitrogen (BUN) and creatinine) and oxidative status (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI)) was measured by ELISA. Histopathological scoring and Caspase-3 staining were performed by Hematoxylin and Eosin (H&E) and immunohistochemically, respectively. Transmission Electron Microscopy (TEM) was used to examine the renal tissues. Our results showed that the DM group presented with severe hyperglycemia, uremia, and a significant oxidative shift, as evidenced by increased MDA/TOS levels and depleted antioxidant defenses. Light microscopy showed extensive glomerular damage, tubular degeneration and inflammatory infiltration in the kidneys of diabetic rats. Immunohistochemical analysis revealed strong Caspase-3 expression in the tubular and glomerular compartments. TEM showed severe podocyte effacement and damage to the glomerular basement membrane (GBM). Notably, Omega-3 supplementation significantly reversed renal dysfunction, restored the pro-oxidant/antioxidant balance and reduced histopathological injury scores. Moreover, Omega-3 treatment efficiently blocked Caspase-3-mediated apoptotic signaling and preserved the ultrastructural integrity of the glomerular filtration barrier (GFB) and tubular mitochondria. Our results demonstrate the potent nephroprotective effects of Omega-3 fatty acids in reducing oxidative stress, preventing programmed cell death and maintaining the stability of the renal parenchyma’s microarchitecture. These findings suggest that Omega-3 fatty acids could be an effective adjuvant therapeutic agent for the management of diabetic nephropathy. Full article

(This article belongs to the Special Issue Antioxidants in Chronic and End-Stage Kidney Disease: Defining Biological and Clinical Plausibility)

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24 pages, 10375 KB

Open AccessArticle

Ethanolic Extract of Sophora moorcroftiana Seeds Attenuates LPS-Induced Inflammation and Oxidative Stress in RAW 264.7 Macrophages via Modulation of the p62/Keap1/Nrf2 Signaling Pathway

by Nianshou Zhao, Hongya Li, Peng Ji, Yanming Wei, Yongli Hua, Yanan Guo and Fanlin Wu

Antioxidants 2026, 15(8), 974; https://doi.org/10.3390/antiox15080974 - 5 Aug 2026

Abstract

Despite the traditional application of Sophora moorcroftiana seeds (SMS) in Tibetan medicine for heat-clearing, damp-drying, anti-inflammatory and detoxifying properties, the anti-inflammatory mechanisms of SMS remain insufficiently understood and warrant systematic investigation. This study evaluated the protective effects of an ethanolic SMS extract against [...] Read more.

Despite the traditional application of Sophora moorcroftiana seeds (SMS) in Tibetan medicine for heat-clearing, damp-drying, anti-inflammatory and detoxifying properties, the anti-inflammatory mechanisms of SMS remain insufficiently understood and warrant systematic investigation. This study evaluated the protective effects of an ethanolic SMS extract against lipopolysaccharide (LPS)-induced oxidative stress and inflammation in RAW 264.7 macrophages, with emphasis on the p62/Keap1/Nrf2 signaling pathway. In vitro, the extract exhibited significant DPPH, ABTS and ·OH radical scavenging activities, as well as ferric-reducing antioxidant power, in a clear concentration dependent manner. An inflammatory model was established by stimulating RAW 264.7 cells with LPS, followed by treatment with graded concentrations of the ethanolic SMS extract. The extract significantly reduced LPS-induced nitric oxide production and decreased the secretion of TNF-α, IL-6 and IL-1β, while suppressing iNOS and COX-2 expression at both mRNA and protein levels. In parallel, the extract alleviated oxidative stress, as evidenced by reduced intracellular reactive oxygen species (ROS) and MDA levels, increased antioxidant defenses including SOD, GSH and CAT, and decreased LDH release. At the protein-expression level, SMS treatment was accompanied by differential changes in p62, Keap1, total Nrf2 and HO-1 expression, suggesting that its effects may involve regulatory processes associated with cellular stress and antioxidant defense. Collectively, the ethanolic extract of SMS attenuated LPS-induced inflammatory and oxidative stress responses in RAW 264.7 macrophages. These effects may be associated with the suppression of inflammatory mediator production, reduction in the cellular oxidative stress burden and modulation of proteins involved in cellular stress responses and antioxidant defense. Full article

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

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Graphical abstract

16 pages, 5501 KB

Open AccessReview

Beyond Food Preservation: Translational Perspectives of Synthetic Antioxidants

by Daniela Vergara, Felipe Lizama, Carlos Arias-Fuentes, Emigdio Chávez-Ángel and Alejandro Castro-Alvarez

Antioxidants 2026, 15(8), 973; https://doi.org/10.3390/antiox15080973 - 5 Aug 2026

Abstract

Synthetic antioxidants are attracting more interest as research moves beyond their traditional use as preservatives in food and materials. Recent studies are exploring how these redox-active molecules might be used in medicine. This review looks at how synthetic antioxidants are made, what is [...] Read more.

Synthetic antioxidants are attracting more interest as research moves beyond their traditional use as preservatives in food and materials. Recent studies are exploring how these redox-active molecules might be used in medicine. This review looks at how synthetic antioxidants are made, what is known about their biological effects, and the challenges of using them for neuroprotection, cancer treatment, organ protection, and regenerative medicine. In this review, synthetic antioxidants are defined as synthetic or semisynthetic small molecules with redox activity. Other antioxidant systems, such as non-phenolic molecules, prodrugs, peptides, metal complexes, nanocarriers, nanozymes, and biomaterials, are mentioned as related but are not considered classic synthetic antioxidants. Some of these compounds and delivery systems have shown promising results in cell, tissue, and animal studies. They have been found to influence neuroinflammation, mitochondrial function, and tumor redox responses, and to protect tissues from ischemic or inflammatory damage. However, most of these candidates are still in preclinical development. Progress is slowed by issues such as inconsistent bioavailability, dose-dependent toxicity, unclear mechanisms of action, a lack of reliable biomarkers, and manufacturing or regulatory challenges, especially for advanced delivery systems. New research highlights the potential of hybrid molecules, organelle-targeted delivery, and systems that respond to specific triggers. Still, there is not enough strong clinical data to support these approaches. Moving forward, the field will need thorough pharmacological studies, careful safety checks, standardized ways to measure effectiveness, and well-designed clinical trials. Full article

(This article belongs to the Special Issue Recent Trends in Nanoantioxidants—2nd Edition)

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25 pages, 9935 KB

Open AccessReview

Oxidative Stress as a Potential Mechanistic Bridge Between Electronic Cigarette Components and Chronic Disease: A Combined Narrative and Bibliometric Analysis

by Rana Abdel Sater, Youssef El Rayess and Sofi G. Julien

Antioxidants 2026, 15(8), 972; https://doi.org/10.3390/antiox15080972 - 5 Aug 2026

Abstract

Despite their introduction two decades ago as cessation tools, vaping devices and electronic cigarettes (ECs) have surged dramatically among adolescents and adults worldwide. The widespread misconception that ECs are harmless has raised substantial concern about their potential contribution to chronic diseases associated with [...] Read more.

Despite their introduction two decades ago as cessation tools, vaping devices and electronic cigarettes (ECs) have surged dramatically among adolescents and adults worldwide. The widespread misconception that ECs are harmless has raised substantial concern about their potential contribution to chronic diseases associated with oxidative stress (OS) pathways. To map this rapidly growing field, we combined a bibliometric analysis of human research on vaping-associated OS over the past decade with a narrative review of EC component toxicology and regulatory updates. The bibliometric analysis of 189 human studies identified four keyword clusters reflecting clinico-epidemiological, biological/mechanistic, methodological, and acute-event research themes. The results of this bibliometric analysis structure the narrative synthesis, which evaluates the chemical constituents of ECs, including e-liquid constituents, device-derived contaminants, and their aerosol by-products, and links them to pathways associated with OS development. Oxidative stress was the most frequent bridging keyword, reflecting predominant academic trends as research shifted from acute-focused investigations toward mechanistic chronic disease research. No prior review has integrated EC component toxicology with bibliometric evidence to map this landscape. This combined approach provides researchers, clinicians, and policymakers with an integrated evidence base and identifies priority areas for future investigation, including long-term exposure thresholds, age- and sex-specific outcomes, and the urgent need for harmonized global regulation. Full article

(This article belongs to the Special Issue Cigarette Smoke and Oxidative Stress)

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