Title Details

List of Contributors xvii

Preface xxi

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