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Clinical Studies
References
Resveratrol is a polyphenolic compound primarily found in red wine, red grape skins, red grape juice, mulberries and in smaller amounts in peanuts. Resveratrol decreases the activity of inflammatory cytokines, which suggests a mechanism for reducing mortality in cardiovascular diseases and cancer.
Resveratrol inhibits the replication of herpes simplex virus. Although the mechanism of this action is not fully known, exposure to Resveratrol within one hour of cellular infection appears to be most effective in arresting viral growth. This suggests that Resveratrol reduces production of proteins needed to regulate viral proliferation.
Resveratrol may be beneficial in atherosclerosis and may be helpful in lowering cholesterol levels, increasing HDL cholesterol levels and preventing cancer, as protection from free-radical damage, in arthritis, to prevent damage to blood vessels, as protection against cardiovascular disease and cancer and as alleviation of menopausal symptoms.
Published Clinical Studiesclin
1
Grape Polyphenol Resveratrol and the Related Molecule 4-Hydroxystilbene Induce Growth Inhibition, Apoptosis, S-Phase Arrest, and Upregulation of Cyclins A, E, and B1 in Human SK-Mel-28 Melanoma Cells.
Larrosa M, Tomas-Barberan FA, Espin JC.
Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Espinardo, Murcia, Spain.
The effect of the naturally occurring polyphenol resveratrol (3,5,4'-trihydroxy-trans-stilbene; RES) on growth, cell cycle, and cyclins A, E, and B1 expression was investigated in the human SK-Mel-28 melanoma cell line. In addition, the structurally related compounds 4-hydroxy-trans-stilbene (4HST), piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene (PICE), and 4-trans-stilbenemethanol (4STMe) were also assayed in order to investigate the requirements of stilbenes to exert activity against melanoma cells. Both RES and 4HST inhibited cell growth in a dose- and time-dependent manner and upregulated the expression of cyclins A, E, and B1 with subsequent irreversible arrest of melanoma cells in the S-phase, concomitant with a decrease in G(0)/G(1) and G(2)/M phases. In addition, potent apoptosis-mediated cell death was detected with the annexin V assay whereas no apoptosis was observed by flow cytometry, which encourages the assay of different methodologies to evaluate the effect of polyphenols on cell lines. The effect of PICE was not evaluated because of its instability in the reaction medium. No effect on cell cycle and cyclins expression was observed when 4STMe was assayed, which supported the critical requirement of the 4'-hydroxystyryl moiety to exert the above effects. In addition, this structural requirement also influenced the cellular uptake of stilbenes. The presence of two extra hydroxyl groups in RES increased its cytotoxicity whereas it diminished its efficiency to inhibit cell growth, upregulate cyclins expression, and arrest cell cycle in the S-phase with respect to 4HST. The present study suggests that the antimelanoma properties of dietary stilbenes, such as grape RES, cannot be ruled out, taking into account previous studies concerning the relationship between plasma and tissue concentrations and pharmacological activity of RES in animal models.
PMID: 14705880 [PubMed - in process]
Syntheses and radical scavenging activities of resveratrol derivatives.2
Lee HJ, Seo JW, Lee BH, Chung KH, Chi DY.
Department of Chemistry, Inha University, 253 Yonghyundong, Namgu, 402-751, Inchon, South Korea
Nine new resveratrol derivatives, having bromo, iodo, and fluoroethyl groups, were designed and synthesized. All compounds having free phenol groups showed good free radical scavenging activity. Among them, 2-bromoresveratrol 19 has a similar free radical scavenging activity to (+)-catechin.
PMID: 14698182 [PubMed - in process]
Combined effects of resveratrol and paclitaxel on lung cancer cells.3
Kubota T, Uemura Y, Kobayashi M, Taguchi H.
Department of Medicine, Kochi Medical School, Kochi, 783-8505, Japan. kubotat@med.kochi-ms.ac.jp
Resveratrol (3,4',5-trihydroxystilbene) is a phytoalexin found in grapes and other food products that can prevent cancer. We studied the in vitro biological activity of this compound by examining its effect on proliferation and inducing apoptosis in three lung cancer cell lines (A549, EBC-1, Lu65). Resveratrol inhibited the growth of A549, EBC-1 and Lu65 lung cancer cells by 50% (ED50) at concentrations between 5-10 microM. We also examined the combined effects in these cells of resveratrol and paclitaxel, an essential chemotherapeutic agent against lung cancer. Although simultaneous exposure to resveratrol plus paclitaxel did not result in significant synergy, resveratrol (10 microM, 3 days) significantly enhanced the subsequent antiproliferative effect of paclitaxel. In addition, resveratrol as well as paclitaxel induced apoptosis in EBC-1 and Lu65 cells, as measured by TUNEL and caspase assays, as well as flow cytometry. Resveratrol (10 microM, 3 days) similarly enhanced the subsequent apoptotic effects of paclitaxel. We examined the effects of resveratrol and paclitaxel on levels of p21waf1, p27kip1, E-cadherin, EGFR and Bcl-2 in EBC-1 cells. Resveratrol (10 microM, 3 days) prior to paclitaxel induced p21waf1 expression approximately 4-fold. These results suggest that resveratrol may be a promising alternative therapy for lung cancer and that lung cancer cells exposed to resveratrol have a lowered threshold for killing by paclitaxel.
PMID: 14666716 [PubMed - in process]
Inhibitory effect of resveratrol on angiotensin II-induced cardiomyocyte hypertrophy.4
Cheng TH, Liu JC, Lin H, Shih NL, Chen YL, Huang MT, Chan P, Cheng CF, Chen JJ.
Department of Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan, Republic of China.
Resveratrol is proposed to account in part for the protective effect of red wine on the cardiovascular system. Angiotensin II (Ang II) is a potent hypertrophic stimulus in cardiomyocytes. In this study, we determined the effect of resveratrol on Ang II-induced cardiomyocyte hypertrophy. Cultured neonatal rat cardiomyocytes were stimulated with Ang II, and [(3)H]leucine incorporation and beta-myosin heavy chain (beta-MyHC) promoter activity were examined. Intracellular reactive oxygen species (ROS) were measured by a redox-sensitive fluorescent dye, 2' 7'-dichlorofluorescin diacetate, and the extracellular signal-regulated kinase (ERK) phosphorylation was examined by Western blotting. Resveratrol inhibited Ang II-increased intracellular ROS levels. Furthermore, resveratrol, as well as the antioxidant N-acetyl-cysteine, decreased Ang II- or H(2)O(2)-increased protein synthesis, beta-MyHC promoter activity, and ERK phosphorylation. In summary, we demonstrate for the first time that resveratrol inhibits Ang II-induced cardiomyocyte hypertrophy via attenuation of ROS generation.
PMID: 14663554 [PubMed - as supplied by publisher]
[In Process Citation]5
Kollar P, Hotolova H.
Farmaceuticka fakulta Veterinarni a farmaceuticke Univerzity, Brno. kollarp@vfu.cz
In recent years many scientific papers have been published concerning the positive effects of wine and its active principles, the polyphenol resveratrol being the most widely discussed compound. The results of epidemiological and experimental studies in man, animals, and in vitro have shown that polyphenols contained in wine, tea, fruit, and vegetables exert a positive effect on both the progression and regression of atherosclerosis, possess an anticancerogenic action, and due to their antioxidative effects they act against other processes connected with the reactive forms of oxygen production and lipid peroxydation in the blood plasma and membranes. Experimental findings have shown that resveratrol protects the cardiovascular system, affects lipid metabolism, and inhibits low-density lipoproteins (LDL) oxidation and blood platelet aggregation. In addition, this natural product is able to inhibit the growth of some tumours and possesses antiinflammatory properties and a number of other biological effects. This report aims to describe and characterize in a summary the biological properties of the principal active principles of wine--flavonoids and polyphenols, with a detailed focus on resveratrol, which has been described as the most interesting agent.
PMID: 14661366 [PubMed - in process]
Red wine ingredient resveratrol protects from beta-amyloid neurotoxicity.6
Savaskan E, Olivieri G, Meier F, Seifritz E, Wirz-Justice A, Muller-Spahn F.
Psychiatric Clinic, University of Basel, Basel, Switzerland. esavaskan@datacomm.ch
BACKGROUND: beta-Amyloid peptide (Abeta), a neutrotoxic substance, has been implicated to a great degree in cell death during the course of AD. Resveratrol, a natural polyphenol mainly found in red wine, has been shown to be cardioprotective and chemoprotective. Since a moderate wine intake correlates with a lower risk for Alzheimer disease (AD), an additional neuroprotective effect has been postulated for resveratrol. OBJECTIVE: The present study aimed at elucidating the possible neuroprotective effects of resveratrol against Abeta-induced neurotoxicity. METHODS: The neuroprotective capacity against Abeta-related oxidative stress was studied in a cell culture model suitable for studying such potentially neuroprotective substances. RESULTS: Resveratrol maintains cell viability and exerts an anti-oxidative action by enhancing the intracellular free-radical scavenger glutathione. CONCLUSION: Our findings suggest that red wine may be neuroprotective through the actions of resveratrol. Copyright 2003 S. Karger AG, Basel
PMID: 14624067 [PubMed - in process]
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