Antioxidants

15 pages, 3345 KiB

Open AccessArticle

Extraction, Characterization, and In Vitro Biological Activity of Polyphenols from Discarded Young Fig Fruits Based on Deep Eutectic Solvents

by Qinqiu Zhang, Yue Peng, Yi Xu, Fan Li, Shuxiang Liu, Danka Bukvicki, Qing Zhang, Shang Lin, Miaomiao Wang, Tianyi Zhang, Dingtao Wu and Wen Qin

Antioxidants 2024, 13(9), 1084; https://doi.org/10.3390/antiox13091084 (registering DOI) - 4 Sep 2024

Abstract

(1) Background: Discarded young fig fruits (DYFFs) result in a waste of resources, such as sparse fruits and residual fruits, and there has been no research on the relationship between phenolic compounds and biological activity in DYFFs (2) Methods: Different deep eutectic solvents [...] Read more.

(1) Background: Discarded young fig fruits (DYFFs) result in a waste of resources, such as sparse fruits and residual fruits, and there has been no research on the relationship between phenolic compounds and biological activity in DYFFs (2) Methods: Different deep eutectic solvents (DESs) and 80% ethanol were used to prepare DYFF extracts, and polyphenol extraction efficiency and bioactivities in the DYFFs extracts were compared. (3) Results: More than 1700 phytochemicals were identified in DYFFs, and thirteen of these typical phenolic compounds were analyzed quantitatively; chlorogenic acid, rutin, luteolin 8-C-glucoside, and epicatechin are the main polyphenols in DYFFs, especially chlorogenic acid with 2720–7980 mg/kg. Ferulic acid, caffeic acid, epicatechin, (+)-catechin, luteolin 8-C-glucoside, rutin, hesperetin, and chlorogenic acid showed different degrees of correlation with in vitro antioxidant activity. Moreover, the highest total phenol content found in the extracts of ChCl-Ethylene glycol (Choline chloride:Ethylene glycol = 1:2) was 8.88 mg GAE/g DW, and all quantitatively analyzed phenolic compounds had high levels in various DESs and 80% ethanol. The 80% ethanol and Choline chloride (ChCl) solvent system showed the greatest antioxidant properties, and the Choline chloride-Urea (Choline chloride: Urea = 1:2) extract of DYFFs exhibited the highest inhibitory activity. (4) Conclusions: DESs have demonstrated potential as promising green solvents, especially the ChCl solvent system, which facilitates the extraction of polyphenols. Full article

(This article belongs to the Special Issue Antioxidant Activities of Phytochemicals in Fruits and Vegetables)

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23 pages, 4370 KiB

Open AccessArticle

Multiple Mechanisms of Action of Sulfodyne^®, a Natural Antioxidant, against Pathogenic Effects of SARS-CoV-2 Infection

by Paul-Henri Romeo, Laurine Conquet, Sébastien Messiaen, Quentin Pascal, Stéphanie G. Moreno, Anne Bravard, Jacqueline Bernardino-Sgherri, Nathalie Dereuddre-Bosquet, Xavier Montagutelli, Roger Le Grand, Vanessa Petit and Federica Ferri

Antioxidants 2024, 13(9), 1083; https://doi.org/10.3390/antiox13091083 (registering DOI) - 4 Sep 2024

Abstract

Few therapeutic options are available to treat COVID-19. The KEAP1/NRF2 pathway, the major redox-responsive pathway, has emerged as a potential therapeutic target for COVID-19 as it regulates redox homeostasis and inflammation that are altered during SARS-CoV-2 infection. Here, we characterized the effects of [...] Read more.

Few therapeutic options are available to treat COVID-19. The KEAP1/NRF2 pathway, the major redox-responsive pathway, has emerged as a potential therapeutic target for COVID-19 as it regulates redox homeostasis and inflammation that are altered during SARS-CoV-2 infection. Here, we characterized the effects of NRF2-agonist Sulfodyne^®, a stabilized natural Sulforaphane, in cellular and animal models of SARS-CoV-2 infection. In pulmonary or colonic epithelial cell lines, Sulfodyne^® elicited a more efficient inhibition of SARS-CoV-2 replication than NRF2-agonists DMF and CDDO. This antiviral activity was not dependent on NRF2 but was associated with the regulation of several metabolic pathways, including the inhibition of ER stress and mTOR signaling, which are activated during SARS-CoV-2 infection. Sulfodyne^® also decreased SARS-CoV-2 mediated inflammatory responses by inhibiting the delayed induction of IFNB1 and type I IFN-stimulated genes in infected epithelial cell lines and by reducing the activation of human by-stander monocytes recruited after SARS-CoV-2 infection. In K18-hACE2 mice infected with SARS-CoV-2, Sulfodyne^® treatment reduced both early lung viral load and disease severity by fine-tuning IFN-beta levels. Altogether, these results provide evidence for multiple mechanisms that underlie the antiviral and anti-inflammatory activities of Sulfodyne^® and pinpoint Sulfodyne^® as a potent therapeutic agent against pathogenic effects of SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue Multi-Target Profile of Antioxidant Compounds, including Repurposing and Combination Strategies)

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27 pages, 3809 KiB

Open AccessArticle

Exploring the Antioxidant and Anti-Inflammatory Potential of Saffron (Crocus sativus) Tepals Extract within the Circular Bioeconomy

by Luisa Frusciante, Michela Geminiani, Behnaz Shabab, Tommaso Olmastroni, Giorgia Scavello, Martina Rossi, Pierfrancesco Mastroeni, Collins Nyaberi Nyong’a, Laura Salvini, Stefania Lamponi, Maria Laura Parisi, Adalgisa Sinicropi, Lorenzo Costa, Ottavia Spiga, Alfonso Trezza and Annalisa Santucci

Antioxidants 2024, 13(9), 1082; https://doi.org/10.3390/antiox13091082 (registering DOI) - 4 Sep 2024

Abstract

Repurposing saffron (Crocus sativus) waste presents a sustainable strategy for generating high-value products within the bioeconomy framework. Typically, flower components are discarded after stigma harvest, resulting in significant waste—350 kg of tepals per kilogram of stigmas. This research employed a comprehensive [...] Read more.

Repurposing saffron (Crocus sativus) waste presents a sustainable strategy for generating high-value products within the bioeconomy framework. Typically, flower components are discarded after stigma harvest, resulting in significant waste—350 kg of tepals per kilogram of stigmas. This research employed a comprehensive approach, integrating bioactivity studies (in vitro and in silico) with Life Cycle Assessment (LCA) evaluations, to extract and assess bioactive compounds from C. sativus tepals sourced in Tuscany, Italy. Phytochemical characterization using UPLC-MS/MS revealed a high abundance and variety of flavonoids in the hydro-ethanolic extract (CST). The antioxidant capacity was validated through various assays, and the ability to mitigate H₂O₂-induced oxidative stress and enhance fermentation was demonstrated in Saccharomyces cerevisiae. This study reports that C. sativus tepals extract reduces oxidative stress and boosts ethanol fermentation in yeast, paving the way for applications in the food and biofuels sectors. Further validation in RAW 264.7 macrophages confirmed CST’s significant anti-inflammatory effects, indicating its potential for pharmaceutical, cosmeceutical, and nutraceutical applications. In silico studies identified potential targets involved in antioxidant and anti-inflammatory processes, shedding light on possible interaction mechanisms with Kaempferol 3-O-sophoroside (KOS-3), the predominant compound in the extract. The integration of LCA studies highlighted the environmental benefits of this approach. Overall, this research underscores the value of using waste-derived extracts through “green” methodologies, offering a model that may provide significant advantages for further evaluations compared to traditional methodologies and supporting the circular bioeconomy. Full article

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5 pages, 183 KiB

Open AccessEditorial

The Multifaceted Aspects of Oxidative Stress in the Skin and Other Tissues

by Reinhart Speeckaert, Marijn M. Speeckaert and Nanja van Geel

Antioxidants 2024, 13(9), 1081; https://doi.org/10.3390/antiox13091081 - 4 Sep 2024

Abstract

Different tissues experience various levels of oxidative stress based on their function and protection from outside environments [...] Full article

(This article belongs to the Special Issue Oxidative Stress in Inflammatory Skin and Tissue Disorders)

18 pages, 3650 KiB

Open AccessArticle

Impaired Upper Airway Muscle Function with Excessive or Deficient Dietary Intake of Selenium in Rats

by David P. Burns, Sarah E. Drummond, Stefanie Wölfel, Kevin H. Murphy, Joanna Szpunar, Ken D. O’Halloran and John J. Mackrill

Antioxidants 2024, 13(9), 1080; https://doi.org/10.3390/antiox13091080 - 4 Sep 2024

Abstract

Obstructive sleep apnoea (OSA) involves impaired upper airway muscle function and is linked to several pathologies including systemic hypertension, daytime somnolence and cognitive decline. Selenium is an essential micronutrient that exerts many of its effects through selenoproteins. Evidence indicates that either deficient or [...] Read more.

Obstructive sleep apnoea (OSA) involves impaired upper airway muscle function and is linked to several pathologies including systemic hypertension, daytime somnolence and cognitive decline. Selenium is an essential micronutrient that exerts many of its effects through selenoproteins. Evidence indicates that either deficient or excessive dietary selenium intake can result in impaired muscle function, termed nutritional myopathy. To investigate the effects of selenium on an upper airway muscle, the sternohyoid, rats were fed on diets containing deficient, normal (0.5 ppm sodium selenite) or excessive (5 ppm selenite) selenium for a period of two weeks. Sternohyoid contractile function was assessed ex vivo. Serum selenium levels and activity of the glutathione antioxidant system were determined by biochemical assays. The abundance of three key muscle selenoproteins (selenoproteins -N, -S and -W (SELENON, SELENOS and SELENOW)) in sternohyoid muscle were quantified by immunoblotting. Levels of these selenoproteins were also compared between rats exposed to chronic intermittent hypoxia, a model of OSA, and sham treated animals. Although having no detectable effect on selected organ masses and whole-body weight, either selenium-deficient or -excessive diets severely impaired sternohyoid contractile function. These changes did not involve altered fibre size distribution. These dietary interventions resulted in corresponding changes in serum selenium concentrations but did not alter the activity of glutathione-dependent antioxidant systems in sternohyoid muscle. Excess dietary selenium increased the abundance of SELENOW protein in sternohyoid muscles but had no effect on SELENON or SELENOS. In contrast, chronic intermittent hypoxia increased SELENON, decreased SELENOW and had no significant effect on SELENOS in sternohyoid muscle. These findings indicate that two-week exposure to selenium-deficient or -excessive diets drastically impaired upper airway muscle function. In the sternohyoid, SELENON, SELENOS and SELENOW proteins show distinct alterations in level following exposure to different dietary selenium intakes, or to chronic intermittent hypoxia. Understanding how alterations in Se and selenoproteins impact sternohyoid muscle function has the potential to be translated into new therapies for prevention or treatment of OSA. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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19 pages, 3314 KiB

Open AccessArticle

Dietary Organic Zinc Supplementation Modifies the Oxidative Genes via RORγ and Epigenetic Regulations in the Ileum of Broiler Chickens Exposed to High-Temperature Stress

by Saber Y. Adam, Madesh Muniyappan, Hao Huang, Wael Ennab, Hao-Yu Liu, Abdelkareem A. Ahmed, Ming-an Sun, Tadelle Dessie, In Ho Kim, Yun Hu, Xugang Luo and Demin Cai

Antioxidants 2024, 13(9), 1079; https://doi.org/10.3390/antiox13091079 - 4 Sep 2024

Abstract

Heat stress (HS) is a significant concern in broiler chickens, which is vital for global meat supply in the dynamic field of poultry farming. The impact of heat stress on the ileum and its influence on the redox homeostatic genes in chickens remains [...] Read more.

Heat stress (HS) is a significant concern in broiler chickens, which is vital for global meat supply in the dynamic field of poultry farming. The impact of heat stress on the ileum and its influence on the redox homeostatic genes in chickens remains unclear. We hypothesized that adding zinc to the feed of heat-stressed broilers would improve their resilience to heat stress. However, this study aimed to explore the effects of organic zinc supplementation under HS conditions on broiler chickens’ intestinal histology and regulation of HS index genes. In this study, 512 Xueshan chickens were divided into four groups: vehicle, HS, 60 mg/kg zinc, and HS + 60 mg/kg zinc groups. Findings revealed that zinc supply positively increased the VH and VH: CD in the ileum of the broilers compared to the HS group, while CD and VW decreased in Zn and HS+Zn supplemented broilers. Zn administration significantly increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and decreased the enzymatic activities of reactive oxygen species (ROS) and malondialdehyde (MDA) compared to the HS group. In addition, Zn administration significantly increased relative ATP, complex I, III, and V enzyme activity compared to the HS group. Furthermore, the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), lactate transporter 3 (LPCAT3), peroxiredoxin (PRX), and transferrin receptor (TFRC) in the protein levels was extremely downregulated in HS+Zn compared to the HS group. Zn supply significantly decreased the enrichment of RORγ, P300, and SRC1 at target loci of ACSL4, LPCAT3, and PRX compared to the HS group. The occupancies of histone active marks H3K9ac, H3K18ac, H3K27ac, H3K4me1, and H3K18bhb at the locus of ACSL4 and LPCAT3 were significantly decreased in HS+Zn compared to the HS group. Moreover, H3K9la and H3K18la at the locus of ACSL4 and LPCAT3 were significantly decreased in HS+Zn compared to the HS group. This study emphasizes that organic Zn is a potential strategy for modulating the oxidative genes ACSL4, LPCAT3, PRX, and TFRC in the ileum of chickens via nuclear receptor RORγ regulation and histone modifications. Full article

(This article belongs to the Special Issue Oxidative Stress in Livestock and Poultry—2nd Edition)

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23 pages, 2879 KiB

Open AccessReview

Exploring the Thioredoxin System as a Therapeutic Target in Cancer: Mechanisms and Implications

by Rebecca Seitz, Deniz Tümen, Claudia Kunst, Phillip Heumann, Stephan Schmid, Arne Kandulski, Martina Müller and Karsten Gülow

Antioxidants 2024, 13(9), 1078; https://doi.org/10.3390/antiox13091078 - 4 Sep 2024

Viewed by 28

Abstract

Cells constantly face the challenge of managing oxidants. In aerobic organisms, oxygen (O₂) is used for energy production, generating reactive oxygen species (ROS) as byproducts of enzymatic reactions. To protect against oxidative damage, cells possess an intricate system of redox scavengers [...] Read more.

Cells constantly face the challenge of managing oxidants. In aerobic organisms, oxygen (O₂) is used for energy production, generating reactive oxygen species (ROS) as byproducts of enzymatic reactions. To protect against oxidative damage, cells possess an intricate system of redox scavengers and antioxidant enzymes, collectively forming the antioxidant defense system. This system maintains the redox equilibrium and enables the generation of localized oxidative signals that regulate essential cellular functions. One key component of this defense is the thioredoxin (Trx) system, which includes Trx, thioredoxin reductase (TrxR), and NADPH. The Trx system reverses oxidation of macromolecules and indirectly neutralizes ROS via peroxiredoxin (Prx). This dual function protects cells from damage accumulation and supports physiological cell signaling. However, the Trx system also shields tumors from oxidative damage, aiding their survival. Due to elevated ROS levels from their metabolism, tumors often rely on the Trx system. In addition, the Trx system regulates critical pathways such as proliferation and neoangiogenesis, which tumors exploit to enhance growth and optimize nutrient and oxygen supply. Consequently, the Trx system is a potential target for cancer therapy. The challenge lies in selectively targeting malignant cells without disrupting the redox equilibrium in healthy cells. The aim of this review article is threefold: first, to elucidate the function of the Trx system; second, to discuss the Trx system as a potential target for cancer therapies; and third, to present the possibilities for inhibiting key components of the Trx system, along with an overview of the latest clinical studies on these inhibitors. Full article

(This article belongs to the Special Issue Redox-Modulating Strategies in Cancer Therapy: Targeted Thioredoxin System Inhibition)

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18 pages, 13325 KiB

Open AccessArticle

Delayed Reproduction, Injury, and Regeneration of Testes in Out-of-Season Breeding of Largemouth Bass (Micropterus nigricans)

by Kuo He, Yi Yang, Zhihong Li, Haoxiao Yan, Kaige Song, Qiao Liu, Liulan Zhao and Song Yang

Antioxidants 2024, 13(9), 1077; https://doi.org/10.3390/antiox13091077 - 4 Sep 2024

Viewed by 122

Abstract

Out-of-season breeding is an effective method for addressing seasonal shortages of fry in aquaculture species such as largemouth bass (LMB) for year-round production. Off-season breeding of LMB can be achieved by subjecting breeding LMB to prolonged low-temperature conditions; however, this can alter reproductive [...] Read more.

Out-of-season breeding is an effective method for addressing seasonal shortages of fry in aquaculture species such as largemouth bass (LMB) for year-round production. Off-season breeding of LMB can be achieved by subjecting breeding LMB to prolonged low-temperature conditions; however, this can alter reproductive rhythms, affecting the quality of their sperm and leading to a decrease in reproductive efficiency. Therefore, it is crucial to investigate issues such as the damage to the testes and the related mechanisms caused by low-temperature stress during out-of-season breeding. In this experiment, we assessed the changes in the testes during this time in LMB by comparing reproductive rhythms, testicular histomorphology, ultrastructure, antioxidant capacity and apoptosis. We synthesized measurements of LMB from three identically treated cement ponds and fish exposed to water temperatures of 13–16 °C to assess the changes in the testes. The results showed that (1) out-of-season reproduction delayed sperm production and promoted sperm redevelopment in LMB, various hormone levels have changed over time (e.g., LH, FSH, and T). (2) The head plasma membrane of LMB spermatozoa was separated, and the middle mitochondria were swollen. (3) The expression levels of antioxidant enzymes (cat, sod, and gpx) were upregulated, and oxidative stress occurred in LMB. (4) The expression levels of apoptosis genes (e.g., bax, bcl2, and caspase3) were upregulated, and apoptosis occurred in LMB due to off-season breeding. Moreover, important genes of the mitochondrial apoptosis pathway (bid, CYT-C) were upregulated, indicating that spermatozoan apoptosis in LMB was probably achieved through the mitochondrial apoptosis pathway. These results suggest the delays, damage, and regeneration of LMB testes. Our findings provide new insights into the molecular mechanisms that trigger changes in sperm quality during out-of-season breeding in fish. Full article

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28 pages, 11496 KiB

Open AccessReview

Caffeine: The Story beyond Oxygen-Induced Lung and Brain Injury in Neonatal Animal Models—A Narrative Review

by Stefanie Endesfelder

Antioxidants 2024, 13(9), 1076; https://doi.org/10.3390/antiox13091076 - 3 Sep 2024

Viewed by 208

Abstract

Caffeine is one of the most commonly used drugs in intensive care to stimulate the respiratory control mechanisms of very preterm infants. Respiratory instability, due to the degree of immaturity at birth, results in apnea of prematurity (AOP), hyperoxic, hypoxic, and intermittent hypoxic [...] Read more.

Caffeine is one of the most commonly used drugs in intensive care to stimulate the respiratory control mechanisms of very preterm infants. Respiratory instability, due to the degree of immaturity at birth, results in apnea of prematurity (AOP), hyperoxic, hypoxic, and intermittent hypoxic episodes. Oxidative stress cannot be avoided as a direct reaction and leads to neurological developmental deficits and even a higher prevalence of respiratory diseases in the further development of premature infants. Due to the proven antioxidant effect of caffeine in early use, largely protective effects on clinical outcomes can be observed. This is also impressively observed in experimental studies of caffeine application in oxidative stress-adapted rodent models of damage to the developing brain and lungs. However, caffeine shows undesirable effects outside these oxygen toxicity injury models. This review shows the effects of caffeine in hyperoxic, hypoxic/hypoxic-ischemic, and intermittent hypoxic rodent injury models, but also the negative effects on the rodent organism when caffeine is administered without exogenous oxidative stress. The narrative analysis of caffeine benefits in cerebral and pulmonary preterm infant models supports protective caffeine use but should be given critical consideration when considering caffeine treatment beyond the recommended corrected gestational age. Full article

(This article belongs to the Special Issue The Role of Antioxidants in Pregnant Women’s and Children’s Health—2nd Edition)

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12 pages, 4204 KiB

Open AccessArticle

The Effect of Light Intensity during Cultivation and Postharvest Storage on Mustard and Kale Microgreen Quality

by Ieva Gudžinskaitė, Kristina Laužikė, Audrius Pukalskas and Giedrė Samuolienė

Antioxidants 2024, 13(9), 1075; https://doi.org/10.3390/antiox13091075 - 3 Sep 2024

Viewed by 139

Abstract

Microgreens are vegetable greens that are harvested early while they are still immature and have just developed cotyledons. One of the disadvantages and a challenge in production is that they exhibit a short shelf life and may be damaged easily. In seeking to [...] Read more.

Microgreens are vegetable greens that are harvested early while they are still immature and have just developed cotyledons. One of the disadvantages and a challenge in production is that they exhibit a short shelf life and may be damaged easily. In seeking to prolong the shelf life, some pre- and postharvest interventions have been investigated. Here, kale and mustard microgreens were grown in a controlled-environment walk-in chamber at +21/17 °C, with ~65% relative air humidity, while maintaining the spectral composition of deep red 61%, blue 20%, white 15%, and far red 4% (150, 200, and 250 µmol m⁻² s⁻¹ photosynthetic photon flux density (PPFD)). Both microgreens seemed to exhibit specific and species-dependent responses. Higher PPFD during growth and storage in light conditions resulted in increased contents of TPC in both microgreens on D₅. Additionally, 150 and 250 PPFD irradiation affected the α-tocopherol content by increasing it during postharvest storage in kale. On D₀ 150 for kale and 200 PPFD for mustard microgreens, β-carotene content increased. D₅ for kale showed insignificant differences, while mustard responded with the highest β-carotene content, under 150 PPFD. Our findings suggest that both microgreens show beneficial outcomes when stored in light compared to dark and that mild photostress is a promising tool for nutritional value improvement and shelf-life prolongation. Full article

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31 pages, 7695 KiB

Open AccessArticle

Unraveling the Protective Role of Oleocanthal and Its Oxidation Product, Oleocanthalic Acid, against Neuroinflammation

by Maria Cristina Barbalace, Michela Freschi, Irene Rinaldi, Lorenzo Zallocco, Marco Malaguti, Clementina Manera, Gabriella Ortore, Mariachiara Zuccarini, Maurizio Ronci, Doretta Cuffaro, Marco Macchia, Silvana Hrelia, Laura Giusti, Maria Digiacomo and Cristina Angeloni

Antioxidants 2024, 13(9), 1074; https://doi.org/10.3390/antiox13091074 - 3 Sep 2024

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Abstract

Neuroinflammation is a critical aspect of various neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. This study investigates the anti-neuroinflammatory properties of oleocanthal and its oxidation product, oleocanthalic acid, using the BV-2 cell line activated with lipopolysaccharide. Our findings revealed that oleocanthal significantly [...] Read more.

Neuroinflammation is a critical aspect of various neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. This study investigates the anti-neuroinflammatory properties of oleocanthal and its oxidation product, oleocanthalic acid, using the BV-2 cell line activated with lipopolysaccharide. Our findings revealed that oleocanthal significantly inhibited the production of pro-inflammatory cytokines and reduced the expression of inflammatory genes, counteracted oxidative stress induced by lipopolysaccharide, and increased cell phagocytic activity. Conversely, oleocanthalic acid was not able to counteract lipopolysaccharide-induced activation. The docking analysis revealed a plausible interaction of oleocanthal, with both CD14 and MD-2 leading to a potential interference with TLR4 signaling. Since our data show that oleocanthal only partially reduces the lipopolysaccharide-induced activation of NF-kB, its action as a TLR4 antagonist alone cannot explain its remarkable effect against neuroinflammation. Proteomic analysis revealed that oleocanthal counteracts the LPS modulation of 31 proteins, including significant targets such as gelsolin, clathrin, ACOD1, and four different isoforms of 14-3-3 protein, indicating new potential molecular targets of the compound. In conclusion, oleocanthal, but not oleocanthalic acid, mitigates neuroinflammation through multiple mechanisms, highlighting a pleiotropic action that is particularly important in the context of neurodegeneration. Full article

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

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20 pages, 29992 KiB

Open AccessArticle

Challenging Sarcopenia: Exploring AdipoRon in Aging Skeletal Muscle as a Healthspan-Extending Shield

by Camille M. Selvais, Maria A. Davis-López de Carrizosa, Romain Versele, Nicolas Dubuisson, Laurence Noel, Sonia M. Brichard and Michel Abou-Samra

Antioxidants 2024, 13(9), 1073; https://doi.org/10.3390/antiox13091073 - 3 Sep 2024

Viewed by 188

Abstract

Sarcopenia, characterized by loss of muscle mass, quality, and function, poses significant risks in aging. We previously demonstrated that long-term treatment with AdipoRon (AR), an adiponectin receptor agonist, alleviated myosteatosis and muscle degeneration in middle-aged obese mice. This study aimed to determine if [...] Read more.

Sarcopenia, characterized by loss of muscle mass, quality, and function, poses significant risks in aging. We previously demonstrated that long-term treatment with AdipoRon (AR), an adiponectin receptor agonist, alleviated myosteatosis and muscle degeneration in middle-aged obese mice. This study aimed to determine if a shorter AR treatment could effectively offset sarcopenia in older mice. Two groups of old mice (20–23 months) were studied, one untreated (O) and one orally-treated with AR (O-AR) at 50 mg/kg/day for three months, compared with control 3-month-old young mice (Y) or 10-month-old young-adult mice (C-10). Results showed that AR remarkably inversed the loss of muscle mass by restoring the sarcopenia index and fiber count, which were greatly diminished with age. Additionally, AR successfully saved muscle quality of O mice by halving the accumulation of tubular aggregates and aberrant mitochondria, through AMPK pathway activation and enhanced autophagy. AR also bolstered muscle function by rescuing mitochondrial activity and improving exercise endurance. Finally, AR markedly curbed muscle fibrosis and mitigated local/systemic inflammation. Thus, a late three-month AR treatment successfully opposed sarcopenia and counteracted various hallmarks of aging, suggesting AR as a promising anti-aging therapy for skeletal muscles, potentially extending healthspan. Full article

(This article belongs to the Topic Advances in Adiponectin)

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17 pages, 3351 KiB

Open AccessArticle

Beneficial Effect of Dimethyl Fumarate Drug Repositioning in a Mouse Model of TDP-43-Dependent Frontotemporal Dementia

by Ignacio Silva-Llanes, Raquel Martín-Baquero, Alicia Berrojo-Armisen, Carmen Rodríguez-Cueto, Javier Fernández-Ruiz, Eva De Lago and Isabel Lastres-Becker

Antioxidants 2024, 13(9), 1072; https://doi.org/10.3390/antiox13091072 - 2 Sep 2024

Viewed by 291

Abstract

Frontotemporal dementia (FTD) causes progressive neurodegeneration in the frontal and temporal lobes, leading to behavioral, cognitive, and language impairments. With no effective treatment available, exploring new therapeutic approaches is critical. Recent research highlights the transcription factor Nuclear Factor erythroid-derived 2-like 2 (NRF2) as [...] Read more.

Frontotemporal dementia (FTD) causes progressive neurodegeneration in the frontal and temporal lobes, leading to behavioral, cognitive, and language impairments. With no effective treatment available, exploring new therapeutic approaches is critical. Recent research highlights the transcription factor Nuclear Factor erythroid-derived 2-like 2 (NRF2) as vital in limiting neurodegeneration, with its activation shown to mitigate FTD-related processes like inflammation. Dimethyl fumarate (DMF), an NRF2 activator, has demonstrated neuroprotective effects in a TAU-dependent FTD mouse model, reducing neurodegeneration and inflammation. This suggests DMF repositioning potential for FTD treatment. Until now, no trial had been conducted to analyze the effect of DMF on TDP-43-dependent FTD. In this study, we aimed to determine the potential therapeutic efficacy of DMF in a TDP-43-related FTD mouse model that exhibits early cognitive impairment. Mice received oral DMF treatment every other day from presymptomatic to symptomatic stages. By post-natal day (PND) 60, an improvement in cognitive function is already evident, becoming even more pronounced by PND90. This cognitive enhancement correlates with the neuroprotection observed in the dentate gyrus and a reduction in astrogliosis in the stratum lacunosum-moleculare zone. At the prefrontal cortex (PFC) level, a neuroprotective effect of DMF is also observed, accompanied by a reduction in astrogliosis. Collectively, our results suggest a potential therapeutic application of DMF for patients with TDP-43-dependent FTD. Full article

(This article belongs to the Special Issue Role of NRF2 Pathway in Neurodegenerative Diseases)

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12 pages, 1694 KiB

Open AccessArticle

Impact of Hypoxia on Neutrophil Degranulation and Inflammatory Response in Alpha-1 Antitrypsin Deficiency Patients

by María Magallón, Silvia Castillo-Corullón, Lucía Bañuls, Teresa Romero, Daniel Pellicer, Alberto Herrejón, María Mercedes Navarro-García, Cruz González and Francisco Dasí

Antioxidants 2024, 13(9), 1071; https://doi.org/10.3390/antiox13091071 - 2 Sep 2024

Viewed by 215

Abstract

Background: Alpha-1 antitrypsin deficiency (AATD) is an inflammatory disorder where neutrophils play a key role. Excessive neutrophil activation leads to local hypoxia and tissue damage. Most research on neutrophil function has been conducted under atmospheric conditions (21% O₂), which may not [...] Read more.

Background: Alpha-1 antitrypsin deficiency (AATD) is an inflammatory disorder where neutrophils play a key role. Excessive neutrophil activation leads to local hypoxia and tissue damage. Most research on neutrophil function has been conducted under atmospheric conditions (21% O₂), which may not represent physiological or pathological conditions. This study aimed to determine the effects of hypoxia on neutrophil degranulation and cytokine production in AATD patients. Methods: Neutrophils isolated from 54 AATD patients (31 MZ; 8 SZ; 15 ZZ) and 7 controls (MM) were exposed to hypoxia (1% O₂) for 4 h. Neutrophil degranulation was assessed by measuring elastase (NE), myeloperoxidase (MPO), lactoferrin, and matrix metalloproteinase-9 (MMP-9) levels using immunoassay-based methods. Pro-inflammatory (IL-8, IL-1 beta, IL-6, and TNF-alpha) and anti-inflammatory (IL-4 and IL-10) cytokine levels were assessed by a Luminex-based method. Results: Our results indicate a significantly increased release of NE (p = 0.015), MPO (p = 0.042), lactoferrin (p = 0.015), and MMP-9 (p = 0.001) compared to controls. Pro-inflammatory cytokines show a significant rise in IL-8 (p = 0.019), a trend towards increased IL-1 beta (p = 0.3196), no change in IL-6 (p = 0.7329), and reduced TNF-alpha (p = 0.006). Anti-inflammatory cytokines show increased IL-4 (p = 0.057) and decreased IL-10 (p = 0.05703). Conclusions: Increased neutrophil degranulation and inflammatory phenotype are observed in AATD neutrophils under physiological hypoxia. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Hypoxia and Human Pathophysiology Settings: Novel Pharmacological Targets)

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17 pages, 1714 KiB

Open AccessArticle

Modulation of Antioxidant Enzyme Expression of In Vitro Culture-Derived Reticulocytes

by Hannah D. Langlands, Deborah K. Shoemark and Ashley M. Toye

Antioxidants 2024, 13(9), 1070; https://doi.org/10.3390/antiox13091070 - 2 Sep 2024

Viewed by 315

Abstract

The regulation of reactive oxygen species (ROS) in red blood cells (RBCs) is crucial for maintaining functionality and lifespan. Indeed, dysregulated ROS occurs in haematological diseases such as sickle cell disease and β-thalassaemia. In order to combat this, RBCs possess high levels of [...] Read more.

The regulation of reactive oxygen species (ROS) in red blood cells (RBCs) is crucial for maintaining functionality and lifespan. Indeed, dysregulated ROS occurs in haematological diseases such as sickle cell disease and β-thalassaemia. In order to combat this, RBCs possess high levels of protective antioxidant enzymes. We aimed to further boost RBC antioxidant capacity by overexpressing peroxiredoxin (Prxs) and glutathione peroxidase (GPxs) enzymes. Multiple antioxidant enzyme cDNAs were individually overexpressed in expanding immortalised erythroblasts using lentivirus, including Prx isoforms 1, 2, and 6 and GPx isoforms 1 and 4. Enhancing Prx protein expression proved straightforward, but GPx overexpression required modifications. For GPx4, these modifications included adding a SECIS element in the 3’UTR, the removal of a mitochondrial-targeting sequence, and removing putative ubiquitination sites. Culture-derived reticulocytes exhibiting enhanced levels of Prx and GPx antioxidant proteins were successfully engineered, demonstrating a novel approach to improve RBC resilience to oxidative stress. Further work is needed to explore the activity of these proteins and their impact on RBC metabolism, but this strategy shows promise for improving RBC function in physiological and pathological contexts and during storage for transfusion. Enhancing the antioxidant capacity of reticulocytes has exciting promise for developing culture-derived RBCs with enhanced resistance to oxidative damage and offers new therapeutic interventions in diseases with elevated oxidative stress. Full article

(This article belongs to the Special Issue Blood Cells and Redox Homeostasis in Health and Disease, 2nd Edition)

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15 pages, 4417 KiB

Open AccessArticle

Aerobic Exercise Protects against Cardiotoxin-Induced Skeletal Muscle Injury in a DDAH1-Dependent Manner

by Fei Feng, Kai Luo, Xinyi Yuan, Ting Lan, Siyu Wang, Xin Xu and Zhongbing Lu

Antioxidants 2024, 13(9), 1069; https://doi.org/10.3390/antiox13091069 - 1 Sep 2024

Viewed by 340

Abstract

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is a critical enzyme that regulates nitric oxide (NO) signaling through the degradation of asymmetric dimethylarginine (ADMA). Previous studies have revealed a link between the beneficial effects of aerobic exercise and the upregulation of DDAH1 in bones and hearts. [...] Read more.

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is a critical enzyme that regulates nitric oxide (NO) signaling through the degradation of asymmetric dimethylarginine (ADMA). Previous studies have revealed a link between the beneficial effects of aerobic exercise and the upregulation of DDAH1 in bones and hearts. We previously reported that skeletal muscle DDAH1 plays a protective role in cardiotoxin (CTX)-induced skeletal muscle injury and regeneration. To determine the effects of aerobic exercise on CTX-induced skeletal muscle injury and the role of DDAH1 in this process, wild-type (WT) mice and skeletal muscle-specific Ddah1-knockout (Ddah1^MKO) mice were subjected to swimming training for 8 weeks and then injected with CTX. In WT mice, swimming training for 8 weeks significantly promoted skeletal muscle regeneration and attenuated inflammation, oxidative stress, and apoptosis in the gastrocnemius (GA) muscle after CTX injection. These phenomena were associated with increases in the protein expression of PAX7, myogenin, MEF2A, eNOS, SOD2, and peroxiredoxin 5 and decreases in iNOS expression in GA muscles. Swimming training also decreased serum ADMA levels and increased serum nitrate/nitrite (NOx) levels and skeletal muscle DDAH1 expression. Interestingly, swimming training in Ddah1^MKO mice had no obvious effect on CTX-induced skeletal muscle injury or regeneration and did not repress the CTX-induced inflammatory response, superoxide generation, or apoptosis. In summary, our data suggest that DDAH1 is important for the protective effect of aerobic exercise on skeletal muscle injury and regeneration. Full article

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

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15 pages, 4185 KiB

Open AccessArticle

Mitigating Doxorubicin-Induced Cardiotoxicity through Quercetin Intervention: An Experimental Study in Rats

by Patricia Lorena Dulf, Camelia Alexandra Coadă, Adrian Florea, Remus Moldovan, Ioana Baldea, Daniel Vasile Dulf, Dan Blendea and Adriana Gabriela Filip

Antioxidants 2024, 13(9), 1068; https://doi.org/10.3390/antiox13091068 - 31 Aug 2024

Viewed by 403

Abstract

Doxorubicin (DOX) is an effective anticancer drug, but its use is limited by dose-dependent heart toxicity. Quercetin is a natural antioxidant frequently studied for its beneficial properties. Moreover, a wide range of dietary supplements are available for human use. This in vivo study [...] Read more.

Doxorubicin (DOX) is an effective anticancer drug, but its use is limited by dose-dependent heart toxicity. Quercetin is a natural antioxidant frequently studied for its beneficial properties. Moreover, a wide range of dietary supplements are available for human use. This in vivo study aimed to explore the potential cardioprotective effects of quercetin in chronic DOX treatment. A total of 32 Wistar rats were randomly divided into four groups: control, DOX, DOX/Q-50, and DOX/Q-100, treated with saline, 2.5 mg/kg body-weight DOX, 2.5 mg/kg body-weight DOX + 50 mg quercetin, and 2.5 mg/kg body-weight DOX + 100 mg quercetin, respectively, for two weeks. Rats were monitored using cardiac ultrasound (US) and markers for cardiac injury. Oxidative damage and ultrastructural changes in the heart were investigated. Chronic DOX treatment led to a decline in cardiac function and elevated values of NT pro-BNP, troponin I, and CK-MB. Quercetin treatment slightly improved certain US parameters, and normalized serum NT pro-BNP levels. Furthermore, DOX-induced SOD1 depletion with consequent Nrf2 activation and DNA damage as shown by an increase in γH2AX and 8HOdG. Quercetin treatment alleviated these alterations. Oral administration of quercetin alleviated serum markers associated with DOX-induced cardiotoxicity. Furthermore, it exhibited a favorable impact on the cardiac US parameters. This suggests that quercetin may have potential cardioprotective properties. Full article

(This article belongs to the Special Issue Role of Oxidative Stress in Cardiac Remodeling and Heart Failure—2nd Edition)

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18 pages, 3156 KiB

Open AccessArticle

Cystathionine Gamma-Lyase Regulates TNF-α-Mediated Injury Response in Human Colonic Epithelial Cells and Colonoids

by Francisco Arroyo Almenas, Gábor Törő, Peter Szaniszlo, Manjit Maskey, Ketan K. Thanki, Walter A. Koltun, Gregory S. Yochum, Irina V. Pinchuk, Celia Chao, Mark R. Hellmich and Katalin Módis

Antioxidants 2024, 13(9), 1067; https://doi.org/10.3390/antiox13091067 - 31 Aug 2024

Viewed by 298

Abstract

Cystathionine gamma-lyase (CSE) and TNF-α are now recognized as key regulators of intestinal homeostasis, inflammation, and wound healing. In colonic epithelial cells, both molecules have been shown to influence a variety of biological processes, but the specific interactions between intracellular signaling pathways regulated [...] Read more.

Cystathionine gamma-lyase (CSE) and TNF-α are now recognized as key regulators of intestinal homeostasis, inflammation, and wound healing. In colonic epithelial cells, both molecules have been shown to influence a variety of biological processes, but the specific interactions between intracellular signaling pathways regulated by CSE and TNF-α are poorly understood. In the present study, we investigated these interactions in normal colonocytes and an organoid model of the healthy human colon using CSE-specific pharmacological inhibitors and siRNA-mediated transient gene silencing in analytical and functional assays in vitro. We demonstrated that CSE and TNF-α mutually regulated each other’s functions in colonic epithelial cells. TNF-α treatment stimulated CSE activity within minutes and upregulated CSE expression after 24 h, increasing endogenous CSE-derived H₂S production. In turn, CSE activity promoted TNF-α-induced NF-ĸB and ERK1/2 activation but did not affect the p38 MAPK signaling pathway. Inhibition of CSE activity completely abolished the TNF-α-induced increase in transepithelial permeability and wound healing. Our data suggest that CSE activity may be essential for effective TNF-α-mediated intestinal injury response. Furthermore, CSE regulation of TNF-α-controlled intracellular signaling pathways could provide new therapeutic targets in diseases of the colon associated with impaired epithelial wound healing. Full article

(This article belongs to the Special Issue Hydrogen Sulfide Signaling in Biological Systems)

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13 pages, 1643 KiB

Open AccessArticle

Health-Promoting Properties of Pectin–Polyphenol Complex Extracted from Olive Oil By-Product Alperujo: Antioxidant, Antiproliferative, and Anti-Inflammatory Activities

by Alejandra Bermúdez-Oria, María Luisa Castejón, Fátima Rubio-Senent, Guillermo Rodríguez-Gutiérrez and Juan Fernández-Bolaños

Antioxidants 2024, 13(9), 1066; https://doi.org/10.3390/antiox13091066 - 30 Aug 2024

Viewed by 336

Abstract

This research explores the health-promoting properties of the pectin–polyphenol complex extracted from alperujo, a by-product of olive oil production. This study investigates the chemical composition and antioxidant activity of the extracts, revealing their high antioxidant activity in vitro. Cell viability assays conducted on [...] Read more.

This research explores the health-promoting properties of the pectin–polyphenol complex extracted from alperujo, a by-product of olive oil production. This study investigates the chemical composition and antioxidant activity of the extracts, revealing their high antioxidant activity in vitro. Cell viability assays conducted on colon carcinoma cells (Caco-2) demonstrate the inhibitory effect of the extracts on cell proliferation. However, the extracts do not affect the viability of differentiated Caco-2 cells, suggesting a selective antiproliferative action. Additionally, the extracts reduce intracellular reactive oxygen species (ROS) and nitrite (NO) production in LPS-stimulated murine peritoneal macrophages. Furthermore, the extracts exhibit anti-inflammatory effects by downregulating the secretion of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in these macrophages. These findings highlight the potential of pectin–polyphenol complexes as functional ingredients with significant health benefits, demonstrating antioxidant, antiproliferative, and anti-inflammatory properties. Full article

(This article belongs to the Special Issue Olive Antioxidants: Extraction, Biological Activity and Practical Applications—2nd Edition)

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17 pages, 1477 KiB

Open AccessReview

Role of NADPH Oxidases in Stroke Recovery

by Dong-Hee Choi, In-Ae Choi and Jongmin Lee

Antioxidants 2024, 13(9), 1065; https://doi.org/10.3390/antiox13091065 - 30 Aug 2024

Viewed by 245

Abstract

Stroke is one of the most significant causes of death and long-term disability globally. Overproduction of reactive oxygen species by NADPH oxidase (NOX) plays an important role in exacerbating oxidative stress and causing neuronal damage after a stroke. There is growing evidence that [...] Read more.

Stroke is one of the most significant causes of death and long-term disability globally. Overproduction of reactive oxygen species by NADPH oxidase (NOX) plays an important role in exacerbating oxidative stress and causing neuronal damage after a stroke. There is growing evidence that NOX inhibition prevents ischemic injury and that the role of NOX in brain damage or recovery depends on specific post-stroke phases. In addition to studies on post-stroke neuroprotection by NOX inhibition, recent reports have also demonstrated the role of NOX in stroke recovery, a critical process for brain adaptation and functional reorganization after a stroke. Therefore, in this review, we investigated the role of NOX in stroke recovery with the aim of integrating preclinical findings into potential therapeutic strategies to improve stroke recovery. Full article

(This article belongs to the Special Issue NADPH Oxidases (NOXs))

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43 pages, 34906 KiB

Open AccessArticle

Impacts of Plu kaow (Houttuynia cordata Thunb.) Ethanolic Extract on Diabetes and Dyslipidemia in STZ Induced Diabetic Rats: Phytochemical Profiling, Cheminformatics Analyses, and Molecular Docking Studies

by Shaikh Shahinur Rahman, Anuwatchakij Klamrak, Napapuch Nopkuesuk, Jaran Nabnueangsap, Piyapon Janpan, Kiattawee Choowongkomon, Jureerut Daduang and Sakda Daduang

Antioxidants 2024, 13(9), 1064; https://doi.org/10.3390/antiox13091064 - 30 Aug 2024

Viewed by 304

Abstract

The increasing prevalence of diabetes and dyslipidemia poses significant health challenges, impacting millions of people globally and leading to high rates of illness and death. This study aimed to explore the potential antidiabetic and hypolipidemic effects of Plu kaow (Houttuynia cordata Thunb.) [...] Read more.

The increasing prevalence of diabetes and dyslipidemia poses significant health challenges, impacting millions of people globally and leading to high rates of illness and death. This study aimed to explore the potential antidiabetic and hypolipidemic effects of Plu kaow (Houttuynia cordata Thunb.) ethanolic extract (PK) in streptozotocin (STZ) induced diabetic rats, focusing on its molecular mechanisms. Diabetes was induced in fasting Long Evans rats using streptozotocin (65 mg/kg b. w.), with glibenclamide (5 mg/kg/day) used as the standard experimental drug. The treated groups received oral supplementation of PK (500 mg/kg/day) for 28 days. The study evaluated blood glucose levels, lipid status, body weight, liver, kidney, and heart function biomarkers, antioxidant activity, and histological examination of various organs. Additionally, untargeted metabolomics, cheminformatics, and molecular docking were employed to elucidate the probable mechanisms of action of PK. Based on metabolomic profiling data, the PK was found to contain various putative antidiabetic agents such as kaempferol 7-neohesperidoside, isochlorogenic acid C, rutin, datiscin, and diosmin and they have been proposed to significantly (p < 0.001) reduce blood glucose levels and modulated hyperlipidemia. PK also improved the tested liver, kidney, and heart function biomarkers and reversed damage to normal pancreatic, liver, kidney, and heart cells in histological analysis. In conclusion, PK shows promise as a potential treatment or management option for diabetes and hyperlipidemia, as well as their associated complications in diabetic rats. Full article

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

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17 pages, 8177 KiB

Open AccessArticle

Antioxidant Capacity, Enzyme Activities Related to Energy Metabolism, and Transcriptome Analysis of Crassostrea hongkongensis Exposed to Hypoxia

by Pingping He, Wei Li, Pinyuan Wei, Linyuan Jiang, Junliang Guan, Yuan Ma, Li Zhang, Yongxian Chen, Yusi Zheng, Xingzhi Zhang and Jinxia Peng

Antioxidants 2024, 13(9), 1063; https://doi.org/10.3390/antiox13091063 - 30 Aug 2024

Viewed by 333

Abstract

Crassostrea hongkongensis (C. hongkongensis) is one of the three most commonly cultivated oyster species in China. Seasonal hypoxia is one of the most serious threats to its metabolism, reproductive behavior, and survival. To investigate the effects of hypoxia stress on the [...] Read more.

Crassostrea hongkongensis (C. hongkongensis) is one of the three most commonly cultivated oyster species in China. Seasonal hypoxia is one of the most serious threats to its metabolism, reproductive behavior, and survival. To investigate the effects of hypoxia stress on the antioxidant capacity and energy metabolism of C. hongkongensis, the total antioxidant capacity (T-AOC), glycogen content, and enzyme activities (phosphofructokinase, PFK; pyruvate kinase, PK; phosphoenolpyruvate carboxykinase, PEPCK) of oysters were determined under normoxic (DO 6 ± 0.2 mg/L) and hypoxic (DO 1.5 mg/L) conditions at 0 h, 6 h, 48 h, and 72 h. We also determined the T-AOC, glycogen content, and enzyme activities of oysters under reoxygenation (recovered to normoxia for 24 h). To further examine the potential molecular regulatory mechanism of hypoxic adaptation, a transcriptome analysis was conducted on the gill of C. hongkongensis under normoxia (N, 72 h), hypoxia (H, 72 h), and reoxygenation (R). After being exposed to hypoxia for 6 h, the T-AOC, glycogen content, and enzyme activities of PK, PFK, and PEPCK in C. hongkongensis were significantly decreased. However, after prolonging the duration of hypoxia exposure for 72 h, the T-AOC, glycogen content, and enzyme activities increased compared to that of 48 h. After 24 h reoxygenation, the T-AOC, glycogen content, and enzyme activity of PK and PFK returned to close to initial levels. In addition, a transcriptome analysis discovered 6097 novel genes by mapping the C. hongkongensis genome with the clean reads. In total, 352 differentially expressed genes (DEGs) were identified in the H vs. N comparison group (235 upregulated and 117 downregulated genes). After recovery to normoxia, 292 DEGs (134 upregulated and 158 downregulated genes) were identified in the R vs. N comparison group, and 632 DEGs were identified (253 upregulated and 379 downregulated genes) in the R vs. H comparison group. The DEGs included some hypoxia-tolerant genes, such as phosphoenolpyruvate carboxykinase (PEPCK), mitochondrial (AOX), tyramine beta-hydroxylase (TBH), superoxide dismutase (SOD), glutathione S-transferase (GST), and egl nine homolog 1 isoform X2 (EGLN1). Additionally, DEGs were significantly enriched in the KEGG pathways that are involved in hypoxia tolerance, including the metabolism of xenobiotics by cytochrome P450 pathways and the HIF-1 signaling pathway. Then, we selected the five hypoxic-tolerant candidate DEGs for real-time quantitative polymerase chain reaction (RT-qPCR) validation, and the results were consistent with the transcriptome sequencing data. These discoveries have increased our understanding of hypoxia tolerance, recovery ability after reoxygenation, and molecular mechanisms governing the responses to hypoxia in C. hongkongensis. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Aquaculture)

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21 pages, 1764 KiB

Open AccessSystematic Review

Redox Homeostasis, Gut Microbiota, and Epigenetics in Neurodegenerative Diseases: A Systematic Review

by Constantin Munteanu, Anca Irina Galaction, Marius Turnea, Corneliu Dan Blendea, Mariana Rotariu and Mădălina Poștaru

Antioxidants 2024, 13(9), 1062; https://doi.org/10.3390/antiox13091062 - 30 Aug 2024

Viewed by 370

Abstract

Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead [...] Read more.

Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead to severe cognitive and motor deficits. A critical component of neurodegenerative disease pathologies is the imbalance between pro-oxidant and antioxidant mechanisms, culminating in oxidative stress. The brain’s high oxygen consumption and lipid-rich environment make it particularly vulnerable to oxidative damage. Pro-oxidants such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) are continuously generated during normal metabolism, counteracted by enzymatic and non-enzymatic antioxidant defenses. In neurodegenerative diseases, this balance is disrupted, leading to neuronal damage. This systematic review explores the roles of oxidative stress, gut microbiota, and epigenetic modifications in neurodegenerative diseases, aiming to elucidate the interplay between these factors and identify potential therapeutic strategies. We conducted a comprehensive search of articles published in 2024 across major databases, focusing on studies examining the relationships between redox homeostasis, gut microbiota, and epigenetic changes in neurodegeneration. A total of 161 studies were included, comprising clinical trials, observational studies, and experimental research. Our findings reveal that oxidative stress plays a central role in the pathogenesis of neurodegenerative diseases, with gut microbiota composition and epigenetic modifications significantly influencing redox balance. Specific bacterial taxa and epigenetic markers were identified as potential modulators of oxidative stress, suggesting novel avenues for therapeutic intervention. Moreover, recent evidence from human and animal studies supports the emerging concept of targeting redox homeostasis through microbiota and epigenetic therapies. Future research should focus on validating these targets in clinical settings and exploring the potential for personalized medicine strategies based on individual microbiota and epigenetic profiles. Full article

(This article belongs to the Special Issue The Interplay of Oxidative Stress, the Gut–Brain Axis, and Neurodegenerative Diseases)

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19 pages, 3293 KiB

Open AccessArticle

Gut Microbiota-Derived Trimethylamine Promotes Inflammation with a Potential Impact on Epigenetic and Mitochondrial Homeostasis in Caco-2 Cells

by Laura Bordoni, Irene Petracci, Giulia Feliziani, Gaia de Simone, Chiara Rucci and Rosita Gabbianelli

Antioxidants 2024, 13(9), 1061; https://doi.org/10.3390/antiox13091061 - 30 Aug 2024

Viewed by 399

Abstract

Trimethylamine (TMA), a byproduct of gut microbiota metabolism from dietary precursors, is not only the precursor of trimethylamine-N-oxide (TMAO) but may also affect gut health. An in vitro model of intestinal epithelium of Caco-2 cells was used to evaluate the impact of TMA [...] Read more.

Trimethylamine (TMA), a byproduct of gut microbiota metabolism from dietary precursors, is not only the precursor of trimethylamine-N-oxide (TMAO) but may also affect gut health. An in vitro model of intestinal epithelium of Caco-2 cells was used to evaluate the impact of TMA on inflammation, paracellular permeability, epigenetics and mitochondrial functions. The expression levels of pro-inflammatory cytokines (IL-6, IL-1β) increased significantly after 24 h exposure to TMA 1 mM. TMA exposure was associated with an upregulation of SIRT1 (TMA 1 mM, 400 μM, 10 μM) and DNMT1 (TMA 1 mM, 400 µM) genes, while DNMT3A expression decreased (TMA 1 mM). In a cell-free model, TMA (from 0.1 µM to 1 mM) induced a dose-dependent reduction in Sirtuin enzyme activity. In Caco-2 cells, TMA reduced total ATP levels and significantly downregulated ND6 expression (TMA 1 mM). TMA excess (1 mM) reduced intracellular mitochondrial DNA copy numbers and increased the methylation of the light-strand promoter in the D-loop area of mtDNA. Also, TMA (1 mM, 400 µM, 10 µM) increased the permeability of Caco-2 epithelium, as evidenced by the reduced transepithelial electrical resistance values. Based on our preliminary results, TMA excess might promote inflammation in intestinal cells and disturb epigenetic and mitochondrial homeostasis. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases 4th Edition)

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37 pages, 2485 KiB

Open AccessReview

The Antitumour Mechanisms of Carotenoids: A Comprehensive Review

by Andrés Baeza-Morales, Miguel Medina-García, Pascual Martínez-Peinado, Sandra Pascual-García, Carolina Pujalte-Satorre, Ana Belén López-Jaén, Rosa María Martínez-Espinosa and José Miguel Sempere-Ortells

Antioxidants 2024, 13(9), 1060; https://doi.org/10.3390/antiox13091060 - 30 Aug 2024

Viewed by 529

Abstract

Carotenoids, known for their antioxidant properties, have garnered significant attention for their potential antitumour activities. This comprehensive review aims to elucidate the diverse mechanisms by which carotenoids exert antitumour effects, focusing on both well-established and novel findings. We explore their role in inducing [...] Read more.

Carotenoids, known for their antioxidant properties, have garnered significant attention for their potential antitumour activities. This comprehensive review aims to elucidate the diverse mechanisms by which carotenoids exert antitumour effects, focusing on both well-established and novel findings. We explore their role in inducing apoptosis, inhibiting cell cycle progression and preventing metastasis by affecting oncogenic and tumour suppressor proteins. The review also explores the pro-oxidant function of carotenoids within cancer cells. In fact, although their overall contribution to cellular antioxidant defences is well known and significant, some carotenoids can exhibit pro-oxidant effects under certain conditions and are able to elevate reactive oxygen species (ROS) levels in tumoural cells, triggering mitochondrial pathways that would lead to cell death. The final balance between their antioxidant and pro-oxidant activities depends on several factors, including the specific carotenoid, its concentration and the redox environment of the cell. Clinical trials are discussed, highlighting the conflicting results of carotenoids in cancer treatment and the importance of personalized approaches. Emerging research on rare carotenoids like bacterioruberin showcases their superior antioxidant capacity and selective cytotoxicity against aggressive cancer subtypes, such as triple-negative breast cancer. Future directions include innovative delivery systems, novel combinations and personalized treatments, aiming to enhance the therapeutic potential of carotenoids. This review highlights the promising yet complex landscape of carotenoid-based cancer therapies, calling for continued research and clinical exploration. Full article

(This article belongs to the Special Issue Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Cancer)

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26 pages, 4809 KiB

Open AccessArticle

Valorizing Tea Waste: Green Synthesis of Iron Nanoparticles for Efficient Dye Removal from Water

by Cristina Rodríguez-Rasero, María F. Alexandre-Franco, Carmen Fernández-González, Vicente Montes-Jiménez and Eduardo M. Cuerda-Correa

Antioxidants 2024, 13(9), 1059; https://doi.org/10.3390/antiox13091059 - 30 Aug 2024

Viewed by 276

Abstract

This study explores the valorization of tea leaf waste by extracting polyphenols through reflux extraction, subsequently using them to synthesize zero-valent iron nanoparticles (nZVI). The in situ generated nanoparticles, when combined with fixed amounts of hydrogen peroxide, facilitated the removal of various dyes [...] Read more.

This study explores the valorization of tea leaf waste by extracting polyphenols through reflux extraction, subsequently using them to synthesize zero-valent iron nanoparticles (nZVI). The in situ generated nanoparticles, when combined with fixed amounts of hydrogen peroxide, facilitated the removal of various dyes (methylene blue, methyl orange, and orange G) via a hetero-catalytic Fenton process. The iron nanoparticles were thoroughly characterized by gas adsorption of N₂ at 77 K, scanning electron microscopy (SEM), Transmission Electron Microscopy (TEM), FT-IR spectroscopy, X-ray diffraction (XRD), and thermal analysis, including thermogravimetric analysis (TG) and temperature-programmed reduction (TPR). A statistical design of experiments and response surface methodology were employed to analyze the influence of polyphenol, Fe(III), and H₂O₂ concentrations on dye removal efficiency. The results demonstrated that optimizing the operational conditions could achieve 100% dye removal efficiency. This study highlights the potential of nZVI synthesized through eco-friendly methods as a promising solution for water decontamination involving diverse model dyes, thus contributing to sustainable waste management and environmental protection. Full article

(This article belongs to the Special Issue Antioxidant Properties and Applications of Food By-Products)

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31 pages, 1133 KiB

Open AccessReview

Oxidative State in Cutaneous Melanoma Progression: A Question of Balance

by Mascia Benedusi, Heaji Lee, Yunsook Lim and Giuseppe Valacchi

Antioxidants 2024, 13(9), 1058; https://doi.org/10.3390/antiox13091058 - 30 Aug 2024

Viewed by 373

Abstract

Reactive oxygen species (ROS) are highly bioactive molecules involved not only in tissue physiology but also in the development of different human conditions, including premature aging, cardiovascular pathologies, neurological and neurodegenerative disorders, inflammatory diseases, and cancer. Among the different human tumors, cutaneous melanoma, [...] Read more.

Reactive oxygen species (ROS) are highly bioactive molecules involved not only in tissue physiology but also in the development of different human conditions, including premature aging, cardiovascular pathologies, neurological and neurodegenerative disorders, inflammatory diseases, and cancer. Among the different human tumors, cutaneous melanoma, the most aggressive and lethal form of skin cancer, is undoubtedly one of the most well-known “ROS-driven tumor”, of which one of the main causes is represented by ultraviolet (UV) rays’ exposure. Although the role of excessive ROS production in melanoma development in pro-tumorigenic cell fate is now well established, little is known about its contribution to the progression of the melanoma metastatic process. Increasing evidence suggests a dual role of ROS in melanoma progression: excessive ROS production may enhance cellular growth and promote therapeutic resistance, but at the same time, it can also have cytotoxic effects on cancer cells, inducing their apoptosis. In this context, the aim of the present work was to focus on the relationship between cell redox state and the signaling pathways directly involved in the metastatic processes. In addition, oxidative or antioxidant therapeutic strategies for metastatic melanoma were also reviewed and discussed. Full article

(This article belongs to the Special Issue Oxidative Stress and Redox Regulation in Chronic Inflammatory Disorders)

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14 pages, 6218 KiB

Open AccessArticle

Sodium Houttuybonate Promotes the Browning of White Adipose Tissue by Inhibiting Ferroptosis via the AMPK-NRF2-HO1 Pathway

by Wenhui Liu, Huren Zou, Danming You, Huijie Zhang and Lingling Xu

Antioxidants 2024, 13(9), 1057; https://doi.org/10.3390/antiox13091057 - 30 Aug 2024

Viewed by 275

Abstract

The rising prevalence of obesity has resulted in an increased demand for innovative and effective treatment strategies. Houttuynia cordata Thunb. (H. cordata) has demonstrated promising potential in preventing obesity. However, the mechanism underlying the anti-obesity effects of H. cordata and its bioactive component, [...] Read more.

The rising prevalence of obesity has resulted in an increased demand for innovative and effective treatment strategies. Houttuynia cordata Thunb. (H. cordata) has demonstrated promising potential in preventing obesity. However, the mechanism underlying the anti-obesity effects of H. cordata and its bioactive component, sodium houttuybonate (SH), remains unclear. Our study reveals that SH treatment promotes the browning of inguinal white adipose tissue (iWAT) and prevents the obesity induced by a high-fat diet. SH significantly mitigates ferroptosis by upregulating glutathione peroxidase 4 (Gpx4) and decreasing malondialdehyde (MDA) levels, while also enhancing superoxide dismutase (SOD) levels. Furthermore, SH promotes the phosphorylation of AMP-activated protein kinase (AMPK), which subsequently increases the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) in the iWAT. However, the effects of SH were attenuated by ML385, an Nrf2 inhibitor. Collectively, our findings suggest that SH induces iWAT browning and prevents diet-induced obesity primarily through the AMPK/NRF2/HO-1 pathway by inhibiting ferroptosis. Full article

(This article belongs to the Special Issue Antioxidant Therapy for Obesity-Related Diseases)

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13 pages, 2343 KiB

Open AccessArticle

Phytochemical-Based Nanoantioxidants Stabilized with Polyvinylpyrrolidone for Enhanced Antibacterial, Antioxidant, and Anti-Inflammatory Activities

by Hyeryeon Oh, Jin Sil Lee, Hyojung Park, Panmo Son, Byoung Seung Jeon, Sang Soo Lee, Daekyung Sung, Jong-Min Lim and Won Il Choi

Antioxidants 2024, 13(9), 1056; https://doi.org/10.3390/antiox13091056 - 30 Aug 2024

Viewed by 303

Abstract

Despite the inhibitory effect of phytoncide (Pht) on food-borne pathogenic bacterial growth, the hydrophobic nature and susceptibility to biodegradation under physiological conditions limits its applications. Here, we developed Pht-loaded polyvinylpyrrolidone (PVP) micelles (Pht@PVP MC) via micelle packing. Pht was solubilized using different types [...] Read more.

Despite the inhibitory effect of phytoncide (Pht) on food-borne pathogenic bacterial growth, the hydrophobic nature and susceptibility to biodegradation under physiological conditions limits its applications. Here, we developed Pht-loaded polyvinylpyrrolidone (PVP) micelles (Pht@PVP MC) via micelle packing. Pht was solubilized using different types of PVP as micellar vehicles. The as-prepared Pht@PVP MCs were characterized using dynamic light scattering and transmission electron microscopy. The sizes of the Pht@PVP MCs were controlled from 301 ± 51 to 80 ± 3 nm by adjusting the PVP content. The polydispersity index of Pht@PVP MC was between 0.21 ± 0.03 and 0.16 ± 0.04, indicating homogeneous size. A colony-counting method was employed to evaluate the improvement in antibacterial activity after Pht encapsulation in PVP micelles. The reactive oxygen species (ROS)-scavenging activity and anti-inflammatory efficacy of Pht@PVP MC were analyzed in a concentration range of 10–100 μg/mL by evaluating in vitro ROS and nitric oxide levels using DCFDA and Griess reagents. PVP with both hydrophobic and hydrophilic moieties improved the aqueous solubility of Pht and stabilized it via steric hindrance. Higher-molecular-weight PVP at higher concentrations resulted in a smaller hydrodynamic diameter of Pht@PVP MC with uniform size distribution. The spherical Pht@PVP MC maintained its size and polydispersity index in a biological buffer for 2 weeks. Pht@PVP MC exhibited enhanced antibacterial activity compared to bare Pht. The growth of Staphylococcus aureus was effectively inhibited by Pht@PVP MC treatment. Furthermore, biocompatible Pht@PVP MC exhibited dose-dependent antioxidant and anti-inflammatory activities in vitro. Overall, Pht@PVP MC is an effective alternative to synthetic antibacterial, antioxidant, and anti-inflammatory chemicals. Full article

(This article belongs to the Special Issue Nanoantioxidants―3rd Edition)

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20 pages, 5278 KiB

Open AccessArticle

Priming of Exogenous Salicylic Acid under Field Conditions Enhances Crop Yield through Resistance to Magnaporthe oryzae by Modulating Phytohormones and Antioxidant Enzymes

by Wannaporn Thepbandit, Anake Srisuwan and Dusit Athinuwat

Antioxidants 2024, 13(9), 1055; https://doi.org/10.3390/antiox13091055 - 30 Aug 2024

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Abstract

This study explores the impact of exogenous salicylic acid (SA) alongside conventional treatment by farmers providing positive (Mancozeb 80 % WP) and negative (water) controls on rice plants (Oryza sativa L.), focusing on antioxidant enzyme activities, phytohormone levels, disease resistance, and yield [...] Read more.

This study explores the impact of exogenous salicylic acid (SA) alongside conventional treatment by farmers providing positive (Mancozeb 80 % WP) and negative (water) controls on rice plants (Oryza sativa L.), focusing on antioxidant enzyme activities, phytohormone levels, disease resistance, and yield components under greenhouse and field conditions. In greenhouse assays, SA application significantly enhanced the activities of peroxidase (POX), polyphenol oxidase (PPO), catalase (CAT), and superoxide dismutase (SOD) within 12–24 h post-inoculation (hpi) with Magnaporthe oryzae. Additionally, SA-treated plants showed higher levels of endogenous SA and indole-3-acetic acid (IAA) within 24 hpi compared to the controls. In terms of disease resistance, SA-treated plants exhibited a reduced severity of rice blast under greenhouse conditions, with a significant decrease in disease symptoms compared to negative control treatment. The field study was extended over three consecutive crop seasons during 2021–2023, further examining the efficacy of SA in regular agricultural practice settings. The SA treatment consistently led to a reduction in rice blast disease severity across all three seasons. Yield-related parameters such as plant height, the number of tillers and panicles per hill, grains per panicle, and 1000-grain weight all showed improvements under SA treatment compared to both positive and negative control treatments. Specifically, SA-treated plants yielded higher grain outputs in all three crop seasons, underscoring the potential of SA as a growth enhancer and as a protective agent against rice blast disease under both controlled and field conditions. These findings state the broad-spectrum benefits of SA application in rice cultivation, highlighting its role not only in bolstering plant defense mechanisms and growth under greenhouse conditions but also in enhancing yield and disease resistance in field settings across multiple crop cycles. This research presents valuable insights into the practical applications of SA in improving rice plant resilience and productivity, offering a promising approach for sustainable agriculture practices. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defense in Plants)

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Antioxidants, Volume 13, Issue 9 (September 2024) – 59 articles

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