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Potential Health Benefits of Resveratrol: Laboratory-Confirmed Mechanisms of Action
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Potential Health Benefits of Resveratrol: Laboratory-Confirmed Mechanisms of Action

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: 20 October 2025 | Viewed by 8387

Special Issue Editor

Prof. Dr. Dariusz Szukiewicz

E-Mail Website
Guest Editor
Department of Biophysics, Physiology and Pathophysiology, Faculty of Health Sciences, Medical University of Warsaw, Chalubinskiego 5 (4th Floor), 02-004 Warsaw, Poland
Interests: inflammation; cytokine network; sirtuins; endothelial signaling; human placenta; stem cells; pathophysiology of diabetes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Resveratrol (3, 5, 4′‐trihydroxystilbene; RSV) is a nonflavonoid polyphenol with a stilbene structure that naturally occurs as phytoalexin (an antimicrobial substance). RSV is found in larger amounts in grapes, peanuts, pistachios, plums, blueberries, cranberries, and cocoa fruits. The plants make RSV to fight fungal infection, ultraviolet radiation, stress, and injury. In the animal and human body, this translates into a number of health-promoting diverse biological activities such as strong antioxidant, anti-inflammatory, antiaging, antidiabetic, cardioprotective, neuroprotective, and anticancer properties. Moreover, based on its ability to bind to and activate the estrogen receptor, RSV is classified as a phytoestrogen.

Regardless of the significant problems with the safe and effective therapeutic use of RSV in clinical practice, which result from its inadequate bioavailability and poor solubility, laboratory test results continue to complement the range of therapeutic applications of RSV.

This Special Issue is dedicated to all aspects of the beneficial effects of RSV that have been confirmed in laboratory conditions and therefore constitute a rationale for further development and continuation of these studies in order to be implemented into clinical practice. When considering your submission, please keep in mind that IJMS is a journal of molecular science; therefore, the manuscript submitted for review should be of an appropriate “molecular” nature.

Prof. Dr. Dariusz Szukiewicz
Guest Editor

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • resveratrol
  • polyphenol
  • phytoalexin
  • phytoestrogen
  • natural compound
  • reactive oxygen species
  • antioxidant effects
  • anti-inflammatory effects
  • antiaging properties
  • antidiabetic properties
  • cardioprotective effects
  • neuroprotective effects
  • anticancer properties

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Published Papers (5 papers)

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Research

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15 pages, 2229 KiB  
Article
Resveratrol Upregulates Antioxidant Factors Expression and Downmodulates Interferon-Inducible Antiviral Factors in Aging
by Iara Grigoletto Fernandes, Luana de M. Oliveira, Milena M. de Souza Andrade, Ricardo W. Alberca, Júlia Cataldo Lima, Emanuella Sarmento Alho de Sousa, Anna Julia Pietrobon, Nátalli Zanete Pereira, Anna Cláudia Calvielli Castelo Branco, Alberto José da Silva Duarte and Maria Notomi Sato
Int. J. Mol. Sci. 2025, 26(5), 2345; https://doi.org/10.3390/ijms26052345 - 6 Mar 2025
Viewed by 641
Abstract
Immunosenescence, a process with a dysfunctional immune response that may favor infection is associated with an increase in inflammatory responses mediated by proinflammatory cytokines, characteristic of inflammaging. Aging and immunosenescence have a relationship relating to oxidative stress and inflammaging. Therefore, natural antioxidant compounds [...] Read more.
Immunosenescence, a process with a dysfunctional immune response that may favor infection is associated with an increase in inflammatory responses mediated by proinflammatory cytokines, characteristic of inflammaging. Aging and immunosenescence have a relationship relating to oxidative stress and inflammaging. Therefore, natural antioxidant compounds could be candidates for the control of the oxidative process. Our purpose was to evaluate the effect of resveratrol (Resv) on the antioxidant, antiviral, and anti-inflammatory responses induced by toll-like receptors (TLRs) 3, 4, and 7/8 agonists stimulation on peripheral blood mononuclear cells (PBMCs) of elderly and healthy female individuals (63–82 years old) and young and healthy female individuals (21–31 years old). Our data show that Resv may upregulate antioxidant factor expression, such as catalase (CAT) and SIRT1, in response to TLR4 and TLR7/8 agonists, similarly in both young and aged groups. Moreover, the Resv anti-inflammatory effect was detected by inhibiting IL-1β, TNF-α, and IL-10 secretion levels, as well as by the chemokines CCL2 and CCL5, induced by TLR4 and TLR7/8 stimulation. Curiously, Resv decreased antiviral genes, such as MxA, STING, and IRF7 expression, possibly by reducing the inflammatory effects of interferon-induced genes. Taken together, our results demonstrate the ability of Resv to stimulate antioxidant factors, leading to a downmodulation of the inflammatory response induced by innate immune stimulation. These findings point out Resv as a strategy to control the upregulation of inflammatory response, even in elderly individuals. Full article
(This article belongs to the Special Issue Potential Health Benefits of Resveratrol: Laboratory-Confirmed Mechanisms of Action)
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19 pages, 1992 KiB  
Article
Resveratrol-Loaded Pluronic Micelles Ameliorate Scopolamine-Induced Cognitive Dysfunction Targeting Acetylcholinesterase Activity and Programmed Cell Death
by Maria Lazarova, Miroslava Stefanova, Elina Tsvetanova, Almira Georgieva, Krasimira Tasheva, Lyubomira Radeva and Krassimira Yoncheva
Int. J. Mol. Sci. 2024, 25(23), 12777; https://doi.org/10.3390/ijms252312777 - 28 Nov 2024
Cited by 2 | Viewed by 1120
Abstract
Numerous experimental studies suggest the potential for resveratrol (RVT) to be useful in the Alzheimer’s disease treatment, but its low bioavailability limits its application. This study aimed to assess the potential of resveratrol-loaded micelles as a neuronal delivery platform to protect rats from [...] Read more.
Numerous experimental studies suggest the potential for resveratrol (RVT) to be useful in the Alzheimer’s disease treatment, but its low bioavailability limits its application. This study aimed to assess the potential of resveratrol-loaded micelles as a neuronal delivery platform to protect rats from scopolamine-induced memory impairment. Resveratrol was incorporated into Pluronic micelles, and the effects of micellar (mRVT) and pure resveratrol (RVT) were compared in the model of scopolamine-induced dementia in male Wistar rats. Memory performance was assessed by a T maze test. The effect of the treatment on specific neurotransmitter levels and protein expression in the cortex and the hippocampus were evaluated biochemically. Our results revealed that the polymeric micelles were in nanoscale (approximately 33 nm) and reached 79% encapsulation efficiency. The treatment with mRVT demonstrated better spatial memory protective effect. The biochemical assays showed that mRVT in a dose of 10 mg/kg enhanced the effects of the pure drug in regard to noradrenalin neurotransmission and acetylcholinesterase inhibitory activity in the hippocampus. Furthermore, micellar resveratrol increased the cAMP-response element-binding protein expression in the cortex and hippocampus of rats as well as the Bcl2/BAX ratio, which indicated an anti-apoptotic effect in the experimental dementia model. In conclusion, our results indicated the potential of a micellar system loaded with resveratrol for neurodegenerative diseases treatment. Full article
(This article belongs to the Special Issue Potential Health Benefits of Resveratrol: Laboratory-Confirmed Mechanisms of Action)
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Review

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20 pages, 1277 KiB  
Review
A Systematic Review on the Molecular Mechanisms of Resveratrol in Protecting Against Osteoporosis
by Ahmad Nazrun Shuid, Nurul Alimah Abdul Nasir, Norasikin Ab Azis, Ahmad Naqib Shuid, Norhafiza Razali, Haryati Ahmad Hairi, Mohd Fairudz Mohd Miswan and Isa Naina Mohamed
Int. J. Mol. Sci. 2025, 26(7), 2893; https://doi.org/10.3390/ijms26072893 - 22 Mar 2025
Viewed by 702
Abstract
Osteoporosis is a prevalent metabolic bone disorder characterized by decreased bone mineral density and increased fracture risk, particularly among aging populations. While conventional pharmacological treatments exist, they often have adverse effects, necessitating the search for alternative therapies. Resveratrol, a naturally occurring polyphenol, has [...] Read more.
Osteoporosis is a prevalent metabolic bone disorder characterized by decreased bone mineral density and increased fracture risk, particularly among aging populations. While conventional pharmacological treatments exist, they often have adverse effects, necessitating the search for alternative therapies. Resveratrol, a naturally occurring polyphenol, has gained significant attention for its potential osteoprotective properties through various molecular mechanisms. This systematic review aims to comprehensively analyze the molecular pathways through which resveratrol protects against osteoporosis. Using an advanced search strategy in the Scopus, PubMed, and Web of Science databases, we identified 513 potentially relevant articles. After title and abstract screening, followed by full-text review, 28 studies met the inclusion criteria. The selected studies comprised 14 in vitro studies, 8 mixed in vitro and in vivo studies, 6 in vivo studies, and 1 cross-sectional study in postmenopausal women. Our findings indicate that resveratrol exerts its osteoprotective effects by enhancing osteoblast differentiation through the activation of the Phosphoinositide 3-Kinase/Protein Kinase B (PI3K/Akt), Sirtuin 1 (SIRT1), AMP-Activated Protein Kinase (AMPK), and GATA Binding Protein 1 (GATA-1) pathways while simultaneously inhibiting osteoclastogenesis by suppressing Mitogen-Activated Protein Kinase (MAPK) and TNF Receptor-Associated Factor 6/Transforming Growth Factor-β-Activated Kinase 1 (TRAF6/TAK1). Additionally, resveratrol mitigates oxidative stress and inflammation-induced bone loss by activating the Hippo Signaling Pathway/Yes-Associated Protein (Hippo/YAP) and Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) pathways and suppressing Reactive Oxygen Species/Hypoxia-Inducible Factor-1 Alpha (ROS/HIF-1α) and NADPH Oxidase 4/Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (Nox4/NF-κB). Despite promising preclinical findings, the low bioavailability of resveratrol remains a significant challenge, highlighting the need for novel delivery strategies to improve its therapeutic potential. This review provides critical insights into the molecular mechanisms of resveratrol in bone health, supporting its potential as a natural alternative for osteoporosis prevention and treatment. Further clinical studies are required to validate its efficacy and establish optimal dosing strategies. Full article
(This article belongs to the Special Issue Potential Health Benefits of Resveratrol: Laboratory-Confirmed Mechanisms of Action)
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25 pages, 1928 KiB  
Review
The Potential Application of Resveratrol and Its Derivatives in Central Nervous System Tumors
by Agnieszka Nowacka, Martyna Śniegocka, Wojciech Smuczyński, Sara Liss, Ewa Ziółkowska, Dominika Bożiłow, Maciej Śniegocki and Michał Wiciński
Int. J. Mol. Sci. 2024, 25(24), 13338; https://doi.org/10.3390/ijms252413338 - 12 Dec 2024
Cited by 1 | Viewed by 1805
Abstract
Resveratrol, a naturally occurring polyphenolic compound found in various plants, has been extensively studied for its broad spectrum of beneficial biological effects. These encompass its potent antioxidant properties, anti-inflammatory activities, anti-aging capabilities, cardioprotective functions, and neuroprotective potential. The diverse biological actions of resveratrol [...] Read more.
Resveratrol, a naturally occurring polyphenolic compound found in various plants, has been extensively studied for its broad spectrum of beneficial biological effects. These encompass its potent antioxidant properties, anti-inflammatory activities, anti-aging capabilities, cardioprotective functions, and neuroprotective potential. The diverse biological actions of resveratrol extend beyond these well-established properties. It also exerts a significant impact on metabolic processes and bioavailability, and critically, it demonstrates the ability to effectively traverse the blood–brain barrier. This capacity to penetrate the central nervous system renders resveratrol a promising therapeutic agent for the management of central nervous system malignancies, as it has been shown to inhibit tumor cell proliferation, induce apoptosis, and modulate key signaling cascades, such as PI3K/Akt, JAK/STAT, and NF-kB. The multifaceted nature of resveratrol’s biological effects, including its influence on diverse physiological processes, underscores its potential as a valuable therapeutic option for the treatment of central nervous system tumors. Full article
(This article belongs to the Special Issue Potential Health Benefits of Resveratrol: Laboratory-Confirmed Mechanisms of Action)
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16 pages, 532 KiB  
Review
Resveratrol and Female Fertility: A Systematic Review
by Alessandro Bertoldo, Damiano Pizzol, Dong Keon Yon, Maura Callegari, Valentina Gobbo, Pierluigi Cuccurese, Laurie Butler, Susanna Caminada, Justin Stebbing, Fiona Richardson, Julia Gawronska and Lee Smith
Int. J. Mol. Sci. 2024, 25(23), 12792; https://doi.org/10.3390/ijms252312792 - 28 Nov 2024
Cited by 1 | Viewed by 3438
Abstract
Resveratrol is a natural polyphenolic compound that may have multiple influences on human health, including antiaging, anti-inflammatory, anti-neoplastic, antioxidant, insulin-sensitizing, cardioprotective and vasodilating activities. Growing evidence also suggests a potential positive effect of resveratrol on female fertility. The aim of the present study [...] Read more.
Resveratrol is a natural polyphenolic compound that may have multiple influences on human health, including antiaging, anti-inflammatory, anti-neoplastic, antioxidant, insulin-sensitizing, cardioprotective and vasodilating activities. Growing evidence also suggests a potential positive effect of resveratrol on female fertility. The aim of the present study was to collate and appraise the scientific literature on the relationship between resveratrol and female fertility. We systematically searched Medline, PubMed, Web of Science and Embase from the databases’ inception (1951, 1951, 1947 and 1900, respectively) until 9th May 2024. All in vivo or in vitro retrospective or prospective studies reporting the effects of resveratrol interventions on women’s fertility were included. We ultimately incorporated twenty-four studies into a systematic review with a narrative summary of the results; of those studies, nine were performed on women seeking natural or assisted fertility, and fifteen were in vitro studies performed on human cells and tissues in different stages of the reproductive cascade. The current literature, though limited, suggests that resveratrol may play a role in female infertility. Specifically, it may significantly and positively impact reproductive outcomes, owing to its potential therapeutic effects improving ovarian function. Further studies are now needed to better understand resveratrol’s effects and define the optimal dosage and periods of intake to maximize beneficial effects, as well as to prevent adverse outcomes on implantation, subsequent pregnancy and the fetus. Full article
(This article belongs to the Special Issue Potential Health Benefits of Resveratrol: Laboratory-Confirmed Mechanisms of Action)
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