Ethnopharmacology...Ethnopharmacology Edited by Michael Heinrich Centre for Pharmacognosy and...

Ethnopharmacology

Ethnopharmacology

Edited by

Michael HeinrichCentre for Pharmacognosy and Phytotherapy/Research Cluster Biodiversity andMedicines, UCL School of PharmacyUniversity of LondonUK

Anna K. JägerDepartment of Drug Design and PharmacologyFaculty of Health and Medicinal SciencesUniversity of CopenhagenDenmark

http://www.ullapharmsci.org/

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Contents

Contributors xvii

Series Foreword xxi

Preface xxiii

Abbreviations xxvii

Ethnopharmacology: The Fundamental Challenges

1 Ethnopharmacology: A Short History of a Multidisciplinary Field of Research 3Michael Heinrich

1.1 Introduction 3Acknowledgements 8References 8

2 Medicinal Plant Research: A Reflection on Translational Tasks 11Anna K Jäger

2.1 Introduction 112.2 Translational research: preclinical research 122.3 Translational research: clinical research 132.4 Reaching the patient 142.5 A ‘developed’ traditional medicine system 14

References 16

3 The Anthropology of Ethnopharmacology 17Ina Vandebroek and Daniel E. Moerman

3.1 Introduction 173.2 Primary example: Traditional medicine in New York City 18

3.2.1 Missing out on cultural context 193.2.2 People change plants due to availability 203.2.3 The spiritual component 21

3.3 An example from ancient Roman architecture 223.4 An example from native North America 23

vi CONTENTS

3.5 Comparative ethnobotany 243.6 Conclusions 26

References 27

4 Quantitative and Comparative Methods in Ethnopharmacology 29Marco Leonti and Caroline S. Weckerle

4.1 Introduction 294.1.1 Materia medica and cultural consensus 294.1.2 The intent of ethnopharmacological projects: Basic and applied research 304.1.3 Ethnopharmacology as cross-cultural endeavour and the concept of emic and etic 30

4.2 Research questions 314.2.1 Descriptive questions 324.2.2 Relational questions 32

4.3 Field research 334.3.1 Data sampling 33

4.4 Analyzing the data 344.4.1 Use-reports for quantification 34

4.5 Pharmacological research 354.6 Contextualization 364.7 Conclusion 37

References 37

5 Biodiversity, Conservation and Ethnopharmacology 41Vernon H. Heywood

5.1 Introduction 415.2 Changing attitudes to the ownership of biodiversity 425.3 Medicinal and aromatic plants as resources 435.4 How many species? 445.5 Chemical diversity 455.6 Wild harvesting and over-collection 455.7 Medicinal plant conservation 465.8 Conservation approaches 465.9 Protected areas 475.10 Community conservation 475.11 Genetic conservation 475.12 Cultivation 485.13 Conclusions 48

References 49

6 Ecopharmacognosy 53Geoffrey A. Cordell

6.1 Introduction 536.2 Sustainable medicines and pharmacognosy 546.3 Ecopharmacognosy: background 556.4 Ecopharmacognosy practices 55

6.4.1 Replacement plant parts 566.4.2 Vegetables as chemical reagents 566.4.3 The ‘Medicine Man’ approach and remote sensing 566.4.4 Dereplication 576.4.5 In silico evaluation of natural products 576.4.6 Biosynthesis of secondary metabolites 586.4.7 Complex traditional medicines 58

CONTENTS vii

6.4.8 Network pharmacology 596.4.9 Can ecopharmacognosy change the dark side of traditional medicine? 59

6.5 Conclusions 60Acknowledgements 60References 60

7 NMR-based Metabolomics and Hyphenated NMR Techniques: A Perfect Matchin Natural Products Research 63Joachim Møllesøe Vinther, Sileshi Gizachew Wubshet and Dan Staerk

7.1 Introduction 637.2 Metabolomics 647.3 Principles of NMR-based metabolomics 657.4 NMR-based metabolomics in natural products research 667.5 Hyphenated NMR techniques 687.6 Principle of HPLC-SPE-NMR 697.7 High-resolution bioassay-coupled HPLC-SPE-NMR 707.8 Combining metabolomics and hyphenated NMR techniques 717.9 Perspectives in ethnopharmacology 72

7.10 Conclusions 72References 72

8 New Medicines Based On Traditional Knowledge: Indigenous and IntellectualProperty Rights from an Ethnopharmacological Perspective 75Michael Heinrich

8.1 Introduction 758.2 The legal framework 768.3 Industrial research in an ethnopharmacological context 778.4 Some case studies 79

8.4.1 Pure natural products as drug leads 798.4.2 Extracts and partially purified preparations as drug leads 81

8.5 Conclusions 83Note 84References 84

9 Ethnopharmacology and Intellectual Property Rights 87Alan Hesketh

9.1 Introduction 879.2 Indigenous community rights and traditional knowledge 889.3 Identifying a partner 89

9.3.1 The foreign partner’s attitude 909.3.2 The advantages of IP 90

9.4 Hurdles in considering IP 919.5 Building an effective IP portfolio 91

9.5.1 Requirements for patentability 929.5.2 The value of different types of patent protection 92

9.6 The patentability of products of nature 939.6.1 Novelty 949.6.2 Novelty and traditional knowledge 949.6.3 Obviousness 94

9.7 Conclusion 95References 95

viii CONTENTS

10 Ethnopharmacology in Elementary, Primary and Secondary Education: CurrentPerspectives and Future Prospects 97Alonso Verde, Diego Rivera, José Ramón Vallejo, José Fajardo, Concepción Obónand Arturo Valdés

10.1 Introduction 9710.2 Ethnopharmacology: a multidisciplinary subject for education 9910.3 Developing an ethnopharmacological curriculum: some strategies 10110.4 Conclusions 104

References 105

The Pharmacological Angle

11 Anti-infective Agents: The Example of Antibacterial Drug Leads 111Maíra Bidart de Macedo, Sofie Clais, Ellen Lanckacker, Louis Maes,Emerson Silva Lima and Paul Cos

11.1 Introduction 11111.2 Bacterial resistance 11211.3 Plant-derived antibacterial agents 112

11.3.1 Direct antibacterial agents 11211.3.2 Antivirulence agents 11311.3.3 Resistance-modifying agents 117

11.4 Basic requirements for successful antimicrobial drug discovery (Cos et al., 2006) 11811.5 Conclusion 119

References 120

12 Searching for New Treatments of Malaria 123Colin W. Wright

12.1 Introduction 12312.2 Traditional herbal remedies as a source of antimalarial lead compounds 12312.3 Developments from established antimalarials 12612.4 Non-traditional medicine sources of potential antimalarials 12712.5 Alternative strategies in the search for natural antimalarial compounds 12912.6 Herbal preparations for the treatment of malaria 13012.7 Conclusion and future prospects 132

References 132

13 CNS Disorders 135Anna K Jäger

13.1 Introduction 13513.2 Epilepsy 13513.3 Depression and anxiety 137

13.3.1 Selective serotonin reuptake inhibitors 13713.3.2 MAO-A inhibitors 13813.3.3 Clinical evidence 138

13.4 Insomnia 13913.5 Sedatives 13913.6 Dementia 139

13.6.1 Countering neurotransmitter abnormalities: acetylcholinesterase inhibitors 14013.6.2 Countering neurotransmitter abnormalities: MAO-B inhibitors 140

CONTENTS ix

13.6.3 Reducing the formation and fibrillation of amyloid β peptides 14113.6.4 Anti-inflammatory and antioxidant activity 141


14 Respiratory Conditions 147Adolfo Andrade-Cetto and Jorge García-Alvarez

14.1 Introduction 14714.1.1 The respiratory system 14714.1.2 Respiratory diseases 14714.1.3 Common cold 14814.1.4 Influenza 14914.1.5 Acute lower respiratory tract infections: acute bronchitis 14914.1.6 Other diseases of the upper respiratory tract: allergic rhinitis and rhinitis 14914.1.7 Chronic lower respiratory tract diseases: COPD 14914.1.8 Lung diseases caused by external agents: hypersensitivity pneumonitis 15014.1.9 Other respiratory diseases principally affecting the interstitium:

idiopathic pulmonary fibrosis 15014.1.10 Suppurative and necrotic lower respiratory tract conditions: pneumonia

with necrosis 15014.1.11 Other pleural diseases: pleural plaque 15114.1.12 Other diseases of the respiratory system: acute respiratory failure 151

14.2 Case studies 15114.2.1 Althaea officinalis L. Malvaceae 15214.2.2 Codeine and noscapine 15314.2.3 Echinacea purpurea (L.) Moench and Ecinacea angustifolia DC. 15314.2.4 Ephedra sinica Stapf. (Ephedraceae) 15414.2.5 Thymus vulgaris L. (Lamiaceae) 155

14.3 Conclusions 155Acknowledgments 156References 156

15 Can there be an Ethnopharmacology of Inflammation? 159Michael Heinrich and Anthony Booker

15.1 Introduction 15915.2 Ethnopharmacology of inflammation: some examples 161

15.2.1 The arnica complex 16215.2.2 Harpagophytum procumbens (Burch.) DC. ex Meisn. (Pedaliaceae) 16315.2.3 Scutellaria baicalensis Georgi (Huang Qin, Baical skullcap; Lamiaceae) 16415.2.4 Curcuma longa L. (Zingiberaceae) 16415.2.5 Capsicum frutescens L. 165


16 Epidermal Growth Factor Receptors and Downstream Signalling Pathwaysas Cancer Treatment Targets for Medicinal Plants 169Ean-Jeong Seo, Ching-Fen Wu, Henny J. Greten and Thomas Efferth

16.1 Role of epidermal growth factor receptors for cancer biology 16916.2 Inhibition of epidermal growth factor signalling by phytochemicals

and medicinal plants 17116.2.1 Natural products as a resource for cancer treatment 171

x CONTENTS

16.2.2 Inhibitors of EGFR signalling 17116.2.3 Inhibitors of HER2/HER3 signalling 172

16.3 Conclusions and perspectives 173References 174

17 From Ethnopharmacological Field Study to Phytochemistry and PreclinicalResearch: The Example of Ghanaian Medicinal Plants for ImprovedWound Healing 179Andreas Hensel, Emelia Kisseih, Matthias Lechtenberg, Frank Petereit,Christian Agyare and Alex Asase

17.1 Introduction 17917.2 Results 180

17.2.1 The start of a research project: validated field study on wound-healing plants 18017.2.2 Before starting laboratory work: who the healers are and some

socioeconomic aspects 18017.2.3 Evaluation of the data collection and cross-referencing to published literature 18117.2.4 The next step: selection of plants for in vitro investigations 18117.2.5 Screening of selected plant extracts: influence on skin cells under in vitro conditions 18117.2.6 Phytochemical aspects of P. muellerianus and the ICH-validated HPLC method

for quality control (ICH, 2014) 19017.2.7 Influence of P. muellerianus on the cell physiology of human skin cells 19217.2.8 Phytochemistry of C. mucronatum 19417.2.9 Influence of C. mucronatum on the cell physiology of human skin cells 194


18 Gynaecological, Andrological and Urological Problems: An EthnopharmacologicalPerspective 199Tinde van Andel, Hugo de Boer and Alexandra Towns

18.1 Introduction 19918.2 Menstrual disorders 200

18.2.1 Dysmenorrhea and uterine spasmolytics 20018.2.2 Uterine spasmogenics 201

18.3 Postpartum use 20118.3.1 Puerperal infections 20118.3.2 Postpartum haemorrhage 20218.3.3 Perineal healing 202

18.4 Vaginal applications 20218.5 Female infertility 20418.6 Andrology 204

18.6.1 Aphrodisiacs and male sterility 20418.7 Urology 206

References 207

19 Ethnopharmacological Aspects of Bone and Joint Health 213Elizabeth M. Williamson

19.1 Introduction 21319.2 Current views of bone and joint disorders 21419.3 Traditional views of bone disorders 216

19.3.1 European traditional herbal medicine 21619.3.2 North America 222

CONTENTS xi

19.3.3 Traditional Chinese medicine 22219.3.4 Ayurveda 223


20 Diabetes and Metabolic Disorders: An Ethnopharmacological Perspective 227Adolfo Andrade Cetto

20.1 Introduction 22720.2 Type-2 diabetes 228

20.2.1 Insulin 22820.2.2 Insulin effects in peripheral tissues 22920.2.3 Insulin resistance (skeletal muscle and adipose tissue) 22920.2.4 Liver 23020.2.5 Gut 230

20.3 Metabolic syndrome 23020.4 Case studies 231

20.4.1 Liver targeting 23120.4.2 Gut targeting 23220.4.3 Insulin targeting 23320.4.4 Obesity and insulin resistance 234

20.5 Conclusions 236Acknowledgments 236References 237

21 The Ethnopharmacology of the Food–Medicine Interface: The Example ofMarketing Traditional Products in Europe 239Gunter P. Eckert

21.1 Introduction 23921.2 Medicinal products for human use 241

21.2.1 Legal framework 24121.2.2 Definition of medicinal products 24121.2.3 Herbal medicinal products 242

21.3 Food 24321.3.1 Definition of food 24321.3.2 Food supplements 24321.3.3 Fortified food 24421.3.4 Novel food 24421.3.5 Functional food 245

21.4 Consumer protection - security and protection against fraud 24521.4.1 Food safety 24621.4.2 Health claims 246

21.5 Intended normal use: the distinction between medicinal products and foods 24721.6 Conclusion 248

References 248

22 Retrospective Treatment-Outcome as a Method of Collecting Clinical Data inEthnopharmacological Surveys 251Bertrand Graz, Merlin Willcox and Elaine Elisabetsky

22.1 Introduction 25122.2 Key concepts: clinical data, outcome and patient progress 25222.3 Evaluation of the effectiveness and safety of traditional medicines 253

xii CONTENTS

22.4 The role of ethnopharmacologists and ethnobotanists 25422.5 Collection of clinical data during ethnopharmacological field studies 25522.6 Example of a method for gathering clinical data during field surveys 255

22.6.1 Defining the health problem 25522.6.2 Research question 25622.6.3 Data collection: ask patients! 25622.6.4 Getting consent: a much debated topic 25622.6.5 Sample size 25722.6.6 Statistical analysis and interpretation 25722.6.7 Results: a research programme leading to the validation of safe

and effective phytomedicines 25922.7 Conclusion: clinical data and field surveys for a positive impact on health 259

References 260

Ethnopharmacology: Regional Perspectives

23 Ethnopharmacology in Sub-Sahara Africa: Current Trends andFuture Perspectives 265Mack Moyo, Adeyemi O. Aremu and Johannes van Staden

23.1 Introduction 26523.2 Role of traditional medicine in Africa 26623.3 Ethnopharmacological research in sub-Saharan Africa 26723.4 Challenges of traditional medicine in Africa 269

23.4.1 Efficacy, toxicology and safety concerns 27023.4.2 Shelf-life, post-harvest physiology and storage 27123.4.3 Conservation challenges of protecting plant resources 272

23.5 Future perspectives 27223.6 Conclusions 273

Acknowledgements 273References 273

24 Ethnopharmacology and Integrative Medicine: An Indian Perspective 279Pulok K. Mukherjee, Sushil K. Chaudhary, Shiv Bahadur and Pratip K. Debnath

24.1 Ethnopharmacology and the development of traditional medicine in India 27924.2 Biological wealth and ancient wisdom 28124.3 Indian systems of medicine 28124.4 Ayurveda: the Indian system of medicine 282

24.4.1 Panchakarma 28224.4.2 Validation of classical Ayurvedic formulation 28324.4.3 Ayurgenomics 28424.4.4 Reverse pharmacology 28624.4.5 Ayurinformatics 286

24.5 Siddha 28624.6 Unani 28724.7 Traditional knowledge digital library 28724.8 Integrated approaches for the development of Indian traditional medicine 288

24.8.1 Strategies and innovations 28824.9 Conclusion 289


CONTENTS xiii

25 Chinese Medicine: Contentions and Global Complexities 293Anthony Booker

25.1 Introduction 29325.2 Ancient concepts meet scientific understanding 29425.3 Traditional and modern dosage forms and application 29625.4 Medicinal plant production in China 29625.5 Quality and safety 29725.6 Aristolochic acids 29825.7 Regulatory requirements 29825.8 Training practitioners of TCM 29925.9 Future prospects 300

References 301

26 Chinese Medicinal Processing: A Characteristic Aspect of theEthnopharmacology of Traditional Chinese Medicine 303Ping Guo, Eric Brand and Zhongzhen Zhao

26.1 Introduction 30326.2 Definition, methods and historical changes in Chinese medicinal processing 304

26.2.1 Definition 30426.2.2 Methods 30426.2.3 Historical changes 308

26.3 Present state of Chinese medicinal processing 31026.3.1 Inconsistency of ancient and current processing methods 31026.3.2 Inconsistency of processing practice in different provinces of China 31026.3.3 Differences in decoction pieces between Hong Kong and mainland China 31126.3.4 Differences in national pharmacopoeias regarding medicinal processing 31126.3.5 Lack of objective quality control standards 31226.3.6 Progress in research 313

26.4 Prospect for future developments in Chinese medicinal processing 315References 315

27 A South-East Asian Perspective on Ethnopharmacology 317Pravit Akarasereenont, Marianne J.R. Datiles, Natchagorn Lumlerdkij,Harisun Yaakob, Jose M. Prieto and Michael Heinrich

27.1 Introduction 31727.2 Ethnopharmacology in Thailand 31927.3 Ethnopharmacology in Malaysia 322

27.3.1 Malay traditional medicine 32227.3.2 Clinical integration of the Malay traditional medicines 32327.3.3 Modern phytotherapeutic products and food supplements from Malay traditional

medicinal plants 32427.3.4 The future direction of Malay TM 325

27.4 Ethnopharmacology in Indonesia 32527.5 Ethnopharmacology in the Philippines 32627.6 Ethnopharmacology in Vietnam 32827.7 Ethnopharmacology in Myanmar, Lao PDR and Cambodia 32827.8 Ethnopharmacology in Singapore and Brunei 32827.9 Conclusion 328

Acknowledgement 329References 329

xiv CONTENTS

28 Historical Approaches in Ethnopharmacology 333Andreas Lardos

28.1 Introduction 33328.2 Historical texts in ethnopharmacological research 334

28.2.1 Documentation of (mainly) medicinal plant knowledge 33428.2.2 Evaluation of medicinal plant knowledge and identification of potential

plant candidates 33428.2.3 Development of (medicinal) plant knowledge 334

28.3 Methodological aspects 33528.4 Challenges in the analysis of historical texts 33528.5 Opportunities offered by a historical approach 33728.6 Conclusions 338

References 339

29 Medical Ethnobotany and Ethnopharmacology of Europe 343Manuel Pardo-de-Santayana, Cassandra L. Quave, Renata Sõukandand Andrea Pieroni

29.1 Introduction 34329.2 A brief history of European medicinal plants studies 34429.3 Modern European medico-ethnobotanical studies 345

29.3.1 The development of ethnobotanical studies in Europe 34529.3.2 Recent medico-ethnobotanical studies in Europe 346

29.4 European ethnomedicinal flora 35029.5 Adaptation, syncretism and resilience of traditional pharmacopoeias 35129.6 Pharmacological studies of European medicinal plants 35129.7 Concluding remarks 352

References 352

30 Ethnopharmacology in the Eastern Mediterranean and the Middle East:‘The Sun Rises from the East, but Shines on the Eastern Mediterranean’ 357Erdem Yesilada

30.1 Introduction 35730.2 Ethnobotany and ethnopharmacology in the Balkan region 35830.3 Modern ethnobotany and ethnopharmacology in the Middle East 35930.4 Ethnobotany and ethnopharmacology in Turkey 36130.5 Concluding remarks 362

References 362

31 Ethnopharmacology in Australia and Oceania 365Graham Lloyd Jones and Nicholas J. Sadgrove

31.1 Introduction 36531.1.1 Australian ethnobotany 36531.1.2 Ethnobotany in Oceania 367

31.2 Ethnopharmacological ‘classics’ 36731.2.1 Scopolamine from the Australian Duboisia 36731.2.2 Polynesian breadfruit and kava used throughout Oceania 368

31.3 Australian aromatic plants 36931.3.1 Eucalyptus 37031.3.2 Melaleuca alternifolia (tea tree oil) 370

CONTENTS xv

31.4 Recent developments: aromatic plants 37131.5 Recent developments: cancer and HIV 37631.6 Conclusion 376

References 377

32 Ethnopharmacology in Central and South America 379Salvador Cañigueral and Jaume Sanz-Biset

32.1 Introduction 37932.2 The development of drugs 381

32.2.1 The case of dragon’s blood 38232.2.2 The essential oil of Cordia verbenacea 38432.2.3 The example of developing ethnopharmacological-based herbal

medicinal products in Guatemala 38532.2.4 The Farmacias Vivas programme 386

32.3 Beyond the development of new drugs 38632.4 Bridging indigenous and western knowledge 38732.5 Hallucinogens 38832.6 Conclusion 389

References 389

33 Perspectives on Ethnopharmacology in Mexico 393Robert Bye and Edelmira Linares

33.1 Introduction 39333.2 Mexican tradition 39433.3 Compilation of medicinal plants 39633.4 Medicinal plant complex 39833.5 Markets and medicinal plants 39933.6 Bioprospection and conservation 39933.7 Conclusions 401


34 Encounters with Elephants: A Personal Perspectiveon Ethnopharmacology 405Peter J. Houghton

34.1 Introduction 40534.2 The primacy of plants 40634.3 Sources: dirty hands and databases 40634.4 From cultural use to chemistry 40734.5 Chemistry as a starter 40734.6 Botany as a basis 40834.7 Of mice and men and microwell plates 40834.8 Aims and ethics 40934.9 Molecules and mixtures 41034.10 Tales of the unexpected 41034.11 The end of the matter 411

References 411

Index 415

Contributors

ChristianAgyareDepartment of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sci-ences, College of Health Sciences, Kwame Nkrumah University of Science and Technology,Ghana

Pravit Akarasereenont Department of Pharmacology, Faculty of Medicine Siriraj Hospital,Mahidol University, Thailand, and Center of Applied Thai Traditional Medicine, Faculty ofMedicine Siriraj Hospital, Mahidol University, Thailand.

AdolfoAndrade-CettoDepartment of Cell Biology, School of Sciences, NationalAutonomousUniversity of Mexico, Mexico

Adeyemi O. Aremu Research Centre for Plant Growth and Development, School of Life Sci-ences, University of KwaZulu-Natal, South Africa

Alex AsaseDepartment of Botany, University of Ghana, GhanaShiv Bahadur School of Natural Product Studies, Department of Pharmaceutical Technology,

Jadavpur University, IndiaMaíra Bidart de Macedo Laboratory of Microbiology, Parasitology and Hygiene, Faculty of

Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, BelgiumAnthony Booker Research Cluster ‘Biodiversity and Medicines’, UCL School of Pharmacy,

UKEric Brand School of Chinese Medicine, Hong Kong Baptist University, ChinaRobert Bye Jardín Botánico del Instituto de Biología, Universidad Nacional Autónoma de

México, MexicoSalvador Cañigueral Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Univer-

sitat de Barcelona, SpainSushil K. Chaudhary School of Natural Product Studies, Department of Pharmaceutical Tech-

nology, Jadavpur University, IndiaSofie Clais Laboratory of Microbiology, Parasitology and Hygiene, Faculty of Pharmaceutical,

Biomedical and Veterinary Sciences, University of Antwerp, BelgiumGeoffrey A. Cordell Natural Products Inc., USAPaul Cos Laboratory of Microbiology, Parasitology and Hygiene, Faculty of Pharmaceutical,

Biomedical and Veterinary Sciences, University of Antwerp, BelgiumMarianne J. Datiles Centre for Pharmacognosy and Phytotherapy/Research Cluster Biodiver-

sity and Medicines, UCL School of Pharmacy, UK

xviii CONTRIBUTORS

Hugo de Boer Naturalis Biodiversity Center, Leiden University, The Netherlands, andDepartment of Organismal Biology, Uppsala University, Sweden, and The Natural HistoryMuseum, University of Oslo, Norway

Pratip K. Debnath Gananath Sen Institute of Ayurveda and Research, IndiaGunter P. Eckert Goethe-University, Campus Riedberg, Department of Pharmacology,

GermanyThomas EfferthDepartment of Pharmaceutical Biology, Institute of Pharmacy and Biochem-

istry, Johannes Gutenberg University, GermanyElaine Elisabetsky Labratório de Etnofarmacologia, Universidade Federal do Rio Grande do

Sul, BrazilJosé Fajardo Instituto Botánico, Jardín Botánico de Castilla La Mancha, Spain, and

Universidad Popular, SpainJorge García-AlvarezDepartment of Cell Biology, School of Sciences, National Autonomous

University of Mexico, MexicoBertrand Graz Social and Preventive Medicine, University of Lausanne, SwitzerlandAndreas Hensel Institute of Pharmaceutical Biology and Phytochemistry, University of

Münster, GermanyHenry J. Greten Abel Salazar Biomedical Sciences Institute, University of Porto, Portugal,

and Heidelberg School of Chinese Medicine, GermanyPing Guo School of Chinese Medicine, Hong Kong Baptist University, ChinaMichael HeinrichCentre for Pharmacognosy and Phytotherapy/Research Cluster Biodiversity

and Medicines, UCL School of Pharmacy, University of London, London, UKAlan Hesketh Indigena Biodiversity Limited, London, UKVernon H. Heywood School of Biological Sciences, University of Reading, UKPeter J. HoughtonDepartment of Pharmacy and Forensic Science, Institute of Pharmaceutical

Sciences, King’s College London, London, UK.Anna K. JägerDepartment of Drug Design and Pharmacology, Faculty of Health and Medic-

inal Sciences, University of Copenhagen, DenmarkEmelia Kisseih Institute of Pharmaceutical Biology and Phytochemistry, University of Mün-

ster, GermanyEllen Lanckacker Laboratory of Microbiology, Parasitology and Hygiene, Faculty of Pharma-

ceutical, Biomedical and Veterinary Sciences, University of Antwerp, BelgiumAndreas LardosResearch Cluster Biodiversity andMedicines/Centre for Pharmacognosy and

Phytotherapy, UCL School of Pharmacy, London, UKMarco Leonti Department of Biomedical Sciences, University of Cagliari, ItalyMatthias Lechtenberg Institute of Pharmaceutical Biology and Phytochemistry, University of

Münster, GermanyGraham Lloyd Jones Pharmaceuticals and Nutraceuticals Group, Centre for Bioactive

Discovery in Health and Ageing, University of New England Armidale, AustraliaEmerson Silva Lima Faculdade de Ciências Farmacêuticas, Universidade Federal do

Amazonas, BrasilEdelmira Linares Jardín Botánico del Instituto de Biología, Universidad Nacional Autónoma

de México, MexicoNatchagorn Lumlerdkij Center of Applied Thai Traditional Medicine, Faculty of Medicine

Siriraj Hospital, Mahidol University, Thailand, and Centre for Pharmacognosy andPhytotherapy/Research Cluster Biodiversity and Medicines, UCL School of Pharmacy,London, UK

CONTRIBUTORS xix

LouisMaesLaboratory ofMicrobiology, Parasitology andHygiene, Faculty of Pharmaceutical,Biomedical and Veterinary Sciences, University of Antwerp, Belgium

Daniel E. Moerman William E Stirton Emeritus Professor of Anthropology, University ofMichigan-Dearborn, USA

Mack Moyo Research Centre for Plant Growth and Development, School of Life Sciences,University of KwaZulu-Natal, South Africa

Pulok K Mukherjee School of Natural Product Studies, Department of Pharmaceutical Tech-nology, Jadavpur University, India

Concepción Obón Depto. de Biología Aplicada, Escuela Politécnica Superior de Orihuela.Universidad Miguel Hernández, Spain

Manuel Pardo-de-Santayana Departamento de Biología (Botánica). Universidad Autónomade Madrid, Spain

Frank Petereit Institute of Pharmaceutical Biology and Phytochemistry, University ofMünster, Germany

Andrea Pieroni University of Gastronomic Sciences, ItalyJose M. Prieto Centre for Pharmacognosy and Phytotherapy/Research Cluster Biodiversity

and Medicines, UCL School of Pharmacy, London, UKCassandra L. Quave Center for the Study of Human Health, Emory University, USA, and

Department of Dermatology, Emory University School of Medicine, USADiego Rivera Depto. Biología Vegetal, Fac. Biología, Universidad de Murcia, SpainJaume Sanz-BisetUnitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat

de Barcelona, SpainNicholas J. Sadgrove Pharmaceuticals and Nutraceuticals Group, Centre for Bioactive Discov-

ery in Health and Ageing, University of New England Armidale, AustraliaEan-Jeong Seo Department of Pharmaceutical Biology, Institute of Pharmacy and

Biochemistry, Johannes Gutenberg University, GermanyRenata Sõukand Estonian Literary Museum, EstoniaDan Staerk Department of Drug Design and Pharmacology, Faculty of Health and Medical

Sciences, University of Copenhagen, DenmarkAlexandra Towns Naturalis Biodiversity Center, Leiden University, The NetherlandsArturo Valdés Instituto Botánico, Jardín Botánico de Castilla La Mancha, SpainJoséRamónVallejoDepto. de TerapéuticaMédico-Quirúrgica, Fac. deMedicina, Universidad

de Extremadura, SpainTinde van Andel Naturalis Biodiversity Center, Leiden University, The NetherlandsJohannes van Staden Research Centre for Plant Growth and Development, School of Life

Sciences, University of KwaZulu-Natal, Pietermaritzburg, Scottsville 3209, South AfricaIna Vandebroek Matthew Calbraith Perry Assistant Curator of Economic Botany and

Caribbean Program Director, The New York Botanical Garden, Bronx, New York, USAAlonso Verde Instituto Los Olmos, Albacete. Spain, and Instituto Botánico, Jardín Botánico

de Castilla La Mancha, SpainJoachim Møllesøe VintherDepartment of Drug Design and Pharmacology, Faculty of Health

and Medical Sciences, University of Copenhagen, DenmarkCaroline S. Weckerle Institute of Systematic Botany, University of Zürich, SwitzerlandMerlin Willcox Nuffield Department of Primary Care Health Sciences, University of

Oxford, UKElizabeth M. Williamson The School of Pharmacy, University of Reading, UKColin W. Wright Bradford School of Pharmacy, University of Bradford, UK

xx CONTRIBUTORS

Ching-Fen Wu Department of Pharmaceutical Biology, Institute of Pharmacy and Biochem-istry, Johannes Gutenberg University, Germany

Sileshi Gizachew WubshetDepartment of Drug Design and Pharmacology, Faculty of Healthand Medical Sciences, University of Copenhagen, Denmark

Harisun Yaakob Institute of Bioproduct Development, Universiti Teknologi Malaysia,Malaysia

Erdem Yesilada Yeditepe University, Faculty of Pharmacy, TurkeyZhongzhen Zhao School of Chinese Medicine, Hong Kong Baptist University, China

Series Foreword

ULLA Pharmacy SeriesTheULLAPharmacy Series is an innovative series of introductory text books for postgraduatestudents and researchers in the pharmaceutical sciences.This series is produced by the ULLA Consortium (European University Consortium for

Pharmaceutical Sciences). The Consortium is a European academic collaboration in researchand teaching of the pharmaceutical sciences that is constantly growing and expanding. TheConsortium was founded in 1992 and consists of pharmacy departments and faculties fromleading universities throughout Europe, namely:

• Faculty of Pharmacy, Uppsala University, Sweden• UCL School of Pharmacy, London, UK• Leiden/Amsterdam Academic Center for Drug Research, University of Leiden and Vrije

Universiteit Amsterdam, The Netherlands• Drug Research Academy, Faculty of Health and Medical Sciences, University of Copen-

hagen, Denmark• Faculty of Pharmacy, University Paris-Sud, France• Department of Pharmacy, University of Parma, Italy• Faculty of Pharmaceutical Sciences, University of Leuven (KU Leuven), Belgium• Faculty of Pharmacy, University of Helsinki, Finland

The editorial board for the ULLA series consists of several academics from these EuropeanInstitutions who are all experts in their individual field of pharmaceutical science.

Previous titles include:

Pharmaceutical ToxicologyPaediatric Drug HandlingMolecular BiopharmaceuticsInternational Research in HealthcareFacilitating Learning in HealthcareBiomedical and Pharmaceutical PolymersInhalation Drug DeliveryGlobal New Drug Development

xxii SERIES FOREWORD

TheULLAPharmacy Series includes state-of-the-art textbooks for students and researchersin pharmacy and the pharmaceutical sciences written or edited by world-reknown expertsbased within the ULLA Consortium.The books provide an overview and critical appraisal of core areas within the fast developing

fields of pharmacy and aim at setting standards in these fields. The books are tailored mostimportantly towards PhD students and other postgraduate students undertaking masters ordiploma courses anywhere in the world. They are equally suited for undergraduates studyingspecific courses and for practising pharmaceutical scientists and community pharmacists.Further information can be found at www.ullapharmsci.org.

http://www.ullapharmsci.org

Preface

Ethnopharmacology is a fast-developing, dynamic area of research. Annually thousands ofpapers on ethnopharmacological topics are now published. Researchers with diverse back-grounds, including pharmaceutical scientists, pharmacologists, anthropologists, biologists,botanists, toxicologists and practitioners/researchers of the diverse medical traditions, areall involved in such research. Ethnopharmacological research is particularly flourishing inmost of the so-called BRICS and MINT countries (Brazil, Russia, India, China, South Africa;México, Indonesia, Nigeria and Turkey), but also in many of the other emerging economies,like Thailand and Malaysia. However, so far there has been no comprehensive and criticalassessment of the state of the art in this important field of research. With this book the editorsand authors hope to fill this gap.Ethnopharmacology is not a very concisely defined field. In fact this book contributes to

a debate about what the core research foci of ethnopharmacology are and how these shouldbe developed further. As one step of the discussion, we invited all contributors to this bookto send us their short definition of ethnopharmacology – a few sent even more than one. Inthe following we summarize these definitions (based on emails received between July andDecember 2014):

• Pravit Akarasereenont (Thailand): A science dealing with the study of the pharmacologyof traditional medicine and focusing on the active substances and their pharmacologicalaction.

• Tinde van Andel (the Netherlands): Ethnopharmacology is the study of medicinal plantuse by various ethnic groups, including indigenous peoples, and the relevance of these tra-ditional medicines for pharmacology in general and for the health of the people using theseplants.

• Adolfo Andrade Cetto (México): Ethnopharmacology is the study and selection of tra-ditionally used, biologically active natural products, with the aim of understanding theirtherapeutic actions.

• Tony Booker (UK): The study of the historical and modern interactions between humansand flora, fauna and minerals, and how these substances, their extracts and the chemicalcompounds derived from them, may be utilized to prevent and treat ill-health in peopleand their dependent animals.

• Robert Bye and Edelmira Linares (México): Ethnopharmacology [is] the study of theinteractions and relationships between humans and biological organisms along with theirbioactive constituents that promote the well-being of humans over social and geographicspaces as well as biological, chronological and cultural times.

xxiv PREFACE

• Paul Cos (Belgium):Ethnopharmacology is themeeting of two sciences, i.e. ethnomedicineand pharmacology

• Marianne Datiles (UK/USA):Ethnopharmacology [is] the study of human knowledge anduse of synthetic and natural medicines in the past, present and potential future. It is ahighly interdisciplinary field that includes pharmacy, chemistry, botany, anthropology, his-tory, nutrition, environmental sciences, public health,medicine and themedical humanities.Many definitions of the field appear to exclude human knowledge ofmedicines, but I wouldconsider this to be an essential area of study within the field.

• Thomas Efferth (Germany): Ethnopharmacology focuses on research on efficacy, safetyand modes of actions of traditional medicines with pharmacological methods.

• Bertrand Graz (Switzerland): Ethnopharmacology is the study of the drugs (or poisons)used by other people.

• Ping Guo, Eric Brand and Zhongzhen Zhao (Hong Kong/China): Ethnopharmacologyrefers to the interdisciplinary scientific study of potentially bioactive substances utilizedby different ethnic or cultural groups.

• Michael Heinrich (UK): Ethnopharmacology is the transdisciplinary study of locally andtraditionally used medicines, integrating approaches from social and natural sciences (andin some cases medicine), often with the goal of contributing to a better and safer use ofthese medicines. More and more it plays a role in helping to develop a more sustainablefuture for people in marginalized regions and as such is becoming even more essential inglobal health.

• Alan Hesketh (UK): The study of the use of plants and other genetic resources by eth-nic groups, especially indigenous communities, and the application of that knowledge todevelop new or improved health products.

• Peter Houghton (UK): The historical, biological, chemical and pharmacological studyof natural substances used by human societies and cultures for medicinal or medicinallyrelated purposes.

• Anna Jäger (Denmark): Ethnopharmacology is a strange word. Investigation of pharma-cological effects and mode of action of traditional practises and medicines, and the activecompounds therein.

• Graham Jones (Australia): Ethnopharmacology constituting a respectful marriagebetween modern science and ancient wisdom with much to be gained in both directions.

• Andreas Lardos (Switzerland): Ethnopharmacology is a multidisciplinary field of researchfocusing on the investigation of plants and other natural products used as medicine inpresent-day as well as historical local or indigenous knowledge systems.

• Marco Leonti (Italy): Ethnopharmacology may be seen as a transdisciplinary medicalself-reflection trying to find a consensus between the emic and the etic perspective.

• Natchagorn Lumlerdkij (UK/Thailand): Ethnopharmacology is a research area thatexplores the pharmacological activity of herbal medicine with appreciation of indigenouswisdom.

• Dan Moerman (USA): Ethnopharmacology is the study of the way people use plants,informing us about the varying ways people create meaning about these living objects.

• Pulok Mukherjee (India): Ethnopharmacology is a multi-disciplinary study dealing withthe observations and experimental investigations of the biological activities of plants andanimals used in traditional medicines of past and present culture. [See also in his chapter:The concept and methods of ethnopharmacological research incorporate elements from

PREFACE xxv

diverse medical practices like Ayurveda and Siddha and scientific disciplines like ethnob-otany/ethnomedicine, anthropology, chemistry, pharmacognosy, pharmacology, biochem-istry, molecular biology, pharmacy etc.]

• José Prieto (UK): Ethnopharmacology: the study of pharmacological interventions in tra-ditional medicinal systems. These interventions consist of the administration of naturaldrugs from any origin (animal, plant, mineral, fungal and/or microbial) usually orally orexternally. However, associated traditional non-pharmacological interventions (such asacupuncture, chiropractic, massage, music and sounds, colours, etc.), and religious or magi-cal ritualsmay greatly contribute to the putative effect of the pharmacological intervention.

• Diego Rivera (Spain): Ethnopharmacology is – despite its appearances – not ethnic phar-macology.

• Diego Rivera (Spain): Ethnopharmacology is the people’s pharmacology, which usuallyblurs with increasing distance from the natural sources of medicinal resources and theincrease in the complexity of systems of manufacture and distribution of medicines.

• Diego Rivera (Spain): Ethnopharmacology is part of the spontaneous response of a givenindividual, family or culture against different diseases and illnesses through the use of nat-ural resources around them, which scientists tend to document, analyse and interpret.

• Diego Rivera (Spain):Ethnopharmacology is related to traditional knowledge and is oftenpart of the TKS, but in itself is a complex of external influences, new practices and othersthat become extinct, with mainline traditions, all in reference to medicinal resources ormateria medica.

• Nicholas Sadgrove and Graham Jones (Australia): Ethnopharmacology seeks to employthe modern scientific method to translate traditional therapeutic empiricism into a biolog-ical story that at first captivates us, then encourages us to experiment with its limitations,then finally persuades us to incorporate it into our accepted pharmacopoeia. The first peo-ple to tell this ‘biological story’ would no doubt be pleased that it has continued to be toldfor much longer and to a wider audience.

• José Ramón Vallejo Villalobos (Spain): Ethnopharmacology is the interdisciplinaryscience that focuses on the study of traditional uses of plants, animals and minerals asdrugs in order to validate their physiological activity and discern the meaning of theircultural uses.

• Alonso Verde, Diego Rivera, José Ramón Vallejo, José Fajardo, Concepción Obón andArturo Valdés (Spain): Ethnopharmacology is an interdisciplinary science focusing on thestudy of chemical composition, therapeutic activity, about natural drugs used by the localpeople and their cultural interpretations.

• LizWilliamson (UK):Ethnopharmacology is the study of naturalmedicines used by peopleof different cultures, and how those medicines may work.

We leave it to the reader to interpret these ideas and to draw conclusions from them. How-ever, the field’s inter- (or trans-) disciplinarity and its unique position at the interface of socio-cultural and natural sciences are two commonalities. This book shows both these unifyingtendencies but also the great variety of ideas that contribute to modern ethnopharmacology.The book is organized into three main sections. It begins with an overview of the sub-

ject, including a brief history, ethnopharmacological methods, the role of intellectual propertyprotection, key analytical approaches, the role of ethnopharmacology in primary/secondaryeducation, and links to biodiversity and ecological research. This part provides the conceptualand methodological basis for the book. Part two looks at ethnopharmacological contributionsto developing modern medicines across a range of conditions, including CNS disorders, cancer,bone and joint health, and parasitic diseases. The final part is devoted to regional perspectives

xxvi PREFACE

covering all continents, providing a state-of-the-art assessment of the status of ethnopharmaco-logical research globally, highlighting the diversity of perspectives on the five continents.We as editors really want to andmust thank all contributors. Contrary to other edited books,

here the editors gave a very clear brief on what the main theme of each chapter should be andwe are very grateful to the contributors for providing their perspectives on these topics.The book also is part of theULLAPharmacy Series (www.ullapharmsci.org), which provides

state-of-the-art, critical insights into a wide range of pharmaceutically relevant topics. ULLAis a European Consortium founded more than 20 years ago and includes nine leading schoolsof pharmacy at European universities in eight countries.

http://www.ullapharmsci.org

Abbreviations

1D one-dimensional2D two-dimensionalAchE acetylcholine esteraseAD Alzheimer’s diseaseADME absorption, distribution, metabolism, and excretion (of a medicine)AGI α-glucosidase inhibitorAHL N-Acyl homoserine lactoneAI autoinducerAIDS acquired immune deficiency syndromeAIP autoinducing peptideANVISA Agência Nacional de Vigilância Sanitária (Brazil)ART artesunateART anti-retroviral therapyATCC American Type Culture CollectionATM African traditional medicineAYUSH Ayurveda, yoga & naturopathy, Unani, Siddha and homoeopathyBFAD Bureau of Food and DrugsBP blood pressureCA chlorogenic acidCaCC calcium-activated chloride channelCAM Complementary and Alternative MedicineCBD Convention on Biological DiversityCET cephalotaxineCEMAT Mesoamerican Centre of Appropriate Technology Studies

(Guatemala)CFDA China Food and Drug AdministrationCFTR cystic fibrosis transmembrane conductance regulatorCHM Chinese herbal medicineCHMP Chinese herbal medicinal productCITES Convention on International Trade in Endangered Species of Wild

Flora and FaunaCM Chinese medicineCNS central nervous systemCOPD chronic obstructive pulmonary disease

xxviii ABBREVIATIONS

COX cyclooxygenaseCOX-2 cyclooxygenase-2CPD continuing professional developmentCSA constitutive salicylic acidCSIR Council for Scientific and Industrial ResearchCT computed tomographyCVD cardiovascular diseaseD-IBS diarrhoea-prominent irritable bowel syndromeDMSO DimethylsulfoxideDOH Department of Health of the PhilippinesDPD 4,5-dihydroxy-2,3-pentadioneECOWAS Economic Community of West African StatesEFSA European Food Safety AuthorityEGFR epidermal growth factor receptorEMA European Medicines AgencyESCOP European Scientific Cooperative on PhytotherapyFDA Food and Drug AdministrationFFA free fatty acidFRLHT Foundation for the Revitalization of Local Health TraditionsGACP good agricultural and collection practiceGBM glioblastoma multiformeGC gas chromatographyGIP glucose-dependent insulinotropic polypeptideGLP good laboratory practiceGMP good manufacturing practiceHDL high-density lipoproteinHER human epidermal growth factor receptorHHT homoharringtonineHIV human immunodeficiency virusHMP herbal medicinal productHMPC Committee for Herbal Medicinal ProductsHPLC high-performance liquid chromatographyHPLC-MS-SPE-NMR high-performance liquid chromatography-mass

spectrometry-solid-phase extraction-nuclear magnetic resonanceHRMS high resolution mass spectrometryHSV herpes simplex virusHTS high throughput screeningICBG International Cooperative Biodiversity GroupICH International Conference on Harmonization (of Technical

Requirements for Registration of Pharmaceuticals forHuman Use)

IDF International Diabetes FederationIgE immunoglobulin EIGF insulin growth factorIGT impaired glucose toleranceIKK IkB kinaseIL-1β interleukin-1βIMSS Instituto Mexicano de Seguro Social

ABBREVIATIONS xxix

iNOS inducible nitric oxide synthaseIP intellectual propertyISCED International Standard Classification of EducationISM&H Department of Indian Systems of Medicines and HomeopathyIUCN International Union for the Conservancy of NatureLC-MS liquid chromatography-mass spectrometryLOX-5 lipoxygenase-5MAP medicinal and aromatic plantMCP monocyte chemo-attractant proteinMDR multidrug resistanceMHRA Medicines and Healthcare Products Regulatory AgencyMIC minimal inhibitory concentrationMIP migration inhibitory proteinMRSA methicillin-resistant Staphylococcus aureusMS mass spectrometryMS metabolic syndromeMTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromideMVDA multivariate data analysisNDM-1 New Delhi metallo-β-lactamase-1NF-kB kappa-light-chain-enhancer B cellsNGO non-governmental organisationNIH National Institutes of HealthNIHM National Institutes of Herbal MedicineNK natural killerNMDA N-methyl-D-aspartateNMPB National Medicinal Plant BoardNMR nuclear magnetic resonanceNSAID non-steroidal anti-inflammatory drugNSCLC non-small cell lung carcinomaOTC over-the-counterPBP penicillin-binding proteinPCA principal component analysisPCR polymerase chain reactionPG prostaglandinPGE2 prostaglandin E2PITAHC traditional and alternative health carePKC protein kinase CPp1 first Philippine pharmacopoeiaQS quorum sensingQSEC quality, safe, efficacious and consistentR&D research and developmentRCT randomized controlled trialRMA resistance-modifying agentRTO retrospective treatment-outcomeSAHG South African Hoodia GrowersSCLC small cell lung carcinomaSERM selective oestrogen receptor modulatorSI selectivity index

xxx ABBREVIATIONS

SPE solid-phase extractionSSRI selective serotonin reuptake inhibitorsSTI sexually transmitted infectionT2D type 2 diabetesTB tuberculosisTCM traditional Chinese medicineTHMP traditional herbal medicinal productsTHR Traditional Herbal Regulation (of the European Union)TK traditional knowledgeTKDL traditional knowledge digital libraryTLR toll-like receptorTM traditional medicineTNF tumour necrosis factorTNFα tumour necrosis factor αTOCSY total correlation spectroscopyTRAMIL Traditional Medicine in the IslandsTRIPS trade-related aspects of intellectual property rightsTRPV1 vanilloid type 1 proteinTTM Thai traditional medicineTTSS type III secretion systemUNAM Universidad Nacional Autónoma de MéxicoUTI urinary tract infectionVEGF vascular endothelial growth factorWHO World Health OrganizationWIMSA Working Group of Indigenous Minorities in Southern AfricaWIPO World Intellectual Property OrganizationWTO World Trade Organization

Ethnopharmacology: TheFundamental Challenges

1Ethnopharmacology: A ShortHistory of a MultidisciplinaryField of ResearchMichael HeinrichCentre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy, University of London, London

1.1 IntroductionEthnopharmacology is an interdisciplinary field of research and as such it is defined by itconcepts (its frame of reference) derived from a range of disciplines and the methodologiesused. There can be no doubt that it is a fast-developing and thriving discipline. Confusingly,a large number of terms are used to describe research, which often uses relatively similarmethods and concepts. However, each of these is distinguished by being placed in a certaintradition of research. Such terms include

• pharmacognosy, first used in 1811 by Johann Adam Schmidt and used very widely todescribe the field of medicinal plant and natural product research

• phytotherapy research, derived from the French concept ‘phytotherapie’ introduced byHenri Leclerq in 1913 and used in various editions of his Précis de Phytothérapie

• phytomedicine, a term introduced much more recently and less well established interna-tionally.

In addition there is a wide range of more descriptive terms, including medicinal plantresearch or natural product research, and there exists a considerable overlap between theseand related terms. Phytotherapy research, for example, focuses on plant-based forms oftreatment within a science-based medical practice and thus distinguishes what has also beencalled ‘rational phytotherapy’ from other more traditional approaches like medical herbalism,

Ethnopharmacology, First Edition. Edited by Michael Heinrich and Anna K. Jäger.© 2015 John Wiley & Sons, Ltd. Published 2015 by John Wiley & Sons, Ltd.

4 CH1 ETHNOPHARMACOLOGY: A SHORT HISTORY OF A MULTIDISCIPLINARY FIELD OF RESEARCH

which relies on an empirical appreciation of ‘medicinal herbs’. Phytotherapy research is bestdescribed as a science embedded in the medical (and pharmaceutical) field (Heinrich, 2013).Contrary to this, at least in a part of the scholarly output, ethnopharmacology incorporatessociocultural concepts and methods.In the broadest sense ethnopharmacology is based on approaches from the sociocultural

sciences and the natural sciences/medicine. As such any historical overview will have to bebased on the development of this scientific approach. However, written accounts of usingherbal medicines and of the wider medical practice are of course available frommany cultures(cf. Leonti, 2011). Importantly, this definition excludes the daily medical practice and the prac-titioners’ observations associated with it. Such descriptions of medicines, as well as reflectionsabout their usefulness, are very much part of traditions like Ayurveda, Kampo, Unnani, Ara-bic medicine, TCM, Aztec medicine, European herbalism or any other regionally or culturallydefined medical practice. Clearly many of these original descriptions do not survive, and as aconsequence today we often only have a few pieces of what was a much larger puzzle.Compared to medical practice (be it in the context of its usage within biomedicine or one of

the regional traditions as exemplified above), in ethnopharmacology there is an added focuson an empirical scientific (e.g. pharmacological, phytochemical, toxicological) evaluation ofsuch therapeutic uses. In very general terms any form of empirical use and ‘medical testing’of a plant for novel uses may be considered an ethnopharmacological approach. The physi-cianWilliamWithering (1741–1799) systematically explored themedical properties of foxglove(Digitalis purpurea L., Scrophulariaceae), which reportedly was used by an English housewifeto treat dropsy. He used the orally transmitted knowledge of British herbalism to developa medicine used by medical doctors. Prior to such studies, herbalism was more of a clinicalpractice interested in the patient’s welfare and less of a systematic study of the virtues andchemical properties of medicinal plants.Juerg Gertsch (2009) provided a short and concise definition: ethnopharmacology uses an

approach where ‘anecdotal efficacy of medicinal plants is put to test in the laboratory. Theethnopharmacologist tries to understand the pharmacological basis of culturally importantplants.’ Similarly, Daniel Moerman (University of Michigan, Dearborn) argued: ‘Essentiallyethnopharmacology is the examination of non-Western (not mine) medicinal plant use interms of Western (my) plant use.’ (Moerman, pers. comm.). Both definitions imply thatethnopharmacology has been a clearly defined field of research certainly since the quest ofthe ‘unknown other’ through Europeans and their descendants started with the explorationsof missionaries, conquerors and explorers. Particularly in the 19th century, many researcherswere involved in colonial explorations. This period is considered by Gertsch (2009) to bethe golden age of ethnopharmacology. Without doubt these travellers in the broadest sensetried to grasp the essence of what ‘other’ people use and how it can be transformed into auseful commodity.Ethnopharmacology investigates the pharmacological and toxicological activities of any

preparation used by humans that has – in the very broadest sense – some beneficial or toxicor other direct pharmacological effects. This field of research is therefore not an exclusivelydescriptive field of research (i.e. describing local or traditional uses or medical practices), butabout the combined anthropological (in a broad sense) and pharmacological–toxicologicalstudy of these preparations. Today, studies describing the use of medicinal and other usefulplants are included within ethnopharmacological research, but these are generally conductedwith the goal that they lead to an experimental study of some of these botanical drugs(cf. Heinrich et al., 2009). At the same time ethnopharmacology is not focused on thedescription of medical effects in the content of a treatment (or medical case histories), but

1.1 INTRODUCTION 5

here again incorporates bioscientific research. The definition used here is therefore somewhatmore focused and highlights the integration of experimental research on the effects of a localor traditional medicine with sociocultural approaches.A classic example of ethnopharmacological research that has led to new medicines is the

‘discovery’ of curare. The study of the botanical origin of the arrow poison curare, its physio-logical (as well as toxic) effects and the compound responsible for these provides a fascinatingexample of an early ethnopharmacological approach. Curare was used by ‘certain wild tribes inSouth America for poisoning their arrows’ (vonHumboldt, 1997). Many other explorers docu-mented this usage and the poison fascinated both researchers and thewider public. Particularlywell known are the detailed descriptions of the process used by Alexander von Humboldt(1769–1859) in 1800 to prepare poisoned arrows in Venezuela. There, von Humboldt met agroup of indigenous people who were celebrating their return from an expedition to obtainthe raw material for making the poison. Von Humboldt describes the ‘chemical laboratory’used:

‘He [an old Indian] was the chemist of the community. With him we saw large cooking pots (Siedekessel)made out of clay, to be used for boiling the plant sap; plainer containers, which speed up the evaporationprocess because of their large surface; banana leaves, rolled to form a cone-shaped bag [and] used to filterthe liquid which may contain varying amounts of fibres. This hut transformed into a laboratory was verytidy and clean.’

(von Humboldt, 1997, p. 88)

And he too faced one of the classical problems of ethnopharmacology:

‘We are unable to make a botanical identification because this tree [which produces the raw materialfor the production of curare] only grows at quite some distance from Esmeralda and because [it] did nothave flowers and fruit. I hadmentioned this type ofmisfortune previously, that themost noteworthy plantscannot be examined by the traveler, while others whose chemical activities are not known [i.e. which arenot used locally] are found covered with thousands of flowers and fruit.’

In a later step Chondrodendron tomentosum Ruiz et Pavon was identified as being thebotanical source of tube curare (named because of the Graminaeous tubes used as storagecontainers). Other species of the Menispermaceae (Chondrodendron spp., Curarea spp. andAbuta spp.) and species of the Loganiaceae (Strychnos spp.) have also been used in theproduction of curares.However, this did not provide any understanding of the pharmacological effects of this

poison. The French physiologist Claude Bernard (1813–1878) is recognized as being the firstto have conducted such research. For example; he provides the following description of thepharmacological effects of curare in some detail: ‘If curare is applied into a living tissue viaan arrow or a poisoned instrument, it results in death more quickly if it gets into the bloodvessels more rapidly. Therefore death occurs more rapidly if one uses dissolved curare insteadof the dried toxin.’ (Bernard, 1966, p. 92 [orig. 1864]). ‘One of the facts noted by all those whoreported on curare is the lack of toxicity of the poison in the gastrointestinal tract. The Indi-ans indeed use curare as a poison and as a remedy for the stomach’ (Bernard, 1966, p. 93). Heshowed that the animals did not show any nervousness and any sign of pain. Instead, the mainsign of death induced by curare is muscular paralysis. If the blood flow in the hind leg of afrog is interrupted using a ligature, but without interrupting the innervation, and it is poisonedvia an injury of the hind leg, it retains its mobility and the animal does not die from curarepoisoning (Bernard, 1966, p. 115). These and subsequent studies allowed a detailed under-standing of the pharmacological effects of curare in causing respiratory paralysis. Later on the


main secondary metabolite responsible for this activity was isolated for the first time from C.tomentosum, and in 1947 the structure of the bisbenzylisoquinoline alkaloid d-tubocurarinewas established. Finally, tubocurarine’s structure was established unequivocally using nuclearmagnetic resonance (NMR) in the 1970s (Heinrich, 2001, 2010).This account describes a sequence of research activities, which in their totality clearly may

today be labelled ethnopharmacogical research. However, at the time it was simply one ofthe many explorations of the unknown followed by the pharmacological investigation of thebotanical drug and later on the identification of the active principles. In essence it was justnormal state-of-the-art pharmacological research using new ‘leads’. In other words it had nospecific claim to be an activity different from mainstream (or normal) pharmacology (in aThomas S. Kuhnian sense). In fact discoveries in the chemistry and pharmacology of naturalproducts are generally linked to species that are of major importance as a medicine or toxin(Heinrich et al., 2012). However ‘Phantastica’ (Holmstedt, 1967) and toxins certainly attractedthe attention of 19th century researchers (and many before and after them). Terms used todescribe this research in the 19th and early 20th century include ‘Pharmakoëthnologie’ used byTschirch (1910) in his classicHandbuch der Pharmakognosie and ‘pharmacoetnologia’. Otherterms used include ‘ethnobotany’ and ‘aboriginal botany’ (both conceptually much broaderterms dealing with useful plants in general). However, all these terms in essence focused onthe description of indigenous medicinal plant use and not so much on their pharmacologicalinvestigation.A paradigm shift in pharmacology, drug development and more broadly in the biosciences

and medicine resulted from the serendipitous discovery of the first antibiotics derived fromthe fungus Penicillum notatum by Alexander Fleming (1881–1955) in 1928 at St Mary’sHospital (London), which were soon afterwards identified as benzylpenicillin and introducedinto clinical practice by a team involving, most importantly, Howard Florey (1898–1968) andErnst B. Chain (1906–1979). These fungal metabolites changed forever the perception and useof plant-derived metabolites as medicines by both scientists and the lay public. Of similarimportance was the advent of synthetic chemistry in the field of pharmacy and its use in thedevelopment of new medicines (which started well before the discovery of the penicillins). In1891 Paul Ehrlich in Germany (1854–1915) for the first time used a synthetic compound asa chemotherapeutic agent – methylene blue in the treatment of mild forms of malaria. Bothdevelopments proved that there were diverse and newer avenues to discover new medicines(Heinrich et al., 2012) and revolutionized drug development during and after the SecondWorld War. At the same time there can be no doubt that this resulted in a decline in aninterest in the classical approaches as described above.None of the research activities discussed in the previous paragraphs were labelled

‘ethnopharmacology’. This term was – to the best of our knowledge – only formallyintroduced in 1967 by Efron et al., who used it in the title of a book on hallucinogens:Ethnopharmacological Search for Psychoactive Drugs (Efron et al., 1970; Holmstedt, 1967).This is much later than, for example, the term ‘ethnobotany’, which in 1896 was coinedby the American botanist William Harshberger describing the study of human plant use.Both ethnopharmacology and ethnobotany investigate the relationship between humans andplants in all its complexity. However, interestingly, in the early years of its usage the term‘ethnopharmacology’ was very much associated with the study of hallucinogenic plants usedby indigenous people throughout the world. Along a similar vein of argument, 19th-centuryresearch into phantastica and other hallucinogenic substances played a crucial role in develop-ing the field of psychopharmacology/neuropharmacology (cf. Holmstedt, 1967). BoHolmstedt(1919–2002), who had a keen interest in toxicology, neuropharmacology and neurotoxicology

1.1 INTRODUCTION 7

as well as in analytical aspects of medicinal plant research, has to be credited with being oneof the first to develop a perspective on what ethnopharmacology can contribute to science.However, his role and contribution has not been researched in detail from the perspective ofthe history of science.In the context of modern ethnopharmacology the focus has moved to understanding the

benefits and risks of commonly used local and traditional plants with the goal of contributing tobetter and safer uses of such resources (e.g. Heinrich, 2006; Heinrich et al., 2009). As in the 19thcentury it requires an integration of pharmacological (or other natural science) approacheswith research on local and traditional uses. After its initial use in the context of hallucinogenicplants the termwas only used occasionally until 1979, when the Journal of Ethnopharmacologywas founded by Laurent Rivier and Jan Bruhn. Here the scope was broadened to ‘a multi-disciplinary area of research concerned with the observation, description, and experimentalinvestigation of indigenous drugs and their biological activity’ (Rivier and Bruhn, 1979).Today, research which claims to use an ethnopharmacological approach is commonly

conducted in the fast-emerging economies of Asia (India, China, where it is often seenas specific research on traditional Chinese medicine (TCM), and South Korea), Americasouth of the Rio Grande (Brazil and Mexico) and Africa (South Africa). The classicalresearch-active countries of the West (USA, UK, Spain, France, Germany and Italy) alsohave some research-active groups (data based on an analysis of the source items documentedin Scopus). The overall research output has also skyrocketed, with a dramatic increase inthe number of papers published since the first paper was published in 1967. A detailedcontent analysis of what is published in the field is beyond the scope of this overview, butif one takes the more than 2000 source items that include the term ‘ethnopharmacology’ inthe keywords, abstract or title, the two therapeutic areas most commonly included are theanti-inflammatory and anti-cancer effects of locally and traditionally used plants, which areincluded in a third and a quarter of these studies, respectively. Gastrointestinal, respiratoryand dermatological conditions are addressed in about 10% each of these studies, with veteri-nary ethnopharmacology accounting for a similar share. All others are of lesser importanceand interestingly only about 5% of all studies incorporate central nervous system (CNS)activities (and even fewer studies include hallucinogenic effects (


In their analysis they identify key areas of relevance in the future, but most importantlythey see the need to build theoretical capacity in ethnopharmacology (Etkin and Elisabetsky,2005, p. 26). This is one foundation for developingmore context-driven and critical approachesin ethnopharmacology (Etkin and Elisabetsky, 2005). As this overview shows, the historicaldevelopment of the field was very much driven by interdisciplinary collaborations generallyled by natural scientists. A more detailed historical analysis will provide a basis to build up the‘theoretical capacity’ the Etkin and Elisabetsky call for.

AcknowledgementsThe history of the field has been an ongoing interest of mine and the ideas presented herehave developed over many years. Some were discussed in more detail previously (especiallyin Heinrich, 2014; Heinrich et al., 2012) and this work presents a new synthesis of theseconcepts. The history of ethnopharmacology has received relatively little attention and a moredetailed study of the developments since the mid-1960s would certainly be highly desirable. Iam grateful to all the colleagues who responded to my query about the field’s history, mostimportantly Lars Bohlin (Sweden), Jan G. Bruhn (Sweden), Elaine Elisabetsky (Brazil),Anna Jäger (Denmark), Marco Leonti (Italy), J. David Phillipson (UK), Laurent Rivier(Switzerland), Dan E. Moerman (Michigan, USA), Gunnar Samuelsson (Sweden) PeterA.G.M. de Smet (the Netherlands) and Caroline Weckerle (Switzerland).

ReferencesBennett, B.C. and Balick, M.J. (2014) Does the name really matter? The importance of botanical

nomenclature and plant taxonomy in biomedical research. Journal of Ethnopharmacology, 152,387–392.

Bernard, C. (1966) Physiologische Untersuchungen über einige amerikanische Gifte. Das Curare, inAusgewählte physiologische Schriften (eds C. Bernard and N. Mani), Huber Verlag. Bern. [Frenchoriginal. 1864], pp. 84–133.

Chan, K., Shaw, D., Simmonds, M.S.J., et al. (2012). Good practice in reviewing and publishing studies onherbal medicine, with special emphasis on traditional Chinese medicine and Chinese materia medica.Journal of Ethnopharmacology, 140, 469–475.

Cos, P., Vlietinck, A.J., Berghe, D.V. and Maes, L. (2006) Anti-infective potential of natural products:How to develop a stronger in vitro ‘proof-of-concept. Journal of Ethnopharmacology, 106, 290–302.

Efron, D., Holmstedt, B. and Kline, N.L. (1970) Ethnopharmacologic Search for Psychoactive Drugs,Government Printing Office, Public Health Service Publications No. 1645 (original 1967), Reprint,Washington, D.C.

Etkin, N.L. and Elisabetsky, E. (2005) Seeking a transdisciplinary and culturally germane science: Thefuture of ethnopharmacology. Journal of Ethnopharmacology, 100 (1–2), 23–26.

Gertsch, J. (2009) How scientific is the science in ethnopharmacology? Historical perspectives andepistemological problems. Journal of Ethnopharmacology, 122, 177–183.

Heinrich, M. (2001) Ethnobotanik und Ethnopharmazie, Eine Einführung, Stuttgart, WissenschaftlicheVerlagsgesellschaft.

Heinrich, M. (2006) La Etnofarmacología – ‘quo vadis? BLACPMA [Boletín Latinoamericana y delCaribe de plantas medicinales y aromáticas, ISSN 0717 7917], 5 (1), 7.

Heinrich, M. (2010) Ethnopharmacology and drug development, in Comprehensive Natural Products II,Chemistry and Biology, Vol. 3 (eds L. Mander and H.-W. Lui), Elsevier, Oxford, pp. 351–381.

Heinrich, M. (2013) Phytotherapy, in Encyclopedia Britannica, http://www.britannica.com/EBchecked/topic/1936369/phytotherapy.

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Heinrich, M. (2014) Ethnopharmacology – quo vadis? Challenges for the future. Revista Brasileira deFarmacognosia 24, 99–102.

Heinrich, M., Edwards, S., Moerman, D.E. and Leonti, M. (2009) Ethnopharmacological Field Studies:A Critical Assessment of their Conceptual Basis and Methods. Journal of Ethnopharmacology, 124,1–17.

Heinrich, M., Barnes, J., Gibbons, S. and Williamson, E.M. (2012) Fundamentals of Pharmacognosy andPhytotherapy, 2nd edn, Churchill Livingston (Elsevier), Edinburgh & London.

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Leonti, M. (2011) The future is written: impact of scripts on the cognition, selection, knowledge andtransmission of medicinal plant use and its implications for ethnobotany and ethnopharmacology.Journal of Ethnopharmacology, 134 (3), 542–555.

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makognosie), 1. Auflage, C.H. Tachnitz, Leipzig.Uzuner, H., Bauer, R., Fan, T.-P., et al. (2012) Traditional Chinese medicine research in the post-genomic

era: Good practice, priorities, challenges and opportunities. Journal of Ethnopharmacology, 140 (3),458–468.

Verspohl, E.J. (2002) Recommended testing in diabetes research. Planta Medica, 68 (7), 581–590.von Humboldt, A. (1997) Die Forschungsreise in den Tropen Amerikas (Hrsg. H. Beck), Wissenschaft-

liche Buchgesellschaft, Darmstadt.

2Medicinal Plant Research: AReflection on TranslationalTasksAnna K JägerDepartment of Drug Design and Pharmacology, Faculty of Health and Medicinal Sciences, University ofCopenhagen, Denmark

2.1 IntroductionAllopathic medicine is based on the underlying principle that drugs and treatments have beenobjectively and scientifically evaluated, whereas traditional medicine systems are based on a‘holistic’ approach integrating medicinal and psychological therapies. In traditional practice,the psychological, spiritual and social aspects play an important role, exploiting the power ofthemind of the patient. This holistic treatment can to some degreemake up for plantmedicinesnot being as effective as allopathic biomedicine.Traditional medicine, which is closely linked with peoples’ cultures, is therefore not going to

vanish if and when allopathic health care becomes available. A study from Kenya showed thatpatients chose to visit a health clinic for some diseases, but preferred a traditional healer inother cases (van der Geest, 1997). In South Africa, traditional healers are flourishing in urbanareas alongside allopathic health care (Mander et al., 1997), thus traditional healing practice isnot dying out ‘when the young flock to the city and forget their culture’, as has been predicted.Despite allopathic and traditional healing systems having a common goal in helping patients,

the two systems are fundamentally too divergent in their views for any meaningful integration.Healers might say that their ancestors guide them, that they know all there is to be known, butI believe there is still place for new knowledge that can be accepted by traditional healers.We as scientists cannot meddle with the non-scientific aspects of traditional medicine, our rolemust be to work on improving the medicinal aspect, the usage of medicinal plants.

Ethnopharmacology, First Edition. Edited by Michael Heinrich and Anna K. Jäger.© 2015 John Wiley & Sons, Ltd. Published 2015 by John Wiley & Sons, Ltd.

12 CH2 MEDICINAL PLANT RESEARCH: A REFLECTION ON TRANSLATIONAL TASKS

In recent years, ‘back-translation’ has become a buzz word in pharmacologicalresearch. However, the good old discipline of ethnopharmacology is and has always beenback-translation. Ethnopharmacology is centred around the patient, observing diagnosis,treatment and treatment outcomes, and then taking these observations back to the laboratoryto investigate the (plant-based) medicines involved. This might lead both to new drugsand to identifying new targets, but most importantly it develops an evidence base for suchpreparations.If the aim is not a new drug lead or, even better, a new target, but improvement of traditional

medicines, what then is our task? Whether we aim at a traditional commercial product or asituation where the healer or patient prepares the remedy, the initial preclinical proceduresare the same. A key assumption underlying this chapter and the other chapters in this book isthat we need evidence-based, safe traditional medicines and medical practice.

2.2 Translational research: preclinical researchTraditional medicine consists of plant, animal and mineral materials. As plant materialconstitutes the major part of traditional medicine, I refer only to plants in this text, but theprinciples are the same for animal-derived materials, and to a degree for minerals.Translational research spans over several disciplines connecting preclinical and clinical work.

In our field we first do back-translation from patient to the laboratory, then forward translationthrough preclinical work, including in vitro methods for elucidating mode of action, in vivostudies, ADME, toxicology and clinical studies, to finally get the medicine (or knowledge onthe medicine) to the patient.The very first step in the forward translation, and in a way the most crucial, is the test

material. The identity of thematerial has to be certain and to be documented. It is required thatthe species investigated are precisely defined using a fully taxonomically validated nomen-clature, which includes the current systematic binominal name and authority. It requiresbotanical expertise to ensure that a particular plant is determined to the right species and‘converted’ from an old name (synonym) to the current name (currently, the best practiceis to use www.theplantlist.org for checking botanical names and families). There oughtnot to be an issue with documentation, it should to be a normal part of good laboratorypractice (GLP), but sadly as a reviewer for many journals I recurrently find problems withthe botanical documentation in the form of vouchers. When authors are requested to providedocumentation, voucher numbers are then provided; I honestly sometime wonder if thesevouchers really exist. I would recommend that scientific journals request a photograph ofthe voucher submitted as supplementary material; Journal of Ethnopharmacology is nowrecommending this practice (Heinrich and Verpoorte, 2014).Where preclinical work on a synthetic compound may have issues with contaminants

from the manufacturing processes, in case of plant extracts we deal with a very complicated,mostly ill-defined matrix. The plant material used for traditional medicine will in most casesvary in concentration of active constituents from batch to batch due to the biological variationin the material. The variation is due to geographical factors, climatic variations and geneticfactors. Ideally, it would be good to make a broad sampling of material to compare the vari-ation before any preclinical work commences. By opting for a NMR-based technique, whichmeasures all constituents, it is possible to see patterns of similarity in cases where the activeconstituent(s) are unknown. With modern NMR-based multivariate analysis it is possible toascertain outliers, so a batch can be chosen that is representative of the general sampling. Theresults then have a better chance of being representative of the species under investigation.

http://www.theplantlist.org

2.3 TRANSLATIONAL RESEARCH: CLINICAL RESEARCH 13

While clinical trials and in vivo experiments are under strict regulation by authorities, the invitro area is not. This has resulted in a situation where many methods are applied. My studentsrecently wanted to compare some antibacterial results with published literature. This proveddifficult. The studies used different inoculum sizes, did not state the concentration of ethanolor dimethyl sulfoxide used to dissolve the extracts, used different numbers of replicates, useddifferent volumes of reactants, incubated for different times, determined inhibition in differentways, and, of course, different test bacteria were used. This highlights the problem we have inour field with a lack of standard methods. It should be possible to perform something as simpleas an antibacterial test in the same way in laboratories all over the world.If we look to a younger research field such as molecular biology, they have benefitted

enormously from having standard methods that everyone uses. Commercial companies havedeveloped kits for these methods, further ensuring comparable results. Such results can thenbe compiled in world-wide databases, for example GeneBank. Of course, contrary to genes,which are made up of the same few components in all living organisms, the variation in theplant matrix is so great that it would be difficult to apply standard methods for extraction – orwould it? Are we just too anarchistic or sloppy to make our extracts in the same way? If wereturn to in vitro testing, here we are beyond the differences in the plant matrix, we have a testsubstance and it is possible to test it by adhering to the same protocols all over the world. TheJournal of Ethnopharmacology has taken the lead with publishing a series of Setting Standardpapers. The series includes the topics of ethnopharmacological field studies (Heinrich et al.,2009), anti-infective agents (Cos et al., 2006), diagnostic procedures in experimental diabetesresearch (Matteucci and Giampietro, 2008) and animal models in diabetes (Froede andMedeiros, 2008). This covers only a fraction of the methods in this wide field, so herewith is acall to anyone who can contribute an adequate setting standard paper to write it.Toxicology is the Achilles’ heel of ethnopharmacology. We all want to promote efficient

and safe traditional medicines, but toxicological aspects of local and traditional medicinalplants are sorely under-investigated. It is relatively clear what the task is, theWHO (2000) hasguidelines for toxicology testing of traditional medicine and many regulatory authorities haveprecise descriptions of what is required for registering herbal products – the same level shouldbe what we want for traditional medicines. Most regulatory authorities require tests for acuteand chronic toxicity, mutagenicity and teratogenicity. Of equal importance is the purity of theherbal substances used medicinally. Assessment of potential interactions of herbal medicineswith other medicines is also an important field.A recent book reviews methods in toxicology testing of medicinal plants and gives an

overview of the toxicology of African medicinal plants (Kuerte, 2014).Toxicological testing is costly, tenacious and does not make a high-impact journal article.

Most of the laboratories undertaking preclinical work on medicinal plants are not geared toperform toxicology testing and academic research institutions do not have the funds to out-source toxicology testing to laboratories running on a commercial basis. I have a dream thatone day a centre will open that will perform toxicology testing on all themajormedicinal plantsfrom all over the world.

2.3 Translational research: clinical researchWhen reading articles in journals in the medicinal plant field, one often reads in the conclusionclaims along the lines of ‘these data support the use of this plant in traditional medicine’. Sadly,these claims are often very broad and are, in fact, not substantiated by the data presented. Thedata might lend support for a pharmacological use for the plant, but it is mostly only a very

14 CH2 MEDICINAL PLANT RESEARCH: A REFLECTION ON TRANSLATIONAL TASKS

small part of the picture and it would not be possible to make any recommendations for use inpatients.Maybe it would be a good exercise to ask yourself, if you put money into a clinical trial, what

preclinical evidence would you want to see as a minimum? Assessing such data, one learns alltoo often that the research in general is scattered and not sufficient. There needs to be muchmore focused research to provide the necessary preclinical evidence for medicinal plants.When a good case has been built on preclinical data and a safe toxicology profile, the next

stumbling block is moving to a clinical trial. Most of the preclinical work on medicinal plantsis today done in academic laboratories by non-medical staff. The laboratory-based researchersinvolved have little contact with clinical trial scientists, the link in the translational chain ismissing. It is imperative that scientists designing and running clinical trials have the propertraining. Clinical trials on traditionalmedicinemustmeet the scientific standards set for clinicaltrials of allopathic drugs. In order to ascertain that a clinical trial has an impact, one mustensure that the research is of a good quality. Far too often meta-analyses of clinical trials onherbal products come to the conclusion that the clinical trials are not of sufficient quality and donot provide new insights. This is tainting herbal medicine.We need to get better at bridging thisstep from preclinical work to clinical trial. We have a problem in persuading allopathic-trainedmedical scientists experienced in clinical trials to conduct trials on traditional medicines. Partof the solution is to raise the quality of the preclinical work. It is encouraging to see that aroundthe world several programmes have been initiated to train clinical scientists to specifically runtrials on traditional medicine (Wilcox et al., 2012).

For clinical trials, the production of the trial medicine under conditions acceptable to theregulatory medicines agency, which must grant permission to perform the clinical trial, mightbe another problem. In some countries it might be difficult to find places that are geared tohandle extractions of larger quantities of plant materials under full good manufacturing prac-tice (GMP). It is essential that all botanical material used for the trial medicine is authenticatedand that chemical profiles for the final product are available.

2.4 Reaching the patientThe final part of the translational process is to get themedicine – nowwith evidence for efficacyand safety – to the patients who need it. If a commercial traditional product is being pro-duced, the marketing rests with the producer, who can be expected to be effective as financialinterests are involved. The situation is different where the preclinical and clinical work hasbeen done with no aim of producing a commercial product, maybe by an academic institu-tion. Indigenous knowledge, patenting and licensing of patents are addressed byAlanHesketh(see Chapter 9). How will the knowledge on medicinal plants reach healers and patients? Incountries with functional traditional healers’ associations it might be possible to disseminatescientific results via their networks. Otherwise, we stand with an immense problem, whichwe as a discipline have not been able to solve in the past (Jäger, 2005). Maybe some clevermobile phone/internet-based app that distributes information on how to prepare safe andeffective herbal medicines could be a way forward?

2.5 A ‘developed’ traditional medicine systemAlthough there is not an even distribution of medicinal plants among the geographical areasof our planet, there is a striking difference in the number of medicinal plants that have

2.5 A ‘DEVELOPED’ TRADITIONAL MEDICINE SYSTEM 15

Central America 50

South America 64

N America 121 Europe 336 Asia 434

Africa 97

Australia 11

Figure 2.1 Estimate of continental origin of commercialized medicinal plants. (Source: Adapted from van Wykand Wink 2004.)

been developed commercially from

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