Covering fundamentals and new developments in phytotherapy, this book combines pharmaceutical sciences and chemistry with clinical issues.
Helps readers better understand phytotherapy and learn the fundamentals of and how to analyze phytotherapeutic agents
Discusses phytotherapy in modern medicine, chemoprevention of disease, and alternatives to western medicines for specific diseases
Chapters summarizes the uses and applications of phytomedicines, by type like Chinese, Greco-Arab, Indian, European, and Ayurvedic
Includes international regulatory perspectives and discusses emerging regulations for various established and emerging markets
Contents
List of Contributors
Preface
1 Phytotherapies Past, Present, and Future 1
Iqbal Ramzan and George Q. Li
1.1 Overview of Phytotherapy 1
1.1.1 Definition 1
1.1.2 International Trend in the Usage of Complementary Medicines 2
1.2 Preclinical Research on Phytotherapies 3
1.2.1 Pharmacognosy and Quality Standardization of Phytotherapies 3
1.2.2 Pharmacological Studies and Identification of Bioactive Compounds 4
1.2.3 Application of Proteomics and Metabolomics in Phytotherapy Research 5
1.3 Clinical Research on Phytotherapies 6
1.3.1 Efficacy of Popular Phytotherapies 6
1.3.2 Chinese Herbal Medicines 7
1.3.3 Food Nutrition and Translational Research 7
1.4 Safety of Phytotherapies 8
1.5 Profile of Research in Complementary Medicine 9
1.5.1 International Profile 9
1.5.2 Australian Profile of Research in Complementary Medicines 10
1.6 Summary and Future Directions 12
References 12
2 Quality Control and Quality Assurance of Phytomedicines: Key Considerations, Methods, and Analytical Challenges 18
Wai Ping Yau, Cheong Hian Goh, and Hwee Ling Koh
2.1 Introduction 18
2.2 Key Considerations in Qc/Qa of Phytomedicines 20
2.2.1 Identification and Good Agricultural and Collection Practices (GACP) 20
2.2.2 Contamination 22
2.2.3 Substitution 25
2.2.4 Adulteration 25
2.2.5 Contents and Standardization 26
2.2.6 Stability 26
2.2.7 Processing 26
2.3 Methods for Qc/Qa of Phytomedicines 27
2.3.1 Macroscopic Evaluation 27
2.3.2 Microscopic Evaluation 27
2.3.3 Physicochemical Analysis 29
2.3.4 Chemical Fingerprinting 29
2.3.5 DNA Fingerprinting 35
2.3.6 Omics Technology 36
2.4 Challenges 37
2.5 Conclusions 40
References 40
3 Preclinical (In Vivo) and Laboratory (In Vitro) Evidence of Phytomedicine Efficacy 49
Mohi Iqbal Mohammed Abdul and Tom Hsun Wei Huang
3.1 Introduction to Development of Drugs from Nature 49
3.2 Use of In Vitro and in Vivo Models in Herb Drug Research: Learning Thus Far 50
3.2.1 In Vitro Assays 50
3.2.2 In Vivo Assays 51
3.3 Cardiovascular and Stroke Related Diseases: In Vitro and In Vivo Focus 53
3.3.1 Cardiovascular Diseases 53
3.3.2 Stroke 55
3.4 Conclusions 60
References 61
4 Clinical Efficacy Trials with Natural Products and Herbal Medicines 65
Christina L. Nance
4.1 Introduction 65
4.2 Trials in Various Disease States 66
4.2.1 Profile: RCT of Natural Product in Rheumatoid Arthritis (RA) 66
4.2.2 Asthma 67
4.2.3 Cancer 68
4.2.4 Cardiovascular Disease 68
4.2.5 Diabetes 69
4.2.6 Dermatology 70
4.2.7 Gastroenterology 70
4.2.8 Viral Infections 72
4.3 Natural Product: Green Tea 73
4.3.1 Green Tea Catechin, Epigallocatechin Gallate (EGCG) 73
4.4 Egcg Clinical Trials 75
4.4.1 Polyphenon E 75
4.4.2 Safety, Toxicity, and Pharmacokinetics 75
4.4.3 Metabolism 76
4.4.4 Clinical Studies 76
4.4.5 Cancer Studies 77
4.5 Human Clinical Study: Egcg and Hiv 1 Infection 78
4.5.1 Translational Medicine: EGCG: Bench to Bedside 78
4.5.2 Phase I Clinical Trial: Polyphenon E in HIV 1 Infection 79
4.6 Conclusion 80
References 80
5 Novel Formulations and Drug Delivery Systems for Phytotherapies 89
Shengpeng Wang, Meiwan Chen, Qi (Tony) Zhou, and Hak Kim Chan
5.1 Limitations of Conventional Formulations for Herbal Medicines 89
5.1.1 Barriers in Physicochemical and Biological Properties 89
5.1.2 Challenges in Quality and Safety Assurance 90
5.1.3 Conventional Formulations Limit the Therapeutic Efficacy of Herbal Medicines 90
5.2 Crucial Issues of Developing Novel Delivery Systems for Herbal Medicines 91
5.2.1 How Novel Delivery Systems Follow the Tradition? 91
5.2.2 Pharmacokinetic Research on Delivery Systems for Herbal Medicines 92
5.2.3 Safety Considerations on Delivery Systems for Herbal Medicines 92
5.3 Novel Delivery Systems of Herbal Medicines 93
5.3.1 Pulmonary Delivery of Herbal Medicines 93
5.3.2 Nanocarriers of Herbal Medicines for Drug/Gene Delivery 94
5.3.3 Surface Modification of Nanocarriers by Herbal Medicines 95
5.3.4 Herbal Medicines as Photosensitizers for Photodynamic Therapy 95
5.4 Summary 96
References 97
6 Phytotherapies Used by Indigenous Populations 101
Bradley S. Simpson and Susan J. Semple
6.1 Introduction 101
6.2 Phytotherapies of Indigenous Australians 103
6.2.1 Introduction 103
6.2.2 Philosophy and Knowledge Transmission 104
6.2.3 Ailments Treated with Medicinal Plants 106
6.2.4 How Plant Medicines Have Been Used 107
6.2.5 Methods of Plant Preparation 109
6.2.6 Prized and Commonly Used Plants in Australian Indigenous Medicine 111
6.3 Challenges of a Changing Environment 114
6.3.1 Safety of Australian Phytotherapies 115
6.3.2 Development and Regulation of Australian Indigenous Medicines 116
6.3.3 Integration of Traditional and Western Medicine in Indigenous Populations 117
6.4 Conclusions 117
References 118
7 Phytotherapies from Traditional Chinese Medicine 122
Michael Rieder
7.1 Traditional Chinese Medicine 122
7.2 Key Concepts in Traditional Chinese Medicine 124
7.3 Herbal Medicine and Traditional Chinese Medicine 126
7.4 Issues in the Development of Phytotherapy from Traditional Chinese Medicine 130
7.5 Phytotherapies Developed from Traditional Chinese Medicine 131
7.6 Huang Qin Tang and the Development of Phy906 134
7.7 Ginseng 136
7.8 Moving Forward 138
References 138
8 Integrating Traditional Greco Arab and Islamic Diet and Herbal Medicines in Research and Clinical Practice 142
Bashar Saad
8.1 Introduction 142
8.2 Food Therapy in Greco Arab and Islamic Medicine 147
8.2.1 Honey 148
8.2.2 Olive Oil 149
8.2.3 Dates 151
8.2.4 Carob (Ceratonia siliqua) 152
8.2.5 Fig (Ficus carica) 153
8.2.6 Pomegranate (Punica granatum) 153
8.2.7 Garlic (Allium sativum) and Onion (Allium cepa) 154
8.2.8 Edible Wild Plants 154
8.3 Medicinal Plants 157
8.3.1 Black Seed (Nigella sativa) 160
8.3.2 Fenugreek (Trigonella foenum graecum) 167
8.3.3 Sage (Salvia officinalis) 168
8.3.4 Khella (Ammi visnaga) 168
8.3.5 Milk Thistle (Silybum marianum) 168
8.3.6 Marjoram (Origanum majorana) 171
8.3.7 Garlic (Allium sativum) and Onion (Allium cepa) 172
8.3.8 Tayun (Inula viscose) 172
8.3.9 Rocket (Eruca sativa) 172
8.3.10 Nettle (Urtica dioica) 173
8.3.11 Peppermint (Mentha piperita) 173
8.3.12 Chamomile (Chamomilla recutita) 174
8.3.13 Coriander (Coriandrum sativum) 175
8.3.14 Anise (Pimpinella anisum) 175
8.3.15 Rosemary (Rosmarinus officinalis) 175
8.3.16 Devil's Dung (Ferula asafetida) 176
8.3.17 Ginger (Zingiber officinale) 176
References 177
9 Evolution of Herbal Medicines in Europe and its Relationship with Modern Medicine 183
Elizabeth M. Williamson and Kelvin Chan
9.1 Background 183
9.2 Historical Perspective 184
9.3 European Herbal Medicine: Relationship with Modern Medicine 194
9.4 Summary 194
References 196
10 Chemical Classification and Chemistry of Phytotherapeutics Constituents 199
Pei H. Cui and Colin C. Duke
10.1 Introduction 199
10.2 Phytochemicals 201
10.2.1 Alkaloids 201
10.2.2 Flavonoids 205
10.2.3 Glycosides and Saponins 208
10.2.4 Phytosterols 209
10.2.5 Fatty Acids 212
10.2.6 Essential Oils 214
10.2.7 Terpenes 214
10.3 Other Phytochemicals 215
10.4 Medicinal Effects Relating to Dietary Intake 217
10.4.1 Anti oxidants 217
10.4.2 Omega 3 Long Chain Fatty Acids and Derivatives 220
10.5 Natural Products as Leads for Drug Development 223
10.5.1 Catechol Moiety of Piceatannol: Implication and Significance 224
10.5.2 SAR Studies for Drug Development 226
10.6 Summary 230
References 230
11 Therapeutic Potential of Ginsenosides in Management of Atherosclerosis 236
Xiao Jing Zhang, Huanxing Su, Yi-Tao Wang, and Jian-Bo Wan
11.1 Introduction 236
11.2 Chemical Diversity of Ginsenosides and Distribution 238
11.3 Anti Atherosclerotic Effects of Ginsenosides 240
11.4 Underlying Mechanisms of Ginsenosides Against Atherosclerosis 244
11.4.1 Regulation of Blood Lipid Profile 244
11.4.2 Anti oxidant Activity 251
11.4.3 Anti vascular Inflammation 252
11.4.4 Effect on Vascular Cells 255
11.4.5 Anti platelet Effects 257
11.4.6 Anti angiogenesis Effects 257
11.5 Conclusions and Future Perspectives 258
Acknowledgments 258
References 258
12 Phytotherapy Pharmacophores for Major Cellular Drug Targets 268
Jennifer A. Ong, Paul W. Groundwater, and David E. Hibbs
12.1 Introduction 268
12.2 What is a Pharmacophore? 269
12.3 Pharmacophore Models of Cardiovascular Drugs 270
12.4 Pharmacophore Models for Anticancer Drugs 285
12.5 Pharmacophore Models for Anti Inflammatory Drugs 290
12.6 Pharmacophore Models for Anti Infective Drugs 297
12.7 Pharmacophore Models for Neurological Drugs 299
12.8 Pharmacophore Models for Miscellaneous Drugs 305
12.9 Conclusions 309
References 309
13 Use of Kava as a Phytotherapeutic Agent and Kava Related Hepatotoxicity 312
Dong Fu and Iqbal Ramzan
13.1 Introduction 312
13.2 Active Components in Kava 313
13.3 Therapeutic Applications of Kava 314
13.4 Pharmacology of Kava 314
13.4.1 Anti psychotic Effects of Kava 314
13.4.2 Anti cancer Effects of Kava 316
13.5 Side Effects of Kava 317
13.6 Hepatotoxicity of Kava 318
13.6.1 Inhibition of Cytochrome P450 Enzymes Activities 318
13.6.2 Reduction of Liver Glutathione 319
13.6.3 Induction of Hepatic Inflammatory Responses 320
13.6.4 Inhibition of Cyclooxygenase Enzyme Activity 320
13.6.5 Inhibition of Hepatic Transporters 321
13.6.6 Damage of Hepatic Mitochondria 321
13.7 Summary and Future Challenges 322
References 323
14 Phytotherapies as New Drug Sources: Gossypol and Curcumin 330
Vivian Wan Yu Liao, Rajeshwar Narlawar, David E. Hibbs, and Paul W. Groundwater
14.1 Botanical Sources of Gossypol and Curcumin 330
14.2 Stereoisomerism, Tautomerism, and Reactivity 332
14.2.1 Stereoisomerism 332
14.2.2 Tautomerism 333
14.2.3 Reactivity 333
14.3 Biological Activity of Gossypol and its Analogues 337
14.3.1 Antifertility 337
14.3.2 Anticancer 338
14.3.3 Antiviral 341
14.3.4 Antimalarial 345
14.3.5 Other Biological Activity 346
14.4 Biological Activity of Curcumin and its Analogues 346
14.4.1 Introduction 346
14.4.2 Anticancer 348
14.4.3 Anti inflammatory and Antioxidant 354
14.4.4 Curcumin in Neurodegenerative Diseases 357
14.4.5 Antimalarial 359
14.4.6 Other Biological Activity 360
References 360
15 Phytotherapies for the Management of Obesity and Diabetes 370
Michel Rapinski and Alain Cuerrier
15.1 Introduction 370
15.2 Plants from the North American Pharmacopoeia 372
15.3 Pharmacological Screening: Providing Empirical Evidence for Phytotherapies 379
15.3.1 Diabetes 379
15.3.2 Obesity 384
15.4 Community Based Participation: Developing Phytotherapies from Traditional Knowledge 385
15.5 Conclusions 387
References 387
16 Phytotherapeutics for Cancer Therapy 394
Daniel M. Y. Sze, Hao Liu, Maureen V. Boost, Raimond Wong, and Stephen Sagar
16.1 Introduction 394
16.2 Anticancer Phytotherapeutics With Nk Enhancement 395
16.2.1 Effects of Clinically Useful Phytocompounds on Cancer Patients' NK Cell Immunity, Quality of Life (QoL), and Overall Survival 395
16.2.2 Commonly Used Phytotherapeutics in Cancer Management 395
16.2.3 Phytotherapeutic Formulae for Cancer via NK Modulation 409
16.3 Conclusions 423
References 425
17 Phytomedicines for Fatty Liver Disease and Functional Gastrointestinal Conditions 429
George Q. Li, Moon Sun Kim, Fangming Jin, and Jun Lae Cho
17.1 Introduction 429
17.2 Phytomedicines for Fld 430
17.2.1 Introduction and Pharmacotherapy 430
17.2.2 Treatment of Fatty Liver with Herbal Medicines 433
17.2.3 Common Herbs Used in Fatty Liver Management 433
17.3 Phytomedicines for Ibs 439
17.3.1 Introduction and Pharmacotherapy 439
17.3.2 Treatment of IBS in Traditional Medicine 440
17.3.3 Common Herbs Used in the Management of IBS 440
17.4 Phytomedicines for Constipation 444
17.4.1 Treatment of Constipation with Herbal Medicines 445
17.4.2 Common Herbs Used in the Management of Constipation 446
17.5 Summary and Future Perspectives 448
References 448
18 Phytomedicines for Inflammatory Conditions 464
Sigrun Chrubasik Hausmann
18.1 Traditional Medicines for Inflammatory Conditions in Europe 464
18.2 Twenty First Century Update on Paids 465
18.3 Oral Extracts from Salix Species 465
18.3.1 Efficacy 467
18.3.2 Safety 467
18.4 Oral Extracts from Harpagophytum procumbens 468
18.4.1 Efficacy 469
18.4.2 Safety 469
18.5 Oral Avocado Soybean Unsaponifiables 469
18.5.1 Efficacy 470
18.5.2 Safety 473
18.6 Oral Extracts From Tripterygium wilfordii 473
18.6.1 Efficacy 473
18.6.2 Safety 474
18.7 Oral Paids Containing Unsaturated Fatty Acids 475
18.7.1 Efficacy 475
18.7.2 Safety 475
18.8 Other Oral Paids 476
18.9 Topical Paids 477
18.9.1 Efficacy 478
18.9.2 Safety 478
References 478
19 Phytotherapies for Infectious Diseases: Are These Really Useful? 483
Gail B. Mahady, Gabrielle Escalante, Pooja Mikkilineni, Laura J. Mahady, Temitope O. Lawal, and Bolanle A. Adeniyi
The History of Medicine 483
19.1 Introduction 484
19.2 Historical Precedent for Natural Products as Antimicrobial Drugs 486
19.3 Are Phytotherapies Useful for the Treatment of Infectious Diseases? 487
19.3.1 Cranberry (Vaccinium macrocarpon Ait) 488
19.3.2 Turmeric (Curcuma longa L.) as an Antimicrobial Agent 492
19.3.3 Ginger (Zingiber officinale L.) as an Antimicrobial Agent 494
19.4 Naturally Occurring Compounds that may Reduce Zoonosis 495
19.5 Synergistic and Additive Effects with Antibiotics 496
19.6 New Emerging Infectious Diseases and those with no Known Treatments 496
19.7 Sars 497
19.8 Reducing Mrsa Carriage 498
19.9 Conclusions 499
References 500
20 Phytomedicines for CNS Disorders: Safety Issues for use with Antiepileptic Drugs 504
Sophia Yui Kau Fong, Rosina Yau Mok, Qiong Gao, Yin Cheong Wong, and Zhong Zuo
20.1 Introduction 504
20.2 Methodology of Systematic Literature Search 506
20.3 Pharmacokinetic Interactions 506
20.3.1 Carbamazepine 507
20.3.2 Phenytoin 507
20.3.3 Valproate 510
20.3.4 Diazepam 511
20.3.5 Phenobarbitone 511
20.3.6 Newer Generations of Antiepileptic Drugs 512
20.4 Pharmacodynamic Interactions 512
20.4.1 Antiepileptic Effects 513
20.4.2 Sedative Effects 517
20.4.3 Anxiolytic Effects 520
20.4.4 Memory Impairment Effects 520
20.4.5 Motor Incoordination Effects 523
20.5 Conclusions 524
References 524
21 Phytotherapies: Drug Interactions in Cancer 536
Andrew J. McLachlan and Stephen J. Clarke
21.1 Introduction 536
21.2 Use of Herbal and Complementary Medicines by People Living with Cancer 537
21.3 Mechanisms of Phytotherapy Drug Interactions 538
21.4 Selected Examples of Phytotherapy Medicines that have the Potential to Cause Drug Interactions in Cancer 540
21.4.1 Black Cohosh (Cimicifuga racemosa) 540
21.4.2 Echinacea (Echinacea purpurea) 541
21.4.3 Fenugreek (Trigonella foenum graecum) 541
21.4.4 Ginkgo Biloba 542
21.4.5 Asian Ginseng (Panax ginseng) 542
21.4.6 Green Tea (Camellia sinensis) 543
21.4.7 Kava Kava (Piper methysticum Forst. f.) 544
21.4.8 Liquorice (Glycyrrhiza uralensis) 544
21.4.9 Milk Thistle (Silybum marianum) 544
21.4.10 St. John's Wort (Hypericum perforatum) 545
21.4.11 Valerian (Valeriana officinalis) 546
21.5 Future Perspectives: Need for Evidence and Advice to Cancer Patients and Physicians 546
21.6 Conclusions 547
Acknowledgments 547
Conflict of Interest 547
References 547
22 Quality Use of Medicines: Considerations in Phytotherapy 554
Lynn Weekes
22.1 Introduction 554
22.1.1 Judicious Use 554
22.1.2 Appropriate Selection 555
22.1.3 Safe and Effective Use 555
22.1.4 The QUM Paradigm 555
22.2 Relevance of Qum for Herbal Medicines 556
22.2.1 Is the QUM Framework Relevant for Herbal Therapies? 556
22.3 Use of Phytotherapies by Consumers 558
22.4 Consumer Attitudes and Beliefs about Herbal Medicines 559
22.4.1 Holistic View of Health and Well Being 559
22.4.2 It is Natural, So it Must be Safe 560
22.5 Applying the Qum Framework to Phytotherapies 561
22.5.1 Judicious Use 561
22.5.2 Appropriate Selection 562
22.5.3 Safe and Effective Use 563
22.5.4 Adverse Reactions 563
22.5.5 Interactions 564
22.5.6 Allergy 565
22.5.7 Safe Formulation 565
22.5.8 Effectiveness 565
22.6 Building Blocks for Quality Use of Herbal Medicines 566
22.6.1 Objective Information and Ethical Promotion 566
22.6.2 Education and Training 568
22.6.3 Systems and Interventions 569
22.6.4 Shared Decision Making 569
22.7 Conclusion 570
References 570
23 Intellectual Property and Patent Issues with Phytotherapy Products 573
Gint Silins, Jennifer Tan, and Kelvin Chan
23.1 Introduction 573
23.1.1 Historical and Current Aspects of Intellectual Property 573
23.1.2 Types of Intellectual Property Rights 574
23.1.3 Worldwide IP Laws Have Yet to Be Harmonized 575
23.2 Ip Rights Phyto Industry 575
23.2.1 IP Protection for Phytotherapy Products and Phytotherapies 575
23.2.2 Patents 576
23.2.3 Patents as IP Assets 576
23.2.4 Patents for Protecting Phyto Inventions 577
23.2.5 Exclusions to Patentability 577
23.3 Brief Overview of Patents and the Patenting Process 578
23.3.1 Patent Searching 578
23.3.2 Patent Ownership 578
23.3.3 Patent Filing 579
23.3.4 Examination and Classification 579
23.3.5 Allowance and Grant 579
23.3.6 Extension of Patent Term 579
23.4 Other Types of IP Rights 585
23.4.1 Trade Secrets 585
23.4.2 Regulatory Exclusivity and Restricted Third Party Access 585
23.4.3 Plant Variety Protection 586
23.4.4 Industrial Designs 586
23.4.5 Trademarks 586
23.5 Patenting Trends for Phytotherapeutics 587
23.6 Traditional Knowledge and IP Rights 587
Disclaimer 589
References 590
24 International Regulatory Status of Phytotherapies 593
Ernest V. Linek
24.1 Introduction 593
24.1.1 Country Law Sources 594
24.1.2 Common Requirement: Good Manufacturing Practices 594
24.2 Specific Country Regulations 596
24.2.1 Current Regulations in Australia 596
24.2.2 Current Regulations in Canada 597
24.2.3 Current Regulations in China 604
24.2.4 Current Regulations in the European Union (EU) 609
24.2.5 Current Regulations in India 616
24.2.6 Current Regulations in Japan 619
24.2.7 Current Regulations: United Kingdom 622
24.2.8 Current Regulations in the United States 625
24.3 Future of Phytotherapies: World Health Organization (Who) 631
Further Reading 634
Index 635
Author
Iqbal Ramzan is the Dean of the Faculty of Pharmacy at the University of Sydney, Australia. He is a registered pharmacist and holds a Diploma of the Australian Institute of Company Directors. Dr. Ramzan also served two terms as a Fellow of The University. He is an author/co-author of over 140 publications in pharmacokinetics, pharmacodynamics, drug assays, and drug metabolism. Dr. Ramzan is a member of several professional committees and councils, including the Director of the Council of Pharmacy Schools (Australia and New Zealand). He also serves on the Australian Government's Pharmaceutical SubCommittee of the Advisory Committee on Prescription Medicines.