Systems Biology for Traditional Chinese Medicine

The application of systems biology methods to TraditionalChinese Medicine

Emphasizing the harmony of the human body with the environment,Traditional Chinese Medicine (TCM) has evolved over thousands ofyears. It is a systemic theory derived from clinical experience,the philosophy of holism and systematology, and the belief that manis an integral part of nature.

Systems Biology for Traditional Chinese Medicinedescribes how the latest methods in systems biology can be appliedto TCM, providing a comprehensive resource for the modernizationand advancement of TCM as well as general drug discovery efforts.It is the first comprehensive work to propose a system–to–systemresearch methodology to study the interaction between TCM and thehuman body and its applications in drug research anddevelopment.

Using three popular traditional Chinesemedicines Shuanglongfang, Qingkailing, andLiushenwan as examples, the authors set forth case examplesdemonstrating how to find material groups, perform efficacyscreenings, and conduct safety evaluations of TCM. The bookalso:

Describes the mechanisms of TCM at the molecular and systemslevels using chemomics, genomics, proteomics, metabolomics, andbioinformatics Places modern scientific technologies within the context ofTCM, helping drug researchers improve experimental designs andstrategies Illustrates how a systems biology approach is compatible withTCM′s traditional, holistic therapeutic strategies and treatmentmodalities Presents topics of current interest, such as integrated globalsystems biology and the application of chemometrics research toherbal medicines

This book not only opens a new pathway for the continueddevelopment of TCM, but also for systems biology. In addition, itfosters collaboration and discussion among Eastern and Westernscientists by applying systems biology to TCM.

FOREWORD ix

PREFACE xiii

ABBREVIATIONS xvii

1 INTRODUCTION OF SYSTEMS BIOLOGY IN TRADITIONAL CHINESEMEDICINE (TCM) 1

1.1 Characteristics and Compatibility Principles of TraditionalChinese Medicine (TCM) 1

1.2 Key Scientifi c Issues in TCM Modernization 9

1.3 Development of Systems Biology 16

1.4 Chemomics Integrated Systems Biology 19

1.5 Research Strategy and Prospective of Systems Biology in TCM25

References 34

2 CHEMOMICS OF TRADITIONAL CHINESE MEDICINE 38

2.1 Characteristics and Research Diffi culties in TCM 39

2.2 Background of TCM Chemomics Proposal and Development45

2.3 Chemomics 52

2.4 Chemomics and the Research of Formulas 58

References 63

3 TECHNOLOGICAL PLATFORM OF TCM CHEMOMICS 66

3.1 Acquisition Methods and Techniques for TCM Chemomics 66

3.2 Characterization Techniques of Chemome–TCM Fingerprinting73

3.3 Information Processing for the Study of TCM Chemomics107

3.4 Development of an Intelligent Quality Control System in theProcess of Chinese Medicine Production 119

References 127

4 PHARMACOKINETIC INVESTIGATION ON TCM FORMULAS BASED ONGLOBAL SYSTEMS BIOLOGY 131

4.1 Pharmacokinetic Characteristics of TCM Formulas 131

4.2 Methodology of Pharmacokinetics of TCM Formulas 133

4.3 Application of PK–PD Model in the Toxicological Research ofLiushen Pills (LSP) 138

4.4 Prospect 143

References 144

5 APPLICATION OF GENOMICS IN THE RESEARCH OF TCM 146

5.1 Genomics and TCM System Research 146

5.2 Prospect of Genomics in TCM Research 148

5.3 Cases of the Application of Genomics in TCM Research 148

References 168

6 PROTEOMICS STUDY OF TCM 171

6.1 Proteomics in TCM Research 171

6.2 A Case Study of Proteomics in TCM 174

6.3 The Application of High Content Screening in TCM Research182

6.4 Limitations and Prospect of TCM Proteomics 186

References 187

7 APPLICATION OF METABONOMICS IN RESEARCH ON TCM 191

7.1 Current Research Situation of Metabonomics 191

7.2 Integration of Quantitative Metabonomics Platform Technology(QMPT) 191

7.3 Application of Metabonomics in the Field of Medicine 194

7.4 Examples of Metabonomic Research on TCM 198

References 206

8 APPLICATION OF CHEMOMETRICS AND BIOINFORMATICS IN TCMRESEARCH 210

8.1 Introduction of Chemometrics 210

8.2 Chemometric Techniques and Their Applications in TCMResearch 211

8.3 Introduction of Bioinformatics 216

8.4 Bioinformatics Techniques and Their Applications in theResearch of TCM 219

8.5 Conclusions 222

References 224

9 STUDY OF INTEGRATED BIOMARKER SYSTEM OF DIABETICNEPHROPATHY 228

9.1 Introduction of Diabetic Nephropathy 228

9.2 Mogensen Staging and TCM Typing of DN 234

9.3 The Metabonomics Study of DN 244

9.4 Condition of Metabolism after Treatment with TangShenFormula (TSF) 278

9.5 Genomics Study of Diabetic Neuropathy 286

9.6 The Integrated Biomarker System of DN 301

9.7 Conclusions 311

References 312

10 CHEMOMICS RESEARCH ON THE TCM FORMULA OF THE QINGKAILINGINJECTION 317

10.1 Chemomics Research of Qingkailing Injection 318

10.2 Pharmacodynamic Evaluation of Qingkailing Injection330

10.3 Research on the Qingkailing Derived Formula 335

10.4 Conclusions 368

References 369

11 INTEGRATED GLOBAL SYSTEMS BIOLOGY FOR THE RESEARCH ANDDEVELOPMENT OF CHINESE MEDICINE SHUANGLONG FORMULA 371

11.1 Brief Introduction to the Shuanglong Formula 371

11.2 Chemomics Study of the Shuanglong Formula 374

11.3 Pharmacodynamic Evaluation of SLF Effective Ingredients384

11.4 Systems Biology Study of the Mechanism of DirectedDifferentiation of Stem Cells Induced by NSLF6 402

11.5 Anti–Myocardial Infarction Effect of NSLF6 426

11.6 Conclusions 429

References 430

12 DEMONSTRATIVE RESEARCH ON THE SAFETY EVALUATION OF LIUSHENPILLS 437

12.1 Introduction 437

12.2 Toxicity Study of Chansu 438

12.3 Chemomics Study of LSP 446

12.4 Assessment of Effectiveness and Safety of LSP 457

12.5 In Vivo Distribution and Metabonomics of LSP andXionghuang 462

12.6 Metabonomic Research of LSP 467

12.7 Conclusions 477

References 478

INDEX 481

GUOAN LUO is Professor in the Institute of Biomedicine and Director of the Modern Research Center for Traditional Chinese Medicine at Tsinghua University in Beijing. Professor Luo is dedicated to the application of systems biology to study and advance TCM. He has published more than 680 peer–reviewed papers and applied for thirty–one patents. Among the many honors he has received for his research achievements are two National Scientific and Technological Advancement Prizes.

YIMING WANG is Professor at Tsinghua University.

QIONGLIN LIANG is Associate Professor at Tsinghua University.

QINGFEI LIU is Assistant Professor at Tsinghua University.