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Resveratrol 2021: Recent Advances in the Application of Resveratrol to Improve Health

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

Deadline for manuscript submissions: closed (15 October 2021) | Viewed by 37756

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Special Issue Editors

Dr. Thomas Netticadan

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Guest Editor

Canadian Centre for Agri-Food Research in Health and Medicine and Agriculture and Agri-Food Canada, Winnipeg, MB, Canada
Interests: cardiovascular disease; bioactive compounds; functional foods
Special Issues, Collections and Topics in MDPI journals

Dr. Jeffrey Wigle

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Guest Editor

1. Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
2. Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
Interests: vascular development; transcription factors; fibroblasts/myofibroblasts and fibrosis
Special Issues, Collections and Topics in MDPI journals

Dr. Pema Raj

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Guest Editor

Canadian Centre for Agri-Food Research in Health and Medicine and Agriculture and Agri-Food Canada, Winnipeg, MB, Canada
Interests: heart failure; nutraceuticals; translational research

Special Issue Information

Dear Colleagues,

Resveratrol is a widely studied plant compound with established benefits against various chronic diseases. Over the years, a wealth of high quality knowledge has been reported on various topics related to many aspects of resveratrol ranging from fundamental in vitro studies to in vivo studies. In addition to direct health-focussed studies, there have been pharmacokinetics investigations aimed at tackling the issue of resveratrol bioavailability and novel studies that have investigated new strategies to produce crops/foods with enhanced levels of resveratol. Meta-analyses and Cochrane reviews on resveratrol still debate the efficacy of resveratol in humans and inform us of the critical need to pursue high-quality investigations to address the controversies in the field of resveratrol and to also provide further compeling evidence to carry forward reseach on resveratrol. Advancement in our knowledge related to various aspects of resveratrol with more innovative studies is needed. In this Special Issue, we invite the submission of articles that focus on new advancements in the use of resveratrol to improve health in animals and humans as given below:

Approaches on the pharmacokinetics and formulations related to resveratol;

Strategies for enhancing the levels of resveratrol in crops/foods;

In vitro studies on resveratrol that report a novel use/proof of concept or mechanistic insights;

In vivo studies that report new findings on the safety and efficacy of resveratrol in preventing or managing animal diseases;

In vivo studies that report new findings on the safety and efficacy of resveratrol in animal models mimicking human disease;

Studies that report new findings on the safety and efficacy of resveratrol in preventing or managing human diseases.

Dr. Thomas Netticadan
Dr. Jeffrey Wigle
Dr. Pema Raj
Guest Editors

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Keywords

Resveratrol
In vitro studies
In vivo studies

Published Papers (10 papers)

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Research

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16 pages, 2214 KiB

Open AccessArticle

Resveratrol, EGCG and Vitamins Modulate Activated T Lymphocytes

by Joseph Schwager, Nicole Seifert, Albine Bompard, Daniel Raederstorff and Igor Bendik

Molecules 2021, 26(18), 5600; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26185600 - 15 Sep 2021

Cited by 8 | Viewed by 2541

Abstract

Vitamins and bioactives, which are constituents of the food chain, modulate T lymphocyte proliferation and differentiation, antibody production, and prevent inflammation and autoimmunity. We investigated the effects of vitamins (vitamin A (VA), D (VD), E (VE)) and bioactives (i.e., resveratrol (Res), epigallocatechin-3-gallate (EGCG)) on the adaptive immune response, as well as their synergistic or antagonistic interactions. Freshly isolated T lymphocytes from healthy individuals were activated with anti-CD3/CD28 antibodies for 4–5 days in the presence of bioactives and were analyzed by cytofluorometry. Interleukins, cytokines, and chemokines were measured by multiple ELISA. Gene expression was measured by quantitative RT-PCR. Res and EGCG increased CD4 surface intensity. EGCG led to an increased proportion of CD8⁺ lymphocytes. Anti-CD3/CD28 activation induced exuberant secretion of interleukins and cytokines by T lymphocyte subsets. VD strongly enhanced T_h2 cytokines (e.g., IL-5, IL-13), whereas Res and EGCG favored secretion of T_h1 cytokines (e.g., IL-2, INF-γ). Res and VD mutually influenced cytokine production, but VD dominated the cytokine secretion pattern. The substances changed gene expression of interleukins and cytokines in a similar way as they did secretion. Collectively, VD strongly modulated cytokine and interleukin production and favored T_h2 functions. Resveratrol and EGCG promoted the T_h1 response. VA and VE had only a marginal effect, but they altered both T_h1 and T_h2 response. In vivo, bioactives might therefore interact with vitamins and support the outcome and extent of the adaptive immune response. Full article

(This article belongs to the Special Issue Resveratrol 2021: Recent Advances in the Application of Resveratrol to Improve Health)

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14 pages, 2344 KiB

Open AccessArticle

Comparative and Combinatorial Effects of Resveratrol and Sacubitril/Valsartan alongside Valsartan on Cardiac Remodeling and Dysfunction in MI-Induced Rats

by Pema Raj, Karen Sayfee, Mihir Parikh, Liping Yu, Jeffrey Wigle, Thomas Netticadan and Shelley Zieroth

Molecules 2021, 26(16), 5006; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26165006 - 18 Aug 2021

Cited by 13 | Viewed by 2777

Abstract

The development and progression of heart failure (HF) due to myocardial infarction (MI) is a major concern even with current optimal therapy. Resveratrol is a plant polyphenol with cardioprotective properties. Sacubitril/valsartan is known to be beneficial in chronic HF patients. In this study, we investigated the comparative and combinatorial benefits of resveratrol with sacubitril/valsartan alongside an active comparator valsartan in MI-induced male Sprague Dawley rats. MI-induced and sham-operated animals received vehicle, resveratrol, sacubitril/valsartan, valsartan alone or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint to assess cardiac structure and function. Cardiac oxidative stress, inflammation, fibrosis, brain natriuretic peptide (BNP), creatinine and neutrophil gelatinase associated lipocalin were measured. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented left ventricular (LV) dilatation and improved LV ejection fraction in MI-induced rats. All treatments also significantly reduced myocardial tissue oxidative stress, inflammation and fibrosis, as well as BNP. Treatment with the combination of sacubitril/valsartan and resveratrol did not show additive effects. In conclusion, resveratrol, sacubitril/valsartan, and valsartan significantly prevented cardiac remodeling and dysfunction in MI-induced rats. The reduction in cardiac remodeling and dysfunction in MI-induced rats was mediated by a reduction in cardiac oxidative stress, inflammation and fibrosis. Full article

(This article belongs to the Special Issue Resveratrol 2021: Recent Advances in the Application of Resveratrol to Improve Health)

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18 pages, 1645 KiB

Open AccessArticle

Resveratrol Butyrate Esters Inhibit Obesity Caused by Perinatal Exposure to Bisphenol A in Female Offspring Rats

by Ming-Kuei Shih, You-Lin Tain, Yu-Wei Chen, Wei-Hsuan Hsu, Yao-Tsung Yeh, Sam K. C. Chang, Jin-Xian Liao and Chih-Yao Hou

Molecules 2021, 26(13), 4010; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26134010 - 30 Jun 2021

Cited by 23 | Viewed by 3721

Abstract

Resveratrol butyrate esters (RBE) are derivatives of resveratrol (RSV) and butyric acid and exhibit biological activity similar to that of RSV but with higher bioavailability. The aim of this study was designed as an animal experiment to explore the effects of RBE on the serum biochemistry, and fat deposits in the offspring rats exposed to bisphenol A (BPA), along with the growth and decline of gut microbiota. We constructed an animal model of perinatal Bisphenol A (BPA) exposure to observe the effects of RBE supplementation on obesity, blood lipids, and intestinal microbiota in female offspring rats. Perinatal exposure to BPA led to weight gain, lipid accumulation, high levels of blood lipids, and deterioration of intestinal microbiota in female offspring rats. RBE supplementation reduced the weight gain and lipid accumulation caused by BPA, optimised the levels of blood lipids, significantly reduced the Firmicutes/Bacteroidetes (F/B) ratio, and increased and decreased the abundance of S24-7 and Lactobacillus, respectively. The analysis of faecal short-chain fatty acid (SCFA) levels revealed that BPA exposure increased the faecal concentration of acetate, which could be reduced via RBE supplementation. However, the faecal concentrations of propionate and butyrate were not only significantly lower than that of acetate, but also did not significantly change in response to BPA exposure or RBE supplementation. Hence, RBE can suppress BPA-induced obesity in female offspring rats, and it demonstrates excellent modulatory activity on intestinal microbiota, with potential applications in perinatological research. Full article

(This article belongs to the Special Issue Resveratrol 2021: Recent Advances in the Application of Resveratrol to Improve Health)

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12 pages, 279 KiB

Open AccessArticle

Comparison of Resveratrol Supplementation and Energy Restriction Effects on Sympathetic Nervous System Activity and Vascular Reactivity: A Randomized Clinical Trial

by Gustavo Henrique Ferreira Gonçalinho, Alessandra Roggerio, Marisa Fernandes da Silva Goes, Solange Desirée Avakian, Dalila Pinheiro Leal, Célia Maria Cassaro Strunz and Antonio de Padua Mansur

Molecules 2021, 26(11), 3168; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26113168 - 26 May 2021

Cited by 11 | Viewed by 3238

Abstract

Background: Chronic sympathetic nervous system activation is associated with endothelial dysfunction and cardiometabolic disease, which may be modulated by resveratrol (RSV) and energy restriction (ER). This study aimed to examine the effects of RSV and ER on plasma noradrenaline (NA), flow-mediated vasodilation (ed-FMD), and endothelium-independent nitrate-mediated vasodilation (ei-NMD). Methods: The study included 48 healthy adults randomized to 30-days intervention of RSV or ER. Results: Waist circumference, total cholesterol, HDL-c, LDL-c, apoA-I, and plasma NA decreased in the ER group, whilst RSV increased apoB and total cholesterol, without changing plasma NA. No effects on vascular reactivity were observed in both groups. Plasma NA change was positively correlated with total cholesterol (r = 0.443; p = 0.002), triglycerides (r = 0.438; p = 0.002), apoA-I (r = 0.467; p = 0.001), apoB (r = 0.318; p = 0.032) changes, and ei-NMD (OR = 1.294; 95%CI: 1.021–1.640). Conclusions: RSV does not improve cardiometabolic risk factors, sympathetic activity, and endothelial function. ER decreases plasma NA and waist circumference as well as improves blood lipids, but does not modify endothelial function. Finally, plasma NA was associated with ei-NMD, which could be attributed to a higher response to nitrate in patients with greater resting sympathetic vasoconstriction. Full article

(This article belongs to the Special Issue Resveratrol 2021: Recent Advances in the Application of Resveratrol to Improve Health)

9 pages, 1632 KiB

Open AccessArticle

Impact of Climatic Conditions on the Resveratrol Concentration in Blend of Vitis vinifera L. cvs. Barbera and Croatina Grape Wines

by Gabriele Rocchetti, Federico Ferrari, Marco Trevisan and Luigi Bavaresco

Molecules 2021, 26(2), 401; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26020401 - 14 Jan 2021

Cited by 7 | Viewed by 1963

Abstract

The aim of this work was to investigate the effect of meteorological conditions on resveratrol concentration of red wines produced in Piacenza viticultural region (Italy). In this regard, six representative estates producing Colli Piacentini Gutturnio DOC (a blend of V. vinifera L. cvs. Barbera and Croatina) vintage wines were analysed for trans- and cis-resveratrol over an 8-year period (1998–2005). Grapes were taken from the same vineyard in each estate by using the same enological practices over the entire investigated period. The meteorological conditions corresponding to the production areas were recorded, and bioclimatic indices were calculated as well. Overall, cis-resveratrol concentration was negatively correlated to Huglin index and August mean temperature, whilst positive correlation coefficients were found when considering the Selianinov index and the rainfall of September. Full article

(This article belongs to the Special Issue Resveratrol 2021: Recent Advances in the Application of Resveratrol to Improve Health)

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14 pages, 1071 KiB

Open AccessReview

Resveratrol against Cardiac Fibrosis: Research Progress in Experimental Animal Models

by Dongmin Yu, Zhixian Tang, Ben Li, Junjian Yu, Wentong Li, Ziyou Liu and Chengnan Tian

Molecules 2021, 26(22), 6860; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26226860 - 13 Nov 2021

Cited by 9 | Viewed by 2943

Abstract

Cardiac fibrosis is a heterogeneous disease, which is characterized by abundant proliferation of interstitial collagen, disordered arrangement, collagen network reconstruction, increased cardiac stiffness, and decreased systolic and diastolic functions, consequently developing into cardiac insufficiency. With several factors participating in and regulating the occurrence and development of cardiac fibrosis, a complex molecular mechanism underlies the disease. Moreover, cardiac fibrosis is closely related to hypertension, myocardial infarction, viral myocarditis, atherosclerosis, and diabetes, which can lead to serious complications such as heart failure, arrhythmia, and sudden cardiac death, thus seriously threatening human life and health. Resveratrol, with the chemical name 3,5,4′-trihydroxy-trans-stilbene, is a polyphenol abundantly present in grapes and red wine. It is known to prevent the occurrence and development of cardiovascular diseases. In addition, it may resist cardiac fibrosis through a variety of growth factors, cytokines, and several cell signaling pathways, thus exerting a protective effect on the heart. Full article

(This article belongs to the Special Issue Resveratrol 2021: Recent Advances in the Application of Resveratrol to Improve Health)

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21 pages, 1055 KiB

Open AccessReview

A Comprehensive Analysis of the Efficacy of Resveratrol in Atherosclerotic Cardiovascular Disease, Myocardial Infarction and Heart Failure

by Pema Raj, Sijo Joseph Thandapilly, Jeffrey Wigle, Shelley Zieroth and Thomas Netticadan

Molecules 2021, 26(21), 6600; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26216600 - 31 Oct 2021

Cited by 20 | Viewed by 3856

Abstract

Atherosclerosis, myocardial infarction (MI) and heart failure (HF) are the main causes of mortality and morbidity around the globe. New therapies are needed to better manage ischemic heart disease and HF as existing strategies are not curative. Resveratrol is a stilbene polyphenolic compound with favorable biological effects that counter chronic diseases. Current evidence suggests that resveratrol is cardioprotective in animal models of atherosclerosis, ischemic heart disease, and HF. Though clinical studies for resveratrol have been promising, evidence remains inadequate to introduce it to the clinical setting. In this narrative review, we have comprehensively discussed the relevant compelling evidence regarding the efficacy of resveratrol as a new therapeutic agent for the management of atherosclerosis, MI and HF. Full article

(This article belongs to the Special Issue Resveratrol 2021: Recent Advances in the Application of Resveratrol to Improve Health)

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8 pages, 724 KiB

Open AccessReview

A Brief Updated Review of Advances to Enhance Resveratrol’s Bioavailability

by Konrad de Vries, Morné Strydom and Vanessa Steenkamp

Molecules 2021, 26(14), 4367; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26144367 - 20 Jul 2021

Cited by 13 | Viewed by 3160

Abstract

Resveratrol (RES) has a low bioavailability. This limitation was addressed in an earlier review and several recommendations were offered. A literature search was conducted in order to determine the extent of the research that was conducted in line with these recommendations, along with new developments in this field. Most of the identified studies were pre-clinical and confirmed the heightened activity of RES analogues compared to their parent compound. Although this has provided additional scientific kudos for these compounds and has strengthened their potential to be developed into phytopharmaceutical products, clinical trials designed to confirm this increased activity remain lacking and are warranted. Full article

(This article belongs to the Special Issue Resveratrol 2021: Recent Advances in the Application of Resveratrol to Improve Health)

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31 pages, 2486 KiB

Open AccessReview

Role of Resveratrol in Prevention and Control of Cardiovascular Disorders and Cardiovascular Complications Related to COVID-19 Disease: Mode of Action and Approaches Explored to Increase Its Bioavailability

by Nikola Gligorijević, Dragana Stanić-Vučinić, Mirjana Radomirović, Marija Stojadinović, Urmila Khulal, Olgica Nedić and Tanja Ćirković Veličković

Molecules 2021, 26(10), 2834; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26102834 - 11 May 2021

Cited by 15 | Viewed by 6873

Abstract

Resveratrol is a phytoalexin produced by many plants as a defense mechanism against stress-inducing conditions. The richest dietary sources of resveratrol are berries and grapes, their juices and wines. Good bioavailability of resveratrol is not reflected in its high biological activity in vivo because of resveratrol isomerization and its poor solubility in aqueous solutions. Proteins, cyclodextrins and nanomaterials have been explored as innovative delivery vehicles for resveratrol to overcome this limitation. Numerous in vitro and in vivo studies demonstrated beneficial effects of resveratrol in cardiovascular diseases (CVD). Main beneficial effects of resveratrol intake are cardioprotective, anti-hypertensive, vasodilatory, anti-diabetic, and improvement of lipid status. As resveratrol can alleviate the numerous factors associated with CVD, it has potential as a functional supplement to reduce COVID-19 illness severity in patients displaying poor prognosis due to cardio-vascular complications. Resveratrol was shown to mitigate the major pathways involved in the pathogenesis of SARS-CoV-2 including regulation of the renin-angiotensin system and expression of angiotensin-converting enzyme 2, stimulation of immune system and downregulation of pro-inflammatory cytokine release. Therefore, several studies already have anticipated potential implementation of resveratrol in COVID-19 treatment. Regular intake of a resveratrol rich diet, or resveratrol-based complementary medicaments, may contribute to a healthier cardio-vascular system, prevention and control of CVD, including COVID-19 disease related complications of CVD. Full article

(This article belongs to the Special Issue Resveratrol 2021: Recent Advances in the Application of Resveratrol to Improve Health)

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10 pages, 285 KiB

Open AccessReview

The Role of Resveratrol in Human Male Fertility

by Laura M. Mongioì, Sarah Perelli, Rosita A. Condorelli, Federica Barbagallo, Andrea Crafa, Rossella Cannarella, Sandro La Vignera and Aldo E. Calogero

Molecules 2021, 26(9), 2495; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26092495 - 24 Apr 2021

Cited by 14 | Viewed by 3886

Abstract

Resveratrol (RSV) (3,4′,5 trihydroxystilbene) is a natural non-flavonoid polyphenol widely present in the Mediterranean diet. In particular, RSV is found in grapes, peanuts, berries, and red wine. Many beneficial effects of this molecule on human health have been reported. In fact, it improves some clinical aspects of various diseases, such as obesity, tumors, hypertension, Alzheimer’s disease, stroke, cardiovascular diseases, and diabetes mellitus. However, little is known about the relationship between this compound and male fertility and the few available results are often controversial. Therefore, this review evaluated the effects of RSV on human male fertility and the mechanisms through which this polyphenol could act on human spermatozoa. Full article

(This article belongs to the Special Issue Resveratrol 2021: Recent Advances in the Application of Resveratrol to Improve Health)

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