Flavonoids exert a multiplicity of biological effects on humans and can have beneficial implications for numerous disease states. Flavonoids and Related Compounds: Bioavailability and Function examines current knowledge regarding the absorption, metabolism, and bioavailability of individual flavonoids and related phenolic compounds. Profiling the latest evidence of their impact on various human pathological conditions, the book summarizes current thinking with regard to the biotransformation and conjugation of individual compounds in the gastrointestinal tract, liver, large intestine, and cells. It highlights a topic that has been largely ignored—namely the extent to which dietary phenolics components undergo metabolism in the large intestine. It also explores the generation of bacterially derived metabolites. Individual chapters discuss which metabolites enter the circulatory system and are likely to offer protective actions against human diseases. Edited by internationally recognized leaders in the field, the book presents contributions by a panel of experts who demonstrate the potential of flavonoids in ameliorating a range of disease states, including cardiovascular disease, Alzheimer’s and Parkinson’s disease and other neurodegenerative disorders, and cancer. The research presented in this volume provides a reliable starting point for further inquiry and experimentation.
Author(s): Jeremy P. E. Spencer, Alan Crozier
Series: Oxidative Stress and Disease 29
Publisher: CRC Press
Year: 2012
Language: English
Pages: xx+452
Flavonoids and Related Compounds: Bioavailability and Function......Page 6
Contents......Page 10
Series Preface......Page 12
Preface......Page 14
Editors......Page 16
Contributors......Page 18
1.1 IntroductIon......Page 22
1.2.1 Absorption of Flavanones......Page 24
1.2.2 Metabolism of Flavanones In Vivo......Page 26
1.2.3 Microbial Metabolism......Page 35
1.2.4 Tissue Distribution......Page 39
1.3.1 Studies in Humans......Page 42
1.3.1.1 Effect of Food Processing and Matrix......Page 58
1.3.2 Studies in Animals......Page 59
References......Page 60
2.1 Introduction......Page 66
2.2 Bioavailability— Absorption, Distribution, Metabolism, and Excretion......Page 70
2.2.1 Analysis of Flavan-3-ol Metabolites......Page 71
2.2.3 Cocoa Flavan-3-ol Monomers......Page 72
2.2.3.1 Matrix Effects......Page 76
2.2.4 Green Tea Flavan-3-ol Monomers......Page 78
2.2.4.1 Dose and Matrix Effects......Page 81
2.2.4.2 Studies with Ileostomists and Colonic Catabolism......Page 83
2.2.5 Proanthocyanidins......Page 88
2.2.6 Black Tea Theaflavins and Thearubigins......Page 89
2.2.6.1 Milk and Matrix Effects......Page 92
References......Page 93
3.1 Introduction......Page 100
3.2.2 Sites of Anthocyanin Absorption......Page 103
3.2.3 In Vivo and In Vitro Bioavailability Estimates......Page 104
3.3 Mechanisms of Absorption......Page 106
3.4.2 Effects of Degradation on Estimates of Bioavailability......Page 107
3.4.3 Effects of Different Anthocyanin-O-Glycosides on Absorption......Page 108
3.4.4 Glucose and Other Factors......Page 109
3.6 Summary......Page 110
References......Page 111
4.1 Introduction......Page 114
4.2 Chemistry and Occurrence of Flavones and Flavonols......Page 115
4.4 Deglycosylation in the Digestive Tract......Page 118
4.5 Absorption and Metabolic Conversions......Page 119
4.6 Molecules Responsible for Cellular Uptake and Transport of Flavonoids......Page 121
4.7 Tissue Distribution of Conjugated Metabolites and the Possibility of Their Deconjugation......Page 122
References......Page 125
5.1 Introduction......Page 130
5.2 Initial Isoflavone Absorption......Page 131
5.3 Isoflavone Metabolism and Secondary Absorption......Page 132
5.4 Distribution, Elimination, and Recovery of Isoflavones......Page 134
5.5.1 The Equol-Producer Phenotype......Page 135
5.6 Factors Affecting Isoflavone Bioavailability......Page 136
5.6.2 Dose Response......Page 137
5.6.4 Age......Page 138
References......Page 139
Contents......Page 144
6.1.2 Effect of Processing and Storage......Page 145
6.3.1 Absorption and Transport Mechanisms......Page 147
6.3.1.2.1 Culture Cell Models......Page 148
6.3.2.1 Gastrointestinal Tract......Page 149
6.3.2.3 Biliary Excretion and Efflux Mechanisms......Page 154
6.3.3 Bioavailability......Page 155
6.3.3.2 Effect on Absorption......Page 156
6.3.3.3 Effect on Metabolism......Page 159
6.4.1 Absorption throughout the Gastrointestinal Tract......Page 160
6.4.3 Bioavailability of Intact Chlorogenic Acids......Page 161
6.4.4 Biphasic Pharmacokinetic Profile of Absorption......Page 164
6.4.6 Extensive Methylation, Sulfation, and Isomerization of Chlorogenic Acid Metabolites......Page 165
6.4.7 Excretion......Page 166
6.5 Analytical Methods Used in Identifying and Quantifying The Products of Metabolism in Plasma and Urine......Page 167
6.6 Summary......Page 168
References......Page 170
7.2 Bioavailability of Phloretin and Derivatives......Page 178
7.3 Bioavailability of Aspalathin and Nothofagin......Page 183
References......Page 185
8.1 Sources of Dietary Resveratrol......Page 188
8.1.1 Grapes and Wines......Page 189
8.1.2 Peanuts......Page 190
8.1.5 Cocoa-Based Products......Page 191
8.1.8 Dietary intake of Resveratrol......Page 192
8.2.1 In Vitro Studies and Animal Models......Page 193
8.2.2 Human Studies......Page 194
8.2.3 Factors Influencing Trans-Resveratrol Metabolism In Vivo......Page 197
8.2.4 Summary of Resveratrol Absorption and Metabolism......Page 198
References......Page 200
9.1 Introduction......Page 204
9.3 Models to Study Bioavailability and Metabolism......Page 205
9.3.1 In Vitro Uptake and Metabolism......Page 208
9.3.2 In Vivo Studies Using Animal Models......Page 209
9.3.3 Human Studies......Page 212
9.4.2 Intestinal Microbiota Metabolism......Page 214
9.4.4 Tissue Distribution......Page 215
9.6 Conclusions......Page 216
References......Page 217
10.1 Introduction......Page 222
10.2 Release and Absorption of Phenolic Compounds and Their Metabolites......Page 223
10.2.1 Flavonols......Page 224
10.2.2 Anthocyanins......Page 225
10.2.3 Flavan-3-ols......Page 228
10.2.5 Isoflavones......Page 231
10.2.6 Phenolic Acids......Page 234
10.2.7 Ellagitannins......Page 237
10.2.8 Plant Lignans......Page 238
10.3 Significance of Phenolic Metabolites for Human Health......Page 240
References......Page 243
Contents......Page 254
11.1 Introduction......Page 255
11.2 Benzoic Acids......Page 257
11.3 Phenylacetic Acids, Tyrosol, 3′-Hydroxytyrosol, and Their Conjugates......Page 258
11.4 Phenylpropionic Acids and Their Conjugates......Page 264
11.5 Hydroxycinnamic Acid Conjugates......Page 270
11.6 Feruloylquinic Acid Conjugates......Page 273
11.8 Tea Flavan-3-ol–Derived Lactones......Page 277
11.9 Lignan Metabolites......Page 279
11.10 Urolithins and Their Conjugates......Page 281
11.11 Flavanone Conjugates......Page 282
11.12 Isoflavone Conjugates......Page 284
11.13 Flavonol Conjugates......Page 287
11.15.1 Overview of the Known Stable Isotopically Labeled Dietary Phenols......Page 289
11.16.1 Overview of the Known Radiolabeled Dietary Phenolics......Page 290
11.17 Summary......Page 295
Reference......Page 297
12.1 Introduction......Page 302
12.2 Chemical Structure, Bioavailability, and Metabolism of Flavan-3-ols and Procyanidins......Page 303
12.3.1 Antioxidant and Redox Regulation by Flavan-3-ols and Procyanidins......Page 304
12.3.2 Modulation of NF-κB by Flavan-3-ols and Procyanidins......Page 306
12.3.3 Modulation of Protein Kinases and Phosphatases by Flavan-3-ols and Procyanidins......Page 308
12.3.4 Modulation of Nfr2 and Other Signaling Pathways by Flavan-3-ols and Procyanidins......Page 309
References......Page 310
13.1 Introduction......Page 316
13.2 Epidemiological Evidence......Page 317
13.3 Effects on Endothelial Function......Page 318
13.4 Effects on Blood Pressure......Page 321
13.6 Mechanisms of Action......Page 322
13.7 Conclusions......Page 323
References......Page 324
14.1 Introduction......Page 330
14.2 Influence of Molecular Structure on the Antihypertensive Effects of Flavonoids......Page 331
14.3 Is the Vasodilator Effect of Flavonoids Endothelium Dependent?......Page 334
14.4 How Are Flavonoids Taken up by Vascular Cells?......Page 335
14.5.1 Nitric Oxide......Page 336
14.6 What Is the Role of the Inhibition of NADPH Oxidase, Uncoupled NO-Synthase, and Xanthine Oxidase by Flavonoids?......Page 338
14.7 How Do Flavonoids Modulate Redox Signaling?......Page 339
14.8 What Is the Effect of Flavonoids on Lipid Metabolism?......Page 341
14.9 How Do Flavonoids Influence Paraoxonase?......Page 342
14.11 How Do Flavonoids Modulate Vascular Ion Channels?......Page 343
14.12 How Do Flavonoids Inhibit Endothelial Inflammation?......Page 344
References......Page 345
Contents......Page 352
15.1 Introduction......Page 353
15.2 Oxidative Stress, Iron, and Neurodegeneration......Page 355
15.2.1 Alzheimer’s Disease......Page 356
15.2.2 Parkinson’s Disease......Page 357
15.3 Epidemiological and Clinical Studies with Green Tea and Its Major Constituent, EGCG: PD and AD Prevalence......Page 359
15.4 Preclinical Animal and Cell Culture Studies with Green Tea and Green Tea Catechins......Page 360
15.5 Neuroprotective Mechanism of the Green Tea Catechin, EGCG......Page 361
15.5.1 Antioxidant-Iron Chelating Activities in Redox and Iron Sensitive Cellular Processes......Page 363
15.5.2 Aggregation of α-Synuclein and Amyloid Precursor Protein......Page 364
15.5.3 Hypoxia Inducible Factor System......Page 365
15.5.4 Regulation of Cell Signaling......Page 366
15.5.4.1 MAPK- and PI-3K-Akt Signaling Systems......Page 367
15.5.4.2 PKC Signaling Pathway......Page 368
15.6 Conclusions and Future Perspectives......Page 369
References......Page 371
16.1 Introduction......Page 384
16.2 Components of the Neuroinflammatory Cascade......Page 385
16.3 Brain Uptake and Cellular Interactions......Page 388
16.3.1 Flavonoid Bioavailability to the Brain......Page 389
16.3.2 Flavonoid Interactions with Cellular Signaling......Page 391
16.4 Inhibition of Neuroinflammation by Flavonoids......Page 392
16.4.1 Flavones......Page 393
16.4.2 Flavonols......Page 400
16.4.3 Isoflavones......Page 401
16.4.5 Flavanones......Page 402
16.5 Summary......Page 403
References......Page 404
17.1 Introduction......Page 414
17.2 Flavonoids: Forms, Sources, and Bioavailability in the Brain......Page 415
17.3 Flavonoids and Brian Health......Page 417
17.4 Flavonoids in Ageing and Cognition......Page 418
17.5 Effects of Berry Flavonoids on Cognitive Health and Related Neuronal Signaling......Page 419
17.6 Summary......Page 424
References......Page 426
18.1 Oral Cancer......Page 434
18.2 Prevention by Flavonoids and Their Glycosides......Page 435
18.3 Prevention by Berries, a Whole Food Approach......Page 437
18.4 Prevention by Methylated Flavones......Page 438
References......Page 442
19.2 Flavonoids and Cancer Risk: Epidemiologic Studies......Page 446
19.3 Free Radicals and DNA Damage in Cancer......Page 449
19.4 Measurement of DNA Damage......Page 450
19.5.1 In Vitro Evidence......Page 451
19.5.2 Evidence from Human Dietary Trials......Page 454
References......Page 461
Index......Page 466
