Antioxidants

20 pages, 6506 KiB

Open AccessArticle

Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression

by Cristina Fernández-Mendívil, Miguel A. Arreola, Lindsay A. Hohsfield, Kim N. Green and Manuela G. Lopez

Antioxidants 2020, 9(7), 644; https://doi.org/10.3390/antiox9070644 - 21 Jul 2020

Cited by 21 | Viewed by 4152

Abstract

Neuroinflammation and oxidative stress are being recognized as characteristic hallmarks in many neurodegenerative diseases, especially those that portray proteinopathy, such as Alzheimer’s disease (AD). Heme-oxygenase 1 (HO-1) is an inducible enzyme with antioxidant and anti-inflammatory properties, while microglia are the immune cells in [...] Read more.

Neuroinflammation and oxidative stress are being recognized as characteristic hallmarks in many neurodegenerative diseases, especially those that portray proteinopathy, such as Alzheimer’s disease (AD). Heme-oxygenase 1 (HO-1) is an inducible enzyme with antioxidant and anti-inflammatory properties, while microglia are the immune cells in the central nervous system. To elucidate the brain expression profile of microglial HO-1 in aging and AD-progression, we have used the 5xFAD (five familial AD mutations) mouse model of AD and their littermates at different ages (four, eight, 12, and 18 months). Total brain expression of HO-1 was increased with aging and such increase was even higher in 5xFAD animals. In co-localization studies, HO-1 expression was mainly found in microglia vs. other brain cells. The percentage of microglial cells expressing HO-1 and the amount of HO-1 expressed within microglia increased progressively with aging. Furthermore, this upregulation was increased by 2–3-fold in the elder 5xFAD mice. In addition, microglia overexpressing HO-1 was predominately found surrounding beta-amyloid plaques. These results were corroborated using postmortem brain samples from AD patients, where microglial HO-1 was found up-regulated in comparison to brain samples from aged matched non-demented patients. This study demonstrates that microglial HO-1 expression increases with aging and especially with AD progression, highlighting HO-1 as a potential biomarker or therapeutic target for AD. Full article

(This article belongs to the Special Issue Pharmacological and Clinical Significance of Heme Oxygenase-1)

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16 pages, 3136 KiB

Open AccessArticle

Lycopene Protects against Smoking-Induced Lung Cancer by Inducing Base Excision Repair

by Junrui Cheng, Baxter Miller, Emilio Balbuena and Abdulkerim Eroglu

Antioxidants 2020, 9(7), 643; https://doi.org/10.3390/antiox9070643 - 21 Jul 2020

Cited by 33 | Viewed by 4814

Abstract

Background: Oxidative stress plays a critical role in lung cancer progression. Carotenoids are efficient antioxidants. The objective of this study was to explore the efficacy of all-trans retinoic acid (ATRA) and carotenoids in cigarette smoke-induced oxidative stress within A549 human lung cancer epithelial [...] Read more.

Background: Oxidative stress plays a critical role in lung cancer progression. Carotenoids are efficient antioxidants. The objective of this study was to explore the efficacy of all-trans retinoic acid (ATRA) and carotenoids in cigarette smoke-induced oxidative stress within A549 human lung cancer epithelial cells. Methods: A549 cells were pretreated with 1-nM, 10-nM, 100-nM, 1-μM and 10-μM ATRA, β-carotene (BC) and lycopene for 24 h, followed by exposure to cigarette smoke using a smoking chamber. Results: The OxyBlot analysis showed that smoking significantly increased oxidative stress, which was inhibited by lycopene at 1 nM and 10 nM (p < 0.05). In the cells exposed to smoke, lycopene increased 8-oxoguanine DNA glycosylase (OGG1) expression at 1 nM, 10 nM, 100 nM, and 1 μM (p < 0.05), but not at 10 μM. Lycopene at lower doses also improved Nei like DNA glycosylases (NEIL1, NEIL2, NEIL3), and connexin-43 (Cx43) protein levels (p < 0.05). Interestingly, lycopene at lower concentrations promoted OGG1 expression within the cells exposed to smoke to an even greater extent than the cells not exposed to smoke (p < 0.01). This may be attributed to the increased SR-B1 mRNA levels with cigarette smoke exposure (p < 0.05). Conclusions: Lycopene treatment at a lower dosage could inhibit smoke-induced oxidative stress and promote genome stability. These novel findings will shed light on the molecular mechanism of lycopene action against lung cancer. Full article

(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)

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20 pages, 2585 KiB

Open AccessArticle

Unraveling the Lipidome and Antioxidant Activity of Native Bifurcaria bifurcata and Invasive Sargassum muticum Seaweeds: A Lipid Perspective on How Systemic Intrusion May Present an Opportunity

by Fábio Santos, João P. Monteiro, Daniela Duarte, Tânia Melo, Diana Lopes, Elisabete da Costa and Maria Rosário Domingues

Antioxidants 2020, 9(7), 642; https://doi.org/10.3390/antiox9070642 - 21 Jul 2020

Cited by 26 | Viewed by 3239

Abstract

Brown seaweeds are known to present components with appealing bioactive properties eliciting great interest for industrial applications. However, their lipid content is generally disregarded beyond their fatty acid (FA) composition. This study thoroughly characterized the lipid profile of two brown seaweeds collected from [...] Read more.

Brown seaweeds are known to present components with appealing bioactive properties eliciting great interest for industrial applications. However, their lipid content is generally disregarded beyond their fatty acid (FA) composition. This study thoroughly characterized the lipid profile of two brown seaweeds collected from Portuguese coast, the native Bifurcaria bifurcata and the invasive Sargassum muticum species, and bioprospecting for antioxidant activity. An integrated state-of-the-art approach including gas chromatography-mass spectrometry (GC–MS) and liquid chromatography-mass spectrometry (HILIC–ESI-MS/MS), allowed a comprehensive picture of FA and polar lipid content. Polar lipid profile of B. bifurcata and S. muticum included 143 and 217 lipid species respectively, distributed between glycolipids, phospholipids, and betaine lipids. Some of the lipid species found have been assigned biological activity and contain of n-3 and n-6 FA. Sargassum muticum presented the highest n-3 FA content. Low concentrations of extracts of both seaweeds displayed antioxidant activity, with S. muticum presenting more promising results. These findings contribute to the nutritional and industrial exploitation of both seaweeds, highlighting their relevance as viable sources of bioactive and added-value compounds. Sargassum muticum presented interesting lipid composition and bioactivity, which may represent an accessible opportunity for the exploitation of this invasive seaweed, especially taking advantage of Sargassum blooms. Full article

(This article belongs to the Special Issue Bioactive Extract Derived Marine Algae in Antioxidants)

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20 pages, 1038 KiB

Open AccessEditor’s ChoiceReview

Redox Imbalances in Ageing and Metabolic Alterations: Implications in Cancer and Cardiac Diseases. An Overview from the Working Group of Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology (SIC)

by Valentina Mercurio, Alessandra Cuomo, Christian Cadeddu Dessalvi, Martino Deidda, Daniela Di Lisi, Giuseppina Novo, Roberta Manganaro, Concetta Zito, Ciro Santoro, Pietro Ameri, Paolo Spallarossa, Eleonora Arboscello, Carlo Gabriele Tocchetti and Claudia Penna

Antioxidants 2020, 9(7), 641; https://doi.org/10.3390/antiox9070641 - 21 Jul 2020

Cited by 24 | Viewed by 3780

Abstract

Metabolic syndrome (MetS) is a well established risk factor for cardiovascular (CV) diseases. In addition, several studies indicate that MetS correlates with the increased risk of cancer in adults. The mechanisms linking MetS and cancer are not fully understood. Several risk factors involved [...] Read more.

Metabolic syndrome (MetS) is a well established risk factor for cardiovascular (CV) diseases. In addition, several studies indicate that MetS correlates with the increased risk of cancer in adults. The mechanisms linking MetS and cancer are not fully understood. Several risk factors involved in MetS are also cancer risk factors, such as the consumption of high calorie-food or high fat intake, low fibre intake, and sedentary lifestyle. Other common aspects of both cancer and MetS are oxidative stress and inflammation. In addition, some anticancer treatments can induce cardiotoxicity, including, for instance, left ventricular (LV) dysfunction and heart failure (HF), endothelial dysfunction and hypertension. In this review, we analyse several aspects of MetS, cancer and cardiotoxicity from anticancer drugs. In particular, we focus on oxidative stress in ageing, cancer and CV diseases, and we analyse the connections among CV risk factors, cancer and cardiotoxicity from anticancer drugs. Full article

(This article belongs to the Special Issue Redox and Nitrosative Signaling and Stress)

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15 pages, 3385 KiB

Open AccessArticle

The Interaction between Mitochondrial Oxidative Stress and Gut Microbiota in the Cardiometabolic Consequences in Diet-Induced Obese Rats

by Adriana Ortega-Hernández, Ernesto Martínez-Martínez, Ruben Gómez-Gordo, Natalia López-Andrés, Amaya Fernández-Celis, Beatriz Gutiérrrez-Miranda, María Luisa Nieto, Teresa Alarcón, Claudio Alba, Dulcenombre Gómez-Garre and Victoria Cachofeiro

Antioxidants 2020, 9(7), 640; https://doi.org/10.3390/antiox9070640 - 21 Jul 2020

Cited by 23 | Viewed by 3692

Abstract

Background: The objective of this study is to determine the role of mitochondrial oxidative stress in the dysbiosis associated with a high fat diet in rats. In addition, the impact of gut microbiota (GM) in the cardiometabolic consequences of diet-induced obesity in rats [...] Read more.

Background: The objective of this study is to determine the role of mitochondrial oxidative stress in the dysbiosis associated with a high fat diet in rats. In addition, the impact of gut microbiota (GM) in the cardiometabolic consequences of diet-induced obesity in rats has been evaluated. Methods: Male Wistar rats were fed either a high fat diet (HFD) or a control (CT) one for 6 weeks. At the third week, one-half of the animals of each group were treated with the mitochondrial antioxidant MitoTempo (MT; 0.7 mgKg⁻¹day⁻¹ i.p). Results: Animals fed an HFD showed a lower microbiota evenness and diversity in comparison to CT rats. This dysbiosis is characterized by a decrease in Firmicutes/Bacteroidetes ratio and relevant changes at family and genera compared with the CT group. This was accompanied by a reduction in colonic mucin-secreting goblet cells. These changes were reversed by MT treatment. The abundance of certain genera could also be relevant in the metabolic consequences of obesity, as well as in the occurrence of cardiac fibrosis associated with obesity. Conclusions: These results support an interaction between GM and mitochondrial oxidative stress and its relation with development of cardiac fibrosis, suggesting new approaches in the management of obesity-related cardiometabolic consequences. Full article

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

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18 pages, 3055 KiB

Open AccessArticle

Anti-Inflammatory and Antioxidant Effects of Regular Consumption of Cooked Ham Enriched with Dietary Phenolics in Diet-Induced Obese Mice

by Antonio Serrano, Antonio González-Sarrías, Francisco A. Tomás-Barberán, Antonio Avellaneda, Amadeo Gironés-Vilaplana, Gema Nieto and Gaspar Ros-Berruezo

Antioxidants 2020, 9(7), 639; https://doi.org/10.3390/antiox9070639 - 21 Jul 2020

Cited by 7 | Viewed by 2954

Abstract

Oxidative damage and chronic inflammation have been proven as one of the major factors associated with obesity, which increases the incidence of non-communicable chronic diseases. In this sense, the development of new functional products aiming at the palliation of oxidative stress and inflammatory [...] Read more.

Oxidative damage and chronic inflammation have been proven as one of the major factors associated with obesity, which increases the incidence of non-communicable chronic diseases. In this sense, the development of new functional products aiming at the palliation of oxidative stress and inflammatory disruption can be a determining factor for public health as seen in previous researches. In this study, a blend of potentially bioavailable dietary phenolics was added to low sodium and low-fat cooked ham. A diet-induced obesity model in C57/BL6J mice has been used for testing the effectiveness of the phenolic blend and the new functionalized product, which bioavailability was tested by UPLC-ESI-QTOF-MS. After obesity induction, different oxidative and inflammatory biomarkers were evaluated. Results in the murine induced obesity model, demonstrate a robust statistically significant improvement in key parameters related with obesity risk in the groups feed with a phenolic-enriched diets (P) + high-fat diet (HFD) and phenolic enriched cooked ham (PECH) + HFD. In both groups there was an improvement in body composition parameters, inflammatory biomarkers and antioxidant enzymes levels. Specifically in the group feed with the phenolic enriched cooked ham (PECH + HFD) there was an improvement of total fat volume (23.08% reduction), spleen index (22.04% of reduction), plasmatic MCP-1 (18% reduction), IL-6 (38.94% reduction), IL-10 (13.28% reduction), TNF-α (21.32% reduction), gut IL-1β (10.86% reduction), gut IL-6 (13.63% reduction) and GPx (60.15% increase) and catalase (91.37% increase) enzymes. Thus, the functionalized ham could be considered an appropriate dietary polyphenol source, which might improve the oxidative and inflammatory status and could finally result in the potential decrease of the risk of certain non-communicable chronic diseases. Full article

(This article belongs to the Special Issue Antioxidants as Functional Ingredient in Meat)

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22 pages, 1954 KiB

Open AccessReview

Can Meat and Meat-Products Induce Oxidative Stress?

by Adrián Macho-González, Alba Garcimartín, María Elvira López-Oliva, Sara Bastida, Juana Benedí, Gaspar Ros, Gema Nieto and Francisco José Sánchez-Muniz

Antioxidants 2020, 9(7), 638; https://doi.org/10.3390/antiox9070638 - 20 Jul 2020

Cited by 41 | Viewed by 6329

Abstract

High meat and meat-products consumption has been related to degenerative diseases. In addition to their saturated fatty acids and cholesterol contents, oxidation products generated during their production, storage, digestion, and metabolization have been largely implicated. This review begins by summarizing the concept of [...] Read more.

High meat and meat-products consumption has been related to degenerative diseases. In addition to their saturated fatty acids and cholesterol contents, oxidation products generated during their production, storage, digestion, and metabolization have been largely implicated. This review begins by summarizing the concept of meat and meat-products by the main international regulatory agencies while highlighting the nutritional importance of their consumption. The review also dials in the controversy of white/red meat classification and insists in the need of more accurate classification based on adequate scores. Since one of the negative arguments that meat receives comes from the association of its consumption with the increase in oxidative stress, main oxidation compounds (malondialdehyde, thermaloxidized compounds, 4-hydroxy-nonenal, oxysterols, or protein carbonyls) generated during its production, storage, and metabolization, are included as a central aspect of the work. The review includes future remarks addressed to study the effects meat consumption in the frame of diet–gene interactions, stressing the importance of knowing the genetic variables that make individuals more susceptible to a possible oxidative stress imbalance or antioxidant protection. The importance of consumed meat/meat-products in the frame of a personalized nutrition reach in plant-food is finally highlighted considering the importance of iron and plant biophenols on the microbiota abundance and plurality, which in turn affect several aspects of our physiology and metabolism. Full article

(This article belongs to the Special Issue Antioxidants as Functional Ingredient in Meat)

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23 pages, 4736 KiB

Open AccessReview

Emerging Strategies to Protect the Skin from Ultraviolet Rays Using Plant-Derived Materials

by Yong Chool Boo

Antioxidants 2020, 9(7), 637; https://doi.org/10.3390/antiox9070637 - 18 Jul 2020

Cited by 48 | Viewed by 9217

Abstract

Sunlight contains a significant amount of ultraviolet (UV) ray, which leads to various effects on homeostasis in the body. Defense strategies to protect from UV rays have been extensively studied, as sunburn, photoaging, and photocarcinogenesis are caused by excessive UV exposure. The primary [...] Read more.

Sunlight contains a significant amount of ultraviolet (UV) ray, which leads to various effects on homeostasis in the body. Defense strategies to protect from UV rays have been extensively studied, as sunburn, photoaging, and photocarcinogenesis are caused by excessive UV exposure. The primary lines of defense against UV damage are melanin and trans-urocanic acid, which are distributed in the stratum corneum. UV rays that pass beyond these lines of defense can lead to oxidative damage. However, cells detect changes due to UV rays as early as possible and initiate cell signaling processes to prevent the occurrence of damage and repair the already occurred damage. Cosmetic and dermatology experts recommend using a sunscreen product to prevent UV-induced damage. A variety of strategies using antioxidants and anti-inflammatory agents have also been developed to complement the skin’s defenses against UV rays. Researchers have examined the use of plant-derived materials to alleviate the occurrence of skin aging, diseases, and cancer caused by UV rays. Furthermore, studies are also underway to determine how to promote melanin production to protect from UV-induced skin damage. This review provides discussion of the damage that occurs in the skin due to UV light and describes potential defense strategies using plant-derived materials. This review aims to assist researchers in understanding the current research in this area and to potentially plan future studies. Full article

(This article belongs to the Special Issue Oxidative Stress and Skin Disease: Genetics, Etiopathogenesis, Possible Therapeutic Approaches of Antioxidant Therapies)

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23 pages, 4164 KiB

Open AccessReview

Genetic Polymorphisms Complicate COVID-19 Therapy: Pivotal Role of HO-1 in Cytokine Storm

by Eddie W. Fakhouri, Stephen J. Peterson, Janish Kothari, Ragin Alex, Joseph I. Shapiro and Nader G. Abraham

Antioxidants 2020, 9(7), 636; https://doi.org/10.3390/antiox9070636 - 18 Jul 2020

Cited by 37 | Viewed by 11257

Abstract

Coronaviruses are very large RNA viruses that originate in animal reservoirs and include severe acute respiratory distress syndrome (SARS) and Middle East respiratory syndrome (MERS) and other inconsequential coronaviruses from human reservoirs like the common cold. SARS-CoV-2, the virus that causes COVID-19 and [...] Read more.

Coronaviruses are very large RNA viruses that originate in animal reservoirs and include severe acute respiratory distress syndrome (SARS) and Middle East respiratory syndrome (MERS) and other inconsequential coronaviruses from human reservoirs like the common cold. SARS-CoV-2, the virus that causes COVID-19 and is believed to originate from bat, quickly spread into a global pandemic. This RNA virus has a special affinity for porphyrins. It invades the cell at the angiotensin converting enzyme-2 (ACE-2) receptor and binds to hemoproteins, resulting in a severe systemic inflammatory response, particularly in high ACE-2 organs like the lungs, heart, and kidney, resulting in systemic disease. The inflammatory response manifested by increased cytokine levels and reactive oxygen species results in inhibition of heme oxygenase (HO-1), with a subsequent loss of cytoprotection. This has been seen in other viral illness like human immunodeficiency virus (HIV), Ebola, and SARS/MERS. There are a number of medications that have been tried with some showing early clinical promise. This illness disproportionately affects patients with obesity, a chronic inflammatory disease with a baseline excess of cytokines. The majority of the medications used in the treatment of COVID-19 are metabolized by cytochrome P450 (CYP) enzymes, primarily CYP2D6. This is further complicated by genetic polymorphisms of CYP2D6, HO-1, ACE, and ACE-2. There is a potential role for HO-1 upregulation to treat/prevent cytokine storm. Current therapy must focus on antivirals and heme oxygenase upregulation. Vaccine development will be the only magic bullet. Full article

(This article belongs to the Special Issue Pharmacological and Clinical Significance of Heme Oxygenase-1)

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25 pages, 327 KiB

Open AccessReview

The Antioxidant Role of Soy and Soy Foods in Human Health

by Gianluca Rizzo

Antioxidants 2020, 9(7), 635; https://doi.org/10.3390/antiox9070635 - 18 Jul 2020

Cited by 37 | Viewed by 6598

Abstract

Oxidative stress seems to play a role in many chronic diseases, such as cardiovascular diseases, diabetes, and some cancers. Research is always looking for effective approaches in the prevention and treatment of these pathologies with safe strategies. Given the central role of nutrition, [...] Read more.

Oxidative stress seems to play a role in many chronic diseases, such as cardiovascular diseases, diabetes, and some cancers. Research is always looking for effective approaches in the prevention and treatment of these pathologies with safe strategies. Given the central role of nutrition, the identification of beneficial healthy foods can be the best key to having a safe and at the same time effective approach. Soy has always aroused great scientific interest but often this attention is galvanized by the interaction with estrogen receptors and related consequences on health. However, soy, soy foods, and soy bioactive substances seem to have antioxidant properties, suggesting their role in quenching reactive oxygen species, although it was frequently mentioned but not studied in depth. The purpose of this review is to summarize the scientific evidence of the antioxidant properties of soy by identifying the human clinical trials available in the literature. A total of 58 manuscripts were individuated through the literature search for the final synthesis. Soy bioactive substances involved in redox processes appear to be multiple and their use seems promising. Other larger clinical trials with adequate standardization and adequate choice of biomarkers will fill the gap currently existing on the suggestive role of soy in antioxidant mechanisms. Full article

(This article belongs to the Special Issue Cellular Oxidative Stress)

14 pages, 287 KiB

Open AccessArticle

Effect of Sechium edule var. nigrum spinosum (Chayote) on Telomerase Levels and Antioxidant Capacity in Older Adults with Metabolic Syndrome

by Graciela Gavia-García, Juana Rosado-Pérez, Itzen Aguiñiga-Sánchez, Edelmiro Santiago-Osorio and Víctor Manuel Mendoza-Núñez

Antioxidants 2020, 9(7), 634; https://doi.org/10.3390/antiox9070634 - 18 Jul 2020

Cited by 5 | Viewed by 3289

Abstract

Patients with metabolic syndrome (MetS) have a redox imbalance, due to a decay in antioxidant capacity. Oxidative stress (OxS) is considered an important modulator of telomere shortening and telomerase activity. One of the fruits that has been associated with an antioxidant effect is [...] Read more.

Patients with metabolic syndrome (MetS) have a redox imbalance, due to a decay in antioxidant capacity. Oxidative stress (OxS) is considered an important modulator of telomere shortening and telomerase activity. One of the fruits that has been associated with an antioxidant effect is Sechium edule and although its properties are well established, there is only one exploratory study evaluating its effectiveness in patients with MetS. The present investigation is a much more robust and controlled study, including a placebo group. Hence, we determined the effect of consumption of the dried fruit powder (500 mg, three times per day) for three months. We measured effects on telomerase levels, antioxidant capacity, and markers for OxS. The study was performed in a sample of 75 older adults: placebo group (n = 30) and experimental group (n = 45) with the diagnosis of MetS according to the National Adult Treatment Panel of the National Cholesterol Program III (NCEP/ATP III) criteria. All markers were measured before and after three months of treatment. There was a statistically significant decrease in lipoperoxides and protein carbonylation with an increased superoxide dismutase (SOD), as well as sustained levels of telomerase in patients who consumed Sechium edule. Our findings suggest that consumption of this fruit has a hypoglycemic, hypotensive, and antioxidant effect, without altering telomerase levels, which could suggest better protection against telomere shortening. Full article

19 pages, 3650 KiB

Open AccessArticle

Targeting the MAPK/ERK and PI3K/AKT Signaling Pathways Affects NRF2, Trx and GSH Antioxidant Systems in Leukemia Cells

by Ewa Jasek-Gajda, Halina Jurkowska, Małgorzata Jasińska and Grzegorz J. Lis

Antioxidants 2020, 9(7), 633; https://doi.org/10.3390/antiox9070633 - 17 Jul 2020

Cited by 44 | Viewed by 7117

Abstract

The mitogen-activated protein kinase (MAPK)/extracellular signal kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signal transduction pathways have been implicated in the pathogenesis of leukemia. The aim of this study was to investigate the effect of the combination of ERK1/2 inhibitor AZD0364 [...] Read more.

The mitogen-activated protein kinase (MAPK)/extracellular signal kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signal transduction pathways have been implicated in the pathogenesis of leukemia. The aim of this study was to investigate the effect of the combination of ERK1/2 inhibitor AZD0364 and PI3K inhibitor ZSTK474 on acute lymphoblastic leukemia (ALL) REH, MOLT-4, acute myeloid leukemia (AML) MOLM-14, and chronic myeloid leukemia (CML) K562 cell lines. To evaluate the interactions of the drugs, cells were treated for 48 h with AZD0364 or ZSTK474 alone and in combination at fixed ratios. The combinatorial effects of both inhibitors were synergistic over a wide range of concentrations in REH, MOLT-4, and MOLM-14 cell lines. However, in K562 cells, the effects were found to be antagonistic. Furthermore, AZD0364 and ZSTK474 significantly decreased both ERK1/2 and AKT activation in REH, MOLT-4, and MOLM-14 cells. The results showed that incubation with both AZD0364 and ZSTK474 inhibited cell viability, increased reactive oxygen species (ROS) production, and induced apoptosis in leukemia cells. We observed that combined treatment with AZD0364 and ZSTK474 affected nuclear factor-κB (NF-κB) and antioxidant protein levels: NF-E2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), thioredoxin (Trx), thioredoxin reductase (TrxR), and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio. These effects were accompanied with decreased antiapoptotic survivin protein level. However, distinct cell line dependent effects were observed. In conclusion, the combination of AZD0364 and ZSTK474 can exert a synergistic anticancer effect in ALL and AML cells, which is associated with the induction of oxidative stress and the involvement of cellular antioxidant defense mechanisms. Full article

(This article belongs to the Special Issue Feature Papers in Antioxidants in 2020)

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18 pages, 2090 KiB

Open AccessArticle

Effects of Processing on Polyphenolic and Volatile Composition and Fruit Quality of Clery Strawberries

by Stefania Garzoli, Francesco Cairone, Simone Carradori, Andrei Mocan, Luigi Menghini, Patrizia Paolicelli, Gunes Ak, Gokhan Zengin and Stefania Cesa

Antioxidants 2020, 9(7), 632; https://doi.org/10.3390/antiox9070632 - 17 Jul 2020

Cited by 14 | Viewed by 2928

Abstract

Strawberries belonging to cultivar Clery (Fragaria x ananassa (Duchesne ex Weston)), cultivated in central Italy were subjected to a multi-methodological experimental study. Fresh and defrosted strawberries were exposed to different processing methods, such as homogenization, thermal and microwave treatments. The homogenate samples [...] Read more.

Strawberries belonging to cultivar Clery (Fragaria x ananassa (Duchesne ex Weston)), cultivated in central Italy were subjected to a multi-methodological experimental study. Fresh and defrosted strawberries were exposed to different processing methods, such as homogenization, thermal and microwave treatments. The homogenate samples were submitted to CIEL*a*b* color analysis and Head-Space GC/MS analysis to determine the impact of these procedures on phytochemical composition. Furthermore, the corresponding strawberry hydroalcoholic extracts were further analyzed by HPLC-DAD for secondary metabolites quantification and by means of spectrophotometric in vitro assays to evaluate their total phenolic and total flavonoid contents and antioxidant activity. These chemical investigations confirmed the richness in bioactive metabolites supporting the extraordinary healthy potential of this fruit as a food ingredient, as well as functional food, highlighting the strong influence of the processing steps which could negatively impact on the polyphenol composition. Despite a more brilliant red color and aroma preservation, non-pasteurized samples were characterized by a lower content of polyphenols and antioxidant activity with respect to pasteurized samples, as also suggested by the PCA analysis of the collected data. Full article

(This article belongs to the Special Issue The Potential of Dietary Antioxidants)

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26 pages, 2633 KiB

Open AccessReview

Potential Role of Phenolic Extracts of Mentha in Managing Oxidative Stress and Alzheimer’s Disease

by Doaa M. Hanafy, Geoffrey E. Burrows, Paul D. Prenzler and Rodney A. Hill

Antioxidants 2020, 9(7), 631; https://doi.org/10.3390/antiox9070631 - 17 Jul 2020

Cited by 11 | Viewed by 4832

Abstract

With an increase in the longevity and thus the proportion of the elderly, especially in developed nations, there is a rise in pathological conditions that accompany ageing, such as neurodegenerative disorders. Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive and [...] Read more.

With an increase in the longevity and thus the proportion of the elderly, especially in developed nations, there is a rise in pathological conditions that accompany ageing, such as neurodegenerative disorders. Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive and memory decline. The pathophysiology of the disease is poorly understood, with several factors contributing to its development, such as oxidative stress, neuroinflammation, cholinergic neuronal apoptotic death, and the accumulation of abnormal proteins in the brain. Current medications are only palliative and cannot stop or reverse the progression of the disease. Recent clinical trials of synthetic compounds for the treatment of AD have failed because of their adverse effects or lack of efficacy. Thus, there is impetus behind the search for drugs from natural origins, in addition to the discovery of novel, conventional therapeutics. Mints have been used traditionally for conditions relevant to the central nervous system. Recent studies showed that mint extracts and/or their phenolic constituents have a neuroprotective potential and can target multiple events of AD. In this review, we provide evidence of the potential role of mint extracts and their derivatives as possible sources of treatments in managing AD. Some of the molecular pathways implicated in the development of AD are reviewed, with focus on apoptosis and some redox pathways, pointing to mechanisms that may be modulated for the treatment of AD, and the need for future research invoking knowledge of these pathways is highlighted. Full article

(This article belongs to the Special Issue Oxidative Stress and Neurodegenerative Disorders)

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15 pages, 3042 KiB

Open AccessReview

Antioxidant and Anti-inflammatory Effect of Nrf2 Inducer Dimethyl Fumarate in Neurodegenerative Diseases

by Sarah A. Scuderi, Alessio Ardizzone, Irene Paterniti, Emanuela Esposito and Michela Campolo

Antioxidants 2020, 9(7), 630; https://doi.org/10.3390/antiox9070630 - 17 Jul 2020

Cited by 69 | Viewed by 5697

Abstract

Neurodegenerative diseases (NDs) represents debilitating conditions characterized by degeneration of neuronal cells in specific brain areas, causing disability and death in patients. In the pathophysiology of NDs, oxidative stress, apoptosis and neuroinflammation have a key role, as demonstrated by in vivo and in [...] Read more.

Neurodegenerative diseases (NDs) represents debilitating conditions characterized by degeneration of neuronal cells in specific brain areas, causing disability and death in patients. In the pathophysiology of NDs, oxidative stress, apoptosis and neuroinflammation have a key role, as demonstrated by in vivo and in vitro models. Therefore, the use of molecules with antioxidant and anti-inflammatory activities represents a possible strategy for the treatment of NDs. Many studies demonstrated the beneficial effects of fumaric acid esters (FAEs) to counteract neuroinflammation and oxidative stress. Among these molecules, dimethyl fumarate (DMF) showed a valid therapeutic approach to slow down neurodegeneration and relieve symptoms in patients with NDs. DMF is a methyl ester of fumaric acid and acts as modulator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation. Therefore, this review aims to examine the potential beneficial effects of DMF to counteract oxidative stress and inflammation in patients with NDs. Full article

(This article belongs to the Special Issue Oxidative Stress and Neurodegenerative Disorders)

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18 pages, 2942 KiB

Open AccessArticle

Novel Antioxidant Packaging Films Based on Poly(ε-Caprolactone) and Almond Skin Extract: Development and Effect on the Oxidative Stability of Fried Almonds

by Arantzazu Valdés García, Nerea Juárez Serrano, Ana Beltrán Sanahuja and María Carmen Garrigós

Antioxidants 2020, 9(7), 629; https://doi.org/10.3390/antiox9070629 - 17 Jul 2020

Cited by 21 | Viewed by 3053

Abstract

Antioxidant films based on poly(ε-caprolactone) (PCL) containing almond skin extract (ASE) were developed for food packaging applications. The effect of ASE incorporation on the morphological, structural, colour, mechanical, thermal, barrier and antioxidant properties of the prepared films were evaluated. The structural, tensile and [...] Read more.

Antioxidant films based on poly(ε-caprolactone) (PCL) containing almond skin extract (ASE) were developed for food packaging applications. The effect of ASE incorporation on the morphological, structural, colour, mechanical, thermal, barrier and antioxidant properties of the prepared films were evaluated. The structural, tensile and thermal properties of the films were not altered due to ASE addition. Although no significant differences were observed for the oxygen permeability of samples, some increase in water absorption and water vapour permeability was observed for active films due to the hydrophilic character of ASE phenolic compounds, suggesting the suitability of this novel packaging for fatty foods conservation. ASE conferred antioxidant properties to PCL films as determined by the DPPH radical scavenging activity. The efficiency of the developed films was evaluated by the real packaging application of fried almonds at different ASE contents (0, 3, 6 wt.%) up to 56 days at 40 °C. The evolution of peroxide and p-anisidine values, hexanal content, fatty acid profile and characteristic spectroscopy bands showed that active films improved fried almonds stability. The results suggested the potential of PCL/ASE films as sustainable and antioxidant food packaging systems to offer protection against lipid oxidation in foods. Full article

(This article belongs to the Special Issue Feature Papers in Antioxidants in 2020)

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17 pages, 774 KiB

Open AccessArticle

New Advances in the Determination of Free and Bound Phenolic Compounds of Banana Passion Fruit Pulp (Passiflora tripartita, var. Mollissima (Kunth) L.H. Bailey) and Their In Vitro Antioxidant and Hypoglycemic Capacities

by Elisa Giambanelli, Ana Maria Gómez-Caravaca, Arancha Ruiz-Torralba, Eduardo Jesús Guerra-Hernández, Jorge Geovanny Figueroa-Hurtado, Belén García-Villanova and Vito Verardo

Antioxidants 2020, 9(7), 628; https://doi.org/10.3390/antiox9070628 - 17 Jul 2020

Cited by 17 | Viewed by 3862

Abstract

Banana passion fruit (Passiflora tripartite L.H. Bailey) is a lesser known species of the genus Passiflora. This fruit typically grows in the Andean region of Ecuador and it is locally known as tumbo, taxo or curuba. The juice of this fruit [...] Read more.

Banana passion fruit (Passiflora tripartite L.H. Bailey) is a lesser known species of the genus Passiflora. This fruit typically grows in the Andean region of Ecuador and it is locally known as tumbo, taxo or curuba. The juice of this fruit is highly appreciated in South America. Extracts of banana passion fruit were characterized for their content levels of free and bound phenolic compounds by high performance liquid chromatography coupled to high resolution mass spectrometry detector (HPLC-ESI-TOF-MS). A total of 82 polar compounds classified as phenolic acid derivatives, organic acids, benzophenones, flavan-3-ols, flavonols and flavones were detected in the extracts. The total phenolic content was 2356 mg 100 g⁻¹ dry matter, with the bound phenolic fraction representing 37.7% of total amounts. Flavan-3-ols, such as (epi)catechin, (epi)azfelechin and their derivatives, were the main phenolic compounds in the free phenolic fraction; however, phenolic acids represented the most abundant class of bound phenolic extracts. The antioxidant and hypoglycemic capacities reported for banana passion fruit were higher than for other fruits. To our knowledge, this is the first time that bound phenolic compounds have been described in banana passion fruit pulp. Full article

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14 pages, 3571 KiB

Open AccessArticle

The Herbal Combination CPA4-1 Inhibits Changes in Retinal Capillaries and Reduction of Retinal Occludin in db/db Mice

by Young Sook Kim, Junghyun Kim, Chan-Sik Kim, Ik Soo Lee, Kyuhyung Jo, Dong Ho Jung, Yun Mi Lee and Jin Sook Kim

Antioxidants 2020, 9(7), 627; https://doi.org/10.3390/antiox9070627 - 16 Jul 2020

Cited by 2 | Viewed by 2592

Abstract

Increased formation of advanced glycation end products (AGEs) plays an important role in the development of diabetic retinopathy (DR) via blood-retinal barrier (BRB) dysfunction, and reduction of AGEs has been suggested as a therapeutic target for DR. In this study, we examined whether [...] Read more.

Increased formation of advanced glycation end products (AGEs) plays an important role in the development of diabetic retinopathy (DR) via blood-retinal barrier (BRB) dysfunction, and reduction of AGEs has been suggested as a therapeutic target for DR. In this study, we examined whether CPA4-1, a herbal combination of Cinnamomi Ramulus and Paeoniae Radix, inhibits AGE formation. CPA4-1 and fenofibrate were tested to ameliorate changes in retinal capillaries and retinal occludin expression in db/db mice, a mouse model of obesity-induced type 2 diabetes. CPA4-1 (100 mg/kg) or fenofibrate (100 mg/kg) were orally administered once a day for 12 weeks. CPA4-1 (the half maximal inhibitory concentration, IC₅₀ = 6.84 ± 0.08 μg/mL) showed approximately 11.44-fold higher inhibitory effect on AGE formation than that of aminoguanidine (AG, the inhibitor of AGEs, IC₅₀ = 78.28 ± 4.24 μg/mL), as well as breaking effect on AGE-bovine serum albumin crosslinking with collagen (IC₅₀ = 1.30 ± 0.37 μg/mL). CPA4-1 treatment ameliorated BRB leakage and tended to increase retinal occludin expression in db/db mice. CPA4-1 or fenofibrate treatment significantly reduced retinal acellular capillary formation in db/db mice. These findings suggested the potential of CPA4-1 as a therapeutic supplement for protection against retinal vascular permeability diseases. Full article

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

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17 pages, 2760 KiB

Open AccessArticle

Erythronium japonicum Alleviates Inflammatory Pain by Inhibiting MAPK Activation and by Suppressing NF-κB Activation via ERK/Nrf2/HO-1 Signaling Pathway

by Joon Park and Yun Tai Kim

Antioxidants 2020, 9(7), 626; https://doi.org/10.3390/antiox9070626 - 16 Jul 2020

Cited by 27 | Viewed by 3382

Abstract

Microglial activation-mediated neuroinflammation influences the development of inflammatory pain. The aim of this study was to investigate the anti-inflammatory effects and mechanisms of aqueous Erythronium japonicum extract (EJE) in microglia activation-mediated inflammatory pain. EJE was found to suppress lipopolysaccharide (LPS)-induced inducible nitric oxide [...] Read more.

Microglial activation-mediated neuroinflammation influences the development of inflammatory pain. The aim of this study was to investigate the anti-inflammatory effects and mechanisms of aqueous Erythronium japonicum extract (EJE) in microglia activation-mediated inflammatory pain. EJE was found to suppress lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), ionized calcium-binding adapter molecule 1 (IBA-1), and pro-inflammatory cytokines in BV2 microglial cells. In addition, LPS-induced c-Jun NH₂ terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation were inhibited by EJE. Intriguingly, EJE also inhibited p65 phosphorylation by activating extracellular signal-regulated kinase-1/2 (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Furthermore, the effects of EJE treatment, such as HO-1 induction and the reduction of NF-ĸB activation, were reversed by ERK1/2 inhibition. In an inflammatory pain mouse model, Complete Freund’s Adjuvant (CFA)-induced mechanical allodynia and foot swelling were alleviated by the oral administration of EJE. Consistent with in vitro results, EJE increased HO-1, while decreasing CFA-induced COX-2, IBA-1, and pro-inflammatory cytokines in the spinal cord. Among the components of EJE, butanol most heavily suppressed LPS-induced microglial activation and increased HO-1 expression. These findings indicate that EJE can alleviate inflammatory pain by inhibiting p38 and JNK and by suppressing NF-ĸB via ERK/Nrf2/HO-1 signaling. Full article

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

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21 pages, 2502 KiB

Open AccessReview

Antioxidant Activity in Supramolecular Carotenoid Complexes Favored by Nonpolar Environment and Disfavored by Hydrogen Bonding

by Yunlong Gao, A. Ligia Focsan and Lowell D. Kispert

Antioxidants 2020, 9(7), 625; https://doi.org/10.3390/antiox9070625 - 16 Jul 2020

Cited by 11 | Viewed by 3311

Abstract

Carotenoids are well-known antioxidants. They have the ability to quench singlet oxygen and scavenge toxic free radicals preventing or reducing damage to living cells. We have found that carotenoids exhibit scavenging ability towards free radicals that increases nearly exponentially with increasing the carotenoid [...] Read more.

Carotenoids are well-known antioxidants. They have the ability to quench singlet oxygen and scavenge toxic free radicals preventing or reducing damage to living cells. We have found that carotenoids exhibit scavenging ability towards free radicals that increases nearly exponentially with increasing the carotenoid oxidation potential. With the oxidation potential being an important parameter in predicting antioxidant activity, we focus here on the different factors affecting it. This paper examines how the chain length and donor/acceptor substituents of carotenoids affect their oxidation potentials but, most importantly, presents the recent progress on the effect of polarity of the environment and orientation of the carotenoids on the oxidation potential in supramolecular complexes. The oxidation potential of a carotenoid in a nonpolar environment was found to be higher than in a polar environment. Moreover, in order to increase the photostability of the carotenoids in supramolecular complexes, a nonpolar environment is desired and the formation of hydrogen bonds should be avoided. Full article

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

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16 pages, 986 KiB

Open AccessEditor’s ChoiceReview

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

by Francesca Silvagno, Annamaria Vernone and Gian Piero Pescarmona

Antioxidants 2020, 9(7), 624; https://doi.org/10.3390/antiox9070624 - 16 Jul 2020

Cited by 144 | Viewed by 31567

Abstract

The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease [...] Read more.

The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease has a mild or even asymptomatic progression. A common denominator in all conditions associated with COVID-19 appears to be the impaired redox homeostasis responsible for reactive oxygen species (ROS) accumulation; therefore, levels of glutathione (GSH), the key anti-oxidant guardian in all tissues, could be critical in extinguishing the exacerbated inflammation that triggers organ failure in COVID-19. The present review provides a biochemical investigation of the mechanisms leading to deadly inflammation in severe COVID-19, counterbalanced by GSH. The pathways competing for GSH are described to illustrate the events concurring to cause a depletion of endogenous GSH stocks. Drawing on evidence from literature that demonstrates the reduced levels of GSH in the main conditions clinically associated with severe disease, we highlight the relevance of restoring GSH levels in the attempt to protect the most vulnerable subjects from severe symptoms of COVID-19. Finally, we discuss the current data about the feasibility of increasing GSH levels, which could be used to prevent and subdue the disease. Full article

(This article belongs to the Special Issue ROS and COVID)

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16 pages, 1562 KiB

Open AccessArticle

Synthesis, In Vitro Antioxidant Properties and Distribution of a New Cyanothiophene-Based Phenolic Compound in Olive Oil-In-Water Emulsions

by Sonia Losada-Barreiro, Matej Sova, Janez Mravljak, Luciano Saso and Carlos Bravo-Díaz

Antioxidants 2020, 9(7), 623; https://doi.org/10.3390/antiox9070623 - 16 Jul 2020

Cited by 2 | Viewed by 2381

Abstract

We synthesized and determined the antioxidant activity and distribution of a new cyanothiophene-based compound, N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-3,5-dihydroxybenzamide (SIM-53B), in intact stripped olive oil-in-water emulsion. The in vitro antioxidant properties of SIM-53B were evaluated and compared to those for Trolox and resveratrol. Addition [...] Read more.

We synthesized and determined the antioxidant activity and distribution of a new cyanothiophene-based compound, N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-3,5-dihydroxybenzamide (SIM-53B), in intact stripped olive oil-in-water emulsion. The in vitro antioxidant properties of SIM-53B were evaluated and compared to those for Trolox and resveratrol. Addition of an emulsifier (Tween 20) creates a narrow region, the aqueous–oil interface, and the distribution of SIM-53B can be described by two partition constants: P_W^I (between aqueous/interfacial regions) and P_O^I (between oil/interfacial regions). The effects of emulsifier concentration expressed in terms of the volume fraction, Φ_I, and O/W ratio were also evaluated on its distribution. SIM-53B is predominantly distributed (>90%) in the interfacial region of 1:9 (O/W) olive oil-in-water emulsions at the lowest emulsifier volume fraction (Φ_I = 0.005) and only a small fraction is located in the aqueous (<5%) and the oil (<5%) regions. Besides, the concentration of SIM-53B in the interfacial region of the emulsions is ~170–190-fold higher than the stoichiometric concentration, emphasizing the compartmentalization effects. Results suggest that the emulsifier volume fraction is a key parameter that may modulate significantly its concentration in the interface. Our study suggests that cyanothiophene-based compounds may be interesting additives for potential lipid protection in biomembranes or other lipid-based systems. Full article

(This article belongs to the Special Issue Modulators of Oxidative Stress: Chemical and Pharmacological Aspects 2021)

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19 pages, 2298 KiB

Open AccessArticle

Anti-Inflammatory Effects of Ribes diacanthum Pall Mediated via Regulation of Nrf2/HO-1 and NF-κB Signaling Pathways in LPS-Stimulated RAW 264.7 Macrophages and a TPA-Induced Dermatitis Animal Model

by Na Yeon Kim, Sun Hee Cheong, Kun Jong Lee, Dai-Eun Sok and Mee Ree Kim

Antioxidants 2020, 9(7), 622; https://doi.org/10.3390/antiox9070622 - 15 Jul 2020

Cited by 17 | Viewed by 4921

Abstract

Ribes diacanthum Pall (RDP) is a Mongolian traditional medicine used to treat renal inflammation. In the present study, we initially investigated the anti-inflammatory effects and mechanisms of action of ethylacetate extract of RDP (EARDP) in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS) and [...] Read more.

Ribes diacanthum Pall (RDP) is a Mongolian traditional medicine used to treat renal inflammation. In the present study, we initially investigated the anti-inflammatory effects and mechanisms of action of ethylacetate extract of RDP (EARDP) in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermatitis in mice. We demonstrated that EARDP protected against LPS-induced cell death by inhibiting intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) production, as well as the synthesis of pro-inflammatory mediators and cytokines, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β. EARDP inhibited the phosphorylation and degradation of inhibitory κB-α (IκB-α) and the activation of nuclear factor (NF)-κB, indicating that the anti-inflammatory effect of EARDP was mediated via the suppression of NF-κB nuclear translocation. In addition, EARDP induced the heme oxygenase-1 (HO-1) expression and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2), indicating that EARDP induced HO-1 via the Nrf2 pathway in RAW 264.7 cells. Furthermore, EARDP significantly suppressed the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. However, ZnPP, a specific inhibitor of HO-1, reversed the EARDP-mediated inhibition of NO and TNF-α production in LPS-stimulated RAW 264.7 macrophages. EARDP blocked the phosphorylation of mitogen-activated protein kinase (MAPK) and Akt in LPS-stimulated RAW 264.7 cells. In the in vivo animal model, EARDP significantly and dose-dependently reduced TPA-induced secretion of TNF-α and IL-6 in mouse ear. Based on these results, EARDP represents a promising natural compound, protective against oxidative stress and inflammatory diseases. Full article

(This article belongs to the Special Issue Antioxidants of Natural Product)

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24 pages, 1612 KiB

Open AccessEditor’s ChoiceReview

Hydrogen Sulfide: From a Toxic Molecule to a Key Molecule of Cell Life

by Angeles Aroca, Cecilia Gotor, Diane C. Bassham and Luis C. Romero

Antioxidants 2020, 9(7), 621; https://doi.org/10.3390/antiox9070621 - 15 Jul 2020

Cited by 89 | Viewed by 9849

Abstract

Hydrogen sulfide (H₂S) has always been considered toxic, but a huge number of articles published more recently showed the beneficial biochemical properties of its endogenous production throughout all regna. In this review, the participation of H₂S in many [...] Read more.

Hydrogen sulfide (H₂S) has always been considered toxic, but a huge number of articles published more recently showed the beneficial biochemical properties of its endogenous production throughout all regna. In this review, the participation of H₂S in many physiological and pathological processes in animals is described, and its importance as a signaling molecule in plant systems is underlined from an evolutionary point of view. H₂S quantification methods are summarized and persulfidation is described as the underlying mechanism of action in plants, animals and bacteria. This review aims to highlight the importance of its crosstalk with other signaling molecules and its fine regulation for the proper function of the cell and its survival. Full article

(This article belongs to the Special Issue Hydrogen Sulfide in Biology)

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16 pages, 2941 KiB

Open AccessArticle

Enteromorpha prolifera Extract Improves Memory in Scopolamine-Treated Mice via Downregulating Amyloid-β Expression and Upregulating BDNF/TrkB Pathway

by Seung Yeon Baek, Fu Yi Li, Da Hee Kim, Su Jin Kim and Mee Ree Kim

Antioxidants 2020, 9(7), 620; https://doi.org/10.3390/antiox9070620 - 15 Jul 2020

Cited by 26 | Viewed by 3784

Abstract

Enteromorpha prolifera, a green alga, has long been used in food diets as well as traditional remedies in East Asia. Our preliminary study demonstrated that an ethyl acetate extract of Enteromorpha prolifera (EAEP) exhibited the strongest antioxidant activity compared to ethanol or [...] Read more.

Enteromorpha prolifera, a green alga, has long been used in food diets as well as traditional remedies in East Asia. Our preliminary study demonstrated that an ethyl acetate extract of Enteromorpha prolifera (EAEP) exhibited the strongest antioxidant activity compared to ethanol or water extracts. Nonetheless, there has been no report on the effect of EAEP on memory impairment due to oxidative damage. This study investigated whether EAEP could attenuate memory deficits in an oxidative stress-induced mouse model. EAEP was orally administered (50 or 100 mg/kg body weight (b.w.)) to mice and then scopolamine was administered. The oral administration of EAEP at 100 mg/kg b.w. significantly restored memory impairments induced by scopolamine, as evaluated by the Morris water maze test, and the passive avoidance test. Further, EAEP upregulated the protein expression of BDNF, p-CREB, p-TrkB, and p-Akt. Moreover, EAEP downregulated the expression of amyloid-β, tau, and APP. The regulation of cholinergic marker enzyme activities and the protection of neuronal cells from oxidative stress-induced cell death in the brain of mice via the downregulation of amyloid-β and the upregulation of the BDNF/TrkB pathway by EAEP suggest its potential as a pharmaceutical candidate to prevent neurodegenerative diseases. Full article

(This article belongs to the Special Issue Antioxidants of Natural Product)

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35 pages, 1022 KiB

Open AccessReview

Potential Health Benefit of Garlic Based on Human Intervention Studies: A Brief Overview

by Johura Ansary, Tamara Yuliett Forbes-Hernández, Emilio Gil, Danila Cianciosi, Jiaojiao Zhang, Maria Elexpuru-Zabaleta, Jesus Simal-Gandara, Francesca Giampieri and Maurizio Battino

Antioxidants 2020, 9(7), 619; https://doi.org/10.3390/antiox9070619 - 15 Jul 2020

Cited by 96 | Viewed by 23919

Abstract

Garlic is a polyphenolic and organosulfur enriched nutraceutical spice consumed since ancient times. Garlic and its secondary metabolites have shown excellent health-promoting and disease-preventing effects on many human common diseases, such as cancer, cardiovascular and metabolic disorders, blood pressure, and diabetes, through its [...] Read more.

Garlic is a polyphenolic and organosulfur enriched nutraceutical spice consumed since ancient times. Garlic and its secondary metabolites have shown excellent health-promoting and disease-preventing effects on many human common diseases, such as cancer, cardiovascular and metabolic disorders, blood pressure, and diabetes, through its antioxidant, anti-inflammatory, and lipid-lowering properties, as demonstrated in several in vitro, in vivo, and clinical studies. The present review aims to provide a comprehensive overview on the consumption of garlic, garlic preparation, garlic extract, and garlic extract-derived bioactive constituents on oxidative stress, inflammation, cancer, cardiovascular and metabolic disorders, skin, bone, and other common diseases. Among the 83 human interventional trials considered, the consumption of garlic has been reported to modulate multiple biomarkers of different diseases; in addition, its combination with drugs or other food matrices has been shown to be safe and to prolong their therapeutic effects. The rapid metabolism and poor bioavailability that have limited the therapeutic use of garlic in the last years are also discussed. Full article

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19 pages, 559 KiB

Open AccessArticle

Antioxidants and Oxidative Stress in Children: Influence of Puberty and Metabolically Unhealthy Status

by Azahara I. Rupérez, María D. Mesa, Augusto Anguita-Ruiz, Esther M. González-Gil, Rocío Vázquez-Cobela, Luis A. Moreno, Ángel Gil, Mercedes Gil-Campos, Rosaura Leis, Gloria Bueno and Concepción M. Aguilera

Antioxidants 2020, 9(7), 618; https://doi.org/10.3390/antiox9070618 - 15 Jul 2020

Cited by 21 | Viewed by 3412

Abstract

Oxidative stress could help explain the relationship between childhood obesity and a metabolically unhealthy (MU) status. Moreover, puberty could also influence this relationship, since it entails physiological cardiometabolic changes. We aimed to evaluate plasma antioxidants and oxidative stress biomarkers in MU and metabolically [...] Read more.

Oxidative stress could help explain the relationship between childhood obesity and a metabolically unhealthy (MU) status. Moreover, puberty could also influence this relationship, since it entails physiological cardiometabolic changes. We aimed to evaluate plasma antioxidants and oxidative stress biomarkers in MU and metabolically healthy (MH) prepubertal and pubertal children and their associations with pro-inflammatory and endothelial damage biomarkers, taking puberty into account. A total of 1444 Spanish children aged 3–17 years (48.9% males, 66% prepubertal, 47.1% with obesity) were recruited. Blood pressure, anthropometric and biochemical parameters were measured, and children were categorized as having a MU or MH status according to risk factors. Retinol, carotenes, tocopherols, total antioxidant capacity (TAC), oxidized low-density lipoprotein and selected pro-inflammatory and endothelial damage biomarkers were analyzed. General linear models adjusted for age, sex, recruitment center and body mass index, partial correlations and stepwise linear regressions were performed. Lower carotenes and tocopherols levels were found in MU than in MH children. Plasma TAC was lower in prepubertal and higher in pubertal children with obesity compared to normal-weight children. Antioxidants and oxidative stress biomarkers showed novel associations with several pro-inflammatory and endothelial damage biomarkers, with pubertal differences, supporting the importance of considering both the antioxidant and oxidative stress status and puberty in the prevention of metabolic diseases in childhood. Full article

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

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20 pages, 1952 KiB

Open AccessReview

Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) and Mitochondrial Dynamics/Mitophagy in Neurological Diseases

by Tae-Cheon Kang

Antioxidants 2020, 9(7), 617; https://doi.org/10.3390/antiox9070617 - 15 Jul 2020

Cited by 60 | Viewed by 5861

Abstract

Mitochondria play an essential role in bioenergetics and respiratory functions for cell viability through numerous biochemical processes. To maintain mitochondria quality control and homeostasis, mitochondrial morphologies change rapidly in response to external insults and changes in metabolic status through fusion and fission (so [...] Read more.

Mitochondria play an essential role in bioenergetics and respiratory functions for cell viability through numerous biochemical processes. To maintain mitochondria quality control and homeostasis, mitochondrial morphologies change rapidly in response to external insults and changes in metabolic status through fusion and fission (so called mitochondrial dynamics). Furthermore, damaged mitochondria are removed via a selective autophagosomal process, referred to as mitophagy. Although mitochondria are one of the sources of reactive oxygen species (ROS), they are themselves vulnerable to oxidative stress. Thus, endogenous antioxidant defense systems play an important role in cell survival under physiological and pathological conditions. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that maintains redox homeostasis by regulating antioxidant-response element (ARE)-dependent transcription and the expression of antioxidant defense enzymes. Although the Nrf2 system is positively associated with mitochondrial biogenesis and mitochondrial quality control, the relationship between Nrf2 signaling and mitochondrial dynamics/mitophagy has not been sufficiently addressed in the literature. This review article describes recent clinical and experimental observations on the relationship between Nrf2 and mitochondrial dynamics/mitophagy in various neurological diseases. Full article

(This article belongs to the Special Issue Keap1/Nrf2 Signaling Pathway)

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13 pages, 1505 KiB

Open AccessArticle

Reduction of Protein Bound Methionine Sulfoxide by a Periplasmic Dimethyl Sulfoxide Reductase

by Lionel Tarrago, Sandrine Grosse, David Lemaire, Laetitia Faure, Mathilde Tribout, Marina I. Siponen, Mila Kojadinovic-Sirinelli, David Pignol, Pascal Arnoux and Monique Sabaty

Antioxidants 2020, 9(7), 616; https://doi.org/10.3390/antiox9070616 - 14 Jul 2020

Cited by 10 | Viewed by 3102

Abstract

In proteins, methionine (Met) can be oxidized into Met sulfoxide (MetO). The ubiquitous methionine sulfoxide reductases (Msr) A and B are thiol-oxidoreductases reducing MetO. Reversible Met oxidation has a wide range of consequences, from protection against oxidative stress to fine-tuned regulation of protein [...] Read more.

In proteins, methionine (Met) can be oxidized into Met sulfoxide (MetO). The ubiquitous methionine sulfoxide reductases (Msr) A and B are thiol-oxidoreductases reducing MetO. Reversible Met oxidation has a wide range of consequences, from protection against oxidative stress to fine-tuned regulation of protein functions. Bacteria distinguish themselves by the production of molybdenum-containing enzymes reducing MetO, such as the periplasmic MsrP which protects proteins during acute oxidative stress. The versatile dimethyl sulfoxide (DMSO) reductases were shown to reduce the free amino acid MetO, but their ability to reduce MetO within proteins was never evaluated. Here, using model oxidized proteins and peptides, enzymatic and mass spectrometry approaches, we showed that the Rhodobacter sphaeroides periplasmic DorA-type DMSO reductase reduces protein bound MetO as efficiently as the free amino acid L-MetO and with catalytic values in the range of those described for the canonical Msrs. The identification of this fourth type of enzyme able to reduce MetO in proteins, conserved across proteobacteria and actinobacteria, suggests that organisms employ enzymatic systems yet undiscovered to regulate protein oxidation states. Full article

(This article belongs to the Special Issue Biological Significance of Methionine Oxidation and Reduction)

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10 pages, 1441 KiB

Open AccessArticle

Glutathione S-Transferase Rescues Motor Neuronal Toxicity in Fly Model of Amyotrophic Lateral Sclerosis

by Sun Joo Cha, Yeo Jeong Han, Hyun-Jun Choi, Hyung-Jun Kim and Kiyoung Kim

Antioxidants 2020, 9(7), 615; https://doi.org/10.3390/antiox9070615 - 14 Jul 2020

Cited by 7 | Viewed by 2891

Abstract

Transactive response DNA-binding protein-43 (TDP-43) is involved in the pathology of familial and sporadic amyotrophic lateral sclerosis (ALS). TDP-43-mediated ALS models in mice, Drosophila melanogaster, and zebrafish exhibit dysfunction of locomotor function, defective neuromuscular junctions, and motor neuron defects. There is currently [...] Read more.

Transactive response DNA-binding protein-43 (TDP-43) is involved in the pathology of familial and sporadic amyotrophic lateral sclerosis (ALS). TDP-43-mediated ALS models in mice, Drosophila melanogaster, and zebrafish exhibit dysfunction of locomotor function, defective neuromuscular junctions, and motor neuron defects. There is currently no effective cure for ALS, and the underlying mechanisms of TDP-43 in ALS remain poorly understood. In this study, a genetic screen was performed to identify modifiers of human TDP-43 (hTDP-43) in a Drosophila model, and glutathione S-transferase omega 2 (GstO2) was found to be involved in hTDP-43 neurotoxicity. GstO2 overexpressed on recovered defective phenotypes resulting from hTDP-43, including defective neuromuscular junction (NMJ) boutons, degenerated motor neuronal axons, and reduced larvae and adult fly locomotive activity, without modulating the levels of hTDP-43 protein expression. GstO2 modulated neurotoxicity by regulating reactive oxygen species (ROS) produced by hTDP-43 in the Drosophila model of ALS. Our results demonstrated that GstO2 was a key regulator in hTDP-43-related ALS pathogenesis and indicated its potential as a therapeutic target for ALS. Full article

(This article belongs to the Special Issue Oxidative Stress and Neurodegenerative Disorders)

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