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British Journal of Pharmacology Mar 2020Resveratrol (trans-3,4',5-trihydroxystilbene) belongs to the family of natural phytoalexins. Resveratrol first came to our attention in 1992, following reports of the... (Review)
Review
Resveratrol (trans-3,4',5-trihydroxystilbene) belongs to the family of natural phytoalexins. Resveratrol first came to our attention in 1992, following reports of the cardioprotective effects of red wine. Thereafter, resveratrol was shown to exert antioxidant, anti-inflammatory, anti-proliferative, and angio-regulatory effects against atherosclerosis, ischaemia, and cardiomyopathy. This article critically reviews the current findings on the molecular basis of resveratrol-mediated cardiovascular benefits, summarizing the broad effects of resveratrol on longevity regulation, energy metabolism, stress resistance, exercise mimetics, circadian clock, and microbiota composition. In addition, this article also provides an update, both preclinically and clinically, on resveratrol-induced cardiovascular protection and discusses the adverse and inconsistent effects of resveratrol reported in both preclinical and clinical studies. Although resveratrol has been claimed as a master anti-aging agent against several age-associated diseases, further detailed mechanistic investigation is still required to thoroughly unravel the therapeutic value of resveratrol against cardiovascular diseases at different stages of disease development. LINKED ARTICLES: This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc.
Topics: Anti-Inflammatory Agents; Antioxidants; Cardiovascular System; Dietary Supplements; Resveratrol
PubMed: 31347157
DOI: 10.1111/bph.14801 -
International Journal of Molecular... Apr 2022Resveratrol is a polyphenol that has been shown to possess many applications in different fields of medicine. This systematic review has drawn attention to the axis... (Review)
Review
Resveratrol is a polyphenol that has been shown to possess many applications in different fields of medicine. This systematic review has drawn attention to the axis between resveratrol and human microbiota, which plays a key role in maintaining an adequate immune response that can lead to different diseases when compromised. Resveratrol can also be an asset in new technologies, such as gene therapy. PubMed, Cochrane Library, Scopus, Web of Science, and Google Scholar were searched to find papers that matched our topic dating from 1 January 2017 up to 18 January 2022, with English-language restriction using the following Boolean keywords: ("resveratrol" AND "microbio*"). Eighteen studies were included as relevant papers matching the purpose of our investigation. Immune response, prevention of thrombotic complications, microbiota, gene therapy, and bone regeneration were retrieved as the main topics. The analyzed studies mostly involved resveratrol supplementation and its effects on human microbiota by trials in vitro, in vivo, and ex vivo. The beneficial activity of resveratrol is evident by analyzing the changes in the host's genetic expression and the gastrointestinal microbial community with its administration. The possibility of identifying individual microbial families may allow to tailor therapeutic plans with targeted polyphenolic diets when associated with microbial dysbiosis, such as inflammatory diseases of the gastrointestinal tract, degenerative diseases, tumors, obesity, diabetes, bone tissue regeneration, and metabolic syndrome.
Topics: Dietary Supplements; Dysbiosis; Gastrointestinal Microbiome; Humans; Obesity; Resveratrol
PubMed: 35409389
DOI: 10.3390/ijms23074027 -
Molecules (Basel, Switzerland) Aug 2022Natural polyphenols have a wide variety of biological activities and are taken into account as healthcare materials. Resveratrol is one such natural polyphenol,... (Review)
Review
Natural polyphenols have a wide variety of biological activities and are taken into account as healthcare materials. Resveratrol is one such natural polyphenol, belonging to a group known as stilbenoids (STBs). Resveratrol (3,5,4'-trihydroxy--stilbene) is mainly found in grapes, wine, nuts, and berries. A wide range of biological activities has been demonstrated by resveratrol, including antimicrobial, antioxidant, antiviral, antifungal, and antiaging effects, and many more are still under research. However, as with many other plant-based polyphenol products, resveratrol suffers from low bioavailability once administered in vivo due to its susceptibility to rapid enzyme degradation by the body's innate immune system before it can exercise its therapeutic influence. Therefore, it is of the utmost importance to ensure the best use of resveratrol by creating a proper resveratrol delivery system. Nanomedicine and nanodelivery systems utilize nanoscale materials as diagnostic tools or to deliver therapeutic agents in a controlled manner to specifically targeted locations. After a brief introduction about polyphenols, this review overviews the physicochemical characteristics of resveratrol, its beneficial effects, and recent advances on novel nanotechnological approaches for its delivery according to the type of nanocarrier utilized. Furthermore, the article summarizes the different potential applications of resveratrol as, for example, a therapeutic and disease-preventing anticancer and antiviral agent.
Topics: Antioxidants; Nanoparticle Drug Delivery System; Polyphenols; Resveratrol; Stilbenes
PubMed: 36014390
DOI: 10.3390/molecules27165154 -
Nutrients Sep 2021Stilbenoids are interesting natural compounds with pleiotropic in vitro and in vivo activity. Their well-documented biological properties include anti-inflammatory... (Review)
Review
Stilbenoids are interesting natural compounds with pleiotropic in vitro and in vivo activity. Their well-documented biological properties include anti-inflammatory effects, anticancer effects, effects on longevity, and many others. Therefore, they are nowadays commonly found in foods and dietary supplements, and used as a part of treatment strategy in various types of diseases. Bioactivity of stilbenoids strongly depends on different types of factors such as dosage, food composition, and synergistic effects with other plant secondary metabolites such as polyphenols or vitamins. In this review, we summarize the existing in vitro, in vivo, and clinical data from published studies addressing the optimization of bioavailability of stilbenoids. Stilbenoids face low bioavailability due to their chemical structure. This can be improved by the use of novel drug delivery systems or enhancers, which are discussed in this review. Current in vitro and in vivo evidence suggests that both approaches are very promising and increase the absorption of the original substance by several times. However, data from more clinical trials are required.
Topics: Animals; Biological Availability; Dietary Supplements; Drug Delivery Systems; Humans; Resveratrol; Stilbenes
PubMed: 34578972
DOI: 10.3390/nu13093095 -
Nutrients Oct 2022Mitochondria participate in the maintenance of cellular homeostasis. Firstly, mitochondria regulate energy metabolism through oxidative phosphorylation. In addition,... (Review)
Review
Mitochondria participate in the maintenance of cellular homeostasis. Firstly, mitochondria regulate energy metabolism through oxidative phosphorylation. In addition, they are involved in cell fate decisions by activating the apoptotic intrinsic pathway. Finally, they work as intracellular signaling hubs as a result of their tight regulation of ion and metabolite concentrations and other critical signaling molecules such as ROS. Aging is a multifactorial process triggered by impairments in different cellular components. Among the various molecular pathways involved, mitochondria are key regulators of longevity. Indeed, mitochondrial deterioration is a critical signature of the aging process. In this scenario, we will focus specifically on the age-related decrease in CoQ levels, an essential component of the electron transport chain (ETC) and an antioxidant, and how CoQ supplementation could benefit the aging process. Generally, any treatment that improves and sustains mitochondrial functionality is a good candidate to counteract age-related mitochondrial dysfunctions. In recent years, heightened attention has been given to natural compounds that modulate mitochondrial function. One of the most famous is resveratrol due to its ability to increase mitochondrial biogenesis and work as an antioxidant agent. This review will discuss recent clinical trials and meta-analyses based on resveratrol and CoQ supplementation, focusing on how these compounds could improve mitochondrial functionality during aging.
Topics: Resveratrol; Antioxidants; Reactive Oxygen Species; Mitochondria; Oxidative Phosphorylation; Oxidative Stress
PubMed: 36297010
DOI: 10.3390/nu14204326 -
Nutrients Feb 2020-resveratrol, a well-known plant phenolic compound, has been intensively investigated due to its association with the so-called French paradox. However, despite its high...
-resveratrol, a well-known plant phenolic compound, has been intensively investigated due to its association with the so-called French paradox. However, despite its high pharmacological potential, -resveratrol has shown relatively low bioavailability. -resveratrol is intensively metabolized in the intestine and liver, yielding metabolites that may be responsible for its high bioactivity. The aim of this study was to investigate and compare the metabolism of -resveratrol (tRes), -resveratrol (cRes) and dihydroresveratrol (dhRes) in an in vitro epithelial model using Caco-2 cell lines. Obtained metabolites of tRes, cRes and dhRes were analyzed by LC/MS Q-TOF, and significant differences in the metabolism of each compound were observed. The majority of tRes was transported unchanged through the Caco-2 cells, while cRes was mostly metabolized. The main metabolite of both and resveratrol observed as a result of colon microbial metabolism, dhRes, was metabolized almost completely, with only traces of the unchanged molecule being found. A sulphate conjugate was identified as the main metabolite of tRes in our model, while a glucuronide conjugate was the major metabolite of cRes and dhRes. Since metabolism of simple phenolics and polyphenols plays a crucial role in their bioavailability, detailed knowledge of their transformation is of high scientific value.
Topics: Biological Availability; Caco-2 Cells; Chromatography, High Pressure Liquid; Humans; Intestinal Mucosa; Permeability; Resveratrol; Stereoisomerism; Stilbenes
PubMed: 32106482
DOI: 10.3390/nu12030595 -
International Journal of Molecular... Nov 2022Resveratrol (3,5,4'-trihydroxy--stilbene), a polyphenol found in grapes, red wine, peanuts, and apples, has been reported to exhibit a wide range of biological and... (Review)
Review
Resveratrol (3,5,4'-trihydroxy--stilbene), a polyphenol found in grapes, red wine, peanuts, and apples, has been reported to exhibit a wide range of biological and pharmacological properties. In addition, resveratrol has been reported to intervene in multiple stages of carcinogenesis. It has also been known to kill several human cancer cells through programmed cell death (PCD) mechanisms such as apoptosis, autophagy, and necroptosis. However, resveratrol has limitations in its use as an anticancer agent because it is susceptible to photoisomerization owing to its unstable double bond, short half-life, and is rapidly metabolized and eliminated. -()-resveratrol is nontoxic, and has several biological and pharmacological activities. However, little is known about the pharmacological properties of the photoisomerized -()-resveratrol. Therefore, many studies on resveratrol derivatives and analogues that can overcome the shortcomings of resveratrol and increase its anticancer activity are underway. This review comprehensively summarizes the literature related to resveratrol-induced PCD, such as apoptosis, autophagy, necroptosis, and the development status of synthetic resveratrol derivatives and analogues as novel anticancer drugs.
Topics: Humans; Resveratrol; Neoplasms; Apoptosis; Stilbenes; Antineoplastic Agents; Drug Discovery
PubMed: 36430164
DOI: 10.3390/ijms232213689 -
Cartilage Dec 2021Advanced glycation end-product (AGE) accumulation is implicated in osteoarthritis (OA) pathogenesis in aging and diabetic populations. Here, we develop a representative...
OBJECTIVE
Advanced glycation end-product (AGE) accumulation is implicated in osteoarthritis (OA) pathogenesis in aging and diabetic populations. Here, we develop a representative nonenzymatic glycation-induced OA cartilage explant culture model and investigate the effectiveness of resveratrol, curcumin, and eugenol in inhibiting AGEs and the structural and biological hallmarks of cartilage degeneration.
DESIGN
Bovine cartilage explants were treated with AGE-bovine serum albumin, threose, and ribose to determine the optimal conditions that induce physiological levels of AGEs while maintaining chondrocyte viability. AGE crosslinks, tissue stiffness, cell viability, metabolism and senescence, nitrite release and loss of glycosaminoglycans were assessed. Explants were cotreated with resveratrol, curcumin, or eugenol to evaluate their anti-AGE properties. Blind docking analysis was conducted to estimate binding energies of drugs with collagen II.
RESULTS
Treatment with 100 mM ribose significantly increased AGE crosslink formation and tissue stiffness, resulting in reduced chondrocyte metabolism and enhanced senescence. Blind docking analysis revealed stronger binding energies of both resveratrol and curcumin than ribose, with glycation sites along a human collagen II fragment, indicating their increased likelihood of competitively inhibiting ribose activity. Resveratrol and curcumin, but not eugenol, successfully inhibited AGE crosslink formation and its associated downstream biological response.
CONCLUSIONS
We establish a cartilage explant model of OA that recapitulates several aspects of aged human cartilage. We find that resveratrol and curcumin are effective anti-AGE therapeutics with the potential to decelerate age-related and diabetes-induced OA. This nonenzymatic glycation-induced model provides a tool for screening OA drugs, to simultaneously evaluate AGE-induced biological and mechanical changes.
Topics: Aged; Cartilage; Curcumin; Glycation End Products, Advanced; Humans; Resveratrol; Sugars
PubMed: 33472415
DOI: 10.1177/1947603520988768 -
Current Neuropharmacology 2022Nowadays, neurodegenerative diseases (NDs), such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis... (Review)
Review
Nowadays, neurodegenerative diseases (NDs), such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a great challenge in different scientific fields, such as neuropharmacology, medicinal chemistry, molecular biology and medicine, as all these pathologies remain incurable, with high socioeconomic impacts and high costs for governmental health services. Due to their severity and multifactorial pathophysiological complexity, the available approved drugs for clinic have not yet shown adequate effectiveness and exhibited very restricted options in the therapeutic arsenal; this highlights the need for continued drug discovery efforts in the academia and industry. In this context, natural products, such as curcumin (1), resveratrol (2) and cannabidiol (CBD, 3) have been recognized as important sources, with promising chemical entities, prototype models and starting materials for medicinal organic chemistry, as their molecular architecture, multifunctional properties and single chemical diversity could facilitate the discovery, optimization and development of innovative drug candidates with improved pharmacodynamics and pharmacokinetics compared to the known drugs and, perhaps, provide a chance for discovering novel effective drugs to combat NDs. In this review, we report the most recent efforts of medicinal chemists worldwide devoted to the exploration of curcumin (1), resveratrol (2) and cannabidiol (CBD, 3) as starting materials or privileged scaffolds in the design of multi-target directed ligands (MTDLs) with potential therapeutic properties against NDs, which have been published in the scientific literature during the last 10 years of research and are available in PubMed, SCOPUS and Web of Science databases.
Topics: Cannabidiol; Curcumin; Drug Design; Humans; Neurodegenerative Diseases; Neuroprotective Agents; Resveratrol
PubMed: 34825873
DOI: 10.2174/1570159X19666210712152532 -
Daru : Journal of Faculty of Pharmacy,... Jun 2023Adiposity and non-alcoholic fatty liver disease (NAFLD) are common characteristics of metabolic syndrome (MS). Understanding the underlying pathogenesis is crucial for...
BACKGROUND
Adiposity and non-alcoholic fatty liver disease (NAFLD) are common characteristics of metabolic syndrome (MS). Understanding the underlying pathogenesis is crucial for the development of new remedies. Resveratrol controls obesity and glycemic disorders in patients with MS.
OBJECTIVES
This study aimed to evaluate the effect of resveratrol and dulaglutide on adipose tissues and liver in rats with MS, declaring their possible mechanisms.
METHODS
Rats allocated as Control, MS (induced by a high fat/ high sucrose diet for eight weeks), MS + Resveratrol (30 mg/kg/day orally), and MS + Dulaglutide (0.6 mg/kg twice weekly SC); drugs administration was in the last four weeks. Serum biochemical measurements were done. Liver and visceral fat were processed for biochemistry, histopathology, and immunohistochemistry.
RESULTS
MS results demonstrated significantly increased systolic and diastolic blood pressure, anthropometric measurements, serum levels of alanine aminotransferase (ALT), glycemic indices, and lipids with decreased HDL-C. Tissue levels of leptin, malondialdehyde (MDA), and TNF-α reactivity significantly increased. Expression of adiponectin, PPARγ, and insulin growth factor-1 (IGF-1) decreased. Also, Western blotting mRNA gene expression of liver SIRT-1 was down-regulated. Resveratrol and dulaglutide significantly and effectively reversed MS complexity, ameliorating all findings, particularly NAFLD and adiposity-induced inflammation. Resveratrol significantly appears superior to dulaglutide regarding the effects on hemodynamics, lipids, adipokines, IGF-1 levels, and adipocyte size. Parallel, dulaglutide has more influence on glycemic control.
CONCLUSION
Protective effects of the drugs may be through correlations between SIRT-1/adipokines/IGF-1 and PPARγ, improving the cross-talk between insulin resistance, obesity markers, liver dysfunction, and TNF-α. Promising multi-beneficial therapies of resveratrol or dulaglutide in MS are recommended clinically for this purpose. Showing the Experimental Design.
Topics: Rats; Animals; Non-alcoholic Fatty Liver Disease; Resveratrol; Metabolic Syndrome; Insulin; Adipokines; PPAR gamma; Insulin-Like Growth Factor I; Adiposity; Tumor Necrosis Factor-alpha; Liver; Obesity; Diet; Lipids; Diet, High-Fat
PubMed: 36991247
DOI: 10.1007/s40199-023-00458-y