Antioxidants

14 pages, 1168 KB

Open AccessReview

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

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

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

Abstract

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

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

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

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23 pages, 6082 KB

Open AccessArticle

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

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

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

Abstract

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

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

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

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19 pages, 1737 KB

Open AccessArticle

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

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

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

Abstract

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

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

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

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18 pages, 2470 KB

Open AccessArticle

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

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

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

Abstract

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

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

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

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28 pages, 6651 KB

Open AccessArticle

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

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

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

Abstract

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

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

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

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24 pages, 2679 KB

Open AccessArticle

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

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

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

Abstract

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

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

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25 pages, 2327 KB

Open AccessArticle

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

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

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

Abstract

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

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

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

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34 pages, 4424 KB

Open AccessArticle

The Flavonoid Extract of Polygonum viviparum L. Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Regulating Intestinal Flora Homeostasis and Uric Acid Levels Through Inhibition of PI3K/AKT/NF-κB/IL-17 Signaling Pathway

by Haoyu Liu, Zhen Yang, Qian Chen, Hongjuan Zhang, Yu Liu, Di Wu, Dan Shao, Shengyi Wang and Baocheng Hao

Antioxidants 2025, 14(10), 1206; https://doi.org/10.3390/antiox14101206 (registering DOI) - 5 Oct 2025

Abstract

Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. [...] Read more.

Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus, Romboutsia, and Enterobacter. Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Antioxidants in Human Health—2nd Edition)

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32 pages, 927 KB

Open AccessReview

Environmental Nephrotoxicity Across the Life Course: Oxidative Stress Mechanisms and Opportunities for Early Intervention

by Chien-Ning Hsu, Chih-Yao Hou, Yu-Wei Chen, Guo-Ping Chang-Chien, Shu-Fen Lin and You-Lin Tain

Antioxidants 2025, 14(10), 1205; https://doi.org/10.3390/antiox14101205 - 4 Oct 2025

Abstract

Chronic kidney disease (CKD) affects nearly 10% of the global population, ranks among the top ten causes of death, and often progresses silently to end-stage disease without timely intervention. Increasing evidence indicates that many adult-onset cases originate in early life through adverse influences [...] Read more.

Chronic kidney disease (CKD) affects nearly 10% of the global population, ranks among the top ten causes of death, and often progresses silently to end-stage disease without timely intervention. Increasing evidence indicates that many adult-onset cases originate in early life through adverse influences on kidney development, a process termed kidney programming within the Developmental Origins of Health and Disease (DOHaD) framework. Environmental pollutants are now recognized as key drivers of kidney injury across the life course. Heavy metals, air pollutants, plastic contaminants such as bisphenol A, phthalates, and micro/nanoplastics—as well as biocontaminants like mycotoxins and aristolochic acid—and chronic light pollution can accumulate in kidney tissue or act systemically to impair function. These exposures promote oxidative stress, inflammation, and endothelial and circadian disruption, culminating in tubular injury, glomerular damage, and fibrosis. Notably, early-life exposures can induce epigenetic modifications that program lifelong susceptibility to CKD and related complications. Oxidative stress is central to these effects, mediating DNA, lipid, and protein damage while influencing developmental reprogramming during gestation. Preclinical studies demonstrate that antioxidant-based interventions may mitigate these processes, providing both renoprotective and reprogramming benefits. This review explores the mechanistic links between environmental pollutants, oxidative stress, and kidney disease and highlights antioxidant strategies as promising avenues for prevention and intervention in vulnerable populations. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Environmental Toxicity—2nd Edition)

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14 pages, 2098 KB

Open AccessReview

Oxidative Stress in Diabetic Retinopathy: A Comprehensive Review of Mechanisms, Biomarkers, and Therapeutic Perspectives

by Tatsuya Mimura and Hidetaka Noma

Antioxidants 2025, 14(10), 1204; https://doi.org/10.3390/antiox14101204 - 4 Oct 2025

Abstract

Diabetic retinopathy (DR) is a leading cause of vision loss globally and represents one of the most common microvascular complications of diabetes. In addition to metabolic disturbances associated with hyperglycemia, oxidative stress has emerged as a critical contributor to the onset and progression [...] Read more.

Diabetic retinopathy (DR) is a leading cause of vision loss globally and represents one of the most common microvascular complications of diabetes. In addition to metabolic disturbances associated with hyperglycemia, oxidative stress has emerged as a critical contributor to the onset and progression of DR. Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense mechanisms, leads to cellular injury, inflammation, and increased vascular permeability. In the diabetic retina, excessive ROS production promotes endothelial cell apoptosis, breakdown of the blood-retinal barrier (BRB), and induction of angiogenic factors such as vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of the pathophysiology of DR, focusing on the molecular mechanisms of oxidative stress. Relevant studies were identified through a structured search of PubMed, Web of Science, and Scopus (2000–2025) using terms such as ‘diabetic retinopathy’, ‘oxidative stress’, and ‘antioxidants’. We explore current knowledge on oxidative stress-related biomarkers and therapeutic strategies targeting oxidative damage, including antioxidant compounds and mitochondrial protective agents. Recent findings from both experimental and clinical studies are summarized, highlighting the translational potential of oxidative stress modulation in DR management. Finally, future research directions are discussed, including biomarker standardization, personalized medicine approaches, and long-term clinical validation of antioxidant-based therapies. A deeper understanding of oxidative stress may offer valuable insights into novel diagnostic and therapeutic strategies for DR. Full article

(This article belongs to the Special Issue Oxidative Stress and Diabetic Retinopathy)

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19 pages, 2189 KB

Open AccessArticle

Dissecting the Interplay Between NRF2 and BACH1 at CsMBEs

by Maria-Armineh Tossounian, Alexander Zhyvoloup, Rakesh Chatterjee and Jerome Gouge

Antioxidants 2025, 14(10), 1203; https://doi.org/10.3390/antiox14101203 - 3 Oct 2025

Abstract

BACH1 (BTB And CNC Homology 1) and NRF2 (Nuclear Factor Erythroid 2-related Factor 2) are transcription factors that regulate antioxidant and iron metabolism genes by competing for binding to cis-regulatory Maf-binding elements (CsMBEs) as heterodimers with small Maf proteins (sMafs). To dissect the [...] Read more.

BACH1 (BTB And CNC Homology 1) and NRF2 (Nuclear Factor Erythroid 2-related Factor 2) are transcription factors that regulate antioxidant and iron metabolism genes by competing for binding to cis-regulatory Maf-binding elements (CsMBEs) as heterodimers with small Maf proteins (sMafs). To dissect the mechanisms underlying this competition, we developed a chimeric tethering system where the DNA-binding domains of BACH1 or NRF2 were covalently linked to sMafG via a flexible, cleavable linker. This design enables efficient heterodimer formation on DNA and circumvents kinetic barriers to partner exchange in the solution. The site-specific fluorescent labelling of proteins allowed for the tracking of complex compositions by electrophoretic mobility shift assays. Both BACH1/sMafG and NRF2/sMafG heterodimers bind CsMBEs with similar affinities. Notably, DNA binding by BACH1 was impaired in a C574-dependent, redox-sensitive manner and promoted the exchange of heterodimer partners. Competition assays demonstrated that BACH1 and NRF2 can displace each other from preformed DNA-bound complexes, with greater efficiency when presented as preassembled heterodimers with sMafG. These findings reveal a redox-sensitive mechanism for regulating transcriptional switches at CsMBEs and highlight how preformed heterodimers facilitate the rapid displacement at target promoters. Full article

(This article belongs to the Special Issue Antioxidant Systems, Transcription Factors and Non-Coding RNAs)

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15 pages, 993 KB

Open AccessReview

Antioxidants in Cardiovascular Health: Implications for Disease Modeling Using Cardiac Organoids

by Gracious R. Ross and Ivor J. Benjamin

Antioxidants 2025, 14(10), 1202; https://doi.org/10.3390/antiox14101202 - 3 Oct 2025

Abstract

Cardiovascular disease remains the leading cause of mortality worldwide, and at its molecular core lies a silent disruptor: oxidative stress. This imbalance between reactive oxygen species (ROS) and antioxidant defenses not only damages cellular components but also orchestrates a cascade of pathological events [...] Read more.

Cardiovascular disease remains the leading cause of mortality worldwide, and at its molecular core lies a silent disruptor: oxidative stress. This imbalance between reactive oxygen species (ROS) and antioxidant defenses not only damages cellular components but also orchestrates a cascade of pathological events across diverse cardiac cell types. In cardiomyocytes, ROS overload impairs contractility and survival, contributing to heart failure and infarction. Cardiac fibroblasts respond by promoting fibrosis through excessive collagen deposition. Macrophages intensify inflammatory responses, such as atherosclerosis, via ROS-mediated lipid oxidation—acting both as mediators of damage and targets for antioxidant intervention. This review examines how oxidative stress affects cardiac cell types and evaluates antioxidant-based therapeutic strategies. Therapeutic approaches include natural antioxidants (e.g., polyphenols and vitamins) and synthetic agents (e.g., enzyme modulators), which show promise in experimental models by improving myocardial remodeling. However, clinical trials reveal inconsistent outcomes, underscoring translational challenges (e.g., clinical biomarkers). Emerging strategies—such as targeted antioxidant delivery, activation of endogenous pathways, and disease modeling using 3D organoids—aim to enhance efficacy. In conclusion, we spotlight innovative technologies—like lab-grown heart tissue models—that help scientists better understand how oxidative stress affects heart health. These tools are bridging the gap between early-stage research and personalized medicine, opening new possibilities for diagnosing and treating heart disease more effectively. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Advances in Redox-Tools and Therapies in Cardiovascular Disease)

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19 pages, 1147 KB

Open AccessArticle

Exploring the Potential of Low-Temperature Vacuum Drying to Improve the Bioactive Compound Content and Health-Promoting Properties of Chilean Wild Murta

by Antonio Vega-Galvez, Alexis Pasten, Elsa Uribe, Nicol Mejias, Isadora Corco, Jacqueline Poblete, Jaime Ortiz-Viedma, Gabriela Valenzuela-Barra, Javier Acevedo-Hernández and Tamar Toledo

Antioxidants 2025, 14(10), 1201; https://doi.org/10.3390/antiox14101201 - 3 Oct 2025

Abstract

For the first time, the effect of low-temperature vacuum drying (LTVD) on wild murta (Ugni molinae Turcz) was evaluated, in comparison with freeze-drying (FD) and vacuum drying (VD), to assess their capacity to preserve bioactive compounds and associated bioactivities. Murta was dried [...] Read more.

For the first time, the effect of low-temperature vacuum drying (LTVD) on wild murta (Ugni molinae Turcz) was evaluated, in comparison with freeze-drying (FD) and vacuum drying (VD), to assess their capacity to preserve bioactive compounds and associated bioactivities. Murta was dried using LTVD at 20, 30, and 40 °C under a constant vacuum of 10 mbar, where FD and VD at 60 °C (VD 60) were included as comparative methods. The content of fatty acids and tocols, along with the retention of bioactive compounds and their antioxidant, anti-inflammatory, cytotoxic, and α-glucosidase inhibitory activities, were systematically analyzed. LTVD- and VD-dried murta exhibited higher polyunsaturated-to-saturated fatty acid ratios (>9.0) and markedly greater tocol contents, whereas FD maintained a more balanced ratio (<5.0) but with lower tocol levels. While FD was most effective in preserving catechin, higher levels of other phenolic compounds were observed in samples dried by LTVD at 20 and 40 °C, as well as VD 60, possibly due to the release of bound forms during processing. The drying method significantly influenced murta bioactivity. LTVD 30 preserved the highest antioxidant capacity, while topical anti-inflammatory effects on skin lesions varied by pathway, with LTVD 40 being the most effective in the TPA model and FD in the AA model. These effects were evaluated only using a topical inflammation model in BALB/c mice of both sexes; dietary effects were not assessed in this study. Regarding other bioactivities, VD 60 extracts excelled in both cytotoxic and α-glucosidase inhibitory effects, whereas FD extracts were the most effective against AGS cells and LTVD 20 against α-glucosidase. In conclusion, LTVD emerges as a promising alternative to FD and VD, showing potential to preserve bioactive compounds and key bioactivities of wild murta, although further studies are needed to elucidate the underlying mechanisms. Full article

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

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3 pages, 149 KB

Open AccessEditorial

Effect of Dietary Antioxidants in Chronic Disease Prevention

by Baojun Xu

Antioxidants 2025, 14(10), 1200; https://doi.org/10.3390/antiox14101200 - 2 Oct 2025

Abstract

Chronic diseases are a major global public health challenge, with increasing incidence and mortality rates [...] Full article

(This article belongs to the Special Issue Effect of Dietary Antioxidants in Chronic Disease Prevention)

30 pages, 2239 KB

Open AccessArticle

Valorization of Hazelnut (Corylus avellana L.) Skin By-Product as a Multifunctional Ingredient for Cosmetic Emulsions

by Teresa Mencherini, Tiziana Esposito, Francesca Sansone, Daniela Eletto, Martina Pannetta, Oihana Gordobil, Anna Lisa Piccinelli, Carlo Ferniani, Giulia Auriemma, Luca Rastrelli and Rita Patrizia Aquino

Antioxidants 2025, 14(10), 1199; https://doi.org/10.3390/antiox14101199 - 2 Oct 2025

Abstract

Roasted hazelnut skins (RHSs), generated as by-products of industrial hazelnut processing, were extracted by pressurized liquid extraction to yield a hydroalcoholic extract (RHS-H). The extract was rich in polyphenols (308.4 ± 4.6 mg GAE/g) and proanthocyanidins (169.3 ± 10 mg CE/g) and showed [...] Read more.

Roasted hazelnut skins (RHSs), generated as by-products of industrial hazelnut processing, were extracted by pressurized liquid extraction to yield a hydroalcoholic extract (RHS-H). The extract was rich in polyphenols (308.4 ± 4.6 mg GAE/g) and proanthocyanidins (169.3 ± 10 mg CE/g) and showed strong antioxidant activity (DPPH EC₅₀ = 5.08 ± 1.08 µg/mL; TEAC = 2.82 ± 0.03 mM Trolox/mg) together with antimicrobial effects against Staphylococcus aureus and Staphylococcus epidermidis. RHS-H also enhanced the UV absorbance of synthetic UV filters. When incorporated into oil-in-water (O/W) cosmetic emulsions at low concentrations (0.2–2% w/w), RHS-H did not affect physicochemical stability: formulations maintained acceptable organoleptic properties, dermocompatible pH (4.7–5.5), electrostatic stability (ζ-potential ranging from –57 to –60 mV), and rheological behavior. Functionally, RHS-H increased the antioxidant activity of emulsions (radical scavenging > 80% vs. 52% in the blank), ensured microbial protection in challenge tests, and enhanced SPF by 9.4% at 0.2% w/w, with further improvements at higher concentrations, reaching broad-spectrum photoprotection (critical wavelength > 370 nm). Overall, RHS-H represents a natural multifunctional ingredient with antioxidant, preservative, and photoprotective properties, providing a sustainable strategy to upcycle hazelnut processing waste and reduce reliance on synthetic additives in cosmetic formulations. Full article

(This article belongs to the Special Issue Natural Antioxidants for Cosmetic Applications)

31 pages, 2721 KB

Open AccessArticle

Phytochemical Composition and Antioxidant Activity of Traditional Plant Extracts with Biocidal Effects and Soil-Enhancing Potential

by Camelia Hodoșan, Cerasela Elena Gîrd, Ștefan-Claudiu Marin, Alexandru Mihalache, Emanuela-Alice Luță, Elena-Iuliana Ioniță, Andrei Biță, Ştefania Gheorghe, Laura Feodorov, Violeta Popovici, Elena Pogurschi, Lucica Nistor, Iulius Sorin Bărbuică and Lăcrămioara Popa

Antioxidants 2025, 14(10), 1198; https://doi.org/10.3390/antiox14101198 - 2 Oct 2025

Abstract

This research provides a comprehensive evaluation of the phytochemical composition, antioxidant potential, and biological properties of four plant species with longstanding use in ethnobotanical traditions: Calendula officinalis, Mentha × piperita, Urtica dioica, and Juglans regia. Plant extracts were obtained [...] Read more.

This research provides a comprehensive evaluation of the phytochemical composition, antioxidant potential, and biological properties of four plant species with longstanding use in ethnobotanical traditions: Calendula officinalis, Mentha × piperita, Urtica dioica, and Juglans regia. Plant extracts were obtained using a range of solvent systems and subsequently analyzed for their content of total polyphenols, flavonoids, and phenolic acids. Ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) enabled the accurate identification and quantification of major polyphenolic constituents. The antioxidant capacity was assessed through a series of in vitro assays, and elemental analysis was conducted to determine microelement content. To evaluate potential ecological implications, acute toxicity was tested using Daphnia magna, while phytotoxic effects were also examined. The results demonstrate pronounced antioxidant activity along with notable biocidal and soil-enhancing properties. These findings underscore the potential of such plant-based formulations as sustainable alternatives to conventional agrochemicals and highlight the relevance of integrating traditional botanical knowledge with modern strategies for enhancing soil quality, crop performance, and environmental sustainability. Full article

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

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24 pages, 2672 KB

Open AccessArticle

Reassessing Whether Biodegradable Microplastics Are Environmentally Friendly: Differences in Earthworm Physiological Responses and Soil Carbon Function Impacts

by Yuze Li, Dongxing Zhou, Hongyan Wang, Wenfei Zhu, Rui Wang and Yucui Ning

Antioxidants 2025, 14(10), 1197; https://doi.org/10.3390/antiox14101197 - 1 Oct 2025

Abstract

Biodegradable plastics are not a primary solution to plastic pollution, and empirical evidence on whether they are environmentally friendly remains lacking. In this study, we systematically compared the toxic effects of traditional microplastics (polypropylene, PP; polystyrene, PS) with biodegradable microplastics (polylactic acid, PLA; [...] Read more.

Biodegradable plastics are not a primary solution to plastic pollution, and empirical evidence on whether they are environmentally friendly remains lacking. In this study, we systematically compared the toxic effects of traditional microplastics (polypropylene, PP; polystyrene, PS) with biodegradable microplastics (polylactic acid, PLA; polyhydroxyalkanoates, PHA) on the haplic phaeozem ecosystem. Through mathematical modeling analysis, it was found that earthworms initially rely on antioxidant enzymes to resist stress, mid-term activation of detoxifying enzymes to repair damage, and maintaining physiological balance through metabolic regulation and immune enhancement in later stages. We elucidated their mechanism differences: PLA and PP caused severe damage to the antioxidant system and cell membrane, with PLA mainly relying on POD to clear peroxides and PP relying on GST. In addition, PLA and PS can induce early neurotoxicity (AChE), while PHA induces late neurotoxicity. Furthermore, this study provides direct evidence proving that biodegradable microplastics are not environmentally friendly by breaking through the one-way research framework of “microplastic biotoxicity” and innovatively constructing a path analysis model that links biological physiological responses with soil ecological functions. We also provide a scientific basis to evaluate the ecological risks of microplastic pollution in soil and the whether biodegradable plastics are truly environmentally friendly. Full article

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16 pages, 629 KB

Open AccessReview

Alcohol-Induced Oxidative Stress and Gut–Liver–Brain Crosstalk: Expanding the Paradigm from ALD to MetALD

by Jeong-Yoon Lee, Young-Min Jee, Keungmo Yang and Tom Ryu

Antioxidants 2025, 14(10), 1196; https://doi.org/10.3390/antiox14101196 - 1 Oct 2025

Abstract

Alcohol-associated liver disease (ALD) includes a spectrum from steatosis and steatohepatitis to cirrhosis and hepatocellular carcinoma driven by oxidative stress, immune activation, and systemic inflammation. Ethanol metabolism through alcohol dehydrogenase, aldehyde dehydrogenase, and cytochrome P450 2E1 generates reactive oxygen and nitrogen species, leading [...] Read more.

Alcohol-associated liver disease (ALD) includes a spectrum from steatosis and steatohepatitis to cirrhosis and hepatocellular carcinoma driven by oxidative stress, immune activation, and systemic inflammation. Ethanol metabolism through alcohol dehydrogenase, aldehyde dehydrogenase, and cytochrome P450 2E1 generates reactive oxygen and nitrogen species, leading to mitochondrial dysfunction, hepatocellular injury, and activation of inflammatory and fibrogenic pathways. Beyond hepatic effects, ALD engages the gut–liver–brain axis, where microbial dysbiosis, blood–brain barrier disruption, and neuroinflammation contribute to cognitive impairment and cerebrovascular risk. The emerging concept, metabolic dysfunction-associated steatotic liver disease and increased alcohol intake (MetALD), presents the synergistic impact of alcohol and metabolic comorbidities, enhancing oxidative injury and fibrosis. This review summarizes key mechanisms connecting oxidative stress to multisystem pathology and highlights the need for precision therapies targeting redox imbalance, immune dysregulation, and gut–brain–liver interactions to improve outcomes in ALD and MetALD. Full article

(This article belongs to the Special Issue Alcohol-Induced Oxidative Stress in Health and Disease, 2nd Edition)

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20 pages, 3633 KB

Open AccessArticle

Dietary Soy Isoflavones Ameliorate Muscle Quality in High-Fat Diet-Fed Rice Field Eels (Monopterus albus) by Modulating Myogenesis, Collagen Synthesis, and Antioxidant Capacity

by Kai Xie, Quan Li, Shuang Zheng, Huahong Wei, Tao Zhou, Yi Hu and Junzhi Zhang

Antioxidants 2025, 14(10), 1195; https://doi.org/10.3390/antiox14101195 - 1 Oct 2025

Abstract

High-fat diets are increasingly used to improve feed efficiency in aquaculture but may deteriorate fillet quality and health; soy isoflavones, plant-derived polyphenols, have emerged as promising modulators of muscle growth, antioxidant defense, and lipid metabolism in fish. This study investigated the effects of [...] Read more.

High-fat diets are increasingly used to improve feed efficiency in aquaculture but may deteriorate fillet quality and health; soy isoflavones, plant-derived polyphenols, have emerged as promising modulators of muscle growth, antioxidant defense, and lipid metabolism in fish. This study investigated the effects of dietary soy isoflavone supplementation on myogenesis, collagen synthesis, fatty-acid composition, and antioxidant capacity in muscle of Monopterus albus fed a high-fat diet. Fish were assigned to four diets: control (CON, 6.16% crude fat), high-fat without soy isoflavones (HSIF0, 11.98% crude fat), and high-fat with 50 mg/kg (HSIF50) or 100 mg/kg (HSIF100) soy isoflavones. HSIF0 significantly elevated whole-body/muscle lipids, reduced ΣSFA/ΣMUFA/Σn-3/Σn-6 ratios (p < 0.05), increased Σn-6 (p < 0.05), impaired water-holding capacity/texture (higher losses, lower hardness/cohesiveness/gumminess/chewiness/resilience) (p < 0.05), induced loosely arranged myofibers with enlarged inter-fiber spaces, downregulated myogenesis (upregulated mstn; downregulated myod/tcap/mrf4/mrf5) and collagen genes (ets1/sp1/p4ha1) (p < 0.05), decreased collagen/hydroxyproline (p < 0.05), and weakened antioxidants (higher MDA/H₂O₂; lower T-AOC/GSH; downregulated nrf2/sod/cat/gpx1/gpx8) (p < 0.05). HSIF50 reversed these effects, enhancing ΣPUFA/Σn-3/EPA+DHA (p < 0.05), restoring structure/gene expression (p < 0.05), and boosting antioxidants (p < 0.05). In contrast, HSIF100 partially diminished benefits, indicating dose-dependency. Overall, 50 mg/kg soy isoflavones optimally mitigated high-fat-induced muscle quality decline via lipid remodeling, structural improvement, collagen promotion, and antioxidant enhancement. Full article

(This article belongs to the Special Issue Antioxidants and Aquaculture: A Synergistic Approach for Sustainable Aquatic Production)

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