Abstract
Plants continuously produce an extraordinary variety of biologically active low-molecular-mass
compounds. Among them, resveratrol (3,5,4′-trihydroxystilbene) is endowed with significant
positive activities by protecting against cardiovascular diseases and preventing the
development and progression of atherosclerosis. Furthermore, the molecule significantly
ameliorates glucose homeostasis in obese mice. These beneficial effects have driven
considerable interest towards resveratrol molecular activities, and intensive efforts
for the identification of the stilbene targets have been made.
The molecule shows a pleiotropic mode of action. Particularly, its cellular targets
are crucial for cell proliferation and differentiation, apoptosis, antioxidant defence
and mitochondrial energy production. The complexity of resveratrol activities might
account for its effectiveness in ameliorating multifactorial processes, including
the onset and/or progression of several degenerative diseases such as myocardial infarction,
atherosclerosis and type 2 diabetes.
This article reports the actions of resveratrol on cardiovascular diseases and the
molecular bases of its activity. We also discuss recent data on the effect of resveratrol
on glucose homeostasis and obesity. Finally, the relevance of the stilbene use in
the development of new pharmacological strategies is evaluated.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Nutrition, Metabolism and Cardiovascular DiseasesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Natural products and plant disease resistance.Nature. 2001; 411: 843-847
- A new class of phytoalexins from grapevines.Experentia. 1977; 33: 151-152
- Effects of ultraviolet irradiation on resveratrol and changes in resveratrol and various of its derivatives in the skins of ripening grapes.Sci Aliments. 1995; 15: 411-422
- Development of methods using phytoalexin (resveratrol) assessment as a selection criterion to screen grapevine in vitro cultures for resistance to grey mould (Botrytis cinerea).Euphytica. 1995; 86: 41-47
- Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.Science. 1997; 275: 218-220
- Resveratrol: from basic science to the clinic.Cell Cycle. 2007; 6: 2495-2510
- Therapeutic potential of resveratrol: the in vivo evidence.Nat Rev Drug Discov. 2006; 5: 493-506
- Resveratrol as an inhibitor of cancerogenesis.in: Aggarwal B.B. Shishodia S. Resveratrol in health and disease. CRC Press Taylor & Francis Group, Boca Raton2006: 233-383
- Substrate-specific activation of sirtuins by resveratrol.J Biol Chem. 2005; 280: 17038-17045
- Mechanism of human SIRT1 activation by resveratrol.J Biol Chem. 2005; 280: 17187-17195
- Wine, alcohol, platelets, and the French paradox for coronary heart disease.Lancet. 1992; 339: 1523-1526
- The positive and negative health effects of alcohol- and the public health implications.J Intern Med. 2009; 265: 407-420
- The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury.Free Radic Biol Med. 1999; 27: 160-169
- Inhibition of human LDL oxidation by resveratrol.Lancet. 1993; 341: 1103-1104
- Beneficial effects of resveratrol on atherosclerosis.J Med Food. 2008; 11: 610-614
- Uptake of diet resveratrol into the human low-density lipoprotein. Identification and quantification of resveratrol metabolites by liquid chromatography coupled with tandem mass spectrometry.Anal Chem. 2005; 77: 3149-3155
- Resveratrol regulates the expression of LXR-alpha in human macrophages.Biochem Biophys Res Commun. 2006; 348: 1047-1054
- Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro.Int J Mol Med. 2002; 9: 77-79
- Resveratrol is a peroxidase-mediated inactivator of COX-1 but not COX-2.J Biol Chem. 2004; 279: 22727-22737
- Inhibitory mechanisms of resveratrol in platelet activation: pivotal roles of p38 MAPK and NO/cyclic GMP.Br J Haematol. 2007; 139: 475-485
- Resveratrol induces vasorelaxation of mesenteric and uterine arteries from female guinea-pigs.Clin Sci (London). 2000; 98: 537-543
- Endothelial function and coronary artery disease.Curr Opin Lipidol. 2001; 12: 383-389
- Role of endothelial dysfunction in atherosclerosis.Circulation. 2004; 109: III27-III32
- The possible implication of trans-resveratrol in the cardioprotective effects of long-term moderate wine consumption.Mol Pharmacol. 2002; 61: 294-302
- Coordinated induction of iNOS-VEGF-KDR-eNOS after resveratrol consumption: a potential mechanism for resveratrol preconditioning of the heart.Vascul Pharmacol. 2005; 42: 281-289
- Inhibition of cyclic strain-induced endothelin-1 gene expression by resveratrol.Hypertension. 2003; 42: 1198-1205
- Resveratrol, a red wine constituent polyphenol, prevents superoxide-dependent inflammatory responses induced by ischemia/reperfusion, platelet-activating factor, or oxidants.Free Radic Biol Med. 2003; 34: 810-817
- Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium.Am J Clin Nutr. 1998; 68: 208-214
- Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation.J Immunol. 2000; 164: 6509-6519
- Protective mechanisms of resveratrol against ischemia-reperfusion-induced damage in hearts obtained from Zucker obese rats: the role of GLUT-4 and endothelin.Am J Physiol Heart Circ Physiol. 2008; 294: H859-H866
- Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: role of nitric oxide, thioredoxin, and heme oxygenase.Free Radic Biol Med. 2007; 43: 720-729
- Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes.FASEB J. 2001; 15: 1798-1800
- Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells.Am J Physiol Heart Circ Physiol. 2009; 297: H1876-H1881
- Protective effects of resveratrol against ischemia-reperfusion.in: Aggarwal B.B. Shishodia S. Resveratrol in health and disease. CRC Press Taylor & Francis Group, Boca Raton2006: 519-537
- Pharmacological preconditioning with resveratrol: role of nitric oxide.Am J Physiol Heart Circ Physiol. 2002; 282: H1988-H1995
- Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1 alpha.Cell. 2006; 127: 1109-1122
- Resveratrol improves health and survival of mice on a high-calorie diet.Nature. 2006; 444: 337-342
- AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity.Nature. 2009; 458: 1056-1060
- A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice.PLoS One. 2008; 6: 2264
- Resveratrol-associated renal toxicity.Toxicol Sci. 2004; 82: 614-619
- Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers.Mol Nutr Food Res. 2009; 53: S7-S15
- High absorption but very low bioavailability of oral resveratrol in humans.Drug Metab Dispos. 2004; 32: 1377-1382
- Measurement of trans-resveratrol, (1)-catechin, and quercetin in rat and human blood and urine by gas chromatography with mass selective detection.Meth Enzymol. 2001; 335: 130-145
- Ultrasensitive assay for three polyphenols (catechin, quercetin and resveratrol) and their conjugates in biological fluids utilizing gas chromatography with mass selective detection.J Chromatogr B Biomed Sci Appl. 2001; 757: 161-172
- Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent.Cancer Epidemiol Biomarkers Prev. 2007; 16: 1246-1252
Article info
Publication history
Accepted:
July 19,
2010
Received in revised form:
July 16,
2010
Received:
January 28,
2010
Identification
Copyright
© 2010 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
