(Food and nutritional components in focus)

In the past three decades there have been major advances in our understanding of the chemistry and function of nutritional components. This has been enhanced by rapid developments in analytical techniques and instrumentation. Chemists, food scientists and nutritionists are, however, separated by divergent skills, and professional disciplines. Hitherto this transdisciplinary divide has been difficult to bridge. The series Food and Nutritional Components in Focus aims to cover in a single volume the chemistry, analysis, function and effects of single components in the diet or its food matrix. Its aim is to embrace scientific disciplines so that information becomes more meaningful and applicable to health in general. The series Food and Nutritional Components in Focus covers the latest knowledge base and has a structured format. Isoflavones has four major sections, namely:

Food and Nutritional Components in Focus Edited by Victor R Preedy Isoflavones Chemistry, Analysis, Function and Effects Isoflavones Chemistry, Analysis, Function and Effects Food and Nutritional Components in Focus Series Editor: Professor Victor R Preedy, School of Medicine, King’s College London, UK Titles in the Series: 1: 2: 3: 4: 5: Vitamin A and Carotenoids: Chemistry, Analysis, Function and Effects Caffeine: Chemistry, Analysis, Function and Effects Dietary Sugars: Chemistry, Analysis, Function and Effects B Vitamins and Folate: Chemistry, Analysis, Function and Effects Isoflavones: Chemistry, Analysis, Function and Effects How to obtain future titles on publication: A standing order plan is available for this series A standing order will bring delivery of each new volume immediately on publication For further information please contact: Book Sales Department, Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge, CB4 0WF, UK Telephone: +44 (0)1223 420066, Fax: +44 (0)1223 420247 Email: booksales@rsc.org Visit our website at http://www.rsc.org/Shop/Books/ Isoflavones Chemistry, Analysis, Function and Effects Edited by Victor R Preedy School of Medicine, King’s College London, UK Food and Nutritional Components in Focus No ISBN: 978-1-84973-419-6 ISSN: 2045-1695 A catalogue record for this book is available from the British Library r The Royal Society of Chemistry 2013 All rights reserved Apart from fair dealing for the purposes of research for non-commercial purposes or for private study, criticism or review, as permitted under the Copyright, Designs and Patents Act 1988 and the Copyright and Related Rights Regulations 2003, this publication may not be reproduced, stored or transmitted, in any form or by any means, without the prior permission in writing of The Royal Society of Chemistry or the copyright owner, or in the case of reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency in the UK, or in accordance with the terms of the licences issued by the appropriate Reproduction Rights Organization outside the UK Enquiries concerning reproduction outside the terms stated here should be sent to The Royal Society of Chemistry at the address printed on this page The RSC is not responsible for individual opinions expressed in this work Published by The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 0WF, UK Registered Charity Number 207890 For further information see our web site at www.rsc.org Printed in the United Kingdom by CPI Group (UK) Ltd, Croydon, CR0 4YY, UK Preface In the past three decades there have been major advances in our understanding of the chemistry and function of nutritional components This has been enhanced by rapid developments in analytical techniques and instrumentation Chemists, food scientists and nutritionists are, however, separated by divergent skills, and professional disciplines Hitherto this transdisciplinary divide has been difficult to bridge The series Food and Nutritional Components in Focus aims to cover in a single volume the chemistry, analysis, function and effects of single components in the diet or its food matrix Its aim is to embrace scientific disciplines so that information becomes more meaningful and applicable to health in general The series Food and Nutritional Components in Focus covers the latest knowledge base and has a structured format Isoflavones has four major sections, namely: Isoflavones in Context Chemistry and Biochemistry Analysis Function and Effects The first section covers phytoestrogens in health and plants, then material on isoflavones in foods and the diet The chemistry and biochemistry section covers structures, bioconversion and biotransformation, the human estrogen receptor, homonuclear NMR spectroscopy, genistein, daidzein, xenoestrogens, methylated derivatives and non-natural isoflavonoids The section on analysis includes foods, beverages, nuts, traditional medicines, herbs, pharmacologically active isoflavones, plasma and urine Methodology encompasses microwaveextraction, HPLC, LC-MS/MS and LC-UV/PDA and many other techniques Finally, the section on function and effects covers ingestion of isoflavones by Food and Nutritional Components in Focus No Isoflavones: Chemistry, Analysis, Function and Effects Edited by Victor R Preedy r The Royal Society of Chemistry 2013 Published by the Royal Society of Chemistry, www.rsc.org v vi Preface different populations, isoflavones in beverages, inherited metabolic diseases, mucopolysaccharidoses, clinical trials, obesity, inflammation in adipose tissue, menopausal vasomotor syndrome, estrogenic activity, testicular function, thyroid function, gastric cancer, learning and memory, prenatal exposure, cell proliferation, bone, NMDA and GABA receptors, and insulin secretion Individual isoflavones are also described, such as daidzein, genistein and glycitein, as well as their derivatives, such as equol and tetrahydroxyisoflavone As isoflavones occur within a complex plant matrix, other estrogenic and bioactive compounds in isoflavones-rich foods, e.g coumestrol, are described for comparative reference Each chapter transcends the intellectual divide with a novel cohort of features namely by containing:     Abstract Summary Points Key Facts (areas of focus explained for the lay person) Definitions of Words and Terms It is designed for chemists, food scientist and nutritionists, as well as healthcare workers and research scientists Contributions are from leading national and international experts, including contributions from worldrenowned institutions Professor Victor R Preedy King’s College London Contents Isoflavones in Context Chapter Phytoestrogens in Health: The Role of Isoflavones Rodney J Baber 1.1 1.2 1.3 1.4 Chapter Introduction Absorption, Metabolism and Excretion of Isoflavones Mechanisms of Action of Isoflavones Clinical Effects of Isoflavones 1.4.1 Cardiovascular Health 1.4.2 The Brain 1.4.3 Bone Health 1.4.4 Breast Cancer 1.4.5 Prostate Cancer 1.4.6 Menopausal Symptoms 1.5 Areas in Dispute Summary Points Key Facts List of Abbreviations References 6 7 8 9 10 10 Phytoestrogens in Plants: With Special Reference to Isoflavones Franz Bucar 14 2.1 2.2 Characterization of Phytoestrogens Distribution of Phytoestrogens in the Plant Kingdom 2.2.1 Phytoestrogens other than Isoflavones 2.2.2 Isoflavones Food and Nutritional Components in Focus No Isoflavones: Chemistry, Analysis, Function and Effects Edited by Victor R Preedy r The Royal Society of Chemistry 2013 Published by the Royal Society of Chemistry, www.rsc.org vii 14 15 15 15 viii Contents 2.3 2.4 2.5 2.6 Chemical Features of Plant Isoflavones Biosynthesis of Isoflavones Localisation of Isoflavones in Plants Biological Function of Isoflavones in Plants 2.6.1 Interaction of Isoflavones with Micro-organisms of the Rhizosphere 2.6.2 Isoflavones as Phytoalexins and Phytoanticipins Summary Points Key Facts Definitions of Words and Terms List of Abbreviations References Chapter 17 18 19 22 22 22 23 24 24 25 26 Isoflavones in Foods and Ingestion in the Diet Baskaran Stephen Inbaraj and Bing Huei Chen 28 3.1 3.2 28 Introduction An Overview of Structure and Analysis of Dietary Isoflavones 3.2.1 Structure 3.2.2 Analysis 3.3 Isoflavone Content in Selected Foods 3.4 Growth, Variety, Environmental and Post-harvest Storage Conditions Affecting Isoflavone Composition in Soybeans 3.5 Isoflavone Composition as Affected by Processing Summary Points Key Facts Definitions of Words and Terms List of Abbreviations References 29 29 29 31 31 36 41 41 41 42 43 Chemistry and Biochemistry Chapter The Chemistry/Biochemistry of the Bioconversion of Isoflavones in Food Preparation Kashif Ghafoor, Fahad Y Al-Juhaimi and Jiyong Park 4.1 4.2 4.3 4.4 Introduction Bioconversion of Isoflavones from Glycosides to Aglycones Enzymatic Transformation of Isoflavone Isomers in Fermented Soymilk b-Glycosidase Reaction during Bioconversion of Isoflavones 49 49 53 54 56 ix Contents Chapter Summary Points Key Facts Definitions of Word and Terms List of Abbreviations References 57 57 57 58 59 Chemistry and Synthesis of Daidzein and its Methylated Derivatives: Formononetin, Isoformononetin, and Dimethyldaidzein Vincent M Carroll, Jeffrey D St Denis, Kyle F Biegasiewicz and Ronny Priefer 61 5.1 5.2 61 63 Introduction Synthesis of Daidzein (1) 5.2.1 Synthesis of Daidzein: BF3 Á OEt2-catalyzed Friedel–Crafts Acylation and Ring Closure 5.2.2 Synthesis of Daidzein: RCM with Grubbs’ Catalyst 5.2.3 Synthesis of Daidzein: I2-Mediated Cyclization 5.2.4 Synthesis of Daidzein: Oxidative Rearrangement with Thallium(III) Nitrate 5.3 Synthesis of Formononetin (2) 5.3.1 Carbonyls as One-carbon Electrophiles 5.3.2 Activated Aldehyde Surrogates as One-carbon Surrogates 5.4 Synthesis of Isoformononetin (3) 5.4.1 Selective Methylation of Daidzein (1) 5.4.2 Suzuki-mediated Synthesis 5.5 Synthesis of Dimethyldaidzein (4) 5.5.1 Synthesis of Dimethyldaidzein: Polymer-supported Iodobenzene Diacetate (PSIBD)-promoted Oxidative Rearrangement 5.5.2 Synthesis of Dimethyldaidzein: Organolead-mediated Arylation Summary Points Key Facts Definitions of Words and Terms List of Abbreviations References Chapter 63 64 64 67 67 69 70 73 73 74 74 76 76 78 79 79 79 80 Non-natural Isoflavonoids Namita Bhan and Mattheos Koffas 83 6.1 6.2 6.3 83 83 85 Introduction Phenylpropanoid and Isoflavonoid Pathways Isoflavanoids 670 milk, cow’s 272, 367, 369, 373, 374, 377 milk, goat’s 374 milk, soy see soy milk miroestrol 583 miso see also fermented foods Brazil 354 Canada 354 composition 32, 34, 445 consumption levels 446 Japan 356 Taiwan 358 USA 358 mitogen-activated protein kinase (MAPK) daidzein 303 equol 589 genistein 133, 443, 444 glycitein 468, 474 Helicobacter pylori 443 inflammation 615 MMPs (matrix metalloproteinases) 468 MOM see methoxymethyl ether monocyte chemoattractant protein-1 (MCP-1) 134 monolithic columns 275–6 mood 472 motor function 304 MPO see myeloperoxidase MPS see mucopolysaccharidoses MRM see multiple reaction monitoring MS/MS see tandem mass spectrometry mucopolysaccharides see glycosaminoglycans (GAGs) mucopolysaccharidoses (MPS) classification 383, 394, 395 clinical symptoms 383 enzyme deficiency 381, 382, 394 pathophysiology 383–4, 394 substrate reduction therapy (SRT) 387–93, 394 transmission 382, 394 Subject Index Mullerian inhibiting substance (MIS) 567 multidrug resistance 298, 310 multimode cavity 181, 191 multiple reaction monitoring (MRM) 204, 224, 226, 228, 319–20, 322, 328 mutagenesis 519, 522, 526 mycoestrogens 14, 16 Mycoforms see formononetin mycorrhizal fungi 22, 69 myelin 305 myeloperoxidase (MPO) 135 myocardial hypoxia 309 NAD see nicotinamide adenine dinucleotide NAD(P)H:quinone oxidoreductase (NQO1) 550–1, 552–3 naringenin binding affinity 88 biosynthesis 159, 161, 387 glycosaminoglycans (GAGs) 390 metabolism 162 structure 20, 161 naringenin chalcone 20, 159, 161, 387 National Health and Nutrition Examination Board (NHANES) 541 natto 32, 358, 445 see also fermented foods natural killer cells equol 588 genistein 5, 588 neuronal plasticity 452, 453, 459 neuroprotective effects 304–5, 472, 586 neurotransmitters 512–13 newborns 486 NF-kB see nuclear factor-kB NHANES (National Health and Nutrition Examination Board) 541 nicotinamide adenine dinucleotide (NAD) 160 nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 384 671 Subject Index nitric oxide (NO) 170, 173, 444, 587, 612, 616 nitric oxide (NO) synthase 302 nitrogen fixation 22, 23, 24, 25, 85, 159 NMDA (N-methyl-D-aspartate) 505–11, 512 NMDA receptors 506–8 NMR see nuclear magnetic resonance (NMR) spectroscopy nodulation 22, 23, 24, 25 NOESY see nuclear Overhauser enhancement spectroscopy nomenclature biochanin A (BCA) 244 daidzein 149, 244, 500 equol 483 formononetin 244 genistein 116, 150, 244 genistin 116 glycitein 500 glycitin 244 non-fermented foods see also soy milk; tofu bioavailability 544 cancer 446, 447 composition 41 genistein 152 b-glucosides 50 p-nonylphenol (NP) glucuronidation 123 hydroxylation 124 industrial uses 125 placenta transfer 122, 124–5 structure 123 sulfation 123–4 NP see p-nonylphenol NQO1 (NAD(P)H:quinone oxidoreductase 1) 550–1, 552–3 nuclear factor erythroid-derived (Nrf1) 138, 139, 140 nuclear factor erythroid-derived (Nrf2) 138, 139, 140, 472–3, 475, 553, 590 nuclear factor-kB (NF-kB) coumestrol 523 daidzein 301, 444, 447 function 475 genistein 134, 444, 447 glycitein 468, 474 Helicobacter pylori 443, 444 inflammation 467–8, 612, 615, 616 isoflavones 616 macrophages 612 puerarin 302, 305 nuclear hormone receptors 173 nuclear magnetic resonance (NMR) spectroscopy chromatography linking 101–2 conformations 102 definition 111 development 94–5 equol 106–7, 108 groundnuts 340 metabolites 103–7, 208 solvents 101, 107, 109 structure elucidation 96–100, 102 theory 110–11 nuclear Overhauser enhancement spectroscopy (NOESY) 98, 100, 103, 111–12 nuclear receptors 593 nucleotide-binding oligomerization domain (NOD1) 443 nutraceuticals 15, 149, 154, 220, 424–5 see also herbal extracts; supplements obesity see also adipose tissue animal models 545–6 coumestrol 520 definition 526, 541, 556 diabetes risk 530, 547 diets 543, 544–5, 546 environmental factors 542 exercise 545 genistein 546–7, 620 global trend 541 guggulsterone 547 health effects 541–2 isoflavone research 550–6 resveratrol 547 treatment 543, 555 672 Oenothera bienis (evening primrose) 628 oestrogen see estrogen omnivores intake levels 351, 353 oncom 32, 357, 361 one-carbon electrophiles 68–71 ontogenesis 25 optic nerves 305 orobol see 5,7,3 ,4 tetrahydroxyisoflavone osteoblasts 467, 473, 599–600, 607 osteoclasts 599, 600, 607 osteoporosis see also bone daidzein 602–3, 605–6 definition 42, 316, 327 equol 601, 602, 605–6 estradiol (E2) 601 estrogen 597, 607 genistein 601, 602, 603, 605–6 herbal extracts 326 lumbar spine 607 recommended daily intake 31 red clover 317 selective estrogen receptor modulators (SERMs) 90 soy 317, 439 vasomotor symptoms 632 osteoprotegerin 600 ovarian cancer 582–3 ovariectomy 460 ovaries 275 oxidation 50–1 oxidative rearrangement 67, 68, 76, 77 oxidative stress cardiovascular disease 587 central nervous system (CNS) 472 diabetes 531 genistein 139, 442 glutathione (GSH) 473 glycitein 472–3 lysosomal storage diseases (LSDs) 384 NAD(P)H:quinone oxidoreductase (NQO1) 550 obesity 542 plants 483 stomach 442, 447 Subject Index p38 phosphorylation 135, 137, 138 p53 pathway 137–9, 138 Paecilomyces militaris 105 palatability 400, 401, 413–14, 415, 416–17 palladium catalysis 64, 67, 71, 74, 78 pancreas 466, 532–3 pancreatic cancer 586–7 Papilionideae fm 15, 23 paracrine regulation 574 parathyroid hormone supplements 317 Parkinson’s disease 304, 457 partial agonism definition 155 genistein 151, 154 parvisoflavone 100 pasteurization 374, 378 pattern profiling 317, 325, 328 PBMCs (peripheral blood mononuclear cells) 302, 303, 305 PCT see pharmacological chaperone therapy PDA see photodiode array (PDA) detection PDGFR (platelet-derived growth factor receptor) 570–1 peanut allergy 305 peanuts 15, 18 peptidoglycan (PGN) 443 percolation 378 perinatal development 487–93 peripheral blood mononuclear cells (PBMCs) 302, 303, 305 peroxisome proliferator activated receptors (PPARs) adipocytes 549, 553–4, 618–19 agonists 71 daidzein 554 definition 155 function 468, 475 genistein 5, 154, 444, 554 glycitein 468, 474 peroxynitrite 303 Pezzuto, Dr John 495 pH effect on stability 36 pharmaceutical research 221, 238 Subject Index pharmacokinetics b-blockers 224 definition 214–15 dose levels 630 genistein 226–8 herbal extracts 317 plasma 226 pharmacological chaperone therapy (PCT) 382, 395 phenotype definition 42 phenylalanine 83, 159, 161, 387, 465, 474 phenylalanine ammonia-lyase (PAL) 83, 84, 159, 161 phenylephrine 302 phenylpropanoic compounds 91 phenylpropanoid pathway 18–19, 83–4, 84, 387, 465, 475 phenylpyruvate 159, 161 phloretin 15, 16 phosphatase and tensin homolog (PTEN) 133 phosphatidylinositol 3-kinase 133, 535 30 -phosphoadenosine -phosphosulfate (PAPS)-sulfotransferases 4–5 phosphodiesterase (PDE3) 619 phosphoinositide 3-kinase/ Akt-dependent pathways 588 phospholipases 535, 622 phosphorylation 503, 508–9, 513, 549, 570, 615 photodiode array (PDA) detection 223, 269 phytoalexins 23, 25, 85, 91, 149 phytoanticipins 23, 25, 149 phytoestrogens administration route 152 cancer research history classification 3, 14, 628 definition 126, 157 sources 628 structure 16, 150, 158 PI-9 (proteinase inhibitor 9) 582–3 pisatin 85 Piscidia erythrina 103 pituitary gland 265, 423, 425, 428, 488, 521, 565 673 PKA see protein kinase A placenta genistein 121–2, 124 xenoestrogens 122, 124–5 planting season differences groundnuts 342 kudzu (Puerariae radix) 298 soybeans 35, 342 white lupine 21–2 plants aglycones 283–4 biosynthesis 18–19, 20, 50, 158–9, 161, 171 cancer prevention 589 environmental factors 280 glycitein 465 glycoconjugates 284 glycosides 264, 284 malonylglucosides 366 maturity effects 21 microbe interaction 22, 149, 158 oxidative stress 483 pathogen defence mechanisms 22–3, 158 storage 62, 89, 465 tissue distribution 19–22, 481 plasma aglycones 166, 198, 224–6, 229 biochanin A 226, 229–30 chromatograms 211 conjugated metabolites 153, 205, 213, 224, 229–30 coumestrol 226 daidzein 202–3, 226, 230, 491 equol 489–90, 491 formononetin 226, 230 genistein 117–18, 202–3, 226, 229–31, 491, 511 glucagon 519 glucose 531 glycitein 466 insulin 519 lipids 531 lipoproteins 170 maternal levels 490, 491 retention times 212 zealarenone 226 674 plasma membrane 537 plasminogen activator inhibitor-1 (PAI-1) 621 platelet-derived growth factor receptor (PDGFR) 570–1 polar molecules 180, 181, 191, 281 Polygonaceae 15 Polygonum cuspidatum see Fallopia japonica polyphenols definition 79 population studies 445–6 see also epidemiology Portugal 377 post-harvest management 192 postmenopausal symptoms see also climacteric syndrome bone health 7, 467 cognitive function 457–9 definition 42 estrogenic activity 439 recommended daily intake 31 self-medication 165–6, 171 postmenopausal women adiposity 621 cognitive function 452 genistein 429 inflammation 621 plasma glucose levels 531 soy intake 133, 600 PPAR see peroxisome proliferator activated receptors precipitation 267–8 precision definition 239, 328 LC-ESI-MS/MS 226 LC-MS/MS 228, 325 prefrontal cortex 456, 457, 458, 459, 460 pregnane X receptor (PXR) 520–1, 522, 590–1 8-prenylnaringenin 583 -prenylpiscerythrone 103, 104 prephenate 159, 161 PRN see prunetin Subject Index processing composition effect 29, 36–40, 50–1, 343, 465 conversion of isoflavones 37, 366, 401–2 progesterone synthesis 132, 570, 586 prospective cohort studies 445 prostacyclin 438 prostaglandins 302, 586, 599, 616, 617, 622 prostate cancer daidzin 301 equol 583–5 genistein 132, 133–4 glycitein 468–9 preventative mechanisms protein engineering 85, 89, 90, 91 protein kinase A (PKA) 503, 532, 534–6, 537–8, 619 protein kinase C (PKC) 503, 535 protein kinase G (PKG) 503 protein tyrosine kinases (PTKs) GABA (g-aminobutyric acid) 503–5 genistein 444, 508–9, 511, 512, 529, 532–3, 538 NMDA (N-methyl-D-aspartate) 508 protein tyrosine phosphates (PTPs) 503, 508 proteinase inhibitor (PI-9) 582–3 proteoglycans 386 prunetin binding affinity 88 structure 318 prunetin (PRN) binding affinity 88 structure 318 toxicity 389 prunetol see genistein Prunus dulcis 418 pterocarpans 23 PTKs see protein tyrosine kinases Pueraria lobata 105 Puerariae radix (kudzu) anti-tumour activity 298–301 Chinese medicine 294, 307–8 Subject Index composition 296–8 optimum harvest 298 roots 295 species 296 puerarin biosynthesis 439 dietary sources 296 health effects 298, 300, 302–5, 308–9, 454, 620 structure 50, 295 supplements 50 purification 344 PXR (pregnane X receptor) 520–1, 522, 590–1 pyran 79 pyruvate 536 quercetin 299, 549 quinone reductase 473, 475, 589–90 quinones 137, 159 radioimmunoassays 273 raloxifene 10, 151 RANKL (receptor activator of nuclear factor-kB (NF-kB) ligand) 599 RCM see ring-closing metathesis reactive oxygen species (ROS) cardiovascular disease 587, 588 diabetes 306, 531 function 538 Helicobacter pylori 442 lysosomal storage diseases (LSDs) 384 macrophages 612 receptor activator of nuclear factor-kB (NF-kB) ligand (RANKL) 599 recommended daily intake 31, 400, 447 iodine 423–4 recommended limit (RL) 355 red clover (Trifolium pratense) analysis 230–1, 237, 289 biochanin A (BCA) 21, 628 composition 220, 616, 629, 640 formononetin 21, 289 675 formononetin (FMN) 628 herbal extracts 361 infertility 149 isoformononetin 79 pasture grazing 149 supplements 4, 317, 354 tissue distribution 21 vasomotor symptoms 628–9, 631–2, 634, 635–6 5a-reductase 564, 566 reference standards 205, 206, 321–2 reproductive system effects see also testis; uterus; vagina coumestrol 520, 525 daidzein 487–8 equol 485, 488, 489, 490, 586 genistein 488, 530 insulin-like growth factors 573 phytoestrogens 265, 296 research history cancer genistein 150 glycitein 474 resistin 619, 620, 623 resorcinol derivatives 627 resveratrol binding affinity 583 health effects 480, 547, 549 research history 495 sources 15, 480 structure 16, 18 retention times 405 reverse phase 112, 205, 222, 260 Rhizobium spp 22, 23, 25, 85, 159, 171 ring-closing metathesis (RCM) 64, 79 RL see recommended limit ROESY see rotating Overhauser effect spectroscopy roots, nitrogen fixation 22 ROS see reactive oxygen species rotating Overhauser effect spectroscopy (ROESY) 98, 99, 111–12 676 SAA (serum amyloid A) 550 Saccharomyces cerevisiae bread 402, 415 semi-synthesis 85–6 SAH see S-adenosylhomocysteine saliva 337, 366, 466 salt intake 441 SAM see S-adenosylmethionine sample preparation 229–37 see also extraction costs 259 gas chromatography (GC) 271 HPLC 334, 335, 404 LC-MS 202 LC-MS/MS 224 U-HPLC 223–4 Sanfilippo disease 382 see also mucopolysaccharidoses (MPS) SARs see structure-activity relationships scanning electron microscopy (SEM) 186 schizophrenia 501 scopolamine 455 seasonal planting differences groundnuts 342 kudzu (Puerariae radix) 298 soybeans 35, 342 white lupine 21–2 secoisolariciresinol digestion 17 sources 15 structure 16, 17 secondary metabolites definition 91 selected ion monitoring (SIM) 203, 204, 224, 271 selected reaction monitoring (SRM) 203 selective estrogen receptor modulators (SERMs) see also raloxifene cancer 90 definition 155 genistein 151, 154, 426, 500–1 osteoporosis 90 phytoestrogens 5, 14 Subject Index selectivity of analysis definition 240, 328 HPLC 221, 222 LC-UV 269–70 mass spectrometry (MS) 272 tandem mass spectrometry (MS/MS) 320–1 semi-synthesis 85–6, 91 seminiferous tubules 564, 565, 575 sensitivity of analysis electrospray ionization (ESI) 224 HPLC 221, 222 LC-MS/MS 325 LC-UV 269–70 mass spectrometry (MS) 272 ultrafast HPLC 226 sensory analysis 417, 418 SERMs see selective estrogen receptor modulators Sertoli cells 564, 565–6, 567, 574 serum amyloid A (SAA) 550 serum analysis 203, 204, 234–6 sex hormone-binding globulin (SHBG) 132, 168, 486, 567 sex hormones 452, 491–2 sexual dimorphism 452, 460, 488 SFE see supercritical fluid extraction SHBG see sex hormone-binding globulin shikimate cascade 159, 160 shoyu (soy sauce) 352, 356 see also fermented foods signal transduction 389 SIM see selected ion monitoring simultaneous analysis food products 268–9 LC/APCI-MS 228 nuclear magnetic resonance (NMR) spectroscopy 101–2 ultrafast HPLC 223, 226 Singapore 357, 358 single mode cavity 181, 192 singlet oxygen 424 Smirnowia iranica 102 smoking 441 Subject Index SNAP-25 (synaptosomal-associated protein of 25 kDa) 536, 538 soaking 37–8, 39, 337, 413 SOD see superoxide dismutase sodium-dependent glucose transporter 116–17 solid phase extraction (SPE) acid hydrolysis 257 definition 215, 260 enzyme hydrolysis 256 food analysis 266 LC/APCI-MS 228 LC-MS/MS 203, 228 nuclear magnetic resonance (NMR) spectroscopy 101–2 plasma 207, 209, 226 simultaneous analysis 224 soy products 246 solubility glucuronidation 466 glycosylation 89 groundnuts 341 polarity effect 185–6 soluble phospholipase A2 (sPLA2) 622 solvent suppression 101 solvents direct extractiopn 245–6 electrospray ionization (ESI) 224 extraction 267 HPLC 209, 222 nuclear magnetic resonance (NMR) spectroscopy 107, 109 polarity 181 sonication 246, 255, 257, 260 Soxhlet extraction definition 79 food analysis 274 method 276 soy analysis 223 time 187 soy analysis 223, 231–3, 237 cancer 7–8, cardiovascular system 6, 447 composition 4, 148–9 677 food range 148, 149, 445–6, 481 genistein 149 health benefits 349 health effects 85, 179, 263, 334, 349, 366, 399, 438, 554 intake levels 7, 9, 400, 511 menopause supplements 354 soy beverages 351 soy flour bread 402–4 composition 34, 51–3, 58 processing 36 soy isolate composition 33, 34 production 37 reproductive system effects 572–3 soy lecithin 33 soy milk see also infant formula absorption, dietary 117 aglycones 373 chromatograms 55 clinical studies 458 composition 33, 34, 58, 351, 357, 359, 368, 465 composition variability 373 17b-estradiol 572 extraction 247–52 fermentation 54–6 glucosides 373 Indonesia 357 optimum ratios 40 production 37, 38–40, 373 stereoisomers 36–7 Taiwan 358 USA 358–9 soy protein isolate 359, 360, 456 soybeans cell walls 186 composition 29, 31–5, 41, 220, 334, 358, 481–2, 629 cotyledons 21, 31, 35 cultivar differences 31–3, 35 fermentation 356, 358 genetically modified 355 678 soybeans (continued) growth differences 33, 35, 131, 179–80, 220 history of use 41, 49, 481 hypocotyls 31, 35 intake levels 132–3, 354, 356, 358, 425 kinako 118, 210, 211, 212 light levels effect on concentration 21 metabolites 105, 107 processing 29, 152, 343, 349–50, 401–2 production volumes 41, 179 roots 21 seasonal planting differences 21–2, 35 soaking 37–8, 39 storage 35 tissue distribution 21, 31 spatial learning 452–4, 456 SPE see solid phase extraction specific loaf volume 405, 410–11, 415 specificity of analysis 221 spectra biochanin A (BCA) 225 daidzein 227 equol 95–6, 97 formononetin 227, 320 genistein 95, 96, 225 glucosides 286, 288, 290 isoformononetin 320 milk, cow’s 272 sperm 565–6, 568–9, 570, 571, 573 spinge 419 ‘‘spirodienone’’ model 159, 162 springiness 408, 411, 419 SREBP (sterol regulatory elementbinding protein) 549 SRM see selected reaction monitoring SRT see substrate reduction therapy stability aglycones 259 alkaline hydrolysis 255 electrospray ionization (ESI) 224 b-glycosides 259 Subject Index glycosylation 89 pH 36 processing 36, 38, 350 temperature 36 stearoyl-CoA desaturase (SCD) 549 Stechell, Dr Kenneth 495 STEPs (striatal-enriched tyrosine phosphatases) 508 stereoisomers definition 42 malonyldaidzin 36–7 malonylgenisitin 36–7 steroid hormones 491–2, 495, 565, 567–8, 573 see also testosterone sterol regulatory element-binding protein (SREBP) 549 stilbene synthase (STS) 84 stilbenes see also resveratrol definition 25 sources 15 structure 84, 158 stomach aglycones 152 digestion 439 storage of soybeans 35 striatal-enriched tyrosine phosphatases (STEPs) 508 structure acetoxy groups 103 acetyldaidzin 30 acetylgenistin 30, 51 acetylglycitin 30 aglycones 19, 21, 30 anthocyanidins 84 anthocyanins 84 3-arylcoumarins 99 basic outline 29, 264 bioavailability 197–8 biochanin A (BCA) 21, 219 bisphenol A (BPA) 123 cajanin 318 catechins 84 chalcones 16, 20, 84, 158 chondroitin sulfate (CS) 385 chorismate 160 cinnamic acid 84 Subject Index cinnamoyl CoAS 84 cladrin 318 compared to flavones 17 p-coumaric acid 84, 161 p-coumaroyl-S-coenzyme A 161 coumestans 158 coumestrol 16, 99, 100, 518 daidzein 16, 20, 21, 30, 53, 79, 96 daidzein 7-O-glucoside-600 -Omalonate 62 daidzin 30, 50, 53, 295 dermatan sulfate (DS) 385 dihydroflavanols 84 dihydrogenistein 120, 136 trans-4 ,7-dihydroxyisoflavan-4ol 102 dimethyldaidzein 62, 76 enterodiol 17 enterolactone 17 equol 95, 482, 484, 494 estradiol (E2) 16, 158, 163, 482, 530, 563 estrogen receptors (ER) 163 4-ethylphenol 120 flavanones 16, 20, 84, 158 flavone comparison 285 flavonoids 16, 158 flavonols 84 formononetin 7-O-glucoside-600 -Omalonate 62 formononetin (FMN) 21, 62, 219, 318 GABAA receptor 502 genistein 16, 20, 21, 115, 150–1, 529–30 genistein-7-O-gentiobioside 340 genistein 7,4 -di-O-sulfate 105 genistin 30, 51, 53, 116 glabrene 103, 104 glabridin 16 glabrone 100 b-glucuronides 118 glycitein 21, 53, 219, 466, 629 glycitin 30, 53 glycosaminoglycans (GAGs) 384 glycosides 19 679 glycosyl groups 103 heparan sulfate (HS) 386 hyaluronates 385 7-hydroxy isoflavone 318 -hydroxy-O-demethylangolensin (DMA) 120, 136 6-hydroxybiochanin A 106 hydroxygenistein 51 hydroxyl groups 103 4-hydroxyphenyl-2-propionic acid 120 ipriflavone 629 irigenin 101 irisflorentine 101 irisolidone 106 iristectorigenin A 101 trans-isoflavan-4-ol 102 isoflavans 95 isoflavone synthase (IFS) 89–90 isoformononetin 62, 74, 318 isoformononetin (IFMN) 62, 74, 318 isoliquiritigenin 20, 161 keratan sulfate (KS) 386 lariciresinol 16 leuconathocyanidins 84 lignanes 158 lignans 16 liquiritigenin 20, 161 luteone 21 malonyl-CoA 84 malonyldaidzin 30 malonylgenistin 30, 51 malonylglycitin 30 matairesinol 16 mediacarpin 318 medicarpin 16 methoxy groups 103, 106 modifications 17, 19 mycoestrogens 16 naringenin 20, 161 naringenin chalcone 20, 161 NMDA receptors 506–8 p-nonylphenol (NP) 123 parvisoflavone 100 phenylalanine 161 phenylpyruvate 161 680 structure (continued) phloretin 16 phytoestrogens 16, 150, 158 -prenylpiscerythrone 103, 104 prephenate 161 prunetin 318 prunetin (PRN) 318 puerarin 50, 295 resveratrol 16, 18 secoisolariciresinol 16, 17 stilbenes 84, 158 sugars 17–18 sulfate groups 103–5 tectorigenin 101, 106 5,6,7,3 -tetrahydroxy-4 methoxyisoflavone 101 5,7,3 ,4 -tetrahydroxyisoflavone (THIF) 136 variation 148–9, 283–4 wighteone 21 xanthohumol 16 zealarenone 16 a-zealarenonol 16 structure-activity relationships (SARs) 157–8, 173 structure elucidation definition 112 genistein-7-O-gentiobioside 340–1 mass spectrometry (MS) 273 nuclear magnetic resonance (NMR) spectroscopy 96–100, 102 substitution 103 substrate reduction therapy (SRT) 382, 388–92, 394, 395 sufu 33, 358 sugars plant glycosides 264, 284 polarity effect 281 structure 17–18 sulfatases 198 sulfate groups 103–5 sulfation bisphenol A (BPA) 123–4 definition 126 excretion 440 genistein 117, 119 Subject Index intestines 4–5 NMR analysis 105 p-nonylphenol 123–4 sulfotransferases (SULTs) genistein 117, 119, 428 intestines 166, 440 placenta 122 xenoestrogens 123–4 supercritical fluid definition 42 supercritical fluid extraction (SFE) 29–30, 181 superoxide 302 superoxide dismutase (SOD) 134, 442, 473, 475 supplemented food definition 276 supplements see also herbal extracts; nutraceuticals analysis 221, 228 climacteric syndromes 169, 458–9 clinical studies 458–9, 621 combined with other drugs 425 compared to dietary sources composition 50, 354, 391–2 equol 600–1 marketing 263–4 red clover 4, 220 soy 573–4, 621 suppliers’ recommended intake 424 Suzuki coupling 66, 67, 73, 74, 79 symbiotic bacteria 25 synaptic plasticity 513, 586 synaptosomal-associated protein of 25 kDa (SNAP-25) 536, 538 syneresis 40 synthetic forms 85, 86, 616, 628 see also specific isoflavone synthesis systems biology definition 292 T3 see 3,5,3 -tri-iodothyroine T4 see thyroxine Taiwan 358 tamoxifen 90, 169, 587, 588 tandem mass spectrometry (MS/MS) algae 233 herbal extracts 319–25, 326 method 292 Subject Index plants 286, 290, 291 serum analysis 203, 204, 226–8, 234–5 urine analysis 203, 234–5 validation 322–5 tea analysis 248–9, 251–2 composition 371, 376, 377 extraction 256 thyroid function 425 tectorigenin 101, 105, 106 tempeh see also fermented foods composition 33, 34, 357, 445 digestion 544 fermentation 37 production 37 temperature conversion of isoflavones 37, 152 effect on groundnut composition 334, 337–9 effect on soybean composition 35, 39, 152, 401 extraction 186, 246, 334, 337–9 stability 36, 350 testicular dysgenesis syndrome (TDS) 575 testis anatomy 563–5, 574–5 development 565–6, 567, 568, 569, 572–3 function 563–5 isoflavones 566–73 testosterone (T) 275, 564, 565–6, 567, 571, 586 3,5,3-500 -tetra-iodothyronine see thyroxine 5,6,7,3 -tetrahydroxy-4 methoxyisoflavone 101 5,7,30 ,40 -tetrahydroxyisoflavone (THIF) binding affinity 88 biosynthesis 135–7, 141 cancer 137–9 endothelial cells 139–40 structure 136 texture profile analysis 405–6, 411, 419 thallium trinitrate (TTN) 67, 68 681 theoretical maximum daily intake (TMDI) 355 thermogravimetric analysis 406, 419 thermoplastic extrusion 351, 361 THIF see 5,7,3 ,4 tetrahydroxyisoflavone thromboembolism 317 thromboxane 588 thromboxane receptors 470–1, 473, 475 thyroglobulin 169, 173, 425, 427, 428 thyroid daidzein 428–9 equol 428 function 169, 423, 429, 433 genistein 426–31 thyroid peroxidase (TPO) 169, 425, 427–8, 433 thyroid replacement therapy thyroid stimulating hormone (TSH) 169, 423, 425, 428, 433 thyroid stimulating releasing hormone (TRH) 433 thyrotropin 428 thyroxine (T4) 169, 423, 425, 427, 428 time-of-flight mass spectrometry (TOF) 103, 282, 290 TLR (Toll-like receptors) 614, 615 TMDI see theoretical maximum daily intake TNFa see tumour necrosis factor-a toasting 51 tofu see also sufu Brazil 354 China 354 composition 33, 34, 357, 360, 361, 445, 465 fermented 357 Hong Kong 355 Indonesia 357 optimum ratios 40 processing 40, 56–7 production 37 Singapore 357 soft 58 USA 358 682 Toll-like receptors (TLR) 614, 615 topoisomerases 426, 442, 444, 501, 522 toxicity 389, 489, 490, 519, 520–1, 525 TPO see thyroid peroxidase traditional medicine 327 see also Chinese medicine transcription factors 623 transferin 567 transforming growth factor (TGF)-b 599 transversal osteotomy 602, 607 TRH see thyroid stimulating releasing hormone 3,5,3 -tri-iodothyroine (T3) 423, 425, 427 tri-iodothyronine (T3) 169 tricarboxylic cycle 536 Trifolium pratense see red clover ,5,7-trihydroxyisoflavone see genistein trypsin inhibitor 54 TSH see thyroid stimulating hormone tumour necrosis factor-a (TNFa) adipocytes 614, 615 estrogen 599 fatty liver 620 genistein 134, 135, 617, 620, 621, 622 insulin resistance 619, 620 isoflavones 614, 619, 620, 623 macrophages 612, 613, 614 puerarin 304, 305 tumour suppressor protein p53 522, 552–3 tuning section 192 tyrosine ammonia-lyase (TAL) 83, 84 tyrosine kinases function 433 genistein 5, 133, 391, 426, 428, 501, 512 UDP-glucose:isoflavone 7-Oglucosyltransferase (IF7GT) 20 UDP-glucuronyltransferases UGTs see uridine diphosphate glucosyltranferases Subject Index UK consumption levels 350–1 dietary sources 352, 353 ultra-performance liquid chromatography (UPLC) 270, 281 ultrasound 260 unfermented foods see non-fermented foods uridine diphosphate glucosyltranferases (UGTs) function 90, 475 genistein 117, 119, 141 glycitein 466 intestines 166 liver 166 placenta 122 protein engineering 85, 89 urine analysis b-blockers 223, 234 daidzein 62, 203, 544 enzymatic hydrolysis 198 equol 359 4-ethylphenol 121 genistein 117, 119, 203, 544 glucuronide conjugates 204, 209–10, 234 kakkalide metabolites 105 simultaneous analysis 223 sulfate conjugates 204, 209–10, 234 USA consumption levels 358–9, 481, 544 obesity 541 soybean production 41 uterus 169 UV detection 205–12, 213, 222–4, 230, 237, 269–70, 285 vacuoles 62, 465 vagina 169, 630 validation procedures 229–37 beverage analysis 247–54 definition 240, 260 herbal extracts 322–5 683 Subject Index vascular endothelial growth factor (VEGF) 444, 447, 468, 469 vascular endothelium vasodilation 170, 302, 470 vasomotor symptoms clinical studies 630–40 isoflavones 8, 439 phytoestrogens 628–9 recommended daily intake 31 vegetables 245, 367, 424, 483 vegetarians 351, 352, 353, 359, 366 VEGF (vascular endothelial growth factor) 444, 447, 468, 469 very low-density lipoproteins (VLDL) 170, 173 vine leaves 18 virilization of external genitalia 575 vitamin D vitamin D receptor 467, 587 Vitis vinifera L., Vitaceae see grapes VLDL see very low-density lipoproteins voltage-gated ion channels 513 Western diets see also specific countries compared to Asian 168, 359, 360, 399, 409, 424 soy food increase 366, 400 soy intake levels 367 white lupine genistein 149 planting season differences 21–2 tissue distribution 21–2 wighteone 21 wine 371, 376, 627 Wittig reactions 64 women bone health thyroid diseases 429 working memory 457, 458, 460 Wacker-Cook tandem reactions 71, 73 water content 419 water holding capacity (WHC) 405, 410, 412, 415 water load 192 waveguide 192 yeast bread 402, 415 semi-synthesis 85–6 stabilising effect 54 xanthohumol 16 xenoestrogens see also coumestrol definition 122, 126, 157 health effects 122, 573 placenta 122, 124–5 zealarenone 14, 16 a-zealarenonol 16 [...]... Biotransformation of Genistein Compounds in the Gastrointestinal Tract 8.1.1 Deglycosylation of Genistin in the Small Intestine 8.1.2 Glucuronidation and Sulfation of Genistein 8.1.3 Hydroxylation of Genistein in the Liver 8.1.4 Breakdown of Genistein and Luminal Excretion 8.1.5 Transfer of Genistein in Placenta A Comparison with Other Xenoestrogens 8.2.1 Chemical Structure of BPA and NP 85 85 86 86 89 89... References Chapter 28 Glycitein in Health Brian R Stephens and Joshua A Bomser 28.1 28.2 28.3 28.4 28.5 28.6 Introduction Absorption Glycitein and Bone Health Glycitein and Cancer Glycitein and Cardiovascular Health Glycitein as an Estrogen Receptor (ER) Agonist 28.7 Glycitein and Memory and Mood 28.8 Glycitein and Oxidative Stress Summary Points Key Facts Definitions of Words and Terms List of Abbreviations... expected, ERa occurs in brain regions involved in regulation of reproduction but both occur, particularly ERb, in brain regions involved in cognition The expression and localization of ERs are dynamic and Phytoestrogens in Health: The Role of Isoflavones 7 can vary depending upon brain region, cell type, hormonal status and neurological condition The effects of isoflavones in the brain may be due to genomic... isoflavone intake than those found in Western countries (Goldin et al 1986) Soybeans contain three primary isoflavones in their glycoside form: genistin, daidzin and glycitin Digestion leads to the cleavage of the sugar moiety and the formation of the respective aglycones: genistein, daidzein and glycitein Red clover has also been used to manufacture supplements for human use Red clover contains four... isoflavones: formononetin, biochanin, daidzein and genistein At physiological concentrations, formononetin does not bind to the ER but is metabolized to daidzein and then by intestinal bacteria to equol, both of which have been shown to have estrogenic properties (Baber 2010) Interest in these compounds began over 20 years ago with research by the US National Cancer Institute exploring possible chemo-preventive... isoflavones and ethnic differences or to a healthy user effect 1.2 Absorption, Metabolism and Excretion of Isoflavones Isoflavone aglycones are absorbed in the upper small intestine by passive diffusion, peaking in the blood within 1 h of being ingested (Sfakianos et al 1997) In contrast, the b-glucosides are not passively absorbed They are hydrolyzed by b-glucosidases from intestinal bacteria or an intestinal... Contents Chapter 32 Genistein and Insulin Secretory Function Dongmin Liu 32.1 32.2 32.3 Introduction Genistein may have Anti-diabetic Effects Genistein at Physiological Concentrations Augments Glucose-stimulated Insulin Secretion (GSIS) in Beta-cells and Pancreatic Islets Summary Points Key Facts Definitions of Words and Terms List of Abbreviations References Chapter 33 Prevention and Management of Obesity... producing indirect effects on estrogenic pathways Other mechanisms by which isoflavones may be cancer protective include antiproliferative effects, tyrosine kinase inhibition, modulation of steroid hormone-metabolizing enzyme activity, induction of apoptosis and inhibition of angiogenesis Dietary isoflavones also reduce circulating and intra-breast estradiol concentrations in monkeys, with a corresponding... metabolites are excreted in the bile and are deconjugated in the lower bowel, allowing them to be reabsorbed again, creating an enterohepatic circulation (Sfakianos et al 1997) Daidzein is metabolized to dihydrodaidzein, which is further metabolized to equol and O-desmethylangolensin (O-DMA) Genistein is transformed to dihydrogenistein and then metabolized to 6-hydroxy-O-DMA Human urinary excretion of these... understanding of estrogen action began in 1996 with the discovery of ERb (Kuiper et al 1996) Although related to ERa, which is located on chromosome 6, ERb is located on chromosome 14 The ligand-binding sites are highly homologous between ERa and ERb However, the few amino acid differences result in isoflavones exerting preferential binding affinity to ERb ERa and ERb are expressed at various concentrations in ... G.W., Chen, G., Radominska-Pandya, A., and Badger, T.M., 2006 Sulfation of the isoflavones genistein and daidzein in human and rat liver and gastrointestinal tract Journal of Medicinal Food 9: 348–355... Genistein Compounds in the Gastrointestinal Tract 8.1.1 Deglycosylation of Genistin in the Small Intestine 8.1.2 Glucuronidation and Sulfation of Genistein 8.1.3 Hydroxylation of Genistein in the Liver... isoflavones: formononetin, biochanin, daidzein and genistein At physiological concentrations, formononetin does not bind to the ER but is metabolized to daidzein and then by intestinal bacteria to