Antioxidants

24 pages, 7319 KiB

Open AccessArticle

Korean Mistletoe (Viscum album var. coloratum) Ethanol Extracts Enhance Intestinal Barrier Function and Alleviate Inflammation

by Ye Jin Yang, Min Jung Kim, Ji Woong Heo, Hun Hwan Kim, Gon Sup Kim, Min Sub Shim, Kwang Youn Kim and Kwang Il Park

Antioxidants 2025, 14(3), 370; https://doi.org/10.3390/antiox14030370 - 20 Mar 2025

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Abstract

Korean mistletoe (Viscum album var. coloratum, KML) offers remarkable therapeutic potential for a variety of diseases. This study aims to evaluate the effects and potential molecular mechanisms of KML ethanol extracts (KMLE), focusing on intestinal barrier function and tight junctions (TJs) [...] Read more.

Korean mistletoe (Viscum album var. coloratum, KML) offers remarkable therapeutic potential for a variety of diseases. This study aims to evaluate the effects and potential molecular mechanisms of KML ethanol extracts (KMLE), focusing on intestinal barrier function and tight junctions (TJs) in an interleukin (IL)-6-induced Caco-2 cell monolayer model and a dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mouse model. KMLE is non-cytotoxic in Caco-2 cells and demonstrated strong antioxidant activity. KMLE alleviated significant barrier dysfunction and protected tight junction proteins (TJPs) in vitro. Furthermore, KMLE alleviated clinical symptoms and histopathological damage, upregulated TJPs, and suppressed the inflammatory cytokines in vivo. Additionally, six bioactive compounds were identified in KMLE by liquid chromatography–tandem mass spectrometry (LC-MS/MS). In conclusion, KMLE ameliorated intestinal barrier dysfunction in vitro and in vivo. These findings underscore the potential of KMLE as a therapeutic agent for UC, providing insights into the mechanisms through anti-inflammatory properties and its ability to restore TJ integrity. Full article

(This article belongs to the Special Issue Significance of Antioxidant Mechanisms in Intestinal Inflammation)

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15 pages, 1076 KiB

Open AccessReview

Production and Role of Nitric Oxide in Endometrial Cancer

by Seung Geun Yeo, Yeon Ju Oh, Jae Min Lee, Joon Hyung Yeo, Sung Soo Kim and Dong Choon Park

Antioxidants 2025, 14(3), 369; https://doi.org/10.3390/antiox14030369 - 20 Mar 2025

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Abstract

Endometrial cancer ranks as the fourth most common cancer among women in the United States. While early-stage treatment is generally effective with a cure rate of approximately 90%, the five-year survival rate dramatically decreases to 10–15% for advanced-stage diagnoses. Consequently, ongoing research seeks [...] Read more.

Endometrial cancer ranks as the fourth most common cancer among women in the United States. While early-stage treatment is generally effective with a cure rate of approximately 90%, the five-year survival rate dramatically decreases to 10–15% for advanced-stage diagnoses. Consequently, ongoing research seeks to improve treatment outcomes for endometrial cancer. Nitric oxide (NO) is implicated in various biological processes, including cancer progression, and is believed to play a significant role in human endometrial cancer. However, its specific function remains controversial. This study aims to elucidate the effects of NO in endometrial cancer through a comprehensive literature review. A thorough review of the literature was conducted using Cochrane Libraries, EMBASE, Google Scholar, PubMed, and SCOPUS databases to assess the induction and role of NO in the development of endometrial cancer. Out of 33 initially reviewed articles, 7 studies were included in the final review after excluding those unrelated to endometrial cancer or NO. Of these, six studies (85.7%) reported increased NO levels in endometrial cancer, whereas one study (14.3%) noted decreased NO levels or a defensive mechanism role. NO production was linked to tumor-promoting effects such as invasiveness, metastasis, angiogenesis, interaction with omental adipose stromal cells (O-ASCs), adipogenesis, and mitochondrial suppression. Conversely, NO also exhibited tumor-suppressive effects, including cell-cycle arrest, apoptosis induction, promotion of cancer stem-like cells, and upregulation of tumor suppressor genes like CDKN1A and RASSF1A. NO production is associated with the pathogenesis, development, and prognosis of endometrial cancer, with effects varying based on NO level fluctuations. Differences in NO production and function were observed according to the type of nitric oxide synthase (NOS) involved, control conditions, subtype, grade, and invasiveness of the cancer, as well as the experimental methodologies employed. NO demonstrated dual action in endometrial cancer: low concentrations promoted tumor growth by protecting cells and inhibiting apoptosis, while high concentrations exerted cytotoxic effects, suppressing tumor growth. However, no studies have precisely defined the concentration thresholds or mechanisms by which NO contributes to either tumorigenesis or tumor suppression in endometrial cancer. To effectively harness the therapeutic potential of NO in treating endometrial cancer, a deeper understanding of these dual-effect mechanisms is necessary. Full article

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29 pages, 8189 KiB

Open AccessArticle

Hydroxytyrosol-Infused Extra Virgin Olive Oil: A Key to Minimizing Oxidation, Boosting Antioxidant Potential, and Enhancing Physicochemical Stability During Frying

by Taha Mehany, José M. González-Sáiz and Consuelo Pizarro

Antioxidants 2025, 14(3), 368; https://doi.org/10.3390/antiox14030368 - 20 Mar 2025

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Abstract

The current research aims to monitor the physicochemical changes in various varieties of extra virgin olive oils (EVOOs) supplemented with exogenous polyphenolic extract from olive fruit, enriched with hydroxytyrosol (HTyr) and its derivatives, compared to numerous refined olive oils, sunflower oil, and high [...] Read more.

The current research aims to monitor the physicochemical changes in various varieties of extra virgin olive oils (EVOOs) supplemented with exogenous polyphenolic extract from olive fruit, enriched with hydroxytyrosol (HTyr) and its derivatives, compared to numerous refined olive oils, sunflower oil, and high oleic sunflower oil under different deep-frying conditions (170–210 °C for 3 to 6 h, with/without added HTyr. Acidity, K₂₃₂, K₂₇₀, ∆K, peroxide value (PV), anisidine value (AnV), TOTOX, refractive index (RI), carotenoids, chlorophyll, and antioxidant capacity using DPPH (2,2-diphenyl-1-picrylhydrazyl) approach were evaluated. The results show that EVOO varieties generally exhibit lower acidity and thermal degradation compared to refined olive oils, particularly when deep-fried at 170 °C for 3 h with exogenous HTyr (the best treatment). Royuela, Koroneiki, Empeltre, Manzanilla, and Arbosana EVOO varieties demonstrated lower K₂₃₂ values (1.36, 1.67, 1.79, 1.82, and 1.81, respectively). Under optimal deep-frying conditions, all EVOO varieties fell within the standard K₂₃₂ limit for EVOO (≤2.5), except for Cornicabra. Regarding K₂₇₀, only Royuela (0.11) and Manzanilla (0.22) were below the standard limit of ≤0.22. These two varieties also exhibited the lowest ΔK values (0.00). The findings further revealed that Royuela, Koroneiki, and Manzanilla had the lowest TOTOX values, with 20.76, 23.38, and 23.85, respectively. Moreover, Koroneiki and Arbosana had the highest carotenoid ratios, with values of 17.5 mg/kg and 13.7 mg/kg, respectively. Koroneiki, Arbosana, and olive oil 1° also displayed the highest chlorophyll concentrations, with values of 50.2, 53.7, and 47.5 mg/kg, respectively. Furthermore, the findings from the best deep-frying treatment indicated that all olive oil categories exhibited high scavenging radical activity toward DPPH, even in refined olive oil categories and low-quality original olive oil due to the addition of HTyr. In conclusion, deep-fried EVOOs enriched with HTyr at 170 °C/3 h are thermally stable, exhibiting low hydrolysis, low oxidation, higher antioxidant potential, and stable chlorophyll and carotenoid levels. The addition of HTyr to deep-frying oils not only enhances the health benefits of EVOO, supporting EFSA health claims but also acts as a promising stabilizer for the olive oil industry, particularly under high-temperature processing conditions over prolonged periods. This highlights its potential for industrial use as a natural alternative to synthetic antioxidants, not only for olive oil but also for other edible oils, with practical applications in the food industry to improve the quality and stability of frying oils. Full article

(This article belongs to the Special Issue Antioxidants from Sustainable Food Sources)

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31 pages, 8897 KiB

Open AccessArticle

Effect of N-Acetylcysteine in Mitochondrial Function, Redox Signaling, and Sirtuin 3 Levels in the Heart During Cardiorenal Syndrome Type 4 Development

by Isabel Amador-Martínez, Omar Emiliano Aparicio-Trejo, Ana Karina Aranda-Rivera, Bismarck Bernabe-Yepes, Omar Noel Medina-Campos, Edilia Tapia, Carlo César Cortés-González, Alejandro Silva-Palacios, Francisco Javier Roldán, Juan Carlos León-Contreras, Rogelio Hernández-Pando, Emma Saavedra, José Guillermo Gonzaga-Sánchez, Zeltzin Alejandra Ceja-Galicia, Laura Gabriela Sánchez-Lozada and José Pedraza-Chaverri

Antioxidants 2025, 14(3), 367; https://doi.org/10.3390/antiox14030367 - 20 Mar 2025

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Abstract

Type 4 cardiorenal syndrome (CRS-4) is a pathology in which chronic kidney disease (CKD) triggers the development of cardiovascular disease. CKD pathophysiology produces alterations that can affect the bioenergetics of heart mitochondria, causing oxidative stress and reducing antioxidant glutathione (GSH) levels. GSH depletion [...] Read more.

Type 4 cardiorenal syndrome (CRS-4) is a pathology in which chronic kidney disease (CKD) triggers the development of cardiovascular disease. CKD pathophysiology produces alterations that can affect the bioenergetics of heart mitochondria, causing oxidative stress and reducing antioxidant glutathione (GSH) levels. GSH depletion alters protein function by affecting post-translational modifications such as S-glutathionylation (RS-SG), exacerbating oxidative stress, and mitochondrial dysfunction. On the other hand, N-acetylcysteine (NAC) is an antioxidant GSH precursor that modulates oxidative stress and RS-SG. Moreover, recent studies have found that NAC can activate the Sirtuin 3 (SIRT3) deacetylase in diseases. However, the role of NAC and its effects on mitochondrial function, redox signaling, and SIRT3 modifications in the heart during CRS-4 have not been studied. This study aimed to investigate the role of NAC in mitochondrial function, redox signaling, and SIRT3 in the hearts of animals with CRS-4 at two months of follow-up. Our results showed that the oral administration of NAC (600 mg/kg/day) improved blood pressure and reduced cardiac fibrosis. NACs’ protective effect was associated with preserving cardiac mitochondrial bioenergetics and decreasing these organelles’ hydrogen peroxide (H₂O₂) production. Additionally, NAC increased GSH levels in heart mitochondria and regulated the redox state, which coincided with an increase in nicotinamide adenine dinucleotide oxidized (NAD⁺) levels and a decrease in mitochondrial acetylated lysines. Finally, NAC increased SIRT3 levels and the activity of superoxide dismutase 2 (SOD-2) in the heart. Thus, treatment with NAC decreases mitochondrial alterations, restores redox signaling, and decreases SIRT3 disturbances during CRS-4 through an antioxidant defense mechanism. Full article

(This article belongs to the Special Issue Antioxidant Therapies in Cardiovascular, Cardiorenal and Metabolic Diseases)

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17 pages, 2504 KiB

Open AccessArticle

Serum CD5L Responds Positively to Selenium and Coenzyme Q₁₀ Supplementation with Relation to Thyroid Hormones, Mortality, and Health-Related Quality-of-Life—A Sub-Analysis of a Double-Blind Randomised Placebo-Controlled Trial in Elderly Low in Selenium

by Urban Alehagen, Jan O. Aaseth, Trine B. Opstad, Anders Larsson, Sabrina Asaad, Lutz Schomburg and Jan Alexander

Antioxidants 2025, 14(3), 366; https://doi.org/10.3390/antiox14030366 - 20 Mar 2025

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Abstract

The Cluster of Differentiation 5-like protein (CD5L) is produced by tissue-resident macrophages. It is an innate immune mediator protein with a multitude of functions, such as binding of invading microorganisms and oxidised LDL, and it is associated with clinical conditions, i.e., atherosclerosis and [...] Read more.

The Cluster of Differentiation 5-like protein (CD5L) is produced by tissue-resident macrophages. It is an innate immune mediator protein with a multitude of functions, such as binding of invading microorganisms and oxidised LDL, and it is associated with clinical conditions, i.e., atherosclerosis and inflammation. The circulating CD5L level has been reported to correlate to selenium status and thyroid hormone activity. In order to test this hypothesis, we analysed CD5L in serum samples from a randomized controlled trial (RCT) with selenium and coenzyme Q₁₀ supplementation and examined associations between CD5L and thyroid hormones, health-related quality-of-life (Hr-QoL), and mortality in an elderly population low in selenium. Circulating levels of CD5L and thyroid hormones were determined in 359 elderly community-living individuals enrolled in an RCT at inclusion and after 48 months of supplementation (179 received selenium and coenzyme Q₁₀, and 180 placebo). Hr-QoL was recorded at both time-points using Short Form 36. Pre-intervention plasma selenium was low, mean 67 µg/L. CD5L correlated positively to free tri-iodothyronine (fT3) and showed an inverse relation with thyroid stimulating hormone (TSH). Low CD5L concentrations at inclusion in the placebo group were associated with increased cardiovascular mortality during 10 years of follow-up, and impaired Hr-QoL at 48 months. Selenium and coenzyme Q₁₀ supplementation significantly increased CD5L and fT3 levels, in association with a better health outcome. The data indicate that circulating CD5L positively responds to selenium and coenzyme Q₁₀ supplementation, correlates with thyroid hormone status, and associates with positive health indices. The observed effect may be due to increased selenium-dependent deiodinase isozyme expression that converts thyroxine (T4) to T3 locally and supports thyroid hormone activities. Whether the observed associations with Hr-QoL and cardiovascular mortality are a direct effect of circulating CD5L or local thyroid hormone activity is unclear and should be further investigated. Full article

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

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29 pages, 3639 KiB

Open AccessArticle

Ultrasound-Assisted Deep Eutectic Solvent Extraction of Antioxidant and Anti-Colorectal Cancer Proteins from Spirulina Biomass: Process Intensification, Characterization, and Bioactivity Evaluation

by May Thu Zin, Thida Kaewkod, Supakit Chaipoot, Gochakorn Kanthakat, Yan-Yu Chen, Benjamas Cheirsilp and Sirasit Srinuanpan

Antioxidants 2025, 14(3), 365; https://doi.org/10.3390/antiox14030365 - 19 Mar 2025

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Abstract

Spirulina, a cyanobacterial biomass, is renowned for its high protein content and bioactive compounds, making it a promising candidate for health-promoting applications. This study explores the ultrasound-assisted deep eutectic solvent (DES) extraction technique for isolating antioxidants and anticancer proteins from Spirulina biomass, [...] Read more.

Spirulina, a cyanobacterial biomass, is renowned for its high protein content and bioactive compounds, making it a promising candidate for health-promoting applications. This study explores the ultrasound-assisted deep eutectic solvent (DES) extraction technique for isolating antioxidants and anticancer proteins from Spirulina biomass, aiming to enhance extraction efficiency and preserve protein bioactivity. The extraction process was optimized using response surface methodology (RSM), varying parameters such as biomass concentration, sonication amplitude, and extraction duration. The optimized extraction conditions—5% biomass concentration, 40% sonication amplitude, and 22-minute extraction—achieved a high protein yield of 80.62%, with a protein concentration of 442.88 mg/g extract and an essential amino acid content of 39.91%. The extracted proteins exhibited remarkable bioactivity, including strong antioxidant properties, with 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of 0.25 mg GAE/g, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging activity of 0.58 mg TE/g, and ferric reducing antioxidant power (PFRAP) of 9.63 mg gallic acid equivalent (GAE)/g. Additionally, the protein extract displayed selective cytotoxicity against colorectal cancer cell lines, with half-maximal inhibitory concentration (IC₅₀) values of 10.25 mg/mL for Caco-2 and 15.40 mg/mL for HT-29 cells, while maintaining low toxicity towards normal Vero cells. Apoptosis rates of 70.43% in Caco-2 and 51.33% in HT-29 cells further confirm the anticancer potential of the extract. The functional properties of the extracted protein, including high foaming capacity (100%), emulsifying capacity (94.05%), and digestibility (85.77%), underscore its potential for diverse applications in food, pharmaceutical, and nutraceutical industries. This eco-friendly and efficient extraction approach aligns with sustainable development goals and offers a viable strategy for harnessing Spirulina’s bioactive potential. Full article

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

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19 pages, 4528 KiB

Open AccessArticle

Therapeutic and Pharmaceutical Potential of Scutellaria baicalensis-Derived Exosomes for Oily Skin Disorders

by Guybin Gong, Mihae Yun, Ohhyuk Kwon and Boyong Kim

Antioxidants 2025, 14(3), 364; https://doi.org/10.3390/antiox14030364 - 19 Mar 2025

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Abstract

Background: Fine dust exposure worsens oily skin by disrupting lipid metabolism and triggering oxidative inflammation. Scutellaria baicalensis extract-induced exosomes (SBEIEs) have shown anti-inflammatory effects by suppressing reactive oxygen species (ROS) and lipid-regulating properties, making them potential therapeutic agents. Methods: Exosomes from fibroblasts treated [...] Read more.

Background: Fine dust exposure worsens oily skin by disrupting lipid metabolism and triggering oxidative inflammation. Scutellaria baicalensis extract-induced exosomes (SBEIEs) have shown anti-inflammatory effects by suppressing reactive oxygen species (ROS) and lipid-regulating properties, making them potential therapeutic agents. Methods: Exosomes from fibroblasts treated with SBEIEs and PM10 were tested on macrophages, adipose-derived stem cells (ASCs), and T lymphocytes. ELISA, flow cytometry, and PCR measured cytokines and gene expression. A 10-day clinical trial evaluated skin hydration, oiliness, and inflammation. Results: SBEIEs increased IRF3 (1.6 times) and suppressed PPARγ in ASCs while enhancing lipolysis markers. Sebaceous gland activity (squalene synthase) decreased by 10%. Macrophages showed increased IRF3, IFN-β, and IL-10 (2.1 times). T cells secreted IL-4 and IL-22 (2–2.33 times). Clinically, SBEIEs improved hydration (21%), reduced oiliness (1.6 times), and decreased inflammation (2.2 times). Conclusions: SBEIEs effectively regulate lipid metabolism, cytokines, and immune responses, showing promise to treat oily and inflamed skin caused by fine dust exposure. Further studies are needed for clinical applications. Full article

(This article belongs to the Special Issue Dietary Antioxidants and Cosmetics—2nd Edition)

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27 pages, 9881 KiB

Open AccessArticle

Anti-TNFα and Anti-IL-1β Monoclonal Antibodies Preserve BV-2 Microglial Homeostasis Under Hypoxia by Mitigating Inflammatory Reactivity and ATF4/MAPK-Mediated Apoptosis

by Linglin Zhang, Chaoqiang Guan, Sudena Wang, Norbert Pfeiffer and Franz H. Grus

Antioxidants 2025, 14(3), 363; https://doi.org/10.3390/antiox14030363 - 19 Mar 2025

Viewed by 365

Abstract

The disruption of microglial homeostasis and cytokine release are critical for neuroinflammation post-injury and strongly implicated in retinal neurodegenerative diseases like glaucoma. This study examines microglial responses to chemical hypoxia induced by cobalt chloride (CoCl₂) in BV-2 murine microglial cells, focusing [...] Read more.

The disruption of microglial homeostasis and cytokine release are critical for neuroinflammation post-injury and strongly implicated in retinal neurodegenerative diseases like glaucoma. This study examines microglial responses to chemical hypoxia induced by cobalt chloride (CoCl₂) in BV-2 murine microglial cells, focusing on signaling pathways and proteomic alterations. We assessed the protective effects of monoclonal antibodies against TNFα and IL-1β. CoCl₂ exposure led to decreased cell viability, reduced mitochondrial membrane potential, increased lactate dehydrogenase release, elevated reactive oxygen species generation, and activation of inflammatory pathways, including nitric oxide synthase (iNOS), STAT1, and NF-κB/NLRP3. These responses were significantly mitigated by treatment with anti-TNFα and anti-IL-1β, suggesting their dual role in reducing microglial damage and inhibiting inflammatory reactivity. Additionally, these treatments reduced apoptosis by modulating ATF4 and the p38 MAPK/caspase-3 pathways. Label-free quantitative mass spectrometry-based proteomics and Gene Ontology revealed that CoCl₂ exposure led to the upregulation of proteins primarily involved in endoplasmic reticulum and catabolic processes, while downregulated proteins are associated with biosynthesis. Anti-TNFα and anti-IL-1β treatments partially restored the proteomic profile toward normalcy, with network analysis identifying heat shock protein family A member 8 (HSPA8) as a central mediator in recovery. These findings offer insights into the pathogenesis of hypoxic microglial impairment and suggest potential therapeutic targets. Full article

(This article belongs to the Special Issue Oxidative Stress and Neuroinflammation in Neurodegenerative Diseases: Mechanisms and Therapies)

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13 pages, 2284 KiB

Open AccessArticle

A Comparative Study of Traditional Sun Drying and Hybrid Solar Drying on Quality, Safety, and Bioactive Compounds in “Pingo de Mel” Fig

by Bárbara R. Henriques, Cláudia M. B. Neves, Marwa Moumni, Gianfranco Romanazzi, Carine Le Bourvellec, Susana M. Cardoso and Dulcineia F. Wessel

Antioxidants 2025, 14(3), 362; https://doi.org/10.3390/antiox14030362 - 19 Mar 2025

Viewed by 1091

Abstract

Figs are highly perishable, with significant losses due to overripening or failure to meet market standards. Drying is essential to extending their shelf life and reducing food waste. This study evaluated the impact of traditional sun drying and hybrid solar drying on the [...] Read more.

Figs are highly perishable, with significant losses due to overripening or failure to meet market standards. Drying is essential to extending their shelf life and reducing food waste. This study evaluated the impact of traditional sun drying and hybrid solar drying on the quality of dried “Pingo de Mel” figs. Sun drying required 5–7 days, while the hybrid solar drying completed the process in 3 days. Both methods resulted in a similar final moisture content (29.43% and 28.14%, respectively), water activity (0.68 and 0.63, respectively), and hardness (2.36 and 2.61 N, respectively). Hybrid solar-dried figs exhibited slightly lower L* values and higher b* values, reflecting a darker appearance with a more pronounced yellow hue. Fresh and sun-dried figs developed fungal growth (Alternaria spp., Aspergillus niger, Cladosporium spp., and Fusarium spp.) within four weeks, while hybrid solar-dried figs remained contamination-free, improving microbial safety. Moreover, hybrid drying preserved higher levels of phenolic compounds, particularly rutin and 5-O-caffeoylquinic acid, along with greater antioxidant activity. Overall, hybrid solar drying offers significant advantages over traditional sun drying by reducing the drying time, enhancing microbial safety, and preserving bioactive compounds, making it a more effective method for fig preservation. Full article

(This article belongs to the Special Issue Antioxidants from Sustainable Food Sources)

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19 pages, 8581 KiB

Open AccessArticle

Growth-Associated Protein-43 Loss Promotes Ca²⁺ and ROS Imbalance in Cardiomyocytes

by Michele Bevere, Caterina Morabito, Delia Verucci, Noemi Di Sinno, Maria A. Mariggiò and Simone Guarnieri

Antioxidants 2025, 14(3), 361; https://doi.org/10.3390/antiox14030361 - 19 Mar 2025

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Abstract

Growth-Associated Protein-43 (GAP-43) is a calmodulin-binding protein, originally found in neurons, that in skeletal muscle regulates the handling of intracellular Ca²⁺ dynamics. According to its role in Ca²⁺ regulation, myotubes from GAP-43 knockout (GAP-43^−/−) mice display alterations in spontaneous [...] Read more.

Growth-Associated Protein-43 (GAP-43) is a calmodulin-binding protein, originally found in neurons, that in skeletal muscle regulates the handling of intracellular Ca²⁺ dynamics. According to its role in Ca²⁺ regulation, myotubes from GAP-43 knockout (GAP-43^−/−) mice display alterations in spontaneous Ca²⁺ oscillations and increased Ca²⁺ release. The emerging hypothesis is that GAP-43 regulates CaM interactions with RyR and DHPR Ca²⁺ channels. The loss of GAP-43 promotes cardiac hypertrophy in newborn GAP-43^−/− mice, extending the physiological role of GAP-43 in cardiac muscle. We investigated the role of GAP-43 in cardiomyocytes derived from the hearts of GAP-43^−/− mice, evaluating intracellular Ca²⁺ variations and the correlation with the levels of reactive oxygen species (ROS), considering their importance in cardiovascular physiology. In GAP-43^−/− cardiomyocytes, we found the increased expression of markers of cardiac hypertrophy, Ca²⁺ alterations, and high mitochondria ROS levels (O₂^•−) together with increased oxidized functional proteins. Treatment with a CaM inhibitor (W7) restored Ca²⁺ and ROS alterations, possibly due to high mitochondrial Ca²⁺ entry by a mitochondrial Ca²⁺ uniporter. Indeed, Ru360 was able to abolish O₂^•− mitochondrial production. Our results suggest that GAP-43 has a key role in the regulation of Ca²⁺ and ROS homeostasis, alterations to which could trigger heart disease. Full article

(This article belongs to the Special Issue Oxidative Stress in Striated Muscle and Other Tissues)

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28 pages, 1589 KiB

Open AccessReview

The Janus Face of Oxidative Stress and Hydrogen Sulfide: Insights into Neurodegenerative Disease Pathogenesis

by Constantin Munteanu, Anca Irina Galaction, Gelu Onose, Marius Turnea and Mariana Rotariu

Antioxidants 2025, 14(3), 360; https://doi.org/10.3390/antiox14030360 - 19 Mar 2025

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Abstract

Oxidative stress plays an essential role in neurodegenerative pathophysiology, acting as both a critical signaling mediator and a driver of neuronal damage. Hydrogen sulfide (H₂S), a versatile gasotransmitter, exhibits a similarly “Janus-faced” nature, acting as a potent antioxidant and cytoprotective molecule [...] Read more.

Oxidative stress plays an essential role in neurodegenerative pathophysiology, acting as both a critical signaling mediator and a driver of neuronal damage. Hydrogen sulfide (H₂S), a versatile gasotransmitter, exhibits a similarly “Janus-faced” nature, acting as a potent antioxidant and cytoprotective molecule at physiological concentrations, but becoming detrimental when dysregulated. This review explores the dual roles of oxidative stress and H₂S in normal cellular physiology and pathophysiology, focusing on neurodegenerative disease progression. We highlight potential therapeutic opportunities for targeting redox and sulfur-based signaling systems in neurodegenerative diseases by elucidating the intricate balance between these opposing forces. Full article

(This article belongs to the Special Issue The Janus Face of Oxidative Stress in Normal and Pathological Conditions)

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23 pages, 2111 KiB

Open AccessArticle

Transfer of Antioxidant Capacity Through Placenta and Colostrum: β-Carotene and Superoxide Dismutase Collaboratively Enhance Integrated Breeding of Sows and Piglets

by Jun Huang, Shengkai Li, Jung Yeol Sung, Shiyan Qiao, Xiangfang Zeng and Junyan Zhou

Antioxidants 2025, 14(3), 359; https://doi.org/10.3390/antiox14030359 - 18 Mar 2025

Viewed by 425

Abstract

Sows and piglets face heightened oxidative stress during gestation and lactation, yet strategies to simultaneously mitigate these challenges remain underexplored. This study investigated the effects of β-carotene and superoxide dismutase (SOD) supplementation on 140 Landrace × Yorkshire sows (parity 3–5) randomly assigned to [...] Read more.

Sows and piglets face heightened oxidative stress during gestation and lactation, yet strategies to simultaneously mitigate these challenges remain underexplored. This study investigated the effects of β-carotene and superoxide dismutase (SOD) supplementation on 140 Landrace × Yorkshire sows (parity 3–5) randomly assigned to (1) a control; (2) long-term low-dose treatment (25 mg/kg β-carotene, 4 mg/kg SOD, or both) throughout gestation–lactation; or (3) short-term high-dose treatment (100 mg/kg β-carotene, 14 mg/kg SOD, or both) administered 7 days pre/post-weaning and farrowing. Our data indicate that the antioxidants enhanced the productive performance of both sows and piglets, with the most pronounced effect observed in the long-term, low-dose combined administration of β-carotene and SOD. The composite antioxidants significantly improved the systemic antioxidant capacity in sows, while concurrently reducing the cortisol and lipopolysaccharide concentrations in the serum. This enhancement contributed to elevations in serum progesterone and prolactin levels at day 40 of gestation and farrowing, respectively, ultimately increasing the number of weaned piglets and decreasing the backfat loss. In addition, the compound antioxidants improved the serum antioxidant indices of piglets, increased the growth hormone concentrations, and improved the litter weight gain. Mechanistically, the placental upregulation of CAT, GPX1, and GLUT3, alongside Claudin1, Occludin, and ZO-1 expression, underpinned improved nutrient transport and barrier function. These findings demonstrate that β-carotene and SOD synergistically transfer antioxidant capacity via placental and colostrum pathways, offering a viable strategy for integrated sow–piglet management. Full article

(This article belongs to the Special Issue Oxidative Stress in Livestock and Poultry—3rd Edition)

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4 pages, 172 KiB

Open AccessEditorial

Impact of Antioxidant and Anti-Inflammatory Functions of HDL in Diseases—2nd Edition

by Carlo Cervellati and Judit Marsillach

Antioxidants 2025, 14(3), 358; https://doi.org/10.3390/antiox14030358 - 18 Mar 2025

Viewed by 276

Abstract

In recent decades, significant advancements in lipidology have profoundly reshaped our understanding of the biological roles of lipids and lipoproteins, particularly high-density lipoproteins (HDLs) [...] Full article

(This article belongs to the Special Issue Impact of Antioxidant and Anti-Inflammatory Functions of HDL in Diseases—2nd Edition)

20 pages, 2358 KiB

Open AccessArticle

Optimization of Microwave-Assisted Extraction of Polyphenols from Crataegus monogyna L.

by Adina I. Gavrila, Emilia J. Damian, Anca Rosca, Ioan Calinescu, Camelia Hodosan and Ioana Popa

Antioxidants 2025, 14(3), 357; https://doi.org/10.3390/antiox14030357 - 18 Mar 2025

Viewed by 361

Abstract

Hawthorns (Crataegus monogyna L.) contain numerous bioactive compounds, with its extracts demonstrating health benefits. This study focused on optimizing a more sustainable extraction method, specifically microwave-assisted extraction (MAE), to obtain polyphenols from hawthorn leaves and flowers. HPLC/UV analysis identified key compounds, including [...] Read more.

Hawthorns (Crataegus monogyna L.) contain numerous bioactive compounds, with its extracts demonstrating health benefits. This study focused on optimizing a more sustainable extraction method, specifically microwave-assisted extraction (MAE), to obtain polyphenols from hawthorn leaves and flowers. HPLC/UV analysis identified key compounds, including gallic and chlorogenic acids, isoquercetin, rutin, hyperoside, vitexin, and quercetin. Principal component analysis (PCA) assessed correlations between extraction conditions, total phenolic content (TPC), and key compounds. PCA grouped conditions into three clusters, with two remaining ungrouped. The highest vitexin, rutin, and isoquercetin contents were achieved at 60 °C for 10 min using 160–500 μm particles in 75% ethanol (20/1 ratio) or 50% ethanol (20/1 and 30/1 ratios). An ungrouped condition (60 °C, 10 min, < 160 μm particles, 50% ethanol, 20/1 ratio) produced a higher TPC and greater gallic acid, chlorogenic acid, and hyperoside concentrations. The TPC and antioxidant activity (AA) of the extracts were optimized using a 2³ full factorial design, with temperature, ethanol concentration, and solvent-to-plant ratio as variables. Optimal MAE conditions (S/P_opt = 20.4 mL/g, T_opt = 65 °C, and EtOH_opt = 60%) yielded a TPC of 116.23 ± 2.85 mg GAE/g DM and an AA of 237.6 ± 6.33 mg TE/g DM using hawthorn leaves and flowers. Summarizing the above, to maximize phytocompound content, a one-factor-at-a-time design identified extraction parameters, but its limitations led to a 2³ full factorial design. The latter effectively optimized the TPC and AA, while PCA revealed correlations between extraction parameters, total phenolics, and key compounds. Full article

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20 pages, 6061 KiB

Open AccessArticle

Antioxidant Activity and Anti-Inflammatory Effect of Blood Orange By-Products in Treated HT-29 and Caco-2 Colorectal Cancer Cell Lines

by Rosa Calvello, Giusy Rita Caponio, Antonia Cianciulli, Chiara Porro, Melania Ruggiero, Giuseppe Celano, Maria De Angelis and Maria Antonietta Panaro

Antioxidants 2025, 14(3), 356; https://doi.org/10.3390/antiox14030356 - 18 Mar 2025

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Abstract

Blood orange peel flour (BO-pf)—a by-product of the citrus supply chain—still contains bioactive molecules with known health benefits, such as antiradical scavenging activity or an antiproliferative activity regarding tumors. In vitro studies have demonstrated that orange polyphenols showed potential involvement in necroptosis. In [...] Read more.

Blood orange peel flour (BO-pf)—a by-product of the citrus supply chain—still contains bioactive molecules with known health benefits, such as antiradical scavenging activity or an antiproliferative activity regarding tumors. In vitro studies have demonstrated that orange polyphenols showed potential involvement in necroptosis. In addition to previous research, we tested BO-pf on two colorectal cancer cell lines. Using HT29 and Caco2 cells, our experiments confirmed the regulation of inflammasome expression. They provided valuable insights into how BO-pf influences the cancer cell features (i.e., viability, proliferation, and pro- and anti-inflammatory activity). Notably, BO-pf extract is a rich source of polyphenolic compounds with antioxidant properties. Western blot and real-time PCR analyses showed that treatment with BO-pf extract demonstrated beneficial effects by influencing the expression of both pro-inflammatory cytokines (IL-1β, IL-6) through the modulation of the TLR4/NF-kB/NLRP3 inflammasome signaling. Moreover, the results of this study demonstrate that BO-pf extracts can enhance the expression of anti-inflammatory cytokines, such as IL-10 and TGFβ, suggesting that BO-pf extracts may represent a promising functional ingredient to counteract the intestinal inflammatory responses involved in IBD. Full article

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

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19 pages, 2016 KiB

Open AccessArticle

Effects of Integrated Extracts of Trigonella foenum-graecum and Asparagus racemosus on Hot Flash-like Symptoms in Ovariectomized Rats

by Fusun Erten, Besir Er, Ramazan Ozmen, Muhammed Tokmak, Ebru Gokdere, Cemal Orhan, Abhijeet A. Morde, Muralidhara Padigaru and Kazim Sahin

Antioxidants 2025, 14(3), 355; https://doi.org/10.3390/antiox14030355 - 18 Mar 2025

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Abstract

Vasomotor symptoms, such as hot flashes (HFs), commonly affect women during menopause, leading to a reduced quality of life. The current study evaluates the combined effect of active components Asparagus racemosus (AR) and Trigonella foenum-graecum (TFG) in a single oral formulation (IAT) for [...] Read more.

Vasomotor symptoms, such as hot flashes (HFs), commonly affect women during menopause, leading to a reduced quality of life. The current study evaluates the combined effect of active components Asparagus racemosus (AR) and Trigonella foenum-graecum (TFG) in a single oral formulation (IAT) for alleviating menopausal symptoms in ovariectomized rats. Following bilateral ovariectomy, the animals were randomly assigned to nine groups: (1) Control, (2) Ovariectomy (OVX), (3) OVX+TA1 (TA: Combination of Trigonella and Asparagus; TFG 30 mg/kg + AR 30 mg/kg), (4) OVX+TA2 (TFG 30 mg/kg + AR 15 mg/kg), (5) OVX+TA3 (TFG 15 mg/kg + AR 30 mg/kg), (6) OVX+TA4 (TFG 40 mg/kg + AR 30 mg/kg), (7) OVX+TA5 (TFG 30 mg/kg + AR 40 mg/kg), (8) OVX+IAT1 (IAT: Integrated Asparagus and Trigonella; TFG+AR integrated extract, 30 mg/kg), and (9) OVX+IAT2 (TFG+AR integrated extract, 60 mg/kg). On the 8th day of treatment, tail and skin temperatures were recorded every 30 min for 24 h. Ovariectomized rats exhibited menopausal symptoms, such as hormonal imbalances and elevated skin temperature. Administration of AR, TFG, and IAT significantly decreased serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and cortisol while increasing estradiol, progesterone, and dopamine (p < 0.0001), effectively alleviating hot flash-like symptoms. Additionally, they mitigated ovariectomy-induced oxidative stress by lowering malondialdehyde (MDA) levels and restoring antioxidant enzyme activity. Ovariectomized rats exhibited increased expression of a proto-oncogene (c-FOS), gonadotropin-releasing hormone (GnRH), Kisspeptin, Neurokinin B (NKB), and Transient receptor potential vanilloid 1 (TRPV1), along with reduced expressing brain-derived neurotrophic factor (BDNF) levels, which were reversed by treatment, especially with the IAT2 combination. The AR and TFG combination, particularly in IAT formulations, showed strong potential in alleviating menopausal symptoms in ovariectomized rats. These findings suggest that the combination of AR and TFG extracts could be a natural alternative for managing postmenopausal symptoms by restoring reproductive hormone levels, regulating lipid profiles, and enhancing antioxidant defense systems. Full article

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

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19 pages, 1982 KiB

Open AccessArticle

Boosting Antioxidant Quality in Cucumber Beverages with Encapsulated Tomato Carotenoids

by Laleh Mozafari, Lorena Martínez-Zamora, Marina Cano-Lamadrid, Perla A. Gómez and Francisco Artés-Hernández

Antioxidants 2025, 14(3), 354; https://doi.org/10.3390/antiox14030354 - 18 Mar 2025

Viewed by 271

Abstract

Tomato by-products are widely generated during processing, which deserve revalorization due to being rich in bioactive compounds that can be incorporated into novel formulas. This study explores the use of tomato by-products as a source of pigments and antioxidant compounds to develop a [...] Read more.

Tomato by-products are widely generated during processing, which deserve revalorization due to being rich in bioactive compounds that can be incorporated into novel formulas. This study explores the use of tomato by-products as a source of pigments and antioxidant compounds to develop a seasoned cucumber beverage enriched with encapsulated carotenoids. Extracts from industrial tomato pomace were obtained using ultrasound-assisted extraction (USAE) and accelerated solvent extraction (ASE), and then encapsulated by spray-drying with inulin (I), maltodextrin (M), or a maltodextrin–inulin blend (MI). The powders were added to a cucumber beverage treated with high hydrostatic pressure (HHP) and stored for 28 days at 4 °C. Physicochemical properties, microbial load, carotenoid content (U-HPLC), free phenolic content (FPC), and total antioxidant capacity (TAC) were monitored. Beverage samples with maltodextrin (ASE-M, USAE-M) and the maltodextrin–inulin blend (ASE-MI, USAE-MI) showed superior color stability and pH maintenance. USAE-MI achieved the highest TAC at the end of storage and ensured microbial safety by reducing mesophilic bacteria, molds, and yeast. During storage, FPC declined (to ~3.5–5 mg 100 mL⁻¹), TAC increased (to ~16–20 mg 100 mL⁻¹), and carotenoid was kept stable (~9–13 mg L⁻¹). These results highlight the potential of combining HHP with tomato by-product encapsulates to improve the shelf life, quality, pigment stability, and antioxidant properties of vegetable-based beverages. Full article

(This article belongs to the Special Issue Antioxidant Capacity of Anthocyanins and Other Vegetal Pigments: Properties, Intake and Health Benefits)

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23 pages, 2852 KiB

Open AccessArticle

Seed Halopriming as an Effective Strategy to Enhance Salt Tolerance in Cakile maritima: Activation of Antioxidant and Genetic Responses

by Roser Tolrà, Carlos González-Cobo, Isabel Corrales, Rosa Padilla and Mercè Llugany

Antioxidants 2025, 14(3), 353; https://doi.org/10.3390/antiox14030353 - 18 Mar 2025

Viewed by 328

Abstract

Global food demand and insecurity are intensifying due to rapid population growth, the loss of arable land, climate change, and pollution. Among the critical challenges in global agriculture is soil salinization, in which high NaCl concentrations can severely inhibit germination and crop establishment. [...] Read more.

Global food demand and insecurity are intensifying due to rapid population growth, the loss of arable land, climate change, and pollution. Among the critical challenges in global agriculture is soil salinization, in which high NaCl concentrations can severely inhibit germination and crop establishment. Cakile maritima, a halophyte from the Brassica genus, can tolerate salinity levels up to 400 mM NaCl, far exceeding the tolerance of most crops, making it a promising model for studying salt stress resistance. This study investigates the effects of seed halopriming as an effective strategy to enhance salt tolerance in C. maritima. The research evaluates germination rates, seedling establishment, mineral status, oxidative stress markers, and genetic responses under increasing NaCl concentrations. Halopriming with NaCl pre-activates the plant’s antioxidant defence mechanisms and upregulates stress-responsive genes, improving the plant’s resilience to saline conditions. While salinity caused significant physiological challenges, primed seeds demonstrated superior performance compared to non-primed controls, with enhanced germination and an improved tolerance to oxidative stress. These findings underscore the potential of halopriming as a cost-effective and sustainable technique to improve crop performance in saline environments. This study highlights the importance of advancing seed priming technologies for developing resilient crops to address global food security challenges in the face of climate change. Full article

(This article belongs to the Special Issue Reactive Oxygen and Nitrogen Species in Plants―2nd Edition)

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28 pages, 13652 KiB

Open AccessArticle

Glucuronolactone Restores the Intestinal Barrier and Redox Balance Partly Through the Nrf2/Akt/FOXO1 Pathway to Alleviate Weaning Stress-Induced Intestinal Dysfunction in Piglets

by Beibei Zhang, Min Tian, Yueqin Qiu, Jing Wu, Chenbin Cui, Shilong Liu, Jing Hou, Chaoyang Tian, Li Wang, Kaiguo Gao, Zongyong Jiang and Xuefen Yang

Antioxidants 2025, 14(3), 352; https://doi.org/10.3390/antiox14030352 - 18 Mar 2025

Viewed by 356

Abstract

(1) Background: Glucuronolactone (GLU) is a glucose metabolite with antioxidant activity. At present, the exact role of it in regulating the intestinal health of piglets under weaning stress is not clear. The purpose of this study is to investigate the effects of GLU [...] Read more.

(1) Background: Glucuronolactone (GLU) is a glucose metabolite with antioxidant activity. At present, the exact role of it in regulating the intestinal health of piglets under weaning stress is not clear. The purpose of this study is to investigate the effects of GLU on the growth performance and intestinal health of piglets under weaning stress and to explore potential mechanisms. (2) Methods: Twenty-four weaned piglets were randomly assigned into two groups, with one group receiving a basal diet and the other group receiving an experimental diet supplemented with 200 mg/kg of GLU. (3) Results: GLU increased the ADG, ADFI, and final body weight of piglets, while reducing the diarrhea rate. Mechanistically, GLU alleviates weaning stress-induced intestinal oxidative stress and inflammatory responses in piglets partly through activating the Nrf2-Akt signaling pathway to suppress the transcriptional activity of FOXO1, while also inhibiting the activation of the TLR4-MAPK signaling pathway to reduce the secretion of pro-inflammatory cytokines. Moreover, GLU increased the relative abundance of Lactobacillus reuteri in the ileum of piglets and improved the composition of the gut microbiota. (4) Conclusions: GLU reduced inflammation and oxidative stress through the Nrf2/Akt/FOXO1 signaling pathway and improved intestinal health, resulting in improved growth performance of the piglets. Full article

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30 pages, 1477 KiB

Open AccessReview

Potential of Curcumin and Its Analogs in Glioblastoma Therapy

by Agnieszka Nowacka, Ewa Ziółkowska, Wojciech Smuczyński, Dominika Bożiłow and Maciej Śniegocki

Antioxidants 2025, 14(3), 351; https://doi.org/10.3390/antiox14030351 - 18 Mar 2025

Viewed by 476

Abstract

Curcumin, a polyphenol found in turmeric, demonstrates multifaceted anti-cancer activity against glioblastoma. Its therapeutic potential stems from its ability to modulate various molecular pathways implicated in glioblastoma development and progression, enhance the effectiveness of radiation therapy, and induce cancer cell death through diverse [...] Read more.

Curcumin, a polyphenol found in turmeric, demonstrates multifaceted anti-cancer activity against glioblastoma. Its therapeutic potential stems from its ability to modulate various molecular pathways implicated in glioblastoma development and progression, enhance the effectiveness of radiation therapy, and induce cancer cell death through diverse mechanisms, including apoptosis, autophagy, and cell cycle arrest. These combined actions make curcumin a promising candidate for glioblastoma treatment, warranting further investigation into its clinical application. In this review, we summarize the latest research on curcumin and its analogs’ potential in glioblastoma therapy. Full article

(This article belongs to the Special Issue Regulatory Effects of Curcumin, 2nd Edition)

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21 pages, 2810 KiB

Open AccessArticle

Myrobalan Fruit Extracts Modulate Immunobiochemical Pathways In Vitro

by Stefanie Hofer, Marcel Jenny, Angela Klein, Kathrin Becker, Lucia Parráková, Florian Überall, Markus Ganzera, Dietmar Fuchs, Hubert Hackl, Pablo Monfort-Lanzas and Johanna M. Gostner

Antioxidants 2025, 14(3), 350; https://doi.org/10.3390/antiox14030350 - 17 Mar 2025

Viewed by 389

Abstract

Myrobalan fruits are important ingredients of traditional remedies, such as the Ayurvedic formulation Triphala or the Tibetan formulation Bras bu 3. Myrobalan-containing remedies are described to have positive effects on metabolism, the cardiovascular system, and the immune system. The chemical composition of botanical [...] Read more.

Myrobalan fruits are important ingredients of traditional remedies, such as the Ayurvedic formulation Triphala or the Tibetan formulation Bras bu 3. Myrobalan-containing remedies are described to have positive effects on metabolism, the cardiovascular system, and the immune system. The chemical composition of botanical mixtures can be very complex, and it is often impossible to identify individual compounds as specific active ingredients, which suggests a multi-target mode of action. In this in vitro study, the effect of myrobalan extracts in human cell models was investigated to gain more information about the molecular mechanism of action and to find possible synergistic effects. Direct and indirect antioxidant effects were investigated, and the activation of immunobiochemical metabolic pathways involved in the cellular immune response was examined in cell lines treated with extracts of the fruits of Phyllanthus emblica, Terminalia chebula and Terminalia bellirica, as well as a combination of them. In particular, a synergistic effect on the activation of the endogenous antioxidant defence system was observed with the combined treatment of the three fruit extracts. An integrated transcriptome analysis of cells treated with a combination of fruit extracts confirmed an effect on immune pathways, oxidative stress, and detoxification processes. This study shows the modulation of various signalling pathways and cellular processes that may be part of the multi-target mechanism of individual and combined myrobalan fruit extracts. Although the results are limited to in vitro data, they contribute to a better understanding of how botanical mixtures work and provide hypotheses for further research. Full article

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19 pages, 4952 KiB

Open AccessArticle

Spermidine Revives Aged Sorghum Seed Germination by Boosting Antioxidant Defense

by Yifan Xing, Huan Zhang, Chunjuan Liu, Chang Liu and Yufei Zhou

Antioxidants 2025, 14(3), 349; https://doi.org/10.3390/antiox14030349 - 17 Mar 2025

Viewed by 419

Abstract

Seed aging has adverse effects on agricultural production, mainly because seed vigor is inhibited. Spermidine can improve seed vitality and germination ability to a certain extent and is essential for plant growth and plant response to stress. This study explored how spermidine counteracted [...] Read more.

Seed aging has adverse effects on agricultural production, mainly because seed vigor is inhibited. Spermidine can improve seed vitality and germination ability to a certain extent and is essential for plant growth and plant response to stress. This study explored how spermidine counteracted aging effects on sorghum seed germination through antioxidant metabolism regulation. Aged seeds showed decreased vigor due to heightened reactive oxygen species (ROS) and diminished antioxidants. Applying spermidine notably enhanced aged seeds’ germination and vigor by boosting antioxidant enzyme activity and curbing ROS. Integrated transcriptomic, proteomic, and metabolomic analyses demonstrated that the majority of differentially expressed genes following exogenous spermidine treatment in aged sorghum seeds were significantly enriched in pathways related to glutathione metabolism, phenylpropanoid, and flavonoid biosynthesis, resulting in increased expression of genes encoding peroxidase, chalcone synthase, and glutathione s-transferase. Exogenous spermidine facilitated the synthesis of peroxidases and glutathione transferases. Analysis of flavonoid pathway intermediates showed a notable increase in antioxidant metabolites like isoquercitrin, underscoring their role in oxidative stress resistance. This multi-omics strategy underscores Spd’s role in boosting aged seeds’ antioxidants, highlighting the molecular basis of seed aging and Spd’s rejuvenating impact. Full article

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24 pages, 2800 KiB

Open AccessArticle

Synergistic Neuroprotective and Immunomodulatory Effects of Cocoa Seed Husk and Guarana Extract: A Nutraceutical Approach for Parkinson’s Disease Management

by Vitória Farina Azzolin, Verônica Farina Azzolin, Euler Esteves Ribeiro, Juliane Santiago Sasso, Douglas Reis Siqueira, Nathalia Cardoso de Afonso Bonotto, Bárbara Osmarin Turra, Marco Aurélio Echart Montano, Ednea Aguiar Maia Ribeiro, Raquel de Souza Praia, Maria Fernanda Mânica-Cattani, Cristina Maranghello, Railla da Silva Maia, Erickson Oliveira dos Santos, Pedro Luis Sosa Gonzalez, Cleideane Cunha Costa, Vanusa Nascimento, Fernanda Barbisan and Ivana Beatrice Mânica da Cruz

Antioxidants 2025, 14(3), 348; https://doi.org/10.3390/antiox14030348 - 15 Mar 2025

Viewed by 598

Abstract

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder linked to oxidative stress, mitochondrial dysfunction, and neuroinflammation. This study evaluates the neurofunctional and immunomodulatory effects of an aqueous extract combining cocoa seed husk and guarana powder (GuaCa). Eighteen extracts were characterized by flavonoid [...] Read more.

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder linked to oxidative stress, mitochondrial dysfunction, and neuroinflammation. This study evaluates the neurofunctional and immunomodulatory effects of an aqueous extract combining cocoa seed husk and guarana powder (GuaCa). Eighteen extracts were characterized by flavonoid and polyphenol content, antioxidant activity, and genoprotective potential. The HCE3 extract, rich in catechins, quercetin, and epigallocatechin gallate, was selected for further analysis in three models: Eisenia fetida earthworms, SH-SY5Y neuron-like cells, and peripheral blood mononuclear cells (PBMCs) from PD patients. Results: The extracts showed antioxidant and genoprotective activity and contained flavonoid. No significant toxicity was observed in Eisenia fetida. In SH-SY5Y cells, GuaCa increased cell viability and brain-derived neurotrophic factor (BDNF) levels and reduced mitochondrial damage by lowering extracellular NDUSF7 (subunit of the NADH dehydrogenase (ubiquinone) complex) levels. In dPD-PBMCs cultures, GuaCa reduced pro-inflammatory cytokine IL-6 levels, indicating immunomodulatory effects. Conclusion: GuaCa shows promise as a nutraceutical for managing neuroinflammation and mitochondrial dysfunction in PD. Further clinical studies are needed to confirm GuaCa extract efficacy and potential for neuroprotective dietary strategies. Full article

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

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23 pages, 7219 KiB

Open AccessReview

A Focus on the Link Between Metal Dyshomeostasis, Norepinephrine, and Protein Aggregation

by Chiara Bacchella, Andrea Capucciati and Enrico Monzani

Antioxidants 2025, 14(3), 347; https://doi.org/10.3390/antiox14030347 - 15 Mar 2025

Viewed by 424

Abstract

Neurodegenerative disorders are one of the main public health problems worldwide and, for this reason, they have attracted the attention of several researchers who aim to better understand the molecular processes linked to the etiology of these disorders, including Alzheimer’s and Parkinson’s diseases. [...] Read more.

Neurodegenerative disorders are one of the main public health problems worldwide and, for this reason, they have attracted the attention of several researchers who aim to better understand the molecular processes linked to the etiology of these disorders, including Alzheimer’s and Parkinson’s diseases. In this review, we describe both the beneficial and toxic effect of norepinephrine (NE) and its connected ROS/metal-mediated pathways, which end in neuromelanin (NM) formation and protein aggregation. In particular, we emphasize the importance of stabilizing the delicate homeostatic balance that regulates (i) the metal/ROS-promoted oxidation of catecholamines, as NE, and (ii) the generation of oxidative by-products capable of covalently and non-covalently modifying neuroproteins, thus altering their stability and their oligomerization; these processes may end in (iii) the incorporation of protein conjugates into vesicles, which then evolve into neuromelanin (NM) organelles. In general, we aim to provide an up-to-date overview of the challenges and controversies emerging from the current literature to delineate a direction for future research. Full article

(This article belongs to the Special Issue Redox Metals and Catecholamines in Neurodegenerative Diseases)

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15 pages, 3152 KiB

Open AccessArticle

Mechanical Loading Induces NRF2 Nuclear Translocation to Epigenetically Remodel Oxidative Stress Defense in Osteocytes

by Yue Guo, Jing Zhang, Luyu Gong, Na Liu, Qiaoqiao Liu, Zhaojun Liu, Baosheng Guo and Jingping Yang

Antioxidants 2025, 14(3), 346; https://doi.org/10.3390/antiox14030346 - 15 Mar 2025

Viewed by 474

Abstract

The mechano-responsiveness of osteocytes is critical for maintaining bone health and associated with a reduced oxidative stress defense, yet the precise molecular mechanisms remain incompletely understood. Here, we address the gap by investigating the epigenetic reprogramming that drives osteocyte responses to mechanical loading. [...] Read more.

The mechano-responsiveness of osteocytes is critical for maintaining bone health and associated with a reduced oxidative stress defense, yet the precise molecular mechanisms remain incompletely understood. Here, we address the gap by investigating the epigenetic reprogramming that drives osteocyte responses to mechanical loading. We found overall remodeling of antioxidant response under mechanical loading and identified NRF2, a key transcription factor in oxidative stress response, which plays a vital role in the epigenetic remodeling of osteocytes. The results showed that mechanical loading enhanced NRF2 protein stability, promoted its nuclear translocation, and activated osteocyte-specific transcriptional programs. In contrast, pharmacological stabilization of NRF2 failed to fully replicate these effects, underscoring the unique role of mechanical stimuli in modulating NRF2 activity and antioxidant function. Our findings highlight the potential therapeutic limitations of NRF2-stabilizing drugs and suggest that combining pharmacological approaches with mechanical interventions could offer more effective treatments to maintain oxidative homeostasis. Full article

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19 pages, 5506 KiB

Open AccessArticle

The Anti-Cancer Role of Pterostilbene in Endometrial Cancer: A Phase II Prospective, Randomized, Window-of-Opportunity Clinical Trial with Megestrol Acetate

by Rosemary N. Senguttuvan, Hyejin Cho, Xiwei Wu, Paul H. Frankel, Nora Ruel, Susan E. Yost, Mehdi Kebria, Ernest Han, Mihae Song, Maria de Leon, Marta Invernizzi, Melissa Eng, Raechelle Tinsley, Behrouz Salehian, Aimin Li, Daniel Schmolze, Sue Chang, Javier Arias-Stella and Thanh H. Dellinger

Antioxidants 2025, 14(3), 345; https://doi.org/10.3390/antiox14030345 - 14 Mar 2025

Viewed by 510

Abstract

Pterostilbene (3,5-dimethoxy-40-hydroxystilbene) is a potent oral antioxidant with a promising role in anti-cancer treatment. In endometrial cancer (EC), in vitro studies demonstrated a synergistic antiproliferative effect of pterostilbene (PT) with megestrol acetate (MA), a common treatment for EC. This is a randomized phase [...] Read more.

Pterostilbene (3,5-dimethoxy-40-hydroxystilbene) is a potent oral antioxidant with a promising role in anti-cancer treatment. In endometrial cancer (EC), in vitro studies demonstrated a synergistic antiproliferative effect of pterostilbene (PT) with megestrol acetate (MA), a common treatment for EC. This is a randomized phase II clinical trial (NCT03671811) of PT+MA vs. MA for three weeks prior to scheduled hysterectomy. The primary objective is to determine the antiproliferative effect of PT+MA vs. MA using Ki-67 index. The secondary objectives are toxicity, histological response, transcriptional changes, and lipid metabolism. A total of 44 patients were enrolled between January 2019 and November 2022 with 23 randomized to Arm 1 (PT+MA) and 21 to Arm 2 (MA). Toxicities included one G3 thromboembolic event (PT+MA) and one G3 hypertension event (MA). Histological responses were high in both arms (>90%). There was no difference in Ki-67 changes, although, when restricted to endometroid subtype, the relative decrease in Ki67 was 33.8% in PT+MA vs. 20.1% in MA alone (p = 0.14). Whole transcriptomic gene profiling of samples before and after PT+MA exposure demonstrated the activation of interferon alpha response pathway and suppression of mTORC1 signaling, hypoxia, oxidative phosphorylation, and IL2-STAT5 signaling. Lipid metabolism analyses did not reveal any significant changes between arms. PT is well-tolerated in the preoperative treatment of EC and demonstrated in vivo anti-cancer effects on the transcriptomic level. Full article

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

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23 pages, 4791 KiB

Open AccessArticle

A Novel Gastrodin Derivative with Neuroprotection Promotes NGF-Mimic Activity by Targeting INSR and ACTN4 to Activate PI3K/Akt Signaling Pathway in PC12 Cells

by Jiayuan Zeng, Jianxia Mo, Makoto Muroi, Hiroyuki Osada, Lan Xiang and Jianhua Qi

Antioxidants 2025, 14(3), 344; https://doi.org/10.3390/antiox14030344 - 14 Mar 2025

Viewed by 491

Abstract

Gastrodin (gas) has been shown to promote neuroprotection and reverse Alzheimer’s disease (AD) pathology. However, its high effective dose limits its potential in treating AD. In this study, a bioassay system using PC12 cells and the nerve growth factor (NGF)-mimic effect was employed [...] Read more.

Gastrodin (gas) has been shown to promote neuroprotection and reverse Alzheimer’s disease (AD) pathology. However, its high effective dose limits its potential in treating AD. In this study, a bioassay system using PC12 cells and the nerve growth factor (NGF)-mimic effect was employed to investigate the structure–activity relationship of gas derivatives. Among the synthesized compounds, GAD037 demonstrated the highest NGF-mimic activity, surpassing gas. Additionally, GAD037 exhibited significant neuroprotective effects, reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, thereby improving the survival of PC12 cells under oxidative stress. It also protected cells from Aβ-induced toxicity. Target protein identification and mechanistic studies revealed that insulin receptor (INSR) and alpha-actinin-4 (ACTN4) are potential targets of GAD037, confirmed through specific inhibitors, small interfering RNA (siRNA) analysis, a cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS). Moreover, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and rat sarcoma (Ras)/protooncogene serine–threonine protein kinase (Raf)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways were found to be involved in the NGF-mimic activity of GAD037. In conclusion, GAD037 exhibits superior NGF-mimic and neuroprotective activities compared to gas, suggesting its potential as a lead compound for anti-AD applications. Full article

(This article belongs to the Special Issue Role of Natural Antioxidants on Neuroprotection)

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26 pages, 14636 KiB

Open AccessArticle

Hepatoprotective Effects of Citri reticulatae Pericarpium and Chaenomelese speciosa (Sweet) Nakai Extracts in Alcohol-Related Liver Injury: Modulation of Oxidative Stress, Lipid Metabolism, and Gut Microbiota

by Shuangshuang Ma, Lingtao Kang, Zhipeng Gao, Zhaoping Pan, Lvhong Huang, Jiaxu Chen, Yanfang Liao, Jiajing Guo and Fuhua Fu

Antioxidants 2025, 14(3), 343; https://doi.org/10.3390/antiox14030343 - 14 Mar 2025

Viewed by 486

Abstract

Chronic and excessive alcohol consumption induces alcohol-related liver injury (ALI), characterized by oxidative stress (OS), disrupted lipid metabolism, and gut microbiota dysbiosis. Given the lack of effective pharmacological treatments, flavonoid-rich fruits have attracted growing attention as potential intervention strategies. This study investigated the [...] Read more.

Chronic and excessive alcohol consumption induces alcohol-related liver injury (ALI), characterized by oxidative stress (OS), disrupted lipid metabolism, and gut microbiota dysbiosis. Given the lack of effective pharmacological treatments, flavonoid-rich fruits have attracted growing attention as potential intervention strategies. This study investigated the independent and combined effects of extracts from Citri reticulatae pericarpium (CRPE) and Chaenomeles speciosa (Sweet) Nakai (CSPE), previously shown to possess hepatoprotective properties, in a mouse model of ethanol-induced chronic ALI. The flavonoid composition of CRPE and CSPE was characterized using LC-MS/MS, and their potential mechanisms of action were further elucidated through transcriptomic analysis. The results showed that CRPE and CSPE, whether administered individually or in combination, effectively alleviated alcohol-induced hepatic histological damage and inflammatory responses. Furthermore, both extracts significantly reduced OS and improved lipid metabolism. Notably, CRPE, CSPE, and their combination regulated the gut microbiota, as shown by increased abundances of beneficial bacteria such as Lactobacillus and Bifidobacterium, along with elevated levels of short-chain fatty acids (SCFAs). These findings highlight that combinations of multiple fruit extracts exhibit significant potential in alleviating ALI by modulating the gut microbiota, providing valuable insights for the development of functional foods. Full article

(This article belongs to the Special Issue Oxidative Stress and Dietary Health: The Role of Functional Foods and Nutritional Supplements)

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16 pages, 8973 KiB

Open AccessArticle

Anti-Toxoplasma and Antioxidant Activity of a Terpene and Methyl-Ester-Rich Subfraction from Pleopeltis crassinervata

by Jhony Anacleto-Santos, Ricardo Mondragón-Flores, Perla Yolanda López-Camacho, María Isabel Rivera-Vivanco, Teresa de Jesús López-Pérez, Brenda Casarrubias-Tabares, Mónica Mondragón-Castelán, Sirenia González-Pozos, Fernando Calzada, Elisa Vega-Ávila and Norma Rivera-Fernández

Antioxidants 2025, 14(3), 342; https://doi.org/10.3390/antiox14030342 - 14 Mar 2025

Viewed by 493

Abstract

Pleopeltis crassinervata has demonstrated antimicrobial effects, including anti-Toxoplasma activity, which has been attributed to the presence of compounds such as terpenes and fatty acid methyl esters. In this study, the effects of P. crassinervata hexane subfraction one (Hsf1) on the Toxoplasma gondii [...] Read more.

Pleopeltis crassinervata has demonstrated antimicrobial effects, including anti-Toxoplasma activity, which has been attributed to the presence of compounds such as terpenes and fatty acid methyl esters. In this study, the effects of P. crassinervata hexane subfraction one (Hsf1) on the Toxoplasma gondii tachyzoite ultrastructure were evaluated using TEM and SEM, and lytic cycle processes such as adhesion, invasion, and proliferation were evaluated using phase-contrast microscopy. Additionally, the antioxidant capacity of the subfraction and its main compounds (phytol and hexadecenoic acid methyl ester) were determined as well as their effects on parasite viability. Hsf1 exhibited a dose-dependent inhibitory effect on the lytic process at a concentration of 47.2 µg/mL. Among the eighteen compounds identified in this subfraction, six were evaluated, of which two (phytol and hexadecanoic acid methyl ester) significantly reduced the viability of T. gondii to 0.11% and 16.6%, respectively, at a concentration of 100 µg/mL. Additionally, Hsf1 demonstrated an antioxidant capacity of 30% as assessed using the ORAC method. The two active compounds also exhibited antioxidant properties, with antioxidant capacities of 13.33% and 33% for hexadecanoic acid methyl ester and phytol, respectively, at concentrations up to 15.4 mg/mL. Hsf1 showed membrane damage and conoid extrusion in T. gondii tachyzoites, suggesting direct interference with the lytic cycle of the parasite. These findings underscore the therapeutic potential of Hsf1 as a promising tool for controlling infections caused by T. gondii, thereby providing an alternative in the search for new antiparasitic agents. However, further research is required to determine the in vivo pharmacological effects and properties of these compounds with potential anti-Toxoplasma activity. Full article

(This article belongs to the Special Issue Antioxidant and Antimicrobial Activity of Plant Extracts and Their Pharmacological Applications)

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41 pages, 1650 KiB

Open AccessReview

The Role of Hydrogen Sulfide in the Regulation of the Pulmonary Vasculature in Health and Disease

by Philip I. Aaronson

Antioxidants 2025, 14(3), 341; https://doi.org/10.3390/antiox14030341 - 14 Mar 2025

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Abstract

The gasotransmitter hydrogen sulfide (H₂S; also termed sulfide) generally acts as a vasodilator in the systemic vasculature but causes a paradoxical constriction of pulmonary arteries (PAs). In light of evidence that a fall in the partial pressure in oxygen (pO₂ [...] Read more.

The gasotransmitter hydrogen sulfide (H₂S; also termed sulfide) generally acts as a vasodilator in the systemic vasculature but causes a paradoxical constriction of pulmonary arteries (PAs). In light of evidence that a fall in the partial pressure in oxygen (pO₂) increases cellular sulfide levels, it was proposed that a rise in sulfide in pulmonary artery smooth muscle cells (PASMCs) is responsible for hypoxic pulmonary vasoconstriction, the contraction of PAs which develops rapidly in lung regions undergoing alveolar hypoxia. In contrast, pulmonary hypertension (PH), a sustained elevation of pulmonary artery pressure (PAP) which can develop in the presence of a diverse array of pathological stimuli, including chronic hypoxia, is associated with a decrease in the expression of sulfide -producing enzymes in PASMCs and a corresponding fall in sulfide production by the lung. Evidence that PAP in animal models of PH can be lowered by administration of exogenous sulfide has led to an interest in using sulfide-donating agents for treating this condition in humans. Notably, intracellular H₂S exists in equilibrium with other sulfur-containing species such as polysulfides and persulfides, and it is these reactive sulfur species which are thought to mediate most of its effects on cells through persulfidation of cysteine thiols on proteins, leading to changes in function in a manner similar to thiol oxidation by reactive oxygen species. This review sets out what is currently known about the mechanisms by which H₂S and related sulfur species exert their actions on pulmonary vascular tone, both acutely and chronically, and discusses the potential of sulfide-releasing drugs as treatments for the different types of PH which arise in humans. Full article

(This article belongs to the Special Issue Role of Redox in Pulmonary Vascular Diseases)

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Antioxidants, Volume 14, Issue 3 (March 2025) – 127 articles

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