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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 54334

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Prof. Dr. José M. Álvarez-Suarez

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Guest Editor

Facultad de Ingeniería y Ciencias Aplicadas (FICA), Universidad de Las Américas, Quito, Ecuador
Interests: antioxidant activity; antimicrobial activities; polyphenol-rich foods; berries; honey
Special Issues, Collections and Topics in MDPI journals

Dr. Abishek Santhakumar

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Guest Editor

School of Dentistry and Medical Sciences, Charles Sturt University, Locked Bag 588, Wagga, NSW 2678, Australia
Interests: dietary antioxidants; functional foods; meatbolic diseases; oxidative stress; food chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue, “Natural Antioxidants”, will cover a selection of recent research topics and current review articles related to the role of natural antioxidants in health and disease. Up-to-date review articles, commentaries, and experimental papers are all welcome.

In recent years, studies in natural compounds with antioxidant activity as chemopreventive and therapeutics for the management of different acute, chronic, and degenerative diseases have tried to explain the mechanisms by which antioxidants exert their beneficial effect on health beyond their simple antioxidant activity. Consequently, research advances include their natural sources, biosynthesis, isolation, chemical characterization, biological effects and their molecular pathways of action. This Special Issue on “Natural Antioxidants” welcomes original research and reviews in the field, with a particular focus on the extraction and characterization of natural bioactive components and their potential use as therapeutics or nutraceuticals, as well as the elucidation of their mechanisms of action, with special attention to molecular pathways in which they may be involved.

Prof. Dr. José M. Álvarez-Suarez
Dr. Abishek Santhakumar
Guest Editors

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Keywords

natural antioxidants
bioactive compounds
dietary intake
dietary phytochemicals
nutrigenetics
nutrigenomics
molecular pathways and extraction and characterization of natural bioactive components

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Published Papers (9 papers)

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Research

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14 pages, 1005 KiB

Open AccessArticle

Novel Insights into the Regulatory Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 in Oxidative Stress and Inflammation of Human Fetal Membranes

by Ramkumar Menon and Morgan R Peltier

Int. J. Mol. Sci. 2020, 21(17), 6139; https://doi.org/10.3390/ijms21176139 - 26 Aug 2020

Cited by 8 | Viewed by 2465

Abstract

Fetal membrane dysfunction in response to oxidative stress (OS) is associated with adverse pregnancy outcomes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is one of the regulators of innate OS response. This study evaluated changes in Nrf2 expression and its downstream targets heme oxygenase (HO-1) and peroxisome proliferator-activated receptor gamma (PPARγ) in fetal membranes during OS and infection in vitro. Furthermore, we tested the roles of sulforaphane (SFN; an extract from cruciferous vegetables) and trigonelline (TRN; an aromatic compound in coffee) in regulating Nrf2 and its targets. Fetal membranes (n = 6) collected at term were placed in an organ explant system were treated with water-soluble cigarette smoke extract (CSE), an OS inducer (1:10), and lipopolysaccharide (LPS; 100 ng/mL). Nrf2 expression, expression, its enhancement by sulforaphane (SFN, 10 µM/mL) and down regulation by TRN (10uM/mL) was determined by western blots. Expression of Nrf2 response elements PPARγ (western) heme oxygenase (HO-1), and IL-6 were quantified by ELISA. CSE and LPS treatment of fetal membranes increased nrf2, but reduced HO-1 and PPARγ and increased IL-6. Co-treatment of SFN, but not with TRN, with CSE and LPS increased Nrf2 substantially, as well as increased HO-1 and PPARγ and reduced IL-6 expression. Risk factor-induced Nrf2 increase is insufficient to generate an antioxidant response in fetal membranes. Sulforaphane may enhance innate antioxidant and anti-inflammatory capacity by increasing NRF-2 expression. Full article

(This article belongs to the Special Issue Natural Antioxidants)

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14 pages, 2571 KiB

Open AccessArticle

Interactions of Calcium with Chlorogenic and Rosmarinic Acids: An Experimental and Theoretical Approach

by Estelle Palierse, Cédric Przybylski, Dalil Brouri, Claude Jolivalt and Thibaud Coradin

Int. J. Mol. Sci. 2020, 21(14), 4948; https://doi.org/10.3390/ijms21144948 - 13 Jul 2020

Cited by 12 | Viewed by 3620

Abstract

Chlorogenic (CA) and rosmarinic (RA) acids are two natural bioactive hydroxycinnamic acids whose antioxidant properties can be modulated by the chelation of metal ions. In this work, the interactions of these two carboxylic phenols with calcium ions and the impact of such interactions on their antioxidant activity were investigated. UV-Vis absorbance, mass spectroscopy and ¹H and ¹³C liquid NMR were used to identify complexes formed by CA and RA with calcium. Antioxidant activities were measured by the Bois method. Density functional theory (DFT) calculations were performed to evaluate the most stable configurations and correlated with NMR data. Taken together, these data suggest that calcium ions mainly interact with the carboxylate groups of both molecules but that this interaction modifies the reactivity of the catechol groups, especially for RA. These results highlight the complex interplay between metal chelation and antioxidant properties of natural carboxylic phenols. Full article

(This article belongs to the Special Issue Natural Antioxidants)

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17 pages, 2570 KiB

Open AccessArticle

Coloured Rice Phenolic Extracts Increase Expression of Genes Associated with Insulin Secretion in Rat Pancreatic Insulinoma β-cells

by Gideon Gatluak Kang, Nidhish Francis, Rodney Hill, Daniel LE Waters, Christopher L. Blanchard and Abishek Bommannan Santhakumar

Int. J. Mol. Sci. 2020, 21(9), 3314; https://doi.org/10.3390/ijms21093314 - 7 May 2020

Cited by 8 | Viewed by 2990

Abstract

Glucose-induced oxidative stress is associated with the overproduction of reactive oxygen species (ROS), which may dysregulate the expression of genes controlling insulin secretion leading to β-cell dysfunction, a hallmark of type 2 diabetes mellitus (T2DM). This study investigated the impact of coloured rice phenolic extracts (CRPEs) on the expression of key genes associated with β-cell function in pancreatic β-cells (INS-1E). These genes included glucose transporter 2 (Glut2), silent mating type information regulation 2 homolog 1 (Sirt1), mitochondrial transcription factor A (Tfam), pancreatic/duodenal homeobox protein 1 (Pdx-1) and insulin 1 (Ins1). INS-1E cells were cultured in high glucose (25 mM) to induce glucotoxic stress conditions (HGSC) and in normal glucose conditions (NGC-11.1 mM) to represent normal β-cell function. Cells were treated with CRPEs derived from two coloured rice cultivars, Purple and Yunlu29-red varieties at concentrations ranged from 50 to 250 µg/mL. CRPEs upregulated the expression of Glut2, Sirt1 and Pdx-1 significantly at 250 µg/mL under HGSC. CRPEs from both cultivars also upregulated Glut2, Sirt1, Tfam, Pdx-1 and Ins1 markedly at 250 µg/mL under NGC with Yunlu29 having the greatest effect. These data suggest that CRPEs may reduce β-cell dysfunction in T2DM by upregulating the expression of genes involved in insulin secretion pathways. Full article

(This article belongs to the Special Issue Natural Antioxidants)

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20 pages, 1190 KiB

Open AccessArticle

Properties of Ginkgo biloba L.: Antioxidant Characterization, Antimicrobial Activities, and Genomic MicroRNA Based Marker Fingerprints

by Katarína Ražná, Zuzanna Sawinska, Eva Ivanišová, Nenad Vukovic, Margarita Terentjeva, Michal Stričík, Przemysław Łukasz Kowalczewski, Lucia Hlavačková, Katarína Rovná, Jana Žiarovská and Miroslava Kačániová

Int. J. Mol. Sci. 2020, 21(9), 3087; https://doi.org/10.3390/ijms21093087 - 27 Apr 2020

Cited by 47 | Viewed by 4890

Abstract

The aim of this study was to characterize extracts from the leaves of Ginkgo biloba L. from selected Slovakian localities in terms of the content of bioactive constituents, antioxidants and their antimicrobial properties. The results indicated that the content of antioxidants was sample-specific, and this specificity was statistically significant. Ginkgo biloba L. from the locality of Košice had the best activity determined by the free radical scavenging activity (DPPH) (1.545 mg Trolox equivalent antioxidant capacity (TEAC)/g fresh matter (FM)) as well as the molybdenum-reducing antioxidant power (35.485 mg TEAC/g FM) methods. The highest content of total polyphenols (2.803 mg gallic acid equivalent (GAE)/g FM) and flavonoids (4.649 μg quercetin equivalent (QE)/g FM) was also detected in this sample. All samples of G. biloba leaf extracts showed significant antimicrobial activity against one or more of the examined bacterial species, and Staphylococcus aureus subsp. aureus CCM 2461 was found to be the most susceptible (minimal inhibition concentration MIC50 and MIC90 values of 64.2 and 72.2 µg/mL, respectively). Based on the results it was concluded that Ginkgo biloba L. extracts can be used as antimicrobial and antioxidant additives. Selected miRNA-based molecular markers were used to examine the environmental adaptability of Ginkgo biloba L. An almost-complete genotype clustering pattern based on locality was determined in the analysis that involved a species-specific gb-miR5261 marker. Morphologically specific exemplar, cv. Ohatsuki, was excluded. Full article

(This article belongs to the Special Issue Natural Antioxidants)

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14 pages, 591 KiB

Open AccessArticle

Influence of Abiotic Stress Factors on the Antioxidant Properties and Polyphenols Profile Composition of Green Barley (Hordeum vulgare L.)

by Przemysław Łukasz Kowalczewski, Dominika Radzikowska, Eva Ivanišová, Artur Szwengiel, Miroslava Kačániová and Zuzanna Sawinska

Int. J. Mol. Sci. 2020, 21(2), 397; https://doi.org/10.3390/ijms21020397 - 8 Jan 2020

Cited by 50 | Viewed by 4124

Abstract

The influence of stress factors on the plant can, on the one hand, lead to worse functioning of the plant and loss of its crop, but on the other, it can have a positive effect on the metabolism of compounds with documented biological activity. In this study, the effect of light and drought intensity on photosynthetic activity and physiological status of two barley varieties, as well as the antimicrobial, antioxidant properties and profile of polyphenolic compounds of green barley were analysed. It was shown that under the conditions of water shortage, the KWS Olof variety showed a smaller decrease in CO₂ assimilation and transpiration and higher values of these parameters at both light intensities. Only in the KWS Olof variety increased stress as a result of increased light intensity. It has also been shown that both the intensity of radiation and drought-related stress have a significant impact on the profile of polyphenolic compounds from green barley, without a simple relationship between the impact of stress factors on the content of polyphenols. Changes in the profile of polyphenolic compounds augmented the antioxidant and antimicrobial activity of the material. This, in turn, proposes the possibility of reducing the applied doses of herbal material thanks to a greater content of active substances in extracts obtained from the plants used to produce medicinal preparations. Full article

(This article belongs to the Special Issue Natural Antioxidants)

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Review

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20 pages, 821 KiB

Open AccessReview

Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immune Activation: Could Such a Scenario Be Helpful to Counteract COVID-19?

by Marta Menegazzi, Rachele Campagnari, Mariarita Bertoldi, Rosalia Crupi, Rosanna Di Paola and Salvatore Cuzzocrea

Int. J. Mol. Sci. 2020, 21(14), 5171; https://doi.org/10.3390/ijms21145171 - 21 Jul 2020

Cited by 74 | Viewed by 13442

Abstract

Some coronavirus disease 2019 (COVID-19) patients develop acute pneumonia which can result in a cytokine storm syndrome in response to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. The most effective anti-inflammatory drugs employed so far in severe COVID-19 belong to the cytokine-directed biological agents, widely used in the management of many autoimmune diseases. In this paper we analyze the efficacy of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea leaves and a well-known antioxidant, in counteracting autoimmune diseases, which are dominated by a massive cytokines production. Indeed, many studies registered that EGCG inhibits signal transducer and activator of transcription (STAT)1/3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factors, whose activities are crucial in a multiplicity of downstream pro-inflammatory signaling pathways. Importantly, the safety of EGCG/green tea extract supplementation is well documented in many clinical trials, as discussed in this review. Since EGCG can restore the natural immunological homeostasis in many different autoimmune diseases, we propose here a supplementation therapy with EGCG in COVID-19 patients. Besides some antiviral and anti-sepsis actions, the major EGCG benefits lie in its anti-fibrotic effect and in the ability to simultaneously downregulate expression and signaling of many inflammatory mediators. In conclusion, EGCG can be considered a potential safe natural supplement to counteract hyper-inflammation growing in COVID-19. Full article

(This article belongs to the Special Issue Natural Antioxidants)

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34 pages, 2187 KiB

Open AccessReview

Nutraceutical Compounds Targeting Inflammasomes in Human Diseases

by Beatriz Castejón-Vega, Francesca Giampieri and José M. Alvarez-Suarez

Int. J. Mol. Sci. 2020, 21(14), 4829; https://doi.org/10.3390/ijms21144829 - 8 Jul 2020

Cited by 16 | Viewed by 5336

Abstract

The macromolecular complex known as “inflammasome” is defined as an intracellular multi-protein complex composed of a sensor receptor (PRR), an adaptor protein and an effector enzyme (caspase-1), which oligomerize when they sense danger, such as how the NLR family, AIM-2 and RIG-1 receptors protect the body against danger via cytokine secretion. Within the NLR members, NLRP3 is the most widely known and studied inflammasome and has been linked to many diseases. Nowadays, people’s interest in their lifestyles and nutritional habits is increasing, mainly due to the large number of diseases that seem to be related to both. The term “nutraceutical” has recently emerged as a hybrid term between “nutrition” and “pharmacological” and it refers to a wide range of bioactive compounds contained in food with relevant effects on human health. The relationship between these compounds and diseases based on inflammatory processes has been widely exposed and the compounds stand out as an alternative to the pathological consequences that inflammatory processes may have, beyond their defense and repair action. Against this backdrop, here we review the results of studies using several nutraceutical compounds in common diseases associated with the inflammation and activation of the NLRP3 inflammasomes complex. In general, it was found that there is a wide range of nutraceuticals with effects through different molecular pathways that affect the activation of the inflammasome complex, with positive effects mainly in cardiovascular, neurological diseases, cancer and type 2 diabetes. Full article

(This article belongs to the Special Issue Natural Antioxidants)

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19 pages, 713 KiB

Open AccessReview

Polyphenols: Modulators of Platelet Function and Platelet Microparticle Generation?

by Borkwei Ed Nignpense, Kenneth A. Chinkwo, Christopher L. Blanchard and Abishek B. Santhakumar

Int. J. Mol. Sci. 2020, 21(1), 146; https://doi.org/10.3390/ijms21010146 - 24 Dec 2019

Cited by 63 | Viewed by 6338

Abstract

Platelets and platelet microparticles (PMPs) play a key role in the pathophysiology of vascular disorders such as coronary artery disease and stroke. In atherosclerosis, for example, the disruption of the plaque exposes endogenous agonists such as collagen, which activates platelets. Platelet hyper-activation and the high levels of PMPs generated in such situations pose a thrombotic risk that can lead to strokes or myocardial infarctions. Interestingly, dietary polyphenols are gaining much attention due to their potential to mimic the antiplatelet activity of treatment drugs such as aspirin and clopidogrel that target the glycoprotein VI (GPVI)–collagen and cyclooxygenease-1 (COX-1)–thromboxane platelet activation pathways respectively. Platelet function tests such as aggregometry and flow cytometry used to monitor the efficacy of antiplatelet drugs can also be used to assess the antiplatelet potential of dietary polyphenols. Despite the low bioavailability of polyphenols, several in vitro and dietary intervention studies have reported antiplatelet effects of polyphenols. This review presents a summary of platelet function in terms of aggregation, secretion, activation marker expression, and PMP release. Furthermore, the review will critically evaluate studies demonstrating the impact of polyphenols on aggregation and PMP release. Full article

(This article belongs to the Special Issue Natural Antioxidants)

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26 pages, 833 KiB

Open AccessReview

Dietary Polyphenols and Gene Expression in Molecular Pathways Associated with Type 2 Diabetes Mellitus: A Review

by Gideon Gatluak Kang, Nidhish Francis, Rodney Hill, Daniel Waters, Christopher Blanchard and Abishek Bommannan Santhakumar

Int. J. Mol. Sci. 2020, 21(1), 140; https://doi.org/10.3390/ijms21010140 - 24 Dec 2019

Cited by 104 | Viewed by 9901

Abstract

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with various contributing factors including genetics, epigenetics, environment and lifestyle such as diet. The hallmarks of T2DM are insulin deficiency (also referred to as β-cell dysfunction) and insulin resistance. Robust evidence suggests that the major mechanism driving impaired β-cell function and insulin signalling is through the action of intracellular reactive oxygen species (ROS)-induced stress. Chronic high blood glucose (hyperglycaemia) and hyperlipidaemia appear to be the primary activators of these pathways. Reactive oxygen species can disrupt intracellular signalling pathways, thereby dysregulating the expression of genes associated with insulin secretion and signalling. Plant-based diets, containing phenolic compounds, have been shown to exhibit remedial benefits by ameliorating insulin secretion and insulin resistance. The literature also provides evidence that polyphenol-rich diets can modulate the expression of genes involved in insulin secretion, insulin signalling, and liver gluconeogenesis pathways. However, whether various polyphenols and phenolic compounds can target specific cellular signalling pathways involved in the pathogenesis of T2DM has not been elucidated. This review aims to evaluate the modulating effects of various polyphenols and phenolic compounds on genes involved in cellular signalling pathways (both in vitro and in vivo from human, animal and cell models) leading to the pathogenesis of T2DM. Full article

(This article belongs to the Special Issue Natural Antioxidants)

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