Resveratrol in cardioprotection: a therapeutic promise of alternative medicine.

Resveratrol, a polyphenol phytoalexin, possesses diverse biochemical and physiological actions, including estrogenic, antiplatelet, and anti-inflammatory properties. Several recent studies determined the cardioprotective abilities of resveratrol. Both in experiments (acute) and in chronic models, resveratrol attenuates myocardial ischemic reperfusion injury, atherosclerosis, and reduces ventricular arrhythmias. It appears that resveratrol-mediated cardioprotection is achieved through the preconditioning effect (the best yet devised method of cardioprotection), rather than direct protection. Thus, resveratrol likely fulfills the definition of a pharmacological preconditioning compound and gives hope to the therapeutic promise of alternative medicine.

[1]  N. Maulik,et al.  Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth factor-angiogenesis and tyrosine kinase receptor Flk-1 , 2006, Cell Biochemistry and Biophysics.

[2]  N. Maulik,et al.  Coordinated induction of iNOS-VEGF-KDR-eNOS after resveratrol consumption: a potential mechanism for resveratrol preconditioning of the heart. , 2005, Vascular pharmacology.

[3]  N. Maulik,et al.  Pharmacological preconditioning with resveratrol: role of CREB-dependent Bcl-2 signaling via adenosine A3 receptor activation. , 2005, American journal of physiology. Heart and circulatory physiology.

[4]  B. Wachowicz,et al.  The protective effects of resveratrol against changes in blood platelet thiols induced by platinum compounds. , 2004, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[5]  L. Hung,et al.  Resveratrol protects myocardial ischemia-reperfusion injury through both NO-dependent and NO-independent mechanisms. , 2004, Free radical biology & medicine.

[6]  Marina Ziche,et al.  Nitric Oxide and Angiogenesis , 2000, Journal of Neuro-Oncology.

[7]  Xianglin Shi,et al.  Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. , 2003, Biochemical and biophysical research communications.

[8]  G. Losa.  Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells , 2003, European journal of clinical investigation.

[9]  S. S. Hall.  In Vino Vitalis? Compounds Activate Life-Extending Genes , 2003, Science.

[10]  G. Mahady,et al.  Resveratrol and Red Wine Extracts Inhibit the Growth of CagA+ Strains of Helicobacter pylori In Vitro , 2003, American Journal of Gastroenterology.

[11]  P. Palatini,et al.  Oral administration of trans-resveratrol to guinea pigs increases cardiac DT-diaphorase and catalase activities, and protects isolated atria from menadione toxicity. , 2003, Life sciences.

[12]  J. Horiguchi,et al.  Resveratrol acts as an estrogen receptor (ER) agonist in breast cancer cells stably transfected with ER α , 2003, International journal of cancer.

[13]  G. Gaetano,et al.  Resveratrol and quercetin down‐regulate tissue factor expression by human stimulated vascular cells , 2003, Journal of thrombosis and haemostasis : JTH.

[14]  R. Korthuis,et al.  Resveratrol, a red wine constituent polyphenol, prevents superoxide-dependent inflammatory responses induced by ischemia/reperfusion, platelet-activating factor, or oxidants. , 2003, Free radical biology & medicine.

[15]  L. Barenghi,et al.  Resveratrol provides late-phase cardioprotection by means of a nitric oxide- and adenosine-mediated mechanism. , 2003, European journal of pharmacology.

[16]  C. Klinge,et al.  Estrogenic activity in white and red wine extracts. , 2003, Journal of agricultural and food chemistry.

[17]  G. Yen,et al.  Effects of Resveratrol and 4-hexylresorcinol on Hydrogen Peroxide-induced Oxidative DNA Damage in Human Lymphocytes , 2003, Free radical research.

[18]  U. Förstermann,et al.  Resveratrol, a Polyphenolic Phytoalexin Present in Red Wine, Enhances Expression and Activity of Endothelial Nitric Oxide Synthase , 2002, Circulation.

[19]  N. Maulik,et al.  Pharmacological preconditioning with resveratrol: role of nitric oxide. , 2002, American journal of physiology. Heart and circulatory physiology.

[20]  N. Maulik,et al.  Pharmacological preconditioning with resveratrol: an insight with iNOS knockout mice. , 2002, American journal of physiology. Heart and circulatory physiology.

[21]  D. Das,et al.  Resveratrol, a Component of Wine and Grapes, in the Prevention of Kidney Disease , 2002, Annals of the New York Academy of Sciences.

[22]  D. Witt,et al.  Resveratrol: Phytoestrogen Effects on Reproductive Physiology and Behavior in Female Rats , 2002, Hormones and Behavior.

[23]  J. Leiro,et al.  The possible implication of trans-Resveratrol in the cardioprotective effects of long-term moderate wine consumption. , 2002, Molecular pharmacology.

[24]  Zhirong Wang,et al.  Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. , 2002, International journal of molecular medicine.

[25]  E. Ignatowicz,et al.  Resveratrol, a natural chemopreventive agent against degenerative diseases. , 2001, Polish journal of pharmacology.

[26]  J. Cooke,et al.  Genetic augmentation of nitric oxide synthase increases the vascular generation of VEGF. , 2001, Cardiovascular research.

[27]  B. Bussolati,et al.  Vascular endothelial growth factor receptor-1 modulates vascular endothelial growth factor-mediated angiogenesis via nitric oxide. , 2001, The American journal of pathology.

[28]  N. Maulik,et al.  Src tyrosine kinase is the trigger but not the mediator of ischemic preconditioning. , 2001, American journal of physiology. Heart and circulatory physiology.

[29]  Y. Miura,et al.  Inhibitory effect of resveratrol on proteinuria, hypoalbuminemia and hyperlipidemia in nephritic rats. , 2001, Life sciences.

[30]  R. S. Lee,et al.  Beneficial effects of astringinin, a resveratrol analogue, on the ischemia and reperfusion damage in rat heart. , 2001, Free radical biology & medicine.

[31]  N. Maulik,et al.  Hypoxia/reoxygenation promotes myocardial angiogenesis via an NF kappa B-dependent mechanism in a rat model of chronic myocardial infarction. , 2001, Journal of molecular and cellular cardiology.

[32]  Á. Tósaki,et al.  Benefits of resveratrol in women's health. , 2001, Drugs under experimental and clinical research.

[33]  N. Maulik,et al.  Regulation of cardiomyocyte apoptosis by redox‐sensitive transcription factors , 2000, FEBS letters.

[34]  C. Klinge,et al.  Resveratrol Acts as a Mixed Agonist / Antagonist for Estrogen Receptors a and b * , 2000 .

[35]  N. Maulik,et al.  SAPKs regulation of ischemic preconditioning. , 2000, American journal of physiology. Heart and circulatory physiology.

[36]  J. Levasseur,et al.  Inducible nitric oxide synthase mediates delayed myocardial protection induced by activation of adenosine A(1) receptors: evidence from gene-knockout mice. , 2000, Circulation.

[37]  A. Zeiher,et al.  Nitric Oxide Down-regulates MKP-3 mRNA Levels , 2000, The Journal of Biological Chemistry.

[38]  R. S. Lee,et al.  Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. , 2000, Cardiovascular research.

[39]  F. Ranelletti,et al.  Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential , 2000, International journal of cancer.

[40]  L. Tessitore,et al.  Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21(CIP) expression. , 2000, Carcinogenesis.

[41]  H. Wiseman.  The therapeutic potential of phytoestrogens , 2000, Expert opinion on investigational drugs.

[42]  E. Castanas,et al.  Wine Antioxidant Polyphenols Inhibit the Proliferation of Human Prostate Cancer Cell Lines , 2000, Nutrition and cancer.

[43]  G. Mahady,et al.  Resveratrol inhibits the growth of helicobacter pylori in vitro , 2000, American Journal of Gastroenterology.

[44]  S. Manna,et al.  Resveratrol Suppresses TNF-Induced Activation of Nuclear Transcription Factors NF-κB, Activator Protein-1, and Apoptosis: Potential Role of Reactive Oxygen Intermediates and Lipid Peroxidation1 , 2000, The Journal of Immunology.

[45]  J. J. Moreno,et al.  Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. , 2000, Biochemical pharmacology.

[46]  Y. Yamori,et al.  Resveratrol attenuates ovariectomy-induced hypertension and bone loss in stroke-prone spontaneously hypertensive rats. , 2000, Journal of nutritional science and vitaminology.

[47]  C. Baines,et al.  Role of mitogen-activated protein kinases in ischemia and reperfusion injury : the good and the bad. , 2000, Circulation research.

[48]  K. Shimamoto,et al.  Roles of tyrosine kinase and protein kinase C in infarct size limitation by repetitive ischemic preconditioning in the rat. , 2000, Journal of cardiovascular pharmacology.

[49]  J. Schlessinger.  New Roles for Src Kinases in Control of Cell Survival and Angiogenesis , 2000, Cell.

[50]  N. Maulik,et al.  Myocardial protection with red wine extract. , 2000, Journal of cardiovascular pharmacology.

[51]  J. Le Bail,et al.  Estrogenic/antiestrogenic and scavenging properties of (E)- and (Z)-resveratrol. , 2000, Life sciences.

[52]  L. Frémont.  Biological effects of resveratrol. , 2000, Life sciences.

[53]  R. T. Rosen,et al.  Isolation and identification of stilbenes in two varieties of Polygonum cuspidatum. , 2000, Journal of agricultural and food chemistry.

[54]  D. Das,et al.  Myocardial protection by Protykin, a novel extract of trans-resveratrol and emodin , 2000, Free radical research.

[55]  J. Downey,et al.  Ischemic preconditioning: from adenosine receptor to KATP channel. , 2000, Annual review of physiology.

[56]  A. Freyberger,et al.  Differential response of immature rat uterine tissue to ethinylestradiol and the red wine constituent resveratrol , 2000, Archives of Toxicology.

[57]  C. Charpentier,et al.  Occurrence of resveratrol and pterostilbene in age-old darakchasava, an ayurvedic medicine from India. , 1999, Journal of ethnopharmacology.

[58]  Y. Takeishi,et al.  Differential regulation of p90 ribosomal S6 kinase and big mitogen-activated protein kinase 1 by ischemia/reperfusion and oxidative stress in perfused guinea pig hearts. , 1999, Circulation research.

[59]  M. C. Pinto,et al.  Resveratrol is a potent inhibitor of the dioxygenase activity of lipoxygenase. , 1999, Journal of agricultural and food chemistry.

[60]  N. Maulik,et al.  Ischemic preconditioning reduces apoptosis by upregulating anti-death gene Bcl-2. , 1999, Circulation.

[61]  P. Ping,et al.  The late phase of ischemic preconditioning is abrogated by targeted disruption of the inducible NO synthase gene. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[62]  P. Ping,et al.  Demonstration of selective protein kinase C-dependent activation of Src and Lck tyrosine kinases during ischemic preconditioning in conscious rabbits. , 1999, Circulation research.

[63]  A. Akhand,et al.  Nitric Oxide Controls Src Kinase Activity through a Sulfhydryl Group Modification-mediated Tyr-527-independent and Tyr-416-linked Mechanism* , 1999, The Journal of Biological Chemistry.

[64]  D. Das,et al.  The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. , 1999, Free radical biology & medicine.

[65]  R. Busse,et al.  Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation , 1999, Nature.

[66]  S. Goldman,et al.  Effects of endothelial and inducible nitric oxide synthases inhibition on circulatory function in rats after myocardial infarction. , 1999, Cardiovascular research.

[67]  S. Cadenas,et al.  Resveratrol, melatonin, vitamin E, and PBN protect against renal oxidative DNA damage induced by the kidney carcinogen KBrO3. , 1999, Free radical biology & medicine.

[68]  G. Serrero,et al.  Resveratrol, a natural product derived from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells , 1999, Journal of cellular physiology.

[69]  Richard E. White,et al.  Resveratrol inhibits MAPK activity and nuclear translocation in coronary artery smooth muscle: reversal of endothelin‐1 stimulatory effects , 1999, FEBS letters.

[70]  M. Miloso,et al.  Resveratrol-induced activation of the mitogen-activated protein kinases, ERK1 and ERK2, in human neuroblastoma SH-SY5Y cells , 1999, Neuroscience Letters.

[71]  R. Fryer,et al.  Importance of PKC and tyrosine kinase in single or multiple cycles of preconditioning in rat hearts. , 1999, American journal of physiology. Heart and circulatory physiology.

[72]  J. Downey,et al.  Ischemic preconditioning depends on interaction between mitochondrial KATP channels and actin cytoskeleton. , 1999, American journal of physiology. Heart and circulatory physiology.

[73]  T. Elattar,et al.  Modulating effect of resveratrol and quercetin on oral cancer cell growth and proliferation. , 1999, Anti-cancer drugs.

[74]  J. Williams,et al.  Resveratrol, a polyphenolic compound found in wine, inhibits tissue factor expression in vascular cells : A possible mechanism for the cardiovascular benefits associated with moderate consumption of wine. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[75]  F. López‐Soriano,et al.  Resveratrol, a natural product present in wine, decreases tumour growth in a rat tumour model. , 1999, Biochemical and biophysical research communications.

[76]  J. Ashby,et al.  Partial and weak oestrogenicity of the red wine constituent resveratrol: consideration of its superagonist activity in MCF‐7 cells and its suggested cardiovascular protective effects , 1999, Journal of applied toxicology : JAT.

[77]  R. de Caterina,et al.  Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium. , 1998, The American journal of clinical nutrition.

[78]  J. Waltenberger,et al.  VEGF-A induces expression of eNOS and iNOS in endothelial cells via VEGF receptor-2 (KDR). , 1998, Biochemical and biophysical research communications.

[79]  R. Gniadecki.  Nongenomic signaling by vitamin D: a new face of Src. , 1998, Biochemical pharmacology.

[80]  Yongge Liu,et al.  Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection? , 1998, Circulation.

[81]  H. Kawakatsu,et al.  Calcium-dependent Epidermal Growth Factor Receptor Transactivation Mediates the Angiotensin II-induced Mitogen-activated Protein Kinase Activation in Vascular Smooth Muscle Cells* , 1998, The Journal of Biological Chemistry.

[82]  C. Cerletti,et al.  Effect of trans‐resveratrol, a natural polyphenolic compound, on human polymorphonuclear leukocyte function , 1998, British journal of pharmacology.

[83]  J. Pezzuto,et al.  Evaluation of the antioxidant potential of natural products. , 1998, Combinatorial chemistry & high throughput screening.

[84]  J. Downey,et al.  Protein tyrosine kinase is downstream of protein kinase C for ischemic preconditioning's anti-infarct effect in the rabbit heart. , 1998, Journal of molecular and cellular cardiology.

[85]  G. Heusch,et al.  Prevention of ischemic preconditioning only by combined inhibition of protein kinase C and protein tyrosine kinase in pigs. , 1998, Journal of molecular and cellular cardiology.

[86]  J. Waltenberger,et al.  The Vascular Endothelial Growth Factor Receptor KDR Activates Multiple Signal Transduction Pathways in Porcine Aortic Endothelial Cells* , 1997, The Journal of Biological Chemistry.

[87]  G. Garcı́a-Cardeña,et al.  Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. , 1997, The Journal of clinical investigation.

[88]  J. Jameson,et al.  Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[89]  B. Reichart,et al.  Selective modulation of inducible nitric oxide synthase isozyme in myocardial infarction. , 1997, Circulation.

[90]  M. Ishida,et al.  c-Src Is Required for Oxidative Stress-mediated Activation of Big Mitogen-activated Protein Kinase 1 (BMK1)* , 1997, The Journal of Biological Chemistry.

[91]  Qingbo Xu,et al.  Discordant Activation of Stress-activated Protein Kinases or c-Jun NH2-terminal Protein Kinases in Tissues of Heat-stressed Mice* , 1997, The Journal of Biological Chemistry.

[92]  J. Isner,et al.  Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium. , 1997, Circulation.

[93]  M. Nehls,et al.  Suppression of Apoptosis by Nitric Oxide via Inhibition of Interleukin-1β–converting Enzyme (ICE)-like and Cysteine Protease Protein (CPP)-32–like Proteases , 1997, The Journal of experimental medicine.

[94]  J. Pezzuto,et al.  Plant-derived anticancer agents. , 1997, Biochemical pharmacology.

[95]  Norman R. Farnsworth,et al.  Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes , 1997, Science.

[96]  N. Maulik,et al.  Ischemic preconditioning triggers the activation of MAP kinases and MAPKAP kinase 2 in rat hearts , 1996, FEBS letters.

[97]  M. G. Pshennikova,et al.  Adaptive Defense of the Organism , 1996 .

[98]  G. T. Elliott.  Pharmacologic Myocardial Preconditioning with Monophosphoryl Lipid A (MLA) Reduces Infarct Size and Stunning in Dogs and Rabbits , 1996, Annals of the New York Academy of Sciences.

[99]  N. Maulik,et al.  Preconditioning Potentiates Molecular Signaling for Myocardial Adaptation to Ischemia a , 1996, Annals of the New York Academy of Sciences.

[100]  L. Brown,et al.  VEGF, flk-1, and flt-1 expression in a rat myocardial infarction model of angiogenesis. , 1996, The American journal of physiology.

[101]  K. M. Cherian,et al.  Myocardial preservation, preconditioning, and adaptation , 1996 .

[102]  R. Johns,et al.  Chronic hypoxia upregulates endothelial and inducible NO synthase gene and protein expression in rat lung. , 1996, The American journal of physiology.

[103]  J. Tillement,et al.  Plasma, urine and tissue levels of trans- and cis-resveratrol (3,4',5-trihydroxystilbene) after short-term or prolonged administration of red wine to rats. , 1996, International journal of tissue reactions.

[104]  N. Maulik,et al.  L-arginine reduces endothelial inflammation and myocardial stunning during ischemia/reperfusion. , 1995, The Annals of thoracic surgery.

[105]  E. Diamandis,et al.  The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. , 1995, Clinica chimica acta; international journal of clinical chemistry.

[106]  W. Bernini,et al.  Antiplatelet activity of synthetic and natural resveratrol in red wine. , 1995, International journal of tissue reactions.

[107]  M. Shibuya,et al.  Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. , 1994, The Journal of biological chemistry.

[108]  J. Woodgett,et al.  The stress-activated protein kinase subfamily of c-Jun kinases , 1994, Nature.

[109]  G. Gross,et al.  Role of nitric oxide, muscarinic receptors, and the ATP-sensitive K+ channel in mediating the effects of acetylcholine to mimic preconditioning in dogs. , 1993, Circulation research.

[110]  N. Maulik,et al.  Interleukin-1 alpha preconditioning reduces myocardial ischemia reperfusion injury. , 1993, Circulation.

[111]  D. Fitzpatrick,et al.  Endothelium-dependent vasorelaxing activity of wine and other grape products. , 1993, The American journal of physiology.

[112]  I. Moraru,et al.  Heat Shock: A New Approach for Myocardial Preservation in Cardiac Surgery , 1992, Circulation.

[113]  S. Renaud,et al.  Wine, alcohol, platelets, and the French paradox for coronary heart disease , 1992, The Lancet.

[114]  G. Gross,et al.  Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs. , 1992, Circulation research.

[115]  D. Das,et al.  Preconditioning the heart by repeated stunning improves myocardial salvage. , 1991, Circulation.

[116]  C. Mcpherson,et al.  ATP-regulated K+ channels protect the myocardium against ischemia/reperfusion damage. , 1991, Circulation research.

[117]  M. Boutjdir,et al.  Effects of glyburide on ischemia-induced changes in extracellular potassium and local myocardial activation: a potential new approach to the management of ischemia-induced malignant ventricular arrhythmias. , 1990, American heart journal.

[118]  R. Berne.  Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow. , 1963, The American journal of physiology.