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Antioxidants
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New Mechanisms of Action of Natural Antioxidants in Health and...
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New Mechanisms of Action of Natural Antioxidants in Health and Disease

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 56769

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Silvana Hrelia

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Guest Editor
Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, 47921 Rimini, Italy
Interests: cellular biochemistry; nutritional biochemistry; oxidative stress; antioxidants; nutraceuticals
Special Issues, Collections and Topics in MDPI journals
Dr. Cristina Angeloni

E-Mail Website
Co-Guest Editor
Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso D’Augusto 237, 47921 Rimini, Italy
Interests: nutritional biochemistry; neurodegenerative diseases; oxidative stress; inflammation; nutraceuticals; ageing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The current understanding of the complex role of ROS in the organism and pathological sequelae of oxidative stress points to the necessity of comprehensive studies of antioxidant reactivities and interactions with cellular constituents. Many of the protective actions of natural antioxidants in health and diseases have been ascribed to their antioxidant properties, but in the last years, many studies have suggested that their classical hydrogen-donating antioxidant activity is unlikely to be the sole explanation for their effects. First of all, natural antioxidants are broadly metabolized in vivo, resulting in significant modifications. Moreover, the concentrations of natural antioxidants and their metabolites in vivo are lower than that usually utilized in vitro. Consequently, natural antioxidants do not exert their biological action in vivo via simply reacting with ROS. Accumulating evidence suggests that the cellular effects of natural antioxidants may be mediated by their interactions with specific proteins central to intracellular signaling cascades, modulating the expression and activity of key proteins, influencing epigenetic mechanisms or modulating gut microbiota.

We invite you to submit your research findings to this Special Issue, which has the aim to present the current state-of-the-art on new mechanisms of action of natural antioxidants in both health and disease. The research can include both in vitro and in vivo studies related to the following topics: antioxidant metabolism and bioavailability, signal transduction modulation, genomic and proteomic studies of purified molecules or antioxidant rich extracts, epigenetic regulation, cell cycle, cytoprotection, and cytotoxicity. Original research articles, review articles, clinical trials, and meta-analyzing studies are welcome.

Prof. Dr. Silvana Hrelia
Prof. Dr. Cristina Angeloni
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Natural antioxidants
  • Oxidative stress
  • Cell biochemistry
  • Signal transduction
  • Metabolism
  • Disease

Related Special Issue

Published Papers (10 papers)

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Editorial

Jump to: Research, Review

5 pages, 192 KiB  
Editorial
New Mechanisms of Action of Natural Antioxidants in Health and Disease
by Silvana Hrelia and Cristina Angeloni
Antioxidants 2020, 9(4), 344; https://doi.org/10.3390/antiox9040344 - 23 Apr 2020
Cited by 37 | Viewed by 4160
Abstract
Natural antioxidants have been proposed to have beneficial effects on health and on different disease states, such as neurodegenerative and cardiovascular diseases, diabetes and cancer [...] Full article
(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease)

Research

Jump to: Editorial, Review

15 pages, 1423 KiB  
Article
Characterization of Antioxidant Potential of Seaweed Extracts for Enrichment of Convenience Food
by Paola Antonia Corsetto, Gigliola Montorfano, Stefania Zava, Irma Colombo, Bergros Ingadottir, Rosa Jonsdottir, Kolbrun Sveinsdottir and Angela Maria Rizzo
Antioxidants 2020, 9(3), 249; https://doi.org/10.3390/antiox9030249 - 19 Mar 2020
Cited by 58 | Viewed by 5069
Abstract
In recent years, there has been a growing interest in natural antioxidants as replacements of synthetic compounds because of increased safety concerns and worldwide trend toward the usage of natural additives in foods. One of the richest sources of natural antioxidants, nowadays largely [...] Read more.
In recent years, there has been a growing interest in natural antioxidants as replacements of synthetic compounds because of increased safety concerns and worldwide trend toward the usage of natural additives in foods. One of the richest sources of natural antioxidants, nowadays largely studied for their potential to decrease the risk of diseases and to improve oxidative stability of food products, are edible brown seaweeds. Nevertheless, their antioxidant mechanisms are slightly evaluated and discussed. The aims of this study were to suggest possible mechanism(s) of Fucus vesiculosus antioxidant action and to assess its bioactivity during the production of enriched rye snacks. Chemical and cell-based assays indicate that the efficient preventive antioxidant action of Fucus vesiculosus extracts is likely due to not only the high polyphenol content, but also their good Fe2+-chelating ability. Moreover, the data collected during the production of Fucus vesiculosus-enriched rye snacks show that this seaweed can increase, in appreciable measure, the antioxidant potential of enriched convenience cereals. This information can be used to design functional foods enriched in natural antioxidant ingredients in order to improve the health of targeted consumers. Full article
(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease)
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17 pages, 2058 KiB  
Article
Beneficial Effects of Fermented Papaya Preparation (FPP®) Supplementation on Redox Balance and Aging in a Mouse Model
by Mariantonia Logozzi, Rossella Di Raimo, Davide Mizzoni, Mauro Andreotti, Massimo Spada, Daniele Macchia and Stefano Fais
Antioxidants 2020, 9(2), 144; https://doi.org/10.3390/antiox9020144 - 07 Feb 2020
Cited by 13 | Viewed by 3943
Abstract
In recent decades much attention has been paid to how dietary antioxidants may positively affect the human health, including the beneficial effects of fermented foods and beverages. Fermented Papaya Preparation (FPP®) has been shown to represent a valuable approach to obtain [...] Read more.
In recent decades much attention has been paid to how dietary antioxidants may positively affect the human health, including the beneficial effects of fermented foods and beverages. Fermented Papaya Preparation (FPP®) has been shown to represent a valuable approach to obtain systemic antioxidants effect. In this study, we wanted to verify whether FPP® had a clear and scientifically supported in vivo anti-aging effect together with the induction of a systemic antioxidant reaction. To this purpose we daily treated a mouse model suitable for aging studies (C57BL/6J) with FPP®-supplemented water from either the 6th weeks (early treatment) or the 51th weeks (late treatment) of age as compared to mice receiving only tap water. After 10 months of FPP® treatment, we evaluated the telomerase activity, antioxidants and Reactive Oxygen Species ROS plasmatic levels and the telomeres length in the bone marrow and ovaries in both mice groups. The results showed that the daily FPP® assumption induced increase in telomeres length in bone marrow and ovary, together with an increase in the plasmatic levels of telomerase activity, and antioxidant levels, with a decrease of ROS. Early treatment resulted to be more effective, suggesting a potential key role of FPP® in preventing the age-related molecular damages. Full article
(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease)
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24 pages, 3780 KiB  
Article
Identification of New Peptides from Fermented Milk Showing Antioxidant Properties: Mechanism of Action
by Federica Tonolo, Federico Fiorese, Laura Moretto, Alessandra Folda, Valeria Scalcon, Alessandro Grinzato, Stefania Ferro, Giorgio Arrigoni, Alberto Bindoli, Emiliano Feller, Marco Bellamio, Oriano Marin and Maria Pia Rigobello
Antioxidants 2020, 9(2), 117; https://doi.org/10.3390/antiox9020117 - 29 Jan 2020
Cited by 70 | Viewed by 6592
Abstract
Due to their beneficial properties, fermented foods are considered important constituents of the human diet. They also contain bioactive peptides, health-promoting compounds studied for a wide range of effects. In this work, several antioxidant peptides extracted from fermented milk proteins were investigated. First, [...] Read more.
Due to their beneficial properties, fermented foods are considered important constituents of the human diet. They also contain bioactive peptides, health-promoting compounds studied for a wide range of effects. In this work, several antioxidant peptides extracted from fermented milk proteins were investigated. First, enriched peptide fractions were purified and analysed for their antioxidant capacity in vitro and in a cellular model. Subsequently, from the most active fractions, 23 peptides were identified by mass spectrometry MS/MS), synthesized and tested. Peptides N-15-M, E-11-F, Q-14-R and A-17-E were selected for their antioxidant effects on Caco-2 cells both in the protection against oxidative stress and inhibition of ROS production. To define their action mechanism, the activation of the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2(Keap1/Nrf2) pathway was studied evaluating the translocation of Nrf2 from cytosol to nucleus. In cells treated with N-15-M, Q-14-R and A-17-E, a higher amount of Nrf2 was found in the nucleus with respect to the control. In addition, the three active peptides, through the activation of Keap1/Nrf2 pathway, led to overexpression and increased activity of antioxidant enzymes. Molecular docking analysis confirmed the potential ability of N-15-M, Q-14-R and A-17-E to bind Keap1, showing their destabilizing effect on Keap1/Nrf2 interaction. Full article
(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease)
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15 pages, 3002 KiB  
Article
The Skin-Whitening Effects of Ectoine via the Suppression of α-MSH-Stimulated Melanogenesis and the Activation of Antioxidant Nrf2 Pathways in UVA-Irradiated Keratinocytes
by You-Cheng Hseu, Xuan-Zao Chen, Yugandhar Vudhya Gowrisankar, Hung-Rong Yen, Jing-Yuan Chuang and Hsin-Ling Yang
Antioxidants 2020, 9(1), 63; https://doi.org/10.3390/antiox9010063 - 10 Jan 2020
Cited by 36 | Viewed by 8797
Abstract
Ultraviolet A (UVA)-irradiation induced reactive oxygen species (ROS) production mediates excessive melanogenesis in skin cells leading to pigmentation. We demonstrated the depigmenting and anti-melanogenic effects of Ectoine, a natural bacterial osmolyte, in UVA-irradiated human (HaCaT) keratinocytes, and the underlying molecular mechanisms were elucidated. [...] Read more.
Ultraviolet A (UVA)-irradiation induced reactive oxygen species (ROS) production mediates excessive melanogenesis in skin cells leading to pigmentation. We demonstrated the depigmenting and anti-melanogenic effects of Ectoine, a natural bacterial osmolyte, in UVA-irradiated human (HaCaT) keratinocytes, and the underlying molecular mechanisms were elucidated. HaCaT cells were pre-treated with low concentrations of Ectoine (0.5–1.5 μM) and assayed for various depigmenting and anti-melanogenic parameters. This pre-treatment significantly downregulated ROS generation, α-melanocyte-stimulating hormone (α-MSH) production, and proopiomelanocortin (POMC) expression in UVA-irradiated HaCaT cells. Also, antioxidant heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase [quinone 1] (NQO-1), and γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC) protein expressions were mediated via the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) whose knockdown indeed impaired this effect signifying the importance of the Nrf2 pathway. Ectoine was mediating the activation of Nrf2 via the p38, protein kinase B (also known as AKT), protein kinase C (PKC), and casein kinase II protein kinase (CKII) pathways. The conditioned medium obtained from the Ectoine pre-treated and UVA-irradiated HaCaT cells downregulated the tyrosinase, tyrosinase-related protein-1 and -2 (TRP-1/-2), cyclic AMP (c-AMP) protein kinase, c-AMP response element-binding protein (CREB), and microphthalmia-associated transcription factor (MITF) expressions leading to melanoma B16F10 cells having inhibited melanin synthesis. Interestingly, this anti-melanogenic effect in α-MSH-stimulated B16F10 cells was observable only at 50–400 μM concentrations of Ectoine, signifying the key role played by Ectoine (0.5–1 μM)-treated keratinocytes in skin whitening effects. We concluded that Ectoine could be used as an effective topical natural cosmetic agent with depigmenting and anti-melanogenic efficacy. Full article
(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease)
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14 pages, 2467 KiB  
Article
Rosmarinus officinalis Essential Oil Improves Scopolamine-Induced Neurobehavioral Changes via Restoration of Cholinergic Function and Brain Antioxidant Status in Zebrafish (Danio rerio)
by Luminita Capatina, Razvan Stefan Boiangiu, Gabriela Dumitru, Edoardo Marco Napoli, Giuseppe Ruberto, Lucian Hritcu and Elena Todirascu-Ciornea
Antioxidants 2020, 9(1), 62; https://doi.org/10.3390/antiox9010062 - 10 Jan 2020
Cited by 35 | Viewed by 5795
Abstract
Rosmarinus officinalis L. is a traditional herb with various therapeutic applications such as antibacterial, antioxidant, anti-inflammatory, antidepressant, and anticholinesterase activities, and can be used for the prevention or treatment of dementia. In the present study, we tested whether Rosmarinus officinalis L. could counteract [...] Read more.
Rosmarinus officinalis L. is a traditional herb with various therapeutic applications such as antibacterial, antioxidant, anti-inflammatory, antidepressant, and anticholinesterase activities, and can be used for the prevention or treatment of dementia. In the present study, we tested whether Rosmarinus officinalis L. could counteract scopolamine-induced anxiety, dementia, and brain oxidative stress in the zebrafish model and tried to find the underlying mechanism. Rosmarinus officinalis L. essential oil (REO: 25, 150, and 300 µL/L) was administered by immersion to zebrafish (Danio rerio) once daily for eight days while scopolamine (100 µM) treatment was delivered 30 min before behavioral tests. The antidepressant and cognitive-enhancing actions of the essential oil in the scopolamine zebrafish model was measured in the novel tank diving test (NTT) and Y-maze test. The chemical composition was identified by Gas chromatograph–Mass spectrometry (GC-MS) analysis. The brain oxidative status and acetylcholinesterase (AChE) activity was also determined. REO reversed scopolamine-induced anxiety, memory impairment, and brain oxidative stress. In addition, a reduced brain AChE activity following the administration of REO in scopolamine-treated fish was observed. In conclusion, REO exerted antidepressant-like effect and cognitive-enhancing action and was able to abolish AChE alteration and brain oxidative stress induced by scopolamine. Full article
(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease)
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21 pages, 4471 KiB  
Article
Anti-Atherosclerotic Effect of Hibiscus Leaf Polyphenols against Tumor Necrosis Factor-alpha-Induced Abnormal Vascular Smooth Muscle Cell Migration and Proliferation
by Cheng-Chung Chou, Chi-Ping Wang, Jing-Hsien Chen and Hui-Hsuan Lin
Antioxidants 2019, 8(12), 620; https://doi.org/10.3390/antiox8120620 - 05 Dec 2019
Cited by 24 | Viewed by 4126
Abstract
The proliferation and migration of vascular smooth muscle cells (VSMCs) are major events in the development of atherosclerosis following stimulation with proinflammatory cytokines, especially tumor necrosis factor-alpha (TNF-α). Plant-derived polyphenols have attracted considerable attention in the prevention of atherosclerosis. Hibiscus leaf has been [...] Read more.
The proliferation and migration of vascular smooth muscle cells (VSMCs) are major events in the development of atherosclerosis following stimulation with proinflammatory cytokines, especially tumor necrosis factor-alpha (TNF-α). Plant-derived polyphenols have attracted considerable attention in the prevention of atherosclerosis. Hibiscus leaf has been showed to inhibit endothelial cell oxidative injury, low-density lipoprotein oxidation, and foam cell formation. In this study, we examined the anti-atherosclerotic effect of Hibiscus leaf polyphenols (HLPs) against abnormal VSMC migration and proliferation in vitro and in vivo. Firstly, VSMC A7r5 cells pretreated with TNF-α were demonstrated to trigger abnormal proliferation and affect matrix metalloproteinase (MMP) activities. Non-cytotoxic doses of HLPs abolished the TNF-α-induced MMP-9 expression and cell migration via inhibiting the protein kinase PKB (also known as Akt)/activator protein-1 (AP-1) pathway. On the other hand, HLP-mediated cell cycle G0/G1 arrest might be exerted by inducing the expressions of p53 and its downstream factors that, in turn, suppress cyclin E/cdk2 activity, preventing retinoblastoma (Rb) phosphorylation and the subsequent dissociation of Rb/E2F complex. HLPs also attenuated reactive oxygen species (ROS) production against TNF-α stimulation. In vivo, HLPs improved atherosclerotic lesions, and abnormal VSMC migration and proliferation. Our data present the first evidence of HLPs as an inhibitor of VSMC dysfunction, and provide a new mechanism for its anti-atherosclerotic activity. Full article
(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease)
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16 pages, 1936 KiB  
Article
Combined Treatment with Three Natural Antioxidants Enhances Neuroprotection in a SH-SY5Y 3D Culture Model
by Pasquale Marrazzo, Cristina Angeloni and Silvana Hrelia
Antioxidants 2019, 8(10), 420; https://doi.org/10.3390/antiox8100420 - 20 Sep 2019
Cited by 32 | Viewed by 5042
Abstract
Currently, the majority of cell-based studies on neurodegeneration are carried out on two-dimensional cultured cells that do not represent the cells residing in the complex microenvironment of the brain. Recent evidence has suggested that three-dimensional (3D) in vitro microenvironments may better model key [...] Read more.
Currently, the majority of cell-based studies on neurodegeneration are carried out on two-dimensional cultured cells that do not represent the cells residing in the complex microenvironment of the brain. Recent evidence has suggested that three-dimensional (3D) in vitro microenvironments may better model key features of brain tissues in order to study molecular mechanisms at the base of neurodegeneration. So far, no drugs have been discovered to prevent or halt the progression of neurodegenerative disorders. New therapeutic interventions can come from phytochemicals that have a broad spectrum of biological activities. On this basis, we evaluated the neuroprotective effect of three phytochemicals (sulforaphane, epigallocatechin gallate, and plumbagin) alone or in combination, focusing on their ability to counteract oxidative stress. The combined treatment was found to be more effective than the single treatments. In particular, the combined treatment increased cell viability and reduced glutathione (GSH) levels, upregulated antioxidant enzymes and insulin-degrading enzymes, and downregulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 and 2 in respect to peroxide-treated cells. Our data suggest that a combination of different phytochemicals could be more effective than a single compound in counteracting neurodegeneration, probably thanks to a pleiotropic mechanism of action. Full article
(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease)
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Review

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16 pages, 2423 KiB  
Review
The Effects and Mechanisms of Cyanidin-3-Glucoside and Its Phenolic Metabolites in Maintaining Intestinal Integrity
by Jijun Tan, Yanli Li, De-Xing Hou and Shusong Wu
Antioxidants 2019, 8(10), 479; https://doi.org/10.3390/antiox8100479 - 12 Oct 2019
Cited by 82 | Viewed by 6529
Abstract
Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin and possesses antioxidant and anti-inflammatory properties. The catabolism of C3G in the gastrointestinal tract could produce bioactive phenolic metabolites, such as protocatechuic acid, phloroglucinaldehyde, vanillic acid, and ferulic acid, which enhance C3G bioavailability and contribute to [...] Read more.
Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin and possesses antioxidant and anti-inflammatory properties. The catabolism of C3G in the gastrointestinal tract could produce bioactive phenolic metabolites, such as protocatechuic acid, phloroglucinaldehyde, vanillic acid, and ferulic acid, which enhance C3G bioavailability and contribute to both mucosal barrier and microbiota. To get an overview of the function and mechanisms of C3G and its phenolic metabolites, we review the accumulated data of the absorption and catabolism of C3G in the gastrointestine, and attempt to give crosstalk between the phenolic metabolites, gut microbiota, and mucosal innate immune signaling pathways. Full article
(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease)
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12 pages, 1046 KiB  
Review
Hormetic and Mitochondria-Related Mechanisms of Antioxidant Action of Phytochemicals
by Rafael Franco, Gemma Navarro and Eva Martínez-Pinilla
Antioxidants 2019, 8(9), 373; https://doi.org/10.3390/antiox8090373 - 04 Sep 2019
Cited by 45 | Viewed by 5818
Abstract
Antioxidant action to afford a health benefit or increased well-being may not be directly exerted by quick reduction-oxidation (REDOX) reactions between the antioxidant and the pro-oxidant molecules in a living being. Furthermore, not all flavonoids or polyphenols derived from plants are beneficial. This [...] Read more.
Antioxidant action to afford a health benefit or increased well-being may not be directly exerted by quick reduction-oxidation (REDOX) reactions between the antioxidant and the pro-oxidant molecules in a living being. Furthermore, not all flavonoids or polyphenols derived from plants are beneficial. This paper aims at discussing the variety of mechanisms underlying the so-called “antioxidant” action. Apart from antioxidant direct mechanisms, indirect ones consisting of fueling and boosting innate detox routes should be considered. One of them, hormesis, involves upregulating enzymes that are needed in innate detox pathways and/or regulating the transcription of the so-called vitagenes. Moreover, there is evidence that some plant-derived compounds may have a direct role in events taking place in mitochondria, which is an organelle prone to oxidative stress if electron transport is faulty. Insights into the potential of molecules able to enter into the electron transport chain would require the determination of their reduction potential. Additionally, it is advisable to know both the oxidized and the reduced structures for each antioxidant candidate. These mechanisms and their related technical developments should help nutraceutical industry to select candidates that are efficacious in physiological conditions to prevent diseases or increase human health. Full article
(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease)
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