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Resveratrol and Its Analogs in Human Diseases

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A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 38091

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Prof. Dr. Anait S. Levenson

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Guest Editor

Department of Biomedical Sciences, College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA
Interests: prostate and breast cancers; molecular mechanisms of cancer progression; pre-clinical mouse models; targeted therapies; natural anticancer agents
Special Issues, Collections and Topics in MDPI journals

Dr. Jorge Luis Espinoza

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Co-Guest Editor

Faculty of Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan
Interests: hematology and oncology; microbe-induced carcinogenesis; cancer drug discovery; parasitic infections; opportunistic microorganisms; immunology; microbiota; infectious diseases; artificial intelligence and medical sciences
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Numerous studies have indicated that resveratrol is a potential dietary chemopreventive and therapeutic agent due to its cardioprotective, anti-inflammatory, anti-oxidative and anti-cancer properties. However, clinical trials with resveratrol have not been too successful owing to resveratrol’s low bioavailability and rapid metabolism, which is the major challenge for dietary phytochemicals. In recent years, however, several resveratrol analogs have attracted attention due to their improved pharmacokinetic properties and pharmacological potency. The potential of resveratrol and analogs for the treatment of various diseases requires further investigation using adequate preclinical models and, vitally, comprehensive clinical trials.

It is our great pleasure to initiate a Special Issue of Nutrients on “Resveratrol and Its Analogs in Human Diseases” to provide an opportunity for researchers to publish their original or up-to-date reviews on the topic of the effects of resveratrol and its analogs in various diseases. It is our hope to welcome manuscripts with advanced knowledge of the mechanisms of action and improved pharmacokinetics for resveratrol and its potent analogs.

Prof. Dr. Anait S Levenson
Dr. J. Luis Espinoza
Guest Editors

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Keywords

Nutraceuticals
Resveratrol
Analogs
Pterostilbene
Gnetin C
Drug metabolism
Pharmacokinetics
Oral bioavailability
Diabetes
Cancer
Immune modulation
Synthetic stilbenes
Cardio-oncology

Published Papers (7 papers)

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Research

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12 pages, 889 KiB

Open AccessArticle

Efficacy and Safety of Resveratrol in Type 1 Diabetes Patients: A Two-Month Preliminary Exploratory Trial

by Ali Movahed, Pema Raj, Iraj Nabipour, Marzieh Mahmoodi, Afshin Ostovar, Mohammadreza Kalantarhormozi and Thomas Netticadan

Nutrients 2020, 12(1), 161; https://doi.org/10.3390/nu12010161 - 06 Jan 2020

Cited by 51 | Viewed by 7193

Abstract

Resveratrol has been reported to be beneficial against diabetes complications. The objective of this study was to evaluate the efficacy of resveratrol in decreasing hyperglycemia in patients with type 1 diabetes (T1D) by a preliminary investigation designed as an exploratory clinical trial. Thirteen patients with T1D from both the sexes participated in this trial. All patients received resveratrol in 500 mg capsules, twice daily for 60 days. Bodyweight, fasting blood sugar (FBS), hemoglobin A1c (HbA1c), insulin, homeostasis model of assessment for insulin resistance (HOMA-IR), homeostasis model of assessment for β-cell function (HOMA-β), and markers of liver and kidney damage, inflammation, and oxidative stress were measured before the intervention, at 30 days and at 60 days. Resveratrol supplementation for 60 days significantly decreased FBS and HbA1c in comparison with the baseline values. Resveratrol treatment also resulted in a decrease in the level of a marker for oxidative stress, malondialdehyde, and an increase in total antioxidant capacity in T1D patients. Insulin, HOMA-IR, HOMA-β, and markers of liver and kidney function and inflammation were not significantly affected by resveratrol treatment. Overall, the results showed that 60 days of resveratrol supplementation exerted strong antidiabetic and antioxidant effects in patients with T1D. Full article

(This article belongs to the Special Issue Resveratrol and Its Analogs in Human Diseases)

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15 pages, 1794 KiB

Open AccessArticle

P-Glycoprotein 1 Affects Chemoactivities of Resveratrol against Human Colorectal Cancer Cells

by Virginie Aires, Didier J Colin, Agnès Doreau, Attilio Di Pietro, Jean-Marie Heydel, Yves Artur, Norbert Latruffe and Dominique Delmas

Nutrients 2019, 11(9), 2098; https://doi.org/10.3390/nu11092098 - 04 Sep 2019

Cited by 24 | Viewed by 4397

Abstract

Resveratrol has been proposed to prevent tumor growth and the different steps of carcinogenesis; nevertheless, these biological effects are sometimes discordant between different cell types. Several hypotheses and works have suggested that the metabolism of resveratrol could be at the origin of a different cellular response. We show here, using colorectal tumor cell lines, that the biological effects of RSV result mainly from its carriage by carriers of the superfamily of ABC transporter, i.e., P-gP, MRP, or BCRP. Using cell lines overexpressing these different transporters, we have been able to highlight the importance of P-gP in the response of cells to RSV. These results were confirmed by invalidating the gene coding for P-gP, which restored the sensitivity of colorectal cells resistant to the polyphenol. Subsequently, the status of P-glycoprotein expression is an important element to be taken into consideration in the cytotoxic activity of resveratrol in colorectal cancer cells. Full article

(This article belongs to the Special Issue Resveratrol and Its Analogs in Human Diseases)

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16 pages, 2978 KiB

Open AccessArticle

MTA1-Dependent Anticancer Activity of Gnetin C in Prostate Cancer

by Avinash Kumar, Kshiti Dholakia, Gabriela Sikorska, Luis A. Martinez and Anait S. Levenson

Nutrients 2019, 11(9), 2096; https://doi.org/10.3390/nu11092096 - 04 Sep 2019

Cited by 16 | Viewed by 3683

Abstract

The overexpression of metastasis-associated protein 1 (MTA1) in prostate cancer (PCa) contributes to tumor aggressiveness and metastasis. We have reported the inhibition of MTA1 by resveratrol and its potent analog pterostilbene in vitro and in vivo. We have demonstrated that pterostilbene treatment blocks the progression of prostatic intraepithelial neoplasia and adenocarcinoma in mouse models by inhibiting MTA1 expression and signaling. In the current study, we investigated the MTA1 targeted anticancer effects of Gnetin C, a resveratrol dimer, in comparison with resveratrol and pterostilbene. Using DU145 and PC3M PCa cells, we found that Gnetin C downregulates MTA1 more potently than resveratrol and pterostilbene. Further, Gnetin C demonstrated significant MTA1-mediated inhibitory effect on cell viability, colony formation, and migration, while showing a more potent induction of cell death than resveratrol or pterostilbene. In addition, we identified Gnetin C-induced substantial ETS2 (erythroblastosis E26 transformation-specific 2) downregulation, which is not only MTA1-dependent, but is also independent of MTA1 as a possible mechanism for the superior anticancer efficacy of Gnetin C in PCa. Together, these findings underscore the importance of novel potent resveratrol dimer, Gnetin C, as a clinically promising agent for the future development of chemopreventive and possibly combinatorial therapeutic approaches in PCa. Full article

(This article belongs to the Special Issue Resveratrol and Its Analogs in Human Diseases)

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23 pages, 2874 KiB

Open AccessArticle

Role of Resveratrol and Selenium on Oxidative Stress and Expression of Antioxidant and Anti-Aging Genes in Immortalized Lymphocytes from Alzheimer’s Disease Patients

by Marta Cosín-Tomàs, Júlia Senserrich, Marta Arumí-Planas, Carolina Alquézar, Mercè Pallàs, Ángeles Martín-Requero, Cristina Suñol, Perla Kaliman and Coral Sanfeliu

Nutrients 2019, 11(8), 1764; https://doi.org/10.3390/nu11081764 - 31 Jul 2019

Cited by 66 | Viewed by 6036

Abstract

Oxidative damage is involved in the pathophysiology of age-related ailments, including Alzheimer’s disease (AD). Studies have shown that the brain tissue and also lymphocytes from AD patients present increased oxidative stress compared to healthy controls (HCs). Here, we use lymphoblastoid cell lines (LCLs) from AD patients and HCs to investigate the role of resveratrol (RV) and selenium (Se) in the reduction of reactive oxygen species (ROS) generated after an oxidative injury. We also studied whether these compounds elicited expression changes in genes involved in the antioxidant cell response and other aging-related mechanisms. AD LCLs showed higher ROS levels than those from HCs in response to H₂O₂ and FeSO₄ oxidative insults. RV triggered a protective response against ROS under control and oxidizing conditions, whereas Se exerted antioxidant effects only in AD LCLs under oxidizing conditions. RV increased the expression of genes encoding known antioxidants (catalase, copper chaperone for superoxide dismutase 1, glutathione S-transferase zeta 1) and anti-aging factors (sirtuin 1 and sirtuin 3) in both AD and HC LCLs. Our findings support RV as a candidate for inducing resilience and protection against AD, and reinforce the value of LCLs as a feasible peripheral cell model for understanding the protective mechanisms of nutraceuticals against oxidative stress in aging and AD. Full article

(This article belongs to the Special Issue Resveratrol and Its Analogs in Human Diseases)

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16 pages, 3651 KiB

Open AccessArticle

Immunomodulatory and Metabolic Changes after Gnetin-C Supplementation in Humans

by Yuya Nakagami, Susumu Suzuki, J. Luis Espinoza, Lam Vu Quang, Megumi Enomoto, Souichi Takasugi, Ayano Nakamura, Takayuki Nakayama, Hiroya Tani, Ichiro Hanamura and Akiyoshi Takami

Nutrients 2019, 11(6), 1403; https://doi.org/10.3390/nu11061403 - 21 Jun 2019

Cited by 20 | Viewed by 5740

Abstract

Gnetin-C is a naturally occurring stilbene derived from the seeds of Gnetum gnemon L., an edible plant native to Southeast Asia that is called melinjo. Although the biological properties and safety of G. gnemon extract, which contains nearly 3% Gnetin-C, have been confirmed in various human studies, whether or not pure Gnetin-C is safe for humans is unclear at present. We conducted a randomized, double-blind, placebo-controlled trial. Healthy subjects were randomly divided into two groups. The interventional group (n = 6) was given Gnetin-C, and the control group (n = 6) was provided a placebo, for 14 days. Lipid profiles, biomarkers of oxidative stress and circulating blood cells were assessed before and after the intervention. All subjects completed the study, with no side effects reported across the study duration. Gnetin-C supplementation demonstrated a statistically significant increase in the absolute number of circulating natural killer (NK) cells expressing the activating receptors NKG2D and NKp46. NK cells derived from subjects who received Gnetin-C for two weeks showed higher cytotoxicity against K562 target cells than those before receiving Gnetin-C. In addition, Gnetin-C also resulted in a significant decrease in the absolute neutrophil count in the blood compared with the placebo. Furthermore, Gnetin-C significantly reduced the levels of uric acid, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total adiponectin, and high-molecular-weight adiponectin. These data indicate that Gnetin-C has biological effects of enhancing the NK activity on circulating human immune cells. The immunomodulatory effects are consistent with a putative improvement in cancer immunosurveillance via the upregulation of the NKG2D receptor. The study was registered with UMIN-CTR, number 000030364, on 12 December 2017. Full article

(This article belongs to the Special Issue Resveratrol and Its Analogs in Human Diseases)

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Review

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16 pages, 833 KiB

Open AccessReview

Can Resveratrol Treatment Control the Progression of Induced Periodontal Disease? A Systematic Review and Meta-Analysis of Preclinical Studies

by Eric Francelino Andrade, Débora Ribeiro Orlando, Amanda Melo Sant’Anna Araújo, James Newton Bizetto Meira de Andrade, Diana Vilela Azzi, Renato Ribeiro de Lima, Adalfredo Rocha Lobo-Júnior and Luciano José Pereira

Nutrients 2019, 11(5), 953; https://doi.org/10.3390/nu11050953 - 26 Apr 2019

Cited by 22 | Viewed by 4969

Abstract

Resveratrol is an anti-inflammatory compound found in several foods. Periodontal disease (PD) is associated to other systemic diseases, and inflammation may be responsible for the association. Consequently, controlling inflammation not only may benefit oral health but also may assist with the management of other chronic inflammatory conditions. We aimed to investigate the effects of resveratrol administration on PD control in preclinical studies. A systematic search was performed for scientific articles using both electronic databases and a manual search using combinations of the following keywords: “resveratrol” OR “3,5,4′-trihydroxystilbene” AND “periodontal disease” OR “periodontitis” OR “gingivitis”. Only in vivo original studies investigating resveratrol treatment on experimental animal models of PD were selected. A quality assessment of the studies was performed using the Animal Research Reporting In Vivo Experiment (ARRIVE) guidelines, and the risk of bias was assessed using the Syrcle tool. The search returned 570 articles, and 11 matched the inclusion criteria. A meta-analysis showed that resveratrol treatment attenuated alveolar bone loss (τ² = 0.0041; 95% CI: −0.14; −0.04). The ARRIVE criteria reported a good quality of studies in general (mean score 28.5 ± 2.5). However, five Syrcle domains indicated a high risk of bias or did not present information clearly. We concluded that, in preclinical studies, resveratrol treatment prevented PD progression. Full article

(This article belongs to the Special Issue Resveratrol and Its Analogs in Human Diseases)

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39 pages, 943 KiB

Open AccessReview

Leveraging the Cardio-Protective and Anticancer Properties of Resveratrol in Cardio-Oncology

by Ibrahim Y. Abdelgawad, Marianne K.O. Grant and Beshay N. Zordoky

Nutrients 2019, 11(3), 627; https://doi.org/10.3390/nu11030627 - 14 Mar 2019

Cited by 24 | Viewed by 5537

Abstract

Cardio-oncology is a clinical/scientific discipline which aims to prevent and/or treat cardiovascular diseases in cancer patients. Although a large number of cancer treatments are known to cause cardiovascular toxicity, they are still widely used because they are highly effective. Unfortunately, therapeutic interventions to prevent and/or treat cancer treatment-induced cardiovascular toxicity have not been established yet. A major challenge for such interventions is to protect the cardiovascular system without compromising the therapeutic benefit of anticancer medications. Intriguingly, the polyphenolic natural compound resveratrol and its analogs have been shown in preclinical studies to protect against cancer treatment-induced cardiovascular toxicity. They have also been shown to possess significant anticancer properties on their own, and to enhance the anticancer effect of other cancer treatments. Thus, they hold significant promise to protect the cardiovascular system and fight the cancer at the same time. In this review, we will discuss the current knowledge regarding the cardio-protective and the anticancer properties of resveratrol and its analogs. Thereafter, we will discuss the challenges that face the clinical application of these agents. To conclude, we will highlight important gaps of knowledge and future research directions to accelerate the translation of these exciting preclinical findings to cancer patient care. Full article

(This article belongs to the Special Issue Resveratrol and Its Analogs in Human Diseases)

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