Resveratrol in Health And Disease

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Format: Hardcover
Pub. Date: 2005-11-01
Publisher(s): CRC Press
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Summary

Practicing evidenced-based medicine some 25 centuries ago, Hippocrates proclaimed "Let food be thy medicine and medicine be thy food." This advice parallels the common American saying, "You are what you eat," and is supported by a National Institute of Health recommendation to consume as many as eight servings of fruits and vegetables daily to prevent common diseases.One of the most therapeutically significant components found in food is the polyphenol resveratrol. First described in Ayurvedic medicine 5000 years ago as a cardiotonic, resveratrol is found in several fruits and vegetables including grapes, peanuts, cranberries, blueberries, mulberries, and jackfruit. A favorite and rich source of resveratrol is red wine.Resveratrol in Health and Disease draws on the expertise of an international panel, representing a cross-section of nutrition-related disciplines, to examine the effects and properties of this legendary nutrient. It explores research that examines a wide range of purported healing and preventive powers:· Cardioprotective agent· Antitumor agent· Angiogenesis inhibitor· Antioxidant· Radioprotective agent· Phytoestrogen source· Antifungal and antibacterial agent· Neuroprotective agent· Modulator of immune system· Anti-inflammatory agentReviewing recent literature, these pages explore the pharmacokinetics and metabolism of resveratrol, consider its molecular targets, and look at its role in modulating gene expression, as well as its impact on the mechanism of apoptosis and cell signaling pathways.Considering the prohibitive costs of modern medicine, the need for readily available products that are safe and efficacious is critical. Consequently, Resveratrol in Health and Disease may well find its own place in history by providing scientists, clinicians, herbalogists, naturopaths, and those they serve, with the first comprehensive overview of this long-lauded tonic.

Table of Contents

Chapter 1 Resveratrol: A Polyphenol for All Seasons 1(16)
Shishir Shishodia and Bharat B. Aggarwal
Introduction
2(1)
Discovery of Resveratrol
2(8)
Salient Features of Resveratrol
4(1)
Resveratrol as a COX-2 Inhibitor
4(4)
Chemosensitization by Resveratrol
8(1)
Radiosensitization by Resveratrol
9(1)
Resveratrol as Antiviral Agent
9(1)
Bioavailability of Resveratrol
10(1)
Clinical Trials with Resveratrol
10(2)
Conclusion
12(1)
Acknowledgments
12(1)
References
13(4)
Chapter 2 Sources and Chemistry of Resveratrol 17(16)
Navindra P. Seeram, Vishal V. Kulkami, and Subhash Padhye
Introduction
17(1)
Sources of Resveratrol
18(5)
Structure of Resveratrol
23(1)
Chemical Analyses of Resveratrol
24(1)
Synthesis of Resveratrol
24(1)
Theoretical and SAR Studies of Resveratrol
25(1)
Conclusion
26(1)
References
27(6)
Chapter 3 Resveratrol as an Antioxidant 33(24)
Catalina Alarcón de la Lastra, Isabel Villegas, and Antonio Ramón Martin
Introduction
33(3)
Resveratrol as Free Radical Scavenger and Antioxidant
36(2)
Effects of Resveratrol on Lipid Peroxidation
38(2)
Effects of Resveratrol on Intracellular Redox State
40(1)
Antioxidant Activity of Resveratrol and Cardioprotection
41(2)
Effects of Resveratrol on Nitrogen Reactive Species Generation
43(1)
Antioxidant Activity of Resveratrol and Hepatoprotection
44(1)
Antioxidant Activity of Resveratrol and Neuroprotection
44(3)
Antioxidant Activity of Resveratrol and Carcinogenesis
47(3)
References
50(7)
Chapter 4 Resveratrol as an Antiproliferative Agent for Cancer 57(28)
Paola Signorelli and Riccardo Ghidoni
Introduction
58(1)
Antiproliferative Effects in Various Types of Cancer
58(13)
Breast Cancer
58(3)
Resveratrol as a Phytoestrogen
59(1)
In Vitro Studies
59(1)
In Vivo Studies
60(1)
Prostate Cancer
61(1)
Resveratrol as a Phytoestrogen
61(1)
In Vitro Studies
61(1)
Colon and Digestive Tract Cancers
62(1)
In Vitro Studies
62(1)
In Vivo Studies
63(1)
Lung Cancer
63(1)
In Vitro Studies
64(1)
In Vivo Studies
64(1)
Melanoma and Skin Cancer
64(2)
In Vitro Studies
65(1)
In Vivo Studies
65(1)
Hepatoma
66(1)
In Vitro Studies
66(1)
In Vivo Studies
66(1)
Cancer of the Brain and Other Nervous Tissues
66(1)
In Vitro Studies
67(1)
In Vivo Studies
67(1)
Cancers of the Female Genital Apparatus
67(2)
Resveratrol as a Phytoestrogen
68(1)
In Vitro Studies
68(1)
Hematological Cancers
69(1)
In Vitro Studies
69(1)
In Vivo Studies
70(1)
Cancers from Other Sites
70(15)
Kidney Cancer
70(1)
Thyroid Cancer
71(1)
Oral Carcinoma
71(1)
Conclusions and Perspectives
71(7)
References
78(7)
Chapter 5 Mechanism of Apoptosis by Resveratrol 85(20)
Shazib Pervaiz and Andrea Lisa Holme
Introduction to Apoptosis
85(3)
Apoptosis in Cancer Therapy
87(1)
Resveratrol as a Mediator of Cell Death
88(5)
Death Receptor-Mediated Apoptosis
88(1)
Mitochondria-Mediated Apoptosis
89(1)
Apoptosis Mediated by Nuclear Factors
90(2)
Resveratrol Affects Nuclear Receptors to Induce Apoptosis
92(1)
Resveratrol: A Pluripotent Phytoalexin
93(5)
Resveratrol Sensitization to Drug-Induced Apoptosis
94(1)
Clinical Relevance: A Conundrum
95(3)
Summary
98(1)
References
98(7)
Chapter 6 Resveratrol as Inhibitor of Cell Survival Signal Transduction 105(14)
Simone Fulda and Klaus-Michael Debatin
Introduction
106(1)
Resveratrol
106(1)
Signal Transduction in Cell Death and Survival
107(2)
Apoptosis
107(1)
Nonapoptotic Forms of Cell Death
107(1)
Inhibitor of Apoptosis Proteins (IAPs)
108(1)
PI3K/AKT Pathway
108(1)
Nuclear Factor-kappaB
109(1)
Resveratrol as Inhibitor of Cell Survival Signaling
109(4)
Inhibition of Antiapoptotic Pathways
109(2)
Inhibition of PI3K/AKT or MAPK Pathway
111(1)
Inhibition of Protein Kinase C (PKC) Superfamily
112(1)
Inhibition of NF-kappaB Pathway
112(1)
Conclusions
113(1)
References
113(6)
Chapter 7 Resveratrol as Inhibitor of Cell Cycle Progression 119(14)
Jen-Kun Lin
Introduction
120(1)
Chemical Structures of Resveratrol and Its Derivatives
121(1)
Cancer Chemopreventive Effects of Resveratrol
122(1)
Apoptotic Effects of Resveratrol
123(1)
Inhibition of Cell Cycle Progression
124(3)
Effects of Resveratrol on the G0/G1 Transition in Human Lymphocytes
124(1)
Effects of Resveratrol on S-Phase Arrest in Prostate Carcinoma LNCaP Cells
125(1)
Effects of Resveratrol on S/G2 Phase Transition in Human Colonic Adenocarcinoma Caco-2 Cells
125(1)
Effects of Resveratrol on G2/M Arrest in Colon Carcinoma HT29 Cells
126(1)
Some Resveratrol Derivatives with Unique Biological Activity
127(2)
Piceatannol (Trans-3,3',4',5-tetrahydroxystilbene)
127(1)
Trans-3,3',4',5,5'-pentahydroxystilbene
127(1)
Trans-3,4,4',5-tetramethoxystilbene (DMU-212)
128(1)
Vaticanol C (A Resveratrol Oligomer)
128(1)
Acknowledgments
129(1)
References
129(4)
Chapter 8 Molecular Targets of Resveratrol: Implications to Health and Disease Prevention 133(16)
Catherine A. O'Brian and Feng Chu
Molecular Targets of Resveratrol: Forestalling Senescence and Preventive Intervention against Cardiovascular, Metabolic, and Neurodegenerative Diseases
133(3)
Molecular Targets of Resveratrol: Cancer Prevention and Therapy
136(7)
Other Molecular Targets of Resveratrol
143(1)
Acknowledgments
143(1)
References
144(5)
Chapter 9 Resveratrol as an Angiogenesis Inhibitor 149(18)
Ebba Bråkenhielm, Renhai Cao, and Yihai Cao
Introduction
149(1)
Antiangiogenic Activity of Resveratrol
150(1)
Antiangiogenic Mechanisms
151(8)
Inhibition of Signaling Pathways of Angiogenesis
151(1)
Effects on Fibrinolysis and Extracellular Proteases as a Potential Antiangiogenic Mechanism
152(2)
Stimulation of eNOS and Its Role in Regulation of Angiogenesis
154(1)
Inhibition of Cellular Adhesion Molecules
154(2)
Inhibition of COX Enzymes and Inflammatory Pathways in Angiogenesis
156(1)
Regulation of Transcription Factors and Nuclear Enzymes
156(2)
Inhibition of Cell Cycle and Induction of Apoptosis
158(1)
Summary
159(1)
References
159(8)
Chapter 10 Resveratrol Modulation of Gene Expression: The Role of Transcription Factors 167(26)
Fulvio Della Ragione, Valeria Cucciolla, Adriana Borriello, and Vincenzo Zappia
Introduction
168(1)
Resveratrol and the Modulation of Inflammatory Response
168(4)
NF-kappaB Pathway
169(1)
AP-1 Modulation
170(2)
Resveratrol and Intracellular Receptors
172(2)
Resveratrol and the Androgen Receptor
172(1)
Resveratrol and the Estrogen Receptor
173(1)
Resveratrol and Aryl Hydrocarbon Receptors
173(1)
Resveratrol and p53
174(3)
Resveratrol and Egr 1 Activation
177(1)
Protein Deacetylase Sirtuins: New Effectors of Resveratrol Activities
178(4)
Sirtuin Functions and Interactions
178(3)
Mechanistic Basis of Resveratrol Activatory Function
181(1)
Resveratrol and SIRT1: Effects on Transcription Factor Activity
181(1)
Conclusions and Perspectives
182(1)
Acknowledgments
183(1)
References
183(10)
Chapter 11 Modulation of Gene Expression by Resveratrol 193(22)
Bhagavathi A. Narayanan and Narayanan K. Narayanan
Introduction
193(1)
Resveratrol and Molecular Targets
194(1)
Genomic Profiling of Resveratrol-Modulated Genes against Prostate Cancer
195(4)
Resveratrol-Modified Transmembrane Proteins, Transglutaminases, and Transcription Factors
199(1)
Effect of Resveratrol on Growth Factors and Hormones
200(1)
Resveratrol-Induced p53-Mediated Molecular Targets
200(2)
Resveratrol Modulates DNA Methylation: Insight from DNA Microarray Analysis
202(1)
Effect of Resveratrol on Methylation of p300 CpG Sites
203(1)
Resveratrol-Modulated Proteins
203(1)
Modulation of Phosphoglycerate Mutase B by Resveratrol
204(4)
Conclusion
208(1)
Acknowledgments
208(1)
References
208(7)
Chapter 12 Resveratrol and Prostaglandin Biosynthesis 215(18)
Lawrence M. Szewczuk and Trevor M. Penning
Introduction
216(2)
Resveratrol
216(1)
Prostaglandin Biosynthesis
217(1)
Catalytic Mechanism of COX
217(1)
COX Isozymes as Drug Targets
218(3)
COX-1 as a Target for Cardioprotective (Antiplatelet) Agents
218(1)
COX-2 as a Target for Antiinflammatory Agents
219(1)
COX-2 as a Target for Cancer Chemotherapeutic Agents
220(1)
Direct Effects of Resveratrol on COX Catalysis
221(6)
Early Findings 221 Resveratrol as a Mechanism-Based Inactivator of the Peroxidase Activity of COX-1
221(3)
Structure—Activity Relationships (SARs) with Resveratrol Analogs
224(2)
[³H]-Resveratrol is Not Covalently Incorporated into COX-1
226(1)
Trapping Resveratrol Radicals as Viniferins
227(1)
Effects of Resveratrol on COX-2 Expression
227(2)
Pharmacokinetics and Efficacy of Resveratrol (and Other m-Hydroquinones)
229(1)
Conclusions
229(1)
References
230(3)
Chapter 13 Resveratrol as an Inhibitor of Carcinogenesis 233(152)
John M. Pezzuto
Introduction
234(1)
Overview of Cancer Chemoprevention Trials Involving Phytochemicals
235(1)
Discovery and Characterization of Natural Product Inhibitors of Carcinogenesis
236(1)
Potential Cancer Chemopreventive Agents from Plants
237(3)
Phenomenon of Resveratrol
240(2)
In Vitro Studies Conducted with Resveratrol
242(1)
Cell Culture Studies Conducted with Resveratrol
243(94)
In Vivo Studies Conducted with Resveratrol
337(24)
Conclusions
361(2)
Acknowledgments
363(1)
References
363(22)
Chapter 14 Resveratrol as an Antitumor Agent In Vivo 385(14)
Francis Raul
Introduction
385(1)
Antitumor Effects and Antitumor Mechanisms In Vivo
386(7)
Skin Cancer
386(1)
Blood Cancer
387(1)
Breast Cancer
388(1)
Lung Cancer
389(1)
Liver Cancer
390(1)
Colorectal and Intestinal Cancers
391(1)
Prostate Cancer
392(1)
Limitations in the Use of Resveratrol as an Antitumor Agent In Vivo
393(1)
Conclusions and Outlook
394(1)
References
395(4)
Chapter 15 Resveratrol as a Sensitizer to Apoptosis-Inducing Stimuli 399(24)
Ali R. Jazirehi and Benjamin Bonavida
Introduction
399(1)
Apoptosis and Resistance to Apoptosis
400(3)
Apoptosis
400(2)
Resistance to Apoptosis
402(1)
Sensitization
403(1)
Anticancer Therapeutic Effects of RSV and RSV Analogs
404(4)
Anticancer Therapeutic Effects of RSV
404(2)
RSV Analogs
406(2)
Chemoprevention
408(1)
Sensitizing Activities of RSV
408(5)
Immuno sensitization
408(2)
Chemo sensitization
410(3)
In Vivo Application of RSV
413(1)
Concluding Remarks
413(3)
Acknowledgment
416(1)
References
416(7)
Chapter 16 Resveratrol as a Radio-Protective Agent 423(16)
Yogeshwer Shukla, Shannon Reagan-Shaw, and Nihal Ahmad
Introduction
424(1)
Solar UV Radiation and Skin Damages
425(1)
Antioxidants in Chemoprevention of Skin Cancer and Other Skin Damages
426(1)
Resveratrol: A Strong Chemopreventive Agent
427(1)
Effects of Resveratrol on Short-Term UVB Damages in Mouse Skin
427(2)
Effects of Resveratrol on Multiple UVB Exposure-Mediated Damages in Mouse Skin
429(3)
Effects of Resveratrol on UVB Exposure-Mediated Damages in Skin Keratinocytes In Vitro
432(1)
Resveratrol: An Enhancer of Therapeutic Response of Ionizing Radiation against Cancer Cells In Vitro
433(1)
Conclusion
434(1)
References
435(4)
Chapter 17 Resveratrol as a Phytoestrogen 439(26)
Barry D. Gehm and Anait S. Levenson
Introduction
439(2)
Resveratrol as a Phytoestrogen
441(15)
Resveratrol and ER Isoforms
441(1)
Resveratrol's Estrogenic and Antiestrogenic Effects
442(24)
In Vitro Studies
442(1)
Reporter Gene Assays
442(1)
Endogenous Gene Expression
446(1)
Gene Expression Profiling
447(1)
Cultured Cell Proliferation
450(1)
Resveratrol: Agonist, Antagonist, or Superagonist?
454(1)
In Vivo Studies
454(2)
Resveratrol and Breast Cancer
456(1)
Are Resveratrol's ER-Mediated Actions Physiologically Relevant?
457(1)
Conclusions
458(1)
Acknowledgments
459(1)
References
459(6)
Chapter 18 Resveratrol as an Antibacterial Agent 465(10)
Gail B. Mahady
Introduction
465(1)
Cardiovascular and Respiratory Bacteria
466(2)
Chlamydia Pneumoniae
466(2)
Gastrointestinal Bacteria
468(1)
Helicobacter Pylori
468(1)
Dermatological Bacteria
469(1)
Thermo acid ophilic Bacteria
470(1)
Aticyclobacillus Acidoterrestris
470(1)
Urogenital Bacteria
470(1)
Neisseria Gonorrhoeae
470(1)
Resveratrol Derivates
470(2)
References
472(3)
Chapter 19 Resveratrol as an Antifungal Agent 475(24)
Marielle Adrian and Philippe Jeandet
Introduction
475(2)
Importance of Resveratrol in the Plant Kingdom
475(1)
Exciting Potential of This Fascinating Compound in Phytopathology
476(1)
Resveratrol Synthesis
477(4)
Biosynthetic Pathway
477(2)
Stilbene Synthase (STS)
479(1)
Induction of Synthesis
480(1)
Antifungal Properties
481(5)
Biotests
482(2)
Correlations between Phytoalexin Production and Disease Resistance
484(1)
Transgenic Plants
485(1)
Detoxification
486(2)
Conclusion
488(1)
References
488(11)
Chapter 20 Protective Effects of Resveratrol in Age-Related Neurodegenerative Diseases and Gene Regulatory Action 499(20)
Sofiyan Saleem, Abdullah Shafique Ahmad, and Sylvain Doré
Introduction
499(4)
Heme Oxygenase
503(2)
Heme
505(2)
Iron
507(1)
Carbon Monoxide (CO)
507(1)
Bilirubin (BR)
508(1)
Summary
508(1)
Acknowledgments
509(1)
References
509(10)
Chapter 21 Protective Effects of Resveratrol against Ischemia-Reperfusion 519(20)
Dipak K. Das
Introduction
519(1)
Resveratrol
520(3)
Resveratrol: A Grape-Derived Natural Antioxidant
520(1)
Resveratrol: A Phytoestrogen
521(1)
Resveratrol: Effective against a Variety of Degenerative Diseases
522(1)
Resveratrol and the Heart
523(2)
Preconditioning with Resveratrol
525(5)
Myocardial Protection with Preconditioning
525(2)
Pharmacological Preconditioning with Resveratrol
527(3)
Summary and Conclusion
530(1)
Acknowledgments
530(1)
References
530(9)
Chapter 22 Resveratrol as Cardioprotective Agent: Evidence from Bench and Bedside 539(18)
Sukesh Burjonroppa and Ken Fujise
Introduction
540(1)
Epidemiological Evidence to Support Resveratrol as a Cardioprotective Agent
541(3)
Red Wine as a Cardioprotective Agent: French Paradox
541(2)
Resveratrol as a Major Bioactive Agent in Red Wine
543(1)
Evidence in Clinical Trials to Support Resveratrol as a Cardioprotective Agent
543(1)
Animal Studies to Support Resveratrol as a Cardioprotective Agent
544(3)
Resveratrol Inhibits Neointimal Hyperplasia after Vascular Injury
544(1)
Resveratrol Inhibits Platelet Activation and Aggregation
544(2)
Resveratrol Dilates Arteries through Nitric Oxide-Mediated Pathways
546(1)
Resveratrol and Atherosclerosis
546(1)
Bench Research to Support Resveratrol as a Cardioprotective Agent
547(3)
Resveratrol Is an Antiendothelin Agent in Vascular Cells
547(1)
Resveratrol Is a Tissue Factor Inhibitor in Vascular Cells
547(1)
Resveratrol Is an Estrogen Receptor Agonist in Vascular Cells
548(1)
Resveratrol Upregulates and Activates p53 Tumor Suppressor Protein in Vascular Cells
548(2)
Epilogue – Ken Fujise
550(1)
Acknowledgment
550(1)
References
550(7)
Chapter 23 Immunomodulation by Resveratrol 557(20)
Subhash C. Gautam, Xiaohua Gao, and Scott A. Dulchaysky
Introduction
557(2)
Immunomodulation by Resveratrol
559(1)
Effect on Inflammatory Processes
559(2)
Modulation of Cell-Mediated Immunity by Resveratrol
561(10)
Effect on Lymphoid Cells
561(1)
Effect on Antigen Presenting Cells
562(1)
Effect on T Cell Proliferation
563(2)
Effect on Cell-Mediated Cytotoxicity
565(3)
Effect on Production of Cytokines
568(2)
Effect on NF-kappaB Activation
570(1)
Conclusion
571(1)
References
571(6)
Chapter 24 Biological Effects of Cis- Versus Trans-Resveratrol 577(24)
Francisco Orallo
Introduction
577(2)
Vasorelaxant Effects of t-RESV in Rat Aorta
579(9)
Initial Experiments
579(1)
L-Arginine—NO-cGMP Pathway
580(8)
Does t-RESV Affect Synthesis/Release of NO from Endothelial Cells?
582(1)
Does t-RESV Affect Inactivation of NO.?
583(3)
Implications of the Increased NO. Levels Induced by t-RESV
586(2)
Vasorelaxant and Other Biological Effects of c-RESV
588(4)
Vasorelaxant Effects of c-RESV in the Rat Aorta
588(2)
Other Biological Effects of c-RESV
590(2)
Concluding Remarks
592(1)
Acknowledgments
593(1)
References
594(7)
Chapter 25 Resveratrol as an Antiinflammatory Agent 601(18)
Young-Joon Surh and Joydeb Kumar Kundu
Introduction
601(1)
Inflammation as a Predisposing Factor for Various Human Diseases
602(2)
Resveratrol: A Natural Antiinflammatory Agent
604(1)
Molecular Mechanisms of the Antiinflammatory Activity of Resveratrol
605(7)
Inhibition of iNOS and COX-2 by Resveratrol
605(5)
Modulation of Transcription Factors Regulating Proinflammatory Genes
610(2)
Effects on the Activation of NF-kappaB
610(1)
Effects on the Activation of AP-1
611(1)
Effects on the Intracellular Upstream Kinases
612(1)
Conclusion
612(1)
Acknowledgment
613(1)
References
613(6)
Chapter 26 Neuroprotective Effects of Resveratrol 619(12)
Ying-Shan Han, Stéphane Bastianetto, and Rémi Quirion
Introduction
619(1)
Neuroprotective Effects of Resveratrol and Its Analogs
620(4)
In Vitro and Animal Studies
620(4)
Structure–Activity Relationships of Resveratrol
624(1)
Potential Mechanisms of Neuroprotective Actions of Resveratrol
624(2)
Antioxidant/Metal-Chelating Activity
624(1)
Effects on Intracellular Signaling Pathways
625(1)
Effects on Transcription Factors and Gene Expression
626(1)
Conclusion and Future Directions
626(1)
References
627(4)
Chapter 27 Pharmacokinetics and Metabolism of Resveratrol 631(12)
Alberto A.E. Bertelli
Introduction
631(1)
Resveratrol Absorption
632(2)
Resveratrol Kinetics in Animals
634(4)
Resveratrol Kinetics in Humans: Are Data from Animal Models Predictive?
638(1)
Resveratrol Bioavailability and Biological Effects
639(2)
References
641(2)
Index 643

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