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Antioxidants—A Risk-Benefit Analysis for Health

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Metabolites".

Deadline for manuscript submissions: closed (30 September 2015) | Viewed by 164003

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Special Issue Editor

Prof. Dr. David D. Kitts

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Guest Editor

Food Science Program, Food Nutrition and Health, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Interests: food chemistry; functional foods; bioactive food components; lipids; antioxidants; health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The identification of molecules with antioxidant activity, and the mechanism(s) that describes this activity, continues to be an active area of academic research and one that has received considerable consumer interest as an important component of health and wellness.

Interest in antioxidant research has evolved over the last four decades, from early studies that identified antioxidant vitamins, to more recent endeavors that include screening for antioxidant activity in numerous plant and plant food sources; the characterization of biochemical and metabolic activity of non-enzymatic food antioxidants in both food matrices and in vivo, and evaluation of efficacy; this including epidemiology studies that have studied the success of antioxidant supplementation in the prevention of disease. The spectrum of risk-benefit analysis research concerning the utility of antioxidants from foods versus dietary supplements has proven to be especially controversial.

This Special Issue will present scientific studies, or reviews, on various viewpoints of antioxidants and their activity attributes. Topics for consideration include identifying antioxidant activities of specific nutrients, or non-nutrients, such as phytochemicals, that contribute to enzymatic and non-enzymatic antioxidant capacity in foods systems and consumers who consume them. In addition, new advances in measuring antioxidant functionality and the conditions for potential synergy between antioxidant molecules, or conversion to pro-oxidant risks, will be described. I invite authors to submit papers for review on this topic, within the scope of Molecules.

Prof. Dr. David D. Kitts
Guest Editor

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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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

antioxidant
reactive oxygen species
biochemical pathways
synergy and pro-oxidant activity

Published Papers (12 papers)

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Research

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1228 KiB

Open AccessArticle

Antioxidant Activity of 3-[N-(Acylhydrazono)ethyl]-4-hydroxy-coumarins

by Antigoni Kotali, Despina A. Nasiopoulou, Constantinos A. Tsoleridis, Philip A. Harris, Christos A. Kontogiorgis and Dimitra J. Hadjipavlou-Litina

Molecules 2016, 21(2), 138; https://doi.org/10.3390/molecules21020138 - 23 Jan 2016

Cited by 20 | Viewed by 5812

Abstract

A series of 3-acylhydrazono-4-hydroxycoumarins were synthesized via condensation of 3-acetyl-4-hydroxycoumarin with appropriate hydrazides. The structures of the newly-synthesized compounds were characterized by spectral and elememental analysis or HRMS measurements. Their antioxidant properties were evaluated by using scavenging effects on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical as well as inhibition of lipid peroxidation. Moreover, their ability to inhibit in vitro soybean lipoxygenase has been investigated. They were found to be capable of rapid inactivation of alkylperoxy radicals. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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1365 KiB

Open AccessArticle

Antiproliferative and Antioxidant Activities and Mycosporine-Like Amino Acid Profiles of Wild-Harvested and Cultivated Edible Canadian Marine Red Macroalgae

by Yasantha Athukorala, Susan Trang, Carmen Kwok and Yvonne V. Yuan

Molecules 2016, 21(1), 119; https://doi.org/10.3390/molecules21010119 - 21 Jan 2016

Cited by 43 | Viewed by 8361

Abstract

Antiproliferative and antioxidant activities and mycosporine-like amino acid (MAA) profiles of methanol extracts from edible wild-harvested (Chondrus crispus, Mastocarpus stellatus, Palmaria palmata) and cultivated (C. crispus) marine red macroalgae were studied herein. Palythine, asterina-330, shinorine, palythinol, porphyra-334 and usujirene MAAs were identified in the macroalgal extracts by LC/MS/MS. Extract reducing activity rankings were (p < 0.001): wild P. palmata > cultivated C. crispus = wild M. stellatus > wild low-UV C. crispus > wild high-UV C. crispus; whereas oxygen radical absorbance capacities were (p < 0.001): wild M. stellatus > wild P. palmata > cultivated C. crispus > wild low-UV C. crispus > wild high-UV C. crispus. Extracts were antiproliferative against HeLa and U-937 cells (p < 0.001) from 0.125–4 mg/mL, 24 h. Wild P. palmata and cultivated C. crispus extracts increased (p < 0.001) HeLa caspase-3/7 activities and the proportion of cells arrested at Sub G₁ (apoptotic) compared to wild-harvested C. crispus and M. stellatus extracts. HeLa cells incubated with wild P. palmata and cultivated C. crispus extracts also exhibited morphological changes characteristic of apoptosis (shrinkage, rounding). Thus, extracts rich in low-polarity usujirene and polar palythine and asterina-330 MAAs were antiproliferative as inducers of apoptosis in HeLa cells. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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1075 KiB

Open AccessArticle

Short-Term and Sub-Chronic Dietary Exposure to Aspalathin-Enriched Green Rooibos (Aspalathus linearis) Extract Affects Rat Liver Function and Antioxidant Status

by Johanna Debora Van der Merwe, Dalene De Beer, Elizabeth Joubert and Wentzel C. A. Gelderblom

Molecules 2015, 20(12), 22674-22690; https://doi.org/10.3390/molecules201219868 - 18 Dec 2015

Cited by 25 | Viewed by 7686 | Correction

Abstract

An aspalathin-enriched green rooibos (Aspalathus linearis) extract (GRE) was fed to male Fischer rats in two independent studies for 28 and 90 days. The average dietary total polyphenol (TP) intake was 756 and 627 mg Gallic acid equivalents (GAE)/kg body weight (bw)/day over 28 and 90 days, respectively, equaling human equivalent doses (HEDs) of 123 and 102 GAE mg/kg bw/day. Aspalathin intake of 295 mg/kg bw/day represents a HED of 48 mg/kg bw/day (90 day study). Consumption of GRE increased feed intake significantly (p < 0.05) compared to the control after 90 days, but no effect on body and organ weight parameters was observed. GRE significantly (p < 0.05) reduced serum total cholesterol and iron levels, whilst significantly (p < 0.05) increasing alkaline phosphatase enzyme activity after 90 days. Endogenous antioxidant enzyme activity in the liver, i.e., catalase and superoxide dismutase activity, was not adversely affected. Glutathione reductase activity significantly (p < 0.05) increased after 28 days, while glutathione (GSH) content was decreased after 90 days, suggesting an altered glutathione redox cycle. Quantitative Real Time polymerase chain reaction (PCR) analysis showed altered expression of certain antioxidant defense and oxidative stress related genes, indicative, among others, of an underlying oxidative stress related to changes in the GSH redox pathway and possible biliary dysfunction. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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1613 KiB

Open AccessArticle

A Comprehensive Study of the Use of Cu(I)/4,4’-Dicarboxy-2,2’-biquinoline Complexes to Measure the Total Reducing Capacity: Application in Herbal Extracts

by Hariane R. Manoel and Horacio D. Moya

Molecules 2015, 20(12), 22411-22421; https://doi.org/10.3390/molecules201219855 - 14 Dec 2015

Cited by 9 | Viewed by 5499

Abstract

A method for the determination of total reducing capacity (TRC) based on the reduction of Cu(II) to Cu(I) by antioxidants in a buffered solution (pH 7.0) containing 4,4′-dicarboxy-2,2′-biquinoline acid (BCA) was developed. Absorbance values at 558 nm characteristic of the Cu(I)/BCA complexes formed were used to determine the TRC of aqueous extracts of twelve Brazilian plants. The TRC values obtained with the suggested method correlated well with values obtained using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method (r² = 0.959). They were also compared with the total polyphenol content (using the Folin-Ciocalteu reagent) and the good agreement (r² = 0.919) indicates that the polyphenols should be responsible for this reducing capacity. The method proposed here (and successfully applied in plant extracts) can be used to measure the TRC of aqueous samples derived from other plants (e.g., teas, juices, beers and wines) and even in biological samples (e.g., serum, urine and follicular fluid). To achieve a structure-activity relationship of the proposed reaction, the reduction capability of 25 standard antioxidants (phenolic derivatives, flavonoids, stilbenoids, vitamins, etc.) was individually evaluated and the apparent molar absorptivity values (at 558 nm) obtained were compared and discussed. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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4068 KiB

Open AccessArticle

Retinoprotective Effects of Bilberry Anthocyanins via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms in a Visible Light-Induced Retinal Degeneration Model in Pigmented Rabbits

by Yong Wang, Liang Zhao, Feng Lu, Xue Yang, Qianchun Deng, Baoping Ji and Fenghong Huang

Molecules 2015, 20(12), 22395-22410; https://doi.org/10.3390/molecules201219785 - 14 Dec 2015

Cited by 63 | Viewed by 10081

Abstract

Excessive visible light exposure can induce damage to retinal cells and contribute to the development or progression of age-related macular degeneration. In this study we created a model of phototoxicity in pigmented rabbits. Furthermore, we investigated the protective effect of bilberry anthocyanin extract (BAE, Table A1) and explored the possible mechanisms of action in this model. The model of light-induced retinal damage was established by the pigmented rabbits exposed to light at 18,000 lx for 2 h, and they were sacrificed on day 7. After administration of BAE at dosages of 250 and 500 mg/kg/day, retinal dysfunction was significantly inhibited in terms of electroretinograms, and the decreased thicknesses of retinal outer nuclear layer and lengths of the outer segments of the photoreceptor cells were suppressed in rabbits with retinal degeneration. BAE attenuated the changes caused by light to certain apoptotic proteins (Bax, Bcl-2, and caspase-3). The extract increased the levels of superoxide dismutase, glutathione peroxidase, and catalase, as well as the total antioxidant capacity, but decreased the malondialdehyde level in the retinal cells. BAE inhibited the light-induced elevation in the levels of proinflammatory cytokines and angiogenic parameters (IL-1β and VEGF). Results showed that visible light-induced retinal degeneration model in pigmented rabbits was successfully established and BAE exhibited protective effects by increasing the antioxidant defense mechanisms, suppressing lipid peroxidation and proinflammatory cytokines, and inhibiting retinal cells apoptosis. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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1757 KiB

Open AccessArticle

Impact of Natural Juice Consumption on Plasma Antioxidant Status: A Systematic Review and Meta-Analysis

by Fernanda S. Tonin, Laiza M. Steimbach, Astrid Wiens, Cássio M. Perlin and Roberto Pontarolo

Molecules 2015, 20(12), 22146-22156; https://doi.org/10.3390/molecules201219834 - 10 Dec 2015

Cited by 28 | Viewed by 7481

Abstract

Background: Oxidative stress may lead to overproduction of reactive species and a decrease in antioxidant defenses, resulting in chronic diseases such as diabetes and cancer. The consumption of natural compounds with an antioxidant profile may be a preventive alternative. Therefore, we aimed to obtain evidence regarding the potential antioxidant activity of juices in human plasma. Methods: A systematic review and meta-analysis was performed, which included randomized controlled trials that compared the use of fruit or vegetable juices vs. placebo or other beverages. An electronic search was conducted in PubMed, Scopus, International Pharmaceutical Abstracts, and SciELO. The outcome measures extracted were related to antioxidant status, e.g., vitamin C, superoxide dismutase (SOD), and catalase (CAT) levels and reduction in malondialdehyde (MDA) and antioxidant capacity measured as TEAC. Results: Twenty-eight trials were identified (n = 1089), of which 16 were used for meta-analysis. No significant differences were observed between juices and placebo with regard to TEAC, SOD, and CAT. However, juices were superior to control in enhancing vitamin C and reducing MDA. Conclusions: Natural juices are possible candidates for the management of oxidative stress. The effects of juices should be further investigated by conducting larger and well-defined trials of longer duration. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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758 KiB

Open AccessArticle

Rapid Estimation of Tocopherol Content in Linseed and Sunflower Oils-Reactivity and Assay

by Tjaša Prevc, Alenka Levart, Irena Kralj Cigić, Janez Salobir, Nataša Poklar Ulrih and Blaž Cigić

Molecules 2015, 20(8), 14777-14790; https://doi.org/10.3390/molecules200814777 - 13 Aug 2015

Cited by 8 | Viewed by 7594

Abstract

The reactivity of tocopherols with 2,2-diphenyl-1-picrylhydrazyl (DPPH) was studied in model systems in order to establish a method for quantifying vitamin E in plant oils. The method was optimized with respect to solvent composition of the assay medium, which has a large influence on the course of reaction of tocopherols with DPPH. The rate of reaction of α-tocopherol with DPPH is higher than that of γ-tocopherol in both protic and aprotic solvents. In ethyl acetate, routinely applied for the analysis of antioxidant potential (AOP) of plant oils, reactions of tocopherols with DPPH are slower and concentration of tocopherols in the assay has a large influence on their molar reactivity. In 2-propanol, however, two electrons are exchanged for both α- and γ-tocopherols, independent of their concentration. 2-propanol is not toxic and is fully compatible with polypropylene labware. The chromatographically determined content of tocopherols and their molar reactivity in the DPPH assay reveal that only tocopherols contribute to the AOP of sunflower oil, whereas the contribution of tocopherols to the AOP of linseed oil is 75%. The DPPH assay in 2-propanol can be applied for rapid and cheap estimation of vitamin E content in plant oils where tocopherols are major antioxidants. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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2653 KiB

Open AccessArticle

Oleanolic Acid, a Compound Present in Grapes and Olives, Protects against Genotoxicity in Human Mammary Epithelial Cells

by Cristina Sánchez-Quesada, Alicia López-Biedma and José J. Gaforio

Molecules 2015, 20(8), 13670-13688; https://doi.org/10.3390/molecules200813670 - 28 Jul 2015

Cited by 27 | Viewed by 9440

Abstract

Oleanolic acid (AO) and maslinic acid (MA) are constituents of the skins of different fruits, including olives and white or red grapes. Although both compounds are known to have beneficial properties against different types of cancers, thus far, there are no studies about their chemopreventive effects in human breast cancer. Thus, we sought to elucidate whether both compounds possess chemopreventive activity. Two cell lines of human breast cancer cells and one noncancerous human mammary epithelial cells were used to determine the effects of OA and MA. The results showed that OA inhibited the proliferation and increased the oxidative stress of highly invasive cells. Additionally, OA decreased oxidative stress and oxidative damage to the DNA in human mammary epithelial cells. These results suggest that OA could act as a chemopreventive agent in human breast cancer and could inhibit the proliferation of highly invasive breast cancer cells. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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Review

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1166 KiB

Open AccessReview

Effects of Brassicaceae Isothiocyanates on Prostate Cancer

by Silvia Novío, María Elena Cartea, Pilar Soengas, Manuel Freire-Garabal and María Jesús Núñez-Iglesias

Molecules 2016, 21(5), 626; https://doi.org/10.3390/molecules21050626 - 12 May 2016

Cited by 34 | Viewed by 7381

Abstract

Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa) is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large source for the development of chemotherapeutic agents, with more than 50% of current anticancer drugs being of natural origin. Isothiocyanates (ITCs) are degradation products from glucosinolates that are present in members of the family Brassicaceae. Although they are known for a variety of therapeutic effects, including antioxidant, immunostimulatory, anti-inflammatory, antiviral and antibacterial properties, nowadays, cell line and animal studies have additionally indicated the chemopreventive action without causing toxic side effects of ITCs. In this way, they can induce cell cycle arrest, activate apoptosis pathways, increase the sensitivity of resistant PCa to available chemodrugs, modulate epigenetic changes and downregulate activated signaling pathways, resulting in the inhibition of cell proliferation, progression and invasion-metastasis. The present review summarizes the chemopreventive role of ITCs with a particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo cancer animal models. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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254 KiB

Open AccessReview

Antioxidant Phytochemicals for the Prevention and Treatment of Chronic Diseases

by Yu-Jie Zhang, Ren-You Gan, Sha Li, Yue Zhou, An-Na Li, Dong-Ping Xu and Hua-Bin Li

Molecules 2015, 20(12), 21138-21156; https://doi.org/10.3390/molecules201219753 - 27 Nov 2015

Cited by 829 | Viewed by 42613

Abstract

Overproduction of oxidants (reactive oxygen species and reactive nitrogen species) in the human body is responsible for the pathogenesis of some diseases. The scavenging of these oxidants is thought to be an effective measure to depress the level of oxidative stress of organisms. It has been reported that intake of vegetables and fruits is inversely associated with the risk of many chronic diseases, and antioxidant phytochemicals in vegetables and fruits are considered to be responsible for these health benefits. Antioxidant phytochemicals can be found in many foods and medicinal plants, and play an important role in the prevention and treatment of chronic diseases caused by oxidative stress. They often possess strong antioxidant and free radical scavenging abilities, as well as anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative diseases. This review summarizes recent progress on the health benefits of antioxidant phytochemicals, and discusses their potential mechanisms in the prevention and treatment of chronic diseases. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

1537 KiB

Open AccessReview

Antioxidants of Edible Mushrooms

by Maja Kozarski, Anita Klaus, Dragica Jakovljevic, Nina Todorovic, Jovana Vunduk, Predrag Petrović, Miomir Niksic, Miroslav M. Vrvic and Leo Van Griensven

Molecules 2015, 20(10), 19489-19525; https://doi.org/10.3390/molecules201019489 - 27 Oct 2015

Cited by 261 | Viewed by 22585

Abstract

Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS) lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants can effectively improve defense mechanisms, but because of their adverse toxic effects under certain conditions, preference is given to natural compounds. Consequently, the requirements for natural, alternative sources of antioxidant foods identified in edible mushrooms, as well as the mechanistic action involved in their antioxidant properties, have increased rapidly. Chemical composition and antioxidant potential of mushrooms have been intensively studied. Edible mushrooms might be used directly in enhancement of antioxidant defenses through dietary supplementation to reduce the level of oxidative stress. Wild or cultivated, they have been related to significant antioxidant properties due to their bioactive compounds, such as polyphenols, polysaccharides, vitamins, carotenoids and minerals. Antioxidant and health benefits, observed in edible mushrooms, seem an additional reason for their traditional use as a popular delicacy food. This review discusses the consumption of edible mushrooms as a powerful instrument in maintaining health, longevity and life quality. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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1285 KiB

Open AccessReview

Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism

by Dun-Xian Tan, Lucien C. Manchester, Eduardo Esteban-Zubero, Zhou Zhou and Russel J. Reiter

Molecules 2015, 20(10), 18886-18906; https://doi.org/10.3390/molecules201018886 - 16 Oct 2015

Cited by 449 | Viewed by 28685

Abstract

Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin’s synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress. Full article

(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)

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