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Dietary Bioactives and Their Metabolites as Modulators of Oxidative Stress and Inflammation

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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 (30 September 2021) | Viewed by 25993

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Special Issue Editors

Dr. Monica Deiana

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Guest Editor

Università degli Studi di Cagliari, Cagliari, Italy
Interests: oxidative stress; lipid peroxidation; inflammation; dietary antioxidants; polyphenols; bioavailability; diet and health

Dr. Gabriele Serreli

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Guest Editor

Università degli Studi di Cagliari, Cagliari, Italy
Interests: human nutrition; oxidative stress; polyphenols; metabolites; bioactive compounds; intracellular signaling

Dr. Giulia Corona

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Guest Editor

University of Roehampton, London, UK
Interests: nutrition; dietary bioactives; phytochemicals; polyphenols; metabolism; bioavailability; diet and health; chronic diseases; cardiovascular health; oxidative stress; inflammation

Special Issue Information

Dear Colleagues,

The regular intake of dietary bioactive compounds may play a key role in health and disease, contributing to an improved state of well‐being, a reduction of risks related to degenerative diseases and even an improvement in the quality of life. Dietary bioactive compounds include phytochemicals, whose activity has been investigated in numerous studies, mainly in in vitro assays and in some instances in vivo in both animal models and human interventions. Experimental evidence has demonstrated their ability to act as antioxidants and anti-inflammatory agents, thus contributing to prevent/slow down chronic diseases. However, the real impact of such compounds on human health is still being debated, as circulating concentrations of phytochemicals after their dietary consumption are often very low, due to their poor bioavailability and extensive metabolization in the gastrointestinal tract and in the liver. Recent advances in the field of phytochemicals are therefore focusing on the bioactivity of their main metabolites, that have been shown to be able to reach concentrations compatible with a biological activity in several tissues. They seem to retain the potential beneficial properties of the parent compounds, which may even be enhanced, acting as signaling molecules, other than direct antioxidants. Nevertheless, most of the mechanistic aspects of their biological activity remains poorly understood.

In this special issue we aim to collect latest researches or review articles that will provide new evidence on the still unexplored areas concerning the metabolites that can be generated in vivo from dietary phytochemicals. In particular, the special issue will be focused on the features of in vivo-formed metabolites, their bioavailability and mostly on the mechanism of their action in various models of human disease (based on cell models/in vitro or in vivo studies) characterized by oxidative imbalance and/or inflammation.

Dr. Monica Deiana
Dr. Gabriele Serreli
Dr. Giulia Corona
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

Phytochemicals
Antioxidants
Polyphenols
Signaling
Mechanisms
Metabolites

Published Papers (9 papers)

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Research

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14 pages, 1589 KiB

Open AccessArticle

Effects of Wine and Tyrosol on the Lipid Metabolic Profile of Subjects at Risk of Cardiovascular Disease: Potential Cardioprotective Role of Ceramides

by Jose Rodríguez-Morató, Anna Boronat, Gabriele Serreli, Laura Enríquez, Alex Gomez-Gomez, Oscar J. Pozo, Montserrat Fitó and Rafael de la Torre

Antioxidants 2021, 10(11), 1679; https://doi.org/10.3390/antiox10111679 - 25 Oct 2021

Cited by 4 | Viewed by 2116

Abstract

Ceramides are a class of sphingolipids which have recently been shown to be better cardiovascular disease (CVD) risk predictors than traditional CVD risk biomarkers. Tyrosol (TYR) is a dietary phenolic compound known to possess cardioprotective effects per se or through its in vivo active metabolite hydroxytyrosol. The purpose of this study was to evaluate the effects of the co-administration of white wine (WW) and TYR on circulating levels of ceramides and other lipids in humans at high CVD risk. Volunteers underwent a randomized controlled crossover clinical trial (4-week duration per intervention) with three different interventions: control, WW, and WW enriched with a capsule of TYR (WW + TYR). Endothelial function cardiovascular biomarkers and plasma lipidomic profile were assessed before and after each intervention. It was found that the WW + TYR intervention resulted in lower levels of three ceramide ratios, associated with an improvement of endothelial function (Cer C16:0/Cer C24:0, Cer C18:0/Cer C24:0, and Cer C24:1/Cer C24:0), when compared to the control intervention. Moreover, WW + TYR was able to minimize the alterations in plasma diacylglycerols concentrations observed following WW. Overall, the results obtained show that the antioxidant TYR administered with WW exerts beneficial effects at the cardiovascular level, in part by modulating blood lipid profile. Full article

(This article belongs to the Special Issue Dietary Bioactives and Their Metabolites as Modulators of Oxidative Stress and Inflammation)

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17 pages, 2802 KiB

Open AccessArticle

Calystegia soldanella Extract Exerts Anti-Oxidative and Anti-Inflammatory Effects via the Regulation of the NF-κB/Nrf-2 Pathways in Mouse Macrophages

by Taekil Eom, In-Hye Kim, Hyung-Joo Kim, YounHee Choi and Taek-Jeong Nam

Antioxidants 2021, 10(10), 1639; https://doi.org/10.3390/antiox10101639 - 18 Oct 2021

Cited by 4 | Viewed by 2187

Abstract

Plant polyphenols are widely used to treat various inflammatory diseases, owing to their ability to suppress reactive oxygen species production and the expression of inflammatory cytokines. Herein, we investigated phenolic compounds from Calystegia soldanella using UPLC Q-TOF MS/MS and their antioxidative and anti-inflammatory activities were analyzed. The C. soldanella ethyl acetate fraction (CsEF) had the strongest antioxidative activity, given its high polyphenol compound content. It also exhibited anti-inflammatory effects, inhibiting the production of inflammatory cytokines such as NO, PGE2, IL-1β, IL-6, and TNF-α in LPS-stimulated mouse macrophages. CsEF activated the nuclear transcription factor Nrf-2, thereby upregulating antioxidant enzymes such as HO-1 and NQO-1 and inhibiting NF-κB expression, which in turn, suppressed the expression of COX-2, iNOS, and inflammatory cytokines, ultimately exerting anti-inflammatory effects. Further, UPLC-Q-TOF-MS/MS was used to analyze the polyphenol compound contents in CsEF. The quercetin glycosides isoquercitrin and quercitrin were the primary flavonoid compounds, while the caffeic acid derivatives, chlorogenic acid and dicaffeoylquinic acid, were the primary phenolic acids. Thus, C. soldanella, which had only a limited use thus far as a medicinal plant, may serve as a natural medicinal resource for treating inflammatory diseases. Full article

(This article belongs to the Special Issue Dietary Bioactives and Their Metabolites as Modulators of Oxidative Stress and Inflammation)

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24 pages, 3415 KiB

Open AccessArticle

Anti-Diabetic and Antioxidant Activities of Red Wine Concentrate Enriched with Polyphenol Compounds under Experimental Diabetes in Rats

by Mariya Sabadashka, Dariya Hertsyk, Paulina Strugała-Danak, Anita Dudek, Olena Kanyuka, Alicja Z. Kucharska, Leonid Kaprelyants and Nataliia Sybirna

Antioxidants 2021, 10(9), 1399; https://doi.org/10.3390/antiox10091399 - 31 Aug 2021

Cited by 6 | Viewed by 3326

Abstract

We obtained red wine concentrate, which was enriched with natural polyphenolic compounds (PC concentrate). The main purpose was to study the hypoglycemic and antioxidant effects of the red wine concentrate, and its impact on key hematological parameters of rats with experimental diabetes mellitus. While administrating the red wine concentrate to rats with diabetes, partial recovering of glucose tolerance was promoted, as well as normalization of glycated hemoglobin level, an increase in the quantity of erythrocytes and hemoglobin concentration. PC concentrate had anti-radical effect, which was determined using 2,2-diphenyl-1-picrylhydrazylradical (DPPH) method and effectively inhibited oxidation of phosphatidylcholine liposomes, induced by 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) as a free radical generator. It was also confirmed that PC concentrate had antioxidant properties in vivo. The contents of lipid peroxidation and protein oxidation products, the activity of catalase, and glutathione peroxidase (GPx) were increased in the plasma of rats with diabetes mellitus. At the same time, the activity of superoxide dismutase (SOD) was decreased. The concentrate of red wine had a corrective effect on investigated indicators and caused their normalization in plasma of diabetic animals. Full article

(This article belongs to the Special Issue Dietary Bioactives and Their Metabolites as Modulators of Oxidative Stress and Inflammation)

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11 pages, 1899 KiB

Open AccessArticle

Perinatal Resveratrol Therapy to Dioxin-Exposed Dams Prevents the Programming of Hypertension in Adult Rat Offspring

by Chien-Ning Hsu, Chih-Hsing Hung, Chih-Yao Hou, Chi-I. Chang and You-Lin Tain

Antioxidants 2021, 10(9), 1393; https://doi.org/10.3390/antiox10091393 - 30 Aug 2021

Cited by 15 | Viewed by 2279

Abstract

Exposure to environmental chemicals during pregnancy and lactation is a contributing factor in gut microbiota dysbiosis and linked to programming of hypertension. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin, induces toxic effects by mediating aryl hydrocarbon receptor (AHR). Resveratrol, a potent antioxidant with prebiotic properties, can possess high affinity for AHR and protect against TCDD-activated AHR attack. We examined whether perinatal resveratrol therapy prevents offspring hypertension programmed by maternal TCDD exposure and whether its beneficial effects are related to reshaping gut microbiota and antagonizing AHR-mediated T helper 17 (TH17) cells responses using a maternal TCDD exposure rat model. Pregnant Sprague-Dawley rats were given a weekly oral dose of TCDD 200 ng/kg for four doses (T), 50 mg/L of resveratrol in drinking water (CR), TCDD + resveratrol (TR), or vehicle (C) in pregnancy and lactation periods. Male offspring (n = 7–8/group) were sacrificed at the age of 12 weeks. Perinatal TCDD exposure caused elevated blood pressure in adult male offspring, which resveratrol supplementation prevented. Additionally, the TCDD-induced programming of hypertension is coincided with the activation of AHR signaling, TH17-induced renal inflammation, and alterations of gut microbiota compositions. Conversely, TCDD-mediated induction of AHR signaling and TH17 responses were restored by maternal resveratrol supplementation. Furthermore, maternal resveratrol supplementation prevented the programming of hypertension and was related to increased genera Bacteroides, ASF356, and Lachnoclostridium. Taken together, these results suggest that the interplay between gut microbiota, AHR-mediated TH17 responses, and renal inflammation in the gut and kidneys may play an important role in the action of resveratrol against TCDD-induced programming of hypertension. Full article

(This article belongs to the Special Issue Dietary Bioactives and Their Metabolites as Modulators of Oxidative Stress and Inflammation)

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14 pages, 2683 KiB

Open AccessArticle

Anthocyanins Promote Learning through Modulation of Synaptic Plasticity Related Proteins in an Animal Model of Ageing

by David Vauzour, Catarina Rendeiro, Alfonsina D’Amato, Pierre Waffo-Téguo, Tristan Richard, Jean Michel Mérillon, Matthew G. Pontifex, Emily Connell, Michael Müller, Laurie T. Butler, Claire M. Williams and Jeremy P. E. Spencer

Antioxidants 2021, 10(8), 1235; https://doi.org/10.3390/antiox10081235 - 31 Jul 2021

Cited by 16 | Viewed by 3255

Abstract

Anthocyanin-rich foods, such as berries, reportedly ameliorate age-related cognitive deficits in both animals and humans. Despite this, investigation into the mechanisms which underpin anthocyanin-mediated learning and memory benefits remains relatively limited. The present study investigates the effects of anthocyanin intake on a spatial working memory paradigm, assessed via the cross-maze apparatus, and relates behavioural test performance to underlying molecular mechanisms. Six-week supplementation with pure anthocyanins (2% w/w), administered throughout the learning phase of the task, improved both spatial and psychomotor performances in aged rats. Behavioural outputs were accompanied by changes in the expression profile of key proteins integral to synaptic function/maintenance, with upregulation of dystrophin, protein kinase B (PKB/Akt) and tyrosine hydroxylase, and downregulation of apoptotic proteins B-cell lymphoma-extra-large (Bcl-xL) and the phosphorylated rapidly accelerated fibrosarcoma (p-Raf). Separate immunoblot analysis supported these observations, indicating increased activation of extracellular signal-related kinase (ERK1), Akt Ser473, mammalian target of rapamycin (mTOR) Ser2448, activity-regulated cytoskeleton-associated protein (Arc/Arg 3.1) and brain-derived neurotrophic factor (BDNF) in response to anthocyanin treatment, whilst α-E-catenin, c-Jun N-terminal kinase (JNK1) and p38 protein levels decreased. Together, these findings suggest that purified anthocyanin consumption enhances spatial learning and motor coordination in aged animals and can be attributed to the modulation of key synaptic proteins, which support integrity and maintenance of synaptic function. Full article

(This article belongs to the Special Issue Dietary Bioactives and Their Metabolites as Modulators of Oxidative Stress and Inflammation)

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16 pages, 1406 KiB

Open AccessArticle

Ex Vivo Study on the Antioxidant Activity of a Winemaking By-Product Polyphenolic Extract (Taurisolo^®) on Human Neutrophils

by Giuseppe Annunziata, Xavier Capó, Maria Magdalena Quetglas-Llabrés, Margalida Monserrat-Mesquida, Silvia Tejada, Josep A. Tur, Roberto Ciampaglia, Fabrizia Guerra, Maria Maisto, Gian Carlo Tenore, Ettore Novellino and Antoni Sureda

Antioxidants 2021, 10(7), 1009; https://doi.org/10.3390/antiox10071009 - 23 Jun 2021

Cited by 10 | Viewed by 2069

Abstract

Oxidative stress (OxS) has been linked to several chronic diseases and is recognized to have both major causes and consequences. The use of antioxidant-based nutraceuticals has been licensed as an optimal tool for management of OxS-related diseases. Currently, great interest is focused on the valorization of agri-food by-products as a source of bioactive compounds, including polyphenols. In this sense, we evaluated the efficacy of a novel nutraceutical formulation based on polyphenolic extract from Aglianico cultivar grape pomace (registered as Taurisolo^®). In particular, we tested both native and in vitro gastrointestinal digested forms. The two extracts have been used to treat ex vivo neutrophils from subjects with metabolic syndrome, reporting a marked antioxidant activity of Taurisolo^®, as shown by its ability to significantly reduce both the levels of reactive oxygen species (ROS) and the activities of catalase and myeloperoxidase in the cell medium after stimulation of neutrophils with phorbol 12-myristate 13-acetate (PMA). Interestingly, we observed an increase in intracellular enzymatic activities in PMA-treated cells, suggesting that Taurisolo^® polyphenols might be able to activate nuclear factors, up-regulating the expression of this target antioxidant gene. In addition, Taurisolo^® reversed the increase in malondialdehyde induced by PMA; reduced the expression of pro-inflammatory genes such as cyclooxygenase 2 (COX-2), tumor necrosis factor alpha (TNFα) and myeloperoxidase (MPO); and induced the expression of the anti-inflammatory cytokine IL-10. Overall, these results suggest the efficacy of Taurisolo^® in contrasting the OxS at blood level, providing evidence for its therapeutic potential in the management of OxS-related pathological conditions in humans. Full article

(This article belongs to the Special Issue Dietary Bioactives and Their Metabolites as Modulators of Oxidative Stress and Inflammation)

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12 pages, 2203 KiB

Open AccessArticle

DNA Protection by an Aronia Juice-Based Food Supplement

by Tamara Bakuradze, Peter Meiser, Jens Galan and Elke Richling

Antioxidants 2021, 10(6), 857; https://doi.org/10.3390/antiox10060857 - 27 May 2021

Cited by 3 | Viewed by 2578

Abstract

Background: This study investigated the effects of an aronia juice-based food supplement on background and total DNA strand breaks in whole blood, and on H₂O₂-induced DNA strand breaks in isolated peripheral blood lymphocytes. Methods: Ninety-one healthy volunteers were randomly selected to consume either the food supplement (2 × 25 mL drinking ampules, n = 45) or no supplement (n = 46) daily for eight weeks. Results: Background DNA strand breaks decreased significantly after four and eight weeks of supplement consumption, compared to baseline (p < 0.05), but the overall effect was low, and neither group showed a decrease in total DNA strand breaks. Conversely, supplement consumption clearly reduced H₂O₂-induced DNA strand breaks ex vivo (p < 0.001), with statistically significant reductions after four and eight weeks, compared to the control group (p < 0.05). Conclusions: Thus, although consuming antioxidant supplements might produce only marginal immediate benefits under healthy conditions, potential preventive effects warrant further investigation. Full article

(This article belongs to the Special Issue Dietary Bioactives and Their Metabolites as Modulators of Oxidative Stress and Inflammation)

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21 pages, 3933 KiB

Open AccessArticle

Aqueous Blackcurrant Extract Improves Insulin Sensitivity and Secretion and Modulates the Gut Microbiome in Non-Obese Type 2 Diabetic Rats

by Hye-Jeong Yang, Ting Zhang, Xuan-Gao Wu, Min-Jung Kim, Young-Ho Kim, Eun-Suk Yang, Yeong-Seok Yoon and Sunmin Park

Antioxidants 2021, 10(5), 756; https://doi.org/10.3390/antiox10050756 - 10 May 2021

Cited by 22 | Viewed by 3090

Abstract

This study was undertaken to determine whether aqueous blackcurrant extracts (BC) improve glucose metabolism and gut microbiomes in non-obese type 2 diabetic animals fed a high-fat diet and to identify the mechanism involved. Partially pancreatectomized male Sprague–Dawley rats were provided a high-fat diet containing 0% (control), 0.2% (L-BC; low dosage), 0.6% (M-BC; medium dosage), and 1.8% (H-BC; high dosage) blackcurrant extracts; 0.2% metformin (positive-C); plus 1.8%, 1.6%, 1.2%, 0%, and 1.6% dextrin, specifically indigestible dextrin, daily for 8 weeks. Daily blackcurrant extract intakes were equivalent to 100, 300, and 900 mg/kg body weight (bw). After a 2 g glucose or maltose/kg bw challenge, serum glucose and insulin concentrations during peak and final states were obviously lower in the M-BC and H-BC groups than in the control group (p < 0.05). Intraperitoneal insulin tolerance testing showed that M-BC and H-BC improved insulin resistance. Hepatic triglyceride deposition, TNF-α expression, and malondialdehyde contents were lower in the M-BC and H-BC groups than in the control group. Improvements in insulin resistance in the M-BC and H-BC groups were associated with reduced inflammation and oxidative stress (p < 0.05). Hyperglycemic clamp testing showed that insulin secretion capacity increased in the acute phase (2 to 10 min) in the M-BC and H-BC groups and that insulin sensitivity in the hyperglycemic state was greater in these groups than in the control group (p < 0.05). Pancreatic β-cell mass was greater in the M-BC, H-BC, and positive-C groups than in the control group. Furthermore, β-cell proliferation appeared to be elevated and apoptosis was suppressed in these three groups (p < 0.05). Serum propionate and butyrate concentrations were higher in the M-BC and H-BC groups than in the control group. BC dose-dependently increased α-diversity of the gut microbiota and predicted the enhancement of oxidative phosphorylation-related microbiome genes and downregulation of carbohydrate digestion and absorption-related genes, as determined by PICRUSt2 analysis. In conclusion, BC enhanced insulin sensitivity and glucose-stimulated insulin secretion, which improved glucose homeostasis, and these improvements were associated with an incremental increase of the α-diversity of gut microbiota and suppressed inflammation and oxidative stress. Full article

(This article belongs to the Special Issue Dietary Bioactives and Their Metabolites as Modulators of Oxidative Stress and Inflammation)

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Review

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28 pages, 1730 KiB

Open AccessReview

Can Polyphenols Inhibit Ferroptosis?

by Marija Lesjak, Nataša Simin and Surjit K. S. Srai

Antioxidants 2022, 11(1), 150; https://doi.org/10.3390/antiox11010150 - 12 Jan 2022

Cited by 15 | Viewed by 3648

Abstract

Polyphenols, a diverse group of naturally occurring molecules commonly found in higher plants, have been heavily investigated over the last two decades due to their potent biological activities—among which the most important are their antioxidant, antimicrobial, anticancer, anti-inflammatory and neuroprotective activities. A common route of polyphenol intake in humans is through the diet. Since they are subjected to excessive metabolism in vivo it has been questioned whether their much-proven in vitro bioactivity could be translated to in vivo systems. Ferroptosis is a newly introduced, iron-dependent, regulated mode of oxidative cell death, characterized by increased lipid peroxidation and the accumulation of toxic lipid peroxides, which are considered to be toxic reactive oxygen species. There is a growing body of evidence that ferroptosis is involved in the development of almost all chronic diseases. Thus, ferroptosis is considered a new therapeutic target for offsetting many diseases, and researchers are putting great expectations on this field of research and medicine. The aim of this review is to critically analyse the potential of polyphenols to modulate ferroptosis and whether they can be considered promising compounds for the alleviation of chronic conditions. Full article

(This article belongs to the Special Issue Dietary Bioactives and Their Metabolites as Modulators of Oxidative Stress and Inflammation)

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