RSC Drug Discovery Edited by James D Adams and Eric J Lien Traditional Chinese Medicine Scientifi c Basis for Its Use ST cr ia ed n i tt ifiio cn Ba al C s ih s fin oe rs Ie t sM Ue sd ei c i n e A d a m s & L ie n Traditional Chinese Medicine Scientific Basis for Its Use RSC Drug Discovery Series Editor-in-Chief Professor David Thurston, Kings College, London, UK Series Editors: Dr David Fox, Vulpine Science ad Learning, UK Professor Salvatore Guccione, University of Catania, Italy Professor Ana Martinez, Instituto de Quimica Medica-CSIC, Spain Professor David Rotella, Northeastern University, USA Advisor to the Board: Professor Robin Ganellin, University College London, UK Titles in the Series: 1: Metabolism, Pharmacokinetics and Toxicity of Functional Groups 2: Emerging Drugs and Targets for Alzheimer’s Disease; Volume 1 3: Emerging Drugs and Targets for Alzheimer’s Disease; Volume 2 4: Accounts in Drug Discovery 5: New Frontiers in Chemical Biology 6: Animal Models for Neurodegenerative Disease 7: Neurodegeneration 8: G Protein-Coupled Receptors 9: Pharmaceutical Process Development 10: Extracellular and Intracellular Signaling 11: New Synthetic Technologies in Medicinal Chemistry 12: New Horizons in Predictive Toxicology 13: Drug Design Strategies: Quantitative Approaches 14: Neglected Diseases and Drug Discovery 15: Biomedical Imaging 16: Pharmaceutical Salts and Cocrystals 17: Polyamine Drug Discovery 18: Proteinases as Drug Targets 19: Kinase Drug Discovery 20: Drug Design Strategies: Computational Techniques and Applications 21: Designing Multi-Target Drugs 22: Nanostructured Biomaterials for Overcoming Biological Barriers 23: Physico-Chemical and Computational Approaches to Drug Discovery 24: Biomarkers for Traumatic Brain Injury 25: Drug Discovery from Natural Products 26: Anti-Inflammatory Drug Discovery 27: New Therapeutic Strategies for Type 2 Diabetes: Small Molecules 28: Drug Discovery for Psychiatric Disorders 29: Organic Chemistry of Drug Degradation 30: Computational Approaches to Nuclear Receptors 31: Traditional Chinese Medicine How to obtain future titles on publication: A standing order plan is available for this series. A standing order will bring delivery of each new volume immediately on publication. For further information please contact: BookSalesDepartment,RoyalSocietyofChemistry,ThomasGrahamHouse, Science Park, Milton Road, Cambridge, CB4 0WF, UK Telephone: +44 (0)1223 420066, Fax: +44 (0)1223 420247, Email: [email protected] Visit our website at www.rsc.org/books Traditional Chinese Medicine ScientificBasisforItsUse Edited by James David Adams Jr School ofPharmacy,UniversityofSouthern California,Los Angeles, CA, USA Email: [email protected] Eric J. Lien School ofPharmacy,UniversityofSouthern California,Los Angeles, CA, USA Email: [email protected] RSC Drug Discovery Series No. 31 ISBN: 978-1-84973-661-9 ISSN: 2041-3203 A catalogue record for this book is available from the British Library # The Royal Society of Chemistry 2013 All rights reserved Apartfromfairdealingforthepurposesofresearchfornon-commercialpurposes or for private study, criticism or review, as permitted under the Copyright, DesignsandPatentsAct1988andtheCopyrightandRelatedRightsRegulations 2003,thispublicationmaynotbereproduced,storedortransmitted,inanyform orbyanymeans,withoutthepriorpermissioninwritingofTheRoyalSocietyof Chemistry or the copyright owner, or in the case of reproduction in accordance withthetermsoflicencesissuedbytheCopyrightLicensingAgencyintheUK,or in accordance with the terms of the licences issued by the appropriate Reproduction Rights Organization outside the UK. Enquiries concerning reproduction outside the terms stated here should be sent to The Royal Society of Chemistry at the address printed on this page. The RSC is not responsible for individual opinions expressed in this work. Published by The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 0WF, UK Registered Charity Number 207890 For further information see our web site at www.rsc.org PrintedintheUnitedKingdombyHenryLingLimited,Dorchester,DT11HD,UK Preface ‘‘I believe in the goodness of the American and Chinese people who remain good friends.’’ Dr Hua Chuen Mei from ‘‘Dr Hua Chuen Mei – May 30, 1925’’ available at www.abeduspress.com. LindaMeiAdams,mywife,isthegrand-daughterofDrHuaChuenMei,who was an American lawyer in Shanghai who defended several Chinese students accusedofriotingintheInternationalSettlementattheLouzaPoliceStationon 30May1925.HewonthecaseinJune1925,whichledtotheMay30Movement in China. My wife and her mother, Eva Lum Mei, taught me to speak Cantonese. My wife’s grand-mother, Polly Lum, used Traditional Chinese Medicine even though her son, son-in-law and grand-son were all Western- trainedMDs.IamgratefultotheMeiandLumfamiliesforhelpingmelearnthe utilityofTraditionalChineseMedicine,evenwhenAmericanMedicinemaynot recognize the utility. I was able to learn the philosophy for using Traditional Chinese Medicine, which differs greatly from the medicine I learned as a Graduate Student of Pharmacology at the University of California San Francisco.Thisphilosophydependsonlivinginbalanceinordertobehealthy. Iwasalsotaughttheimportanceofspiritualityinhealth,sincehealthrequiresa healthybody,mindandspirit.Mypoembelowis‘‘bekindtoyourself,bekindto others, allow God to love you.’’ My Chinese name, below, is Ha Cheen Sing, SummerThousand Honest,andwasgiventomebymymother-in-law. 跟自己做慈善 跟第二的人做慈善 讓上帝愛你 夏千诚 RSCDrugDiscoverySeriesNo.31 TraditionalChineseMedicine:ScientificBasisforItsUse EditedbyJamesDavidAdams,Jr.andEricJ.Lien #TheRoyalSocietyofChemistry2013 PublishedbytheRoyalSocietyofChemistry,www.rsc.org v vi Preface I am grateful to Professor Eric Lien for encouraging me to think about the Science involved in Traditional Chinese Medicine. This has been a great challenge for me and resulted in this book. I am grateful to all the authors of the chapters who have applied their great expertise in this book. James David Adams Jr, PhD Associate Professor of Pharmacology and Pharmaceutical Sciences School of Pharmacy, University of Southern California Los Angeles, CA, USA Knowledge and Health Knowledge and learning have no limits. Teaching and learning reinforce each other. Education should not discriminate against anyone. Doing good deeds brings the most happiness. Newknowledgecanpromotegoodhealth,enhanceproductivityandcontribute tolongevity. Sustain vitality and youthfulness as long as possible. Good memories will last forever. Eric J. Lien, PhD Professor Emeritus School of Pharmacy, University of Southern California Los Angeles, CA, USA Contents Chapter 1 The Traditional and Scientific Bases for Traditional Chinese Medicine: Communication Between Traditional Practitioners, Physicians and Scientists 1 James D. Adams Jr and Eric J. Lien 1.1 Introduction 1 1.2 The Basis of Traditional Chinese Medicine 2 1.3 Disease Causation 4 1.4 Disease Prevention 6 1.5 TheTraditionalApproachtotheTreatmentofDisease 7 1.6 Randomized, Placebo-Controlled Clinical Trials 7 1.7 Therapy Must Allow the Body to Heal Itself 8 1.8 Conclusion 9 References 10 Chapter 2 Structure–Activity Relationship Analysis of Plant-Derived Compounds 11 Eric J. Lien, Linda L. Lien and James D. Adams 2.1 Introduction 11 2.2 Structure–Activity Relationship Analysis 12 2.2.1 FromNaturalSourcestoSyntheticCompounds 12 2.2.2 From Estradiol, Phytoestrogens to Synthetic Diethylstilbestrol 13 2.3 Medicinal Diet (Yao San) 14 2.4 Immunostimulating (Fu-zhen) Herbs 15 References 16 RSCDrugDiscoverySeriesNo.31 TraditionalChineseMedicine:ScientificBasisforItsUse EditedbyJamesDavidAdams,Jr.andEricJ.Lien #TheRoyalSocietyofChemistry2013 PublishedbytheRoyalSocietyofChemistry,www.rsc.org vii viii Contents Chapter 3 Huang Di Nei Jing and the Treatment of Low Back Pain 17 Minchen Wang (Vince) 3.1 Significance of Low Back Pain (LBP) 17 3.1.1 Prevalence of LBP 17 3.1.2 Human Cost 17 3.1.3 Medical Cost and Societal Cost 18 3.2 Scope of the Problem – What Is Involved in LBP? 18 3.2.1 Diversity of Causes and Diagnosis 18 3.2.2 Practical Considerations of LBP 18 3.3 Introduction to Huang Di Nei Jing 19 3.3.1 Overview 19 3.3.2 Historical Perspectives 20 3.3.3 The Significance of the Nei Jing 20 3.4 Treatment of LBP According to the Nei Jing 25 3.4.1 Overview of Pain in the Nei Jing 25 3.4.2 Pain and Qi Stagnation in the Nei Jing 25 3.4.3 Key Features of the Nei Jing’s LBP Treatment 27 3.5 Modern Day LBP Treatment 28 3.5.1 Features of Modern Acupuncture for LBP Treatment 29 3.5.2 Summary of LBP Treatment Comparisons 30 3.6 Scientific Basis of LBP Treatment 31 3.6.1 Strategies for LBP Treatment 31 3.6.2 The Nature of the Pain 31 3.6.3 Summary of Scientific Principles for LBP Treatment 41 3.7 A Rational Approach to LBP Treatment Based on the Nei Jing 41 3.7.1 Mapping the Low Back for Point Selection 42 3.7.2 Treatment Guide for LBP 43 3.8 Conclusion 45 References 46 Chapter 4 Understanding Ch’i: The Life-Force Energy that Determines Vitality, Health and Wellbeing 48 Marcia R. Babcock 4.1 TheOriginoftheUniverse:theCosmologyofCh’iand Its Manifest Forms as Yin and Yang 48 4.2 Ch’i as Life Force Is Described in Many Cultures 50 4.3 Perceiving and Measuring Ch’i 50 4.4 Historical Measurement of Vital Energy Using Scientific Methods 51 Contents ix 4.5 Modern Western Doctors Interested in the Energy Field Surrounding Human Beings 51 4.6 Comparison of TCM and Ayurveda 52 4.7 Cultivation of Ch’i: Improving the Quality and Strength of Ch’i Flows 52 4.8 Energy Healing Practices Across the World 53 4.9 Chinese Practices to Balance and Facilitate Ch’i Flow 53 4.9.1 Traditional Chinese Medicine 53 4.9.2 What Can Happen to the Ch’i? 54 4.9.3 TCM: Acupuncture and Moxibustion 54 4.9.4 TCM: Herbal Medicine 54 4.9.5 TCM: Massage (Tui Na) 55 4.10 Movement/Exercise 55 4.10.1 T’ai Chi Ch’uan 55 4.10.2 Pa Kua Chang 56 4.10.3 Hsing I 56 4.11 Ch’i Kung 57 4.12 Geomancy 57 4.12.1 Geomancy: The application of ch’i to divination 57 4.12.2 Geomancy: Feng Shui 58 References 58 Chapter 5 When Modern Computational Systems Biology Meets Traditional Chinese Medicine 61 Calvin Yu-Chian Chen 5.1 Introduction 61 5.2 Modernizing Traditional Chinese Medicine for a Global Stage 62 5.3 TCM in Drug Discovery: Application from the Molecular Level 63 5.4 Futuristic Drug Discovery: the Top-Down and Bottom-Up Systematic View 63 5.5 Unleashing the Potential of TCM Through Systems Biology 66 5.6 An Example of a Systems Approach to TCM Drug Development 70 5.7 Integration of TCM with Systems Biology: A Long Way to Go 73 5.7.1 Science Should Be Open Access 73 5.7.2 Pharmacological Data Have Limited Applicability in Investigating Novel Leads 75 5.7.3 Bigger Is Not Better in Terms of TCM Drug Compound Screening 75