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Resveratrol News & Views: From the Molecular Mechanism to Nutritional and Biomedical Applications

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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 (30 November 2022) | Viewed by 19346

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Special Issue Editors

Prof. Dr. Luciana Mosca

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Guest Editor

Department of Biochemical Sciences, Sapienza University, p.le Aldo Moro, 5, 00185 Rome, Italy
Interests: oxidative stress; reactive oxygen species; neurodegeneration; Alzheimer’s disease; Parkinson’s disease; probiotics; polyphenols; flavonoids; anthocyanins, LC/MS
Special Issues, Collections and Topics in MDPI journals

Dr. Roberto Mattioli

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Department of Biochemical Sciences, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Interests: polyphenols; natural products; NaDES; inflammation; oxidative stress
Special Issues, Collections and Topics in MDPI journals

Dr. Antonio Francioso

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Guest Editor

Department of Biochemical Sciences, Sapienza University, p.le Aldo Moro, 5, 00185 Rome, Italy
Interests: natural products isolation and identification; chromatography; mass spectrometry; bio-organic and green chemistry; sulfur-containing compounds; polyphenols; iridoids and phenolic secoiridoids; c-glycosyl secondary metabolites; neurochemistry; anti-inflamatory and neuroprotective compounds
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products have been used by mankind since ancient times, and the interest in natural bioactive compounds has recently been on the rise because medicinal plants still represent a good potential source of novel bioactive compounds. Among natural substances, polyphenols represent an attractive family of compounds involved in the modulation of inflammation and oxidative stress. One of the most interesting polyphenols is Resveratrol, a phytoalexin present in plants such as grapes, peanuts, blueberries, and the Japanese knotweed. Many in vitro and in vivo studies indicate that Resveratrol could be potentially useful in the treatment of cancer and cardiovascular, neurodegenerative, autoimmune, metabolic, and dermatological diseases through the modulation of the signal cascades mediated by NFkB and Nrf2 nuclear factors. It is also well known for its antiaging properties due to its action on SIRT-1.

However, one of the major drawbacks of this compound is that its poor bioavailability remains to be solved, and the fact that the targets of its mechanism of action are still not completely unraveled. This Special Issue aims to attract papers reporting recent evidence and views on resveratrol, and which describe new potential mechanisms of action and the use of this compound in food supplements, nutraceuticals and medical devices. The main topics for discussion are:

Molecular mechanisms of Resveratrol action;
Bioavailability of Resveratrol;
Use of Resveratrol as food supplement, cosmetic or medical device;
Innovative products to improve Resveratrol activity (in cosmetics, medical devices, nanoformulations, nutraceuticals, and food supplements);
New strategies to enhance Resveratrol level in foods or crops.

Prof. Dr. Luciana Mosca
Dr. Roberto Mattioli
Dr. Antonio Francioso
Guest Editors

Manuscript Submission Information

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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

resveratrol
resveratrol analogues
antioxidant activity
anti-inflammatory activity
anticancer activity
cardio- and neuro-protective effects
metabolic effects

Published Papers (7 papers)

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Research

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24 pages, 5765 KiB

Open AccessArticle

Piezo1 Mechano-Activation Is Augmented by Resveratrol and Differs between Colorectal Cancer Cells of Primary and Metastatic Origin

by Joshua D. Greenlee, Kevin Liu, Maria Lopez-Cavestany and Michael R. King

Molecules 2022, 27(17), 5430; https://doi.org/10.3390/molecules27175430 - 25 Aug 2022

Cited by 8 | Viewed by 2083

Abstract

Cancer cells must survive aberrant fluid shear stress (FSS) in the circulation to metastasize. Herein, we investigate the role that FSS has on colorectal cancer cell apoptosis, proliferation, membrane damage, calcium influx, and therapeutic sensitization. We tested this using SW480 (primary tumor) and SW620 cells (lymph node metastasis) derived from the same patient. The cells were exposed to either shear pulses, modeling millisecond intervals of high FSS seen in regions of turbulent flow, or sustained shear to model average magnitudes experienced by circulating tumor cells. SW480 cells were significantly more sensitive to FSS-induced death than their metastatic counterparts. Shear pulses caused significant cell membrane damage, while constant shear decreased cell proliferation and increased the expression of CD133. To investigate the role of mechanosensitive ion channels, we treated cells with the Piezo1 agonist Yoda1, which increased intracellular calcium. Pretreatment with resveratrol further increased the calcium influx via the lipid-raft colocalization of Piezo1. However, minimal changes in apoptosis were observed due to calcium saturation, as predicted via a computational model of apoptosis. Furthermore, SW480 cells had increased levels of Piezo1, calcium influx, and TRAIL-mediated apoptosis compared to SW620 cells, highlighting differences in the mechano-activation of metastatic cells, which may be a necessary element for successful dissemination in vivo. Full article

(This article belongs to the Special Issue Resveratrol News & Views: From the Molecular Mechanism to Nutritional and Biomedical Applications)

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14 pages, 3248 KiB

Open AccessArticle

Resveratrol Effects on the Reproductive System in Ovariectomized Rats: Deciphering Possible Mechanisms

by Ganna Zaychenko, Olena Stryga, Oksana Sinitsyna, Anna Doroshenko, Oksana Sulaieva, Tetyana Falalyeyeva and Nazarii Kobyliak

Molecules 2022, 27(15), 4916; https://doi.org/10.3390/molecules27154916 - 2 Aug 2022

Cited by 4 | Viewed by 1908

Abstract

Phytoestrogen resveratrol (R) has been demonstrated to benefit human reproductive health. However, R bioavailability and pharmacokinetics are still problematic under oral supplementation. We used an experimental vaginal gel with R and hyaluronic acid (HA) to improve bioavailability and pharmacokinetic properties. The study aimed to assess the impact of vaginal R-HA gel on the reproductive system in ovariectomized rats. Methods: The study was carried out on Wistar female rats. It investigated the body weight, tail temperature, vaginal pH, estrogen and progesterone blood levels, and immunohistochemical biomarkers (COX2, Casp-3, Bcl-2, and VEGF). Animals were divided into control animals; ovariectomized rats (OVX); and OVX group treated with vaginal 0.5% R-HA gel (0.5%, 0.1 mL, daily 28 days). Results: The R-HA gel’s therapeutic effect was manifested by slowing weight gain by 17% (p < 0.001), less pronounced symptom of fever at the root of the tail by 9% (p < 0.001) and lowering the vaginal pH to 4.4–4.5 compared with OVX rats. The anti-inflammatory effect and the reduction of COX-2 expression in vagina were accompanied by antiapoptotic impact of RA-H on endometrium, associated with the decreased Casp-3 expression (p < 0.001) and elevated Bcl-2 score in endometrial glands (p = 0.01). Together with enhanced VEGF expression in endometrial glands (p < 0.001) and stromal cells (p = 0.007), these changes prevented endometrial atrophy (p < 0.001) after ovariectomy. Thus, this study substantiates the feasibility of developing an innovative topical drug with R and HA for treating hypoestrogenic disorders. Full article

(This article belongs to the Special Issue Resveratrol News & Views: From the Molecular Mechanism to Nutritional and Biomedical Applications)

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11 pages, 1439 KiB

Open AccessArticle

Resveratrol Decreases the Invasion Potential of Gastric Cancer Cells

by Daniel Rojo, Alejandro Madrid, Sebastián San Martín, Mario Párraga, Maria Aparecida Silva Pinhal, Joan Villena and Manuel Valenzuela-Valderrama

Molecules 2022, 27(10), 3047; https://doi.org/10.3390/molecules27103047 - 10 May 2022

Cited by 10 | Viewed by 1938

Abstract

The cancer-preventive agent Resveratrol (RSV) [3,5,4′-trihydroxytrans-stilbene] is a widely recognized antioxidant molecule with antitumoral potential against several types of cancers, including prostate, hepatic, breast, skin, colorectal, and pancreatic. Herein, we studied the effect of RSV on the cell viability and invasion potential of gastric cancer cells. AGS and MKN45 cells were treated with different doses of RSV (0–200 μM) for 24 h. Cell viability was determined using the Sulphorhodamine B dye (SRB) assay. For invasion assays, gastric cells were pre-treated with RSV (5–25 μM) for 24 h and then seeded in a Transwell chamber with coating Matrigel. The results obtained showed that RSV inhibited invasion potential in both cell lines. Moreover, to elucidate the mechanism implicated in this process, we analyzed the effects of RSV on SOD, heparanase, and NF-κB transcriptional activity. The results indicated that RSV increased SOD activity in a dose-dependent manner. Conversely, RSV significantly reduced the DNA-binding activity of NF-κB and the enzymatic activity of heparanase in similar conditions, which was determined using ELISA-like assays. In summary, these results show that RSV increases SOD activity but decreases NF-kB transcriptional activity and heparanase enzymatic activity, which correlates with the attenuation of invasion potential in gastric cancer cells. To our knowledge, no previous study has described the effect of RSV on heparanase activity. This article proposes that heparanase could be a key effector in the invasive events occurring during gastric cancer metastasis. Full article

(This article belongs to the Special Issue Resveratrol News & Views: From the Molecular Mechanism to Nutritional and Biomedical Applications)

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12 pages, 2587 KiB

Open AccessArticle

Effect of Natural Deep Eutectic Solvents on trans-Resveratrol Photo-Chemical Induced Isomerization and 2,4,6-Trihydroxyphenanthrene Electro-Cyclic Formation

by Roberto Mattioli, Daniel Di Risola, Rodolfo Federico, Alessia Ciogli, Francesco Gasparrini, Claudio Villani, Mario Fontana, Anna Maggiore, Maria d’Erme, Luciana Mosca and Antonio Francioso

Molecules 2022, 27(7), 2348; https://doi.org/10.3390/molecules27072348 - 6 Apr 2022

Cited by 5 | Viewed by 2262

Abstract

trans-Resveratrol is a natural bioactive compound with well-recognized health promoting effects. When exposed to UV light, this compound can undergo a photochemically induced trans/cis isomerization and a 6π electrochemical cyclization with the subsequent formation of 2,4,6-trihydroxyphenanthrene (THP). THP is a potentially harmful compound which can exert genotoxic effects. In this work we improved the chromatographic separation and determination of the two resveratrol isomers and of THP by using a non-commercial pentafluorophenyl stationary phase. We assessed the effect of natural deep eutectic solvents (NaDES) as possible photo-protective agents by evaluating cis-resveratrol isomer and THP formation under different UV-light exposure conditions with the aim of enhancing resveratrol photostability and inhibiting THP production. Our results demonstrate a marked photoprotective effect exerted by glycerol-containing NaDES, and in particular by proline/glycerol NaDES, which exerts a strong inhibitory effect on the photochemical isomerization of resveratrol and significantly limits the formation of the toxic derivative THP. Considering the presence of resveratrol in various commercial products, these results are of note in view of the potential genotoxic risk associated with its photochemical degradation products and in view of the need for the development of green, eco-sustainable and biocompatible resveratrol photo-stable formulations. Full article

(This article belongs to the Special Issue Resveratrol News & Views: From the Molecular Mechanism to Nutritional and Biomedical Applications)

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Review

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19 pages, 686 KiB

Open AccessReview

Progress in the Preclinical and Clinical Study of Resveratrol for Vascular Metabolic Disease

by Dongxiao Fan, Chenshu Liu, Zhongyu Zhang, Kan Huang, Tengyao Wang, Sifan Chen and Zilun Li

Molecules 2022, 27(21), 7524; https://doi.org/10.3390/molecules27217524 - 3 Nov 2022

Cited by 10 | Viewed by 1894

Abstract

Vascular metabolic dysfunction presents in various diseases, such as atherosclerosis, hypertension, and diabetes mellitus. Due to the high prevalence of these diseases, it is important to explore treatment strategies to protect vascular function. Resveratrol (RSV), a natural polyphenolic phytochemical, is regarded as an agent to regulate metabolic pathways. Many studies have proven that RSV has beneficial effects on improving metabolism in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), which provide new directions to treat vascular metabolic diseases. Herein, we overviewed that RSV could regulate cell metabolism activity by inhibiting glucose uptake, suppressing glycolysis, preventing cells from fatty acid-related damages, reducing lipogenesis, increasing fatty acid oxidation, enhancing lipolysis, elevating uptake and synthesis of glutamine, and increasing NO release. Furthermore, in clinical trials, although the results from different studies remain controversial, we proposed that RSV had better therapeutic effects at high concentrations and for patients with metabolic disorders. Full article

(This article belongs to the Special Issue Resveratrol News & Views: From the Molecular Mechanism to Nutritional and Biomedical Applications)

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38 pages, 1556 KiB

Open AccessReview

Potential Therapeutic Targets of Resveratrol, a Plant Polyphenol, and Its Role in the Therapy of Various Types of Cancer

by Saleh A. Almatroodi, Mohammed A. Alsahli, Abdullah S. M. Aljohani, Fahad A. Alhumaydhi, Ali Yousif Babiker, Amjad Ali Khan and Arshad Husain Rahmani

Molecules 2022, 27(9), 2665; https://doi.org/10.3390/molecules27092665 - 21 Apr 2022

Cited by 30 | Viewed by 4292

Abstract

Cancer is among the most prominent causes of mortality worldwide. Different cancer therapy modes employed, including chemotherapy and radiotherapy, have been reported to be significant in cancer management, but the side effects associated with these treatment strategies are still a health problem. Therefore, alternative anticancer drugs based on medicinal plants or their active compounds have been generating attention because of their less serious side effects. Medicinal plants are an excellent source of phytochemicals that have been recognized to have health-prompting effects through modulating cell signaling pathways. Resveratrol is a well-known polyphenolic molecule with antioxidant, anti-inflammatory, and health-prompting effects among which its anticancer role has been best defined. Additionally, this polyphenol has confirmed its role in cancer management because it activates tumor suppressor genes, suppresses cell proliferation, induces apoptosis, inhibits angiogenesis, and modulates several other cell signaling molecules. The anticancer potential of resveratrol is recognized in numerous in vivo and in vitro studies. Previous experimental data suggested that resveratrol may be valuable in cancer management or improve the efficacy of drugs when given with anticancer drugs. This review emphasizes the potential role of resveratrol as an anticancer drug by modulating numerous cells signaling pathways in different types of cancer. Full article

(This article belongs to the Special Issue Resveratrol News & Views: From the Molecular Mechanism to Nutritional and Biomedical Applications)

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13 pages, 1147 KiB

Open AccessReview

The Importance of Nutraceuticals in COVID-19: What’s the Role of Resveratrol?

by Elisa Domi, Malvina Hoxha, Entela Kolovani, Domenico Tricarico and Bruno Zappacosta

Molecules 2022, 27(8), 2376; https://doi.org/10.3390/molecules27082376 - 7 Apr 2022

Cited by 16 | Viewed by 3120

Abstract

Since COVID-19 has affected global public health, there has been an urgency to find a solution to limit both the number of infections, and the aggressiveness of the disease once infected. The main characteristic of this infection is represented by a strong alteration of the immune system which, day by day, increases the risk of mortality, and can lead to a multiorgan dysfunction. Because nutritional profile can influence patient’s immunity, we focus our interest on resveratrol, a polyphenolic compound known for its immunomodulating and anti-inflammatory properties. We reviewed all the information concerning the different roles of resveratrol in COVID-19 pathophysiology using PubMed and Scopus as the main databases. Interestingly, we find out that resveratrol may exert its role through different mechanisms. In fact, it has antiviral activity inhibiting virus entrance in cells and viral replication. Resveratrol also improves autophagy and decreases pro-inflammatory agents expression acting as an anti-inflammatory agent. It regulates immune cell response and pro-inflammatory cytokines and prevents the onset of thrombotic events that usually occur in COVID-19 patients. Since resveratrol acts through different mechanisms, the effect could be enhanced, making a totally natural agent particularly effective as an adjuvant in anti COVID-19 therapy. Full article

(This article belongs to the Special Issue Resveratrol News & Views: From the Molecular Mechanism to Nutritional and Biomedical Applications)

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