Mass spectrometry-based metabolomics offer new opportunities for biomarker discovery in complex diseases and may provide pathological understanding of diseases beyond traditional technologies. It is the systematic analysis of low-molecular-weight metabolites in biological samples and has been applied to discovering and identifying the perturbed pathways. Currently, mass spectrometry-based metabolomics has become an important tool in clinical research and the diagnosis of human disease.
Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines comprehensively presents the current state, challenges, and applications of high-throughput mass spectrometry-based metabolomics such as metabolites analysis, biomarker discovery, technical challenges, discovery of natural product, mechanism interpretation of action, discovery of active ingredients, clinical application and precision medicine, and enhancing their biomedical value in a real world of biomedicine, shedding light on the potential for spectrometry-based metabolomics. It highlights the value of mass spectrometry-based metabolomics and metabolism to address the complexity of herbal medicines in systems pharmacology, especially, to link phytochemical analysis with the assessment of pharmacological effect and therapeutic potential. Each chapter has been laid out with introduction, method, up-to-date literature, identification of biomarker, and applications - Covers the current state, challenges, and applications of high-throughput mass spectrometry-based metabolomics in the discovery of biomarker, active ingredients, natural product, etc. - Constitutes a unique and indispensable practical guide for any phytochemistry or related laboratory, and provides hands-on description of new techniques - Provides a guide for new practitioners of pharmacologists, pharmacological scholars, drug developers, botanist, researchers of traditional medicines.
Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines provides a landmark of mass spectrometry-based metabolomics research and a beneficial guideline to graduate students and researchers in academia, industry, and technology transfer organizations in all biomedical science fields.
Table of Contents
Preface xiii
1 Current State of the Art of High-Throughput Metabolomics 1
Aihua Zhang, Qiang Yang, Hui Sun, and Xijun Wang
1.1 Introduction 1
1.2 Metabolomics 1
1.3 Mass Spectrometry Technology 2
1.4 Recent Advancements and Applications 4
1.4.1 Disease Diagnoses and Metabolism 4
1.4.2 Metabolic Mechanisms 6
1.4.3 Drug Efficacy 7
1.4.4 Nutrition 7
1.4.5 Plant Biology 8
1.5 Limitation 8
1.6 Conclusions and Future Perspectives 9
Acknowledgments 9
References 9
2 Innovations in Analytical Techniques of Metabolomics 19
Ling Kong, Aihua Zhang, Shi Qiu, and Xijun Wang
2.1 Introduction 19
2.2 Current Analytical Technologies of Metabolomics 20
2.3 Chromatography Platform 21
2.3.1 Gas Chromatography Technique 21
2.3.2 Liquid Chromatography Technique 21
2.3.3 Supercritical Fluid Chromatography Technique 22
2.3.4 Capillary Electrophoresis Chromatography Technique 22
2.4 Mass Spectrometry Platform 23
2.4.1 GC-MS Technique 23
2.4.2 LC-MS Technique 24
2.4.3 SFC-MS Technique 24
2.4.4 CE-MS Technique 24
2.5 Nuclear Magnetic Resonance Platform 25
2.6 Comprehensive and Multidimensional Analytical Platform 25
2.7 Conclusions 25
Acknowledgments 26
References 26
3 Sample Preparation Method for Mass Spectrometry-Based Metabolomics 33
Shi Qiu, Aihua Zhang, Hui Sun, and Xijun Wang
3.1 Introduction 33
3.2 Sample Collection and Storage 34
3.2.1 Urine 34
3.2.2 Plasma and Serum 35
3.2.3 Cerebrospinal Fluids 35
3.2.4 Tissue Homogenates 35
3.2.5 Saliva 36
3.3 Sample Preparation and Processing 36
3.4 Application 37
3.5 Future Development 38
Acknowledgments 38
References 38
4 Multivariate Data Analysis Approach for Mass Spectrometry-Based Metabolomics 45
Junling Ren, Aihua Zhang, Ling Kong, and Xijun Wang
4.1 Introduction 45
4.2 Separation-Based MS Techniques 46
4.2.1 Gas Chromatography-Mass Spectrometry 46
4.2.2 Liquid Chromatography-Mass Spectrometry 46
4.2.2.1 Reversed-Phase Liquid Chromatography-Mass Spectrometry 47
4.2.2.2 Hydrophilic Interaction Chromatography-Mass Spectrometry 47
4.2.2.3 Supercritical Fluid Chromatography-Mass Spectrometry 48
4.2.3 Capillary Electrophoresis-Mass Spectrometry 48
4.2.4 Ion Mobility-Mass Spectrometry 49
4.3 Separation-Free MS Techniques 49
4.3.1 Direct Infusion-Mass Spectrometry 49
4.3.2 Matrix-Assisted Laser Desorption Ionization-Mass Spectrometry 50
4.3.3 Mass Spectrometry Imaging 50
4.3.4 Direct Analysis in Real Time-Mass Spectrometry 51
4.4 Tools for MS Result Analysis 51
4.5 Multivariate Statistical Analysis Approach for Data Analysis 53
4.6 Limitations and Challenges 57
4.7 Conclusions and Future Perspectives 58
Acknowledgments 60
References 60
5 Mass Spectrometry-Driven Metabolomics for Metabolites and Metabolic Pathway Analysis 67
Aihua Zhang, Hui Sun, Shi Qiu, and Xijun Wang
5.1 Introduction 67
5.2 Mass Spectrometry-Driven Metabolomics for Biomarker Discovery 69
5.3 Data Extraction and Analysis for Metabolites and Metabolic Pathway 69
5.4 Biomarker Identification 70
5.5 Applications 70
5.6 Conclusions 73
Acknowledgments 73
References 73
6 Metabolomics as Drivers for Biomarker Discovery and Mechanism Interpretation 81
Wanying Wang, Aihua Zhang, Hui Sun, Guangli Yan, and Xijun Wang
6.1 Introduction 81
6.2 Metabolomics for Biomarker Discovery 82
6.3 Metabolomics for Mechanism Interpretation 83
6.4 Application 85
6.5 Current Trends and Future Perspectives 88
6.6 Conclusions 89
Acknowledgments 89
References 89
7 Current Status of Technical Challenges in Mass Spectrometry-Driven Metabolomics 97
Shi Qiu, Aihua Zhang, Hui Sun, and Xijun Wang
7.1 Introduction 97
7.2 Metabolic Fingerprinting and Profiling 98
7.3 Non-targeted or Targeted Metabolomics 99
7.4 Metabolite Identification Bottleneck 99
7.5 Quality Control Bottleneck 101
7.6 Mass Spectrometry Techniques 102
7.6.1 LC-MS 102
7.6.2 GC-MS 103
7.6.3 NMR-MS 104
7.7 Prospects 105
7.8 Conclusions 105
Acknowledgments 105
References 106
8 The Application of Metabolomics in Cancer Management 113
Aihua Zhang, Hui Sun, and Xijun Wang
8.1 Introduction 113
8.2 Epidemiology and Diagnosis 114
8.3 Prospective Biomarkers 114
8.4 Metabolomics Screening Biomarkers 117
8.5 Conclusions and Future Directions 117
Acknowledgments 118
References 118
9 Metabolomics in Coronary Heart Disease: From Biomarker Identification to Pathomechanism Insights 123
Hui Sun, Aihua Zhang, Shi Qiu, and Xijun Wang
9.1 Introduction 123
9.2 Predicament 126
9.3 Metabolomics for CHD 126
9.4 Biomarker Dilemma 127
9.5 Lipid Metabolism 128
9.6 Treatment of Herbal Medicine 128
9.7 Conclusions and Future Direction 129
Acknowledgments 129
References 130
10 Metabolomics Applications in Neurological Disease 135
Shi Qiu, Ying Han, Aihua Zhang, Hui Sun, and Xijun Wang
10.1 Introduction 135
10.2 CSF Sampling 136
10.3 Application of Metabolomics in CNS 136
10.4 Future Direction 137
10.5 Conclusions 138
Acknowledgments 139
References 139
11 Metabolomics Toward Precision Medicine 143
Aihua Zhang, Shi Qiu, Hui Sun, Guangli Yan, and Xijun Wang
11.1 Introduction 143
11.2 Precision Medicine: A New Era of Medicine 144
11.3 Precision Biomarkers 145
11.4 Metabolomics as a Powerful Tool for Potential Biomarkers 146
11.5 Practical Application of Metabolomics 147
11.6 Precision Medicine for Herbal Medicine 148
11.7 Conclusions and Future Perspectives 150
Acknowledgments 151
References 151
12 Mass Spectrometry-Based Metabolomics Toward Biological Function Analysis 157
Shi Qiu, Wanying Wang, Aihua Zhang, and Xijun Wang
12.1 Introduction 157
12.2 Current Trend and Challenge of Disease Phenotype 158
12.3 Advances in Mass Spectrometry Analytic Technique 158
12.4 Advantages of Mass Spectrometry-Based Metabolomics 159
12.5 Mass Spectrometry-Based Metabolomics for Biological Function 159
12.6 Limitations of MS-Based Metabolomics 165
12.7 Future Perspectives 165
12.8 Conclusions 166
Acknowledgments 166
References 166
13 Mass Spectrometry-Driven Active Ingredients Discovery from Herbal Medicine 171
Wanying Wang, Aihua Zhang, Shi Qiu, and Xijun Wang
13.1 Introduction 171
13.2 An Overview of Herbal Medicine 172
13.3 Mass Spectrometry to Identify the Chemical Constituents 173
13.4 Mass Spectrometry for Constituent Analysis In Vivo 173
13.5 Mass Spectrometry-Based Chinmedomics Strategy 175
13.6 Application 175
13.7 Conclusions and Future Perspectives 176
Acknowledgments 177
References 177
14 Metabolomics Application in Herbal Medicine 185
Wanying Wang, Aihua Zhang, Hui Sun, and Xijun Wang
14.1 Introduction 185
14.2 Metabolomic Dissection of Herbal Medicine 186
14.3 Application in Herbal Medicine 189
14.3.1 Effect Evaluations 189
14.3.2 Mechanism Explorations 192
14.3.3 Quality Control Analyses 193
14.4 Conclusions 194
Acknowledgments 194
References 194
15 Mass Spectrometry-Based Metabolomics Insights into the Mode of Action of Natural Products 199
Junling Ren, Aihua Zhang, Hui Sun, and Xijun Wang
15.1 Introduction 199
15.2 Metabolomics: An Overview 200
15.2.1 Comprehensive Metabolomics for Metabolites Detection 200
15.2.2 Understanding Pharmacological Effects 200
15.2.3 Discovery of Biomarkers and Targets 201
15.2.4 Screen Bioactive Natural Products 201
15.3 Superiority of MS-Based Metabolomics 201
15.3.1 Enhanced MS Coverage for Small-Molecule Metabolites 202
15.3.2 MS-Based Metabolomics Guided Biochemical Analysis 202
15.3.3 Identify Molecular Mechanisms by Integrating MS with Databases 202
15.4 Mass Spectrometry Techniques Employed in Metabolomics 202
15.4.1 Gas Chromatography-Mass Spectrometry 203
15.4.2 Liquid Chromatography-Mass Spectrometry 203
15.4.3 Capillary Electrophoresis-Mass Spectrometry 203
15.4.4 Ion Mobility-Mass Spectrometry 204
15.4.5 Mass Spectrometry Imaging 204
15.4.6 New Challenges in MS-Based Metabolomics 204
15.5 Challenges of Natural Products 205
15.6 Herbal Ingredients: Current Research and Applications 205
15.6.1 Various Analytical Strategies for Herbal Ingredients 205
15.6.2 Effective Constituents In Vitro and In Vivo 206
15.7 MS in Natural Product 206
15.7.1 Qualitative Analysis 206
15.7.2 Quantitative Analysis 207
15.7.3 Mechanism Analysis of Action 207
15.8 MS-Based Metabolomics in Bioactive Ingredients 208
15.8.1 Reveal Efficacy of HMs 208
15.8.2 High-Throughput Analysis of HMs 209
15.8.3 Discovery of Quality Markers 209
15.8.4 Toxicity Explorations 211
15.8.5 Potential Impacts on Drug Discovery 211
15.9 Conclusions and Future Perspective 212
Acknowledgment 212
References 213
16 Mass Spectrometry-Driven Lipidomics for Biomarker, Molecular Mechanism, and Therapy 223
Qiang Yang, Shi Qiu, Aihua Zhang, and Xijun Wang
16.1 Introduction 223
16.2 Lipidomics Method 223
16.2.1 Targeted Lipidomics 224
16.2.2 Non-targeted Lipidomics 225
16.3 Sample Preparation 225
16.4 Analytical Techniques in Lipidomics 227
16.4.1 Liquid Chromatography-Mass Spectrometry 227
16.4.2 Gas Chromatography-Mass Spectrometry 228
16.4.3 Supercritical Fluid Chromatography-Mass Spectrometry 228
16.4.4 Ion Mobility-Mass Spectrometry 228
16.4.5 Mass Spectrometry Imaging 229
16.4.6 Shotgun Lipidomics 229
16.5 Lipidomics for Biomarker Discovery 229
16.6 Application of MS-Based Lipidomics 230
16.6.1 Efficacy Analysis 230
16.6.2 Food Science 231
16.6.3 Environment 231
16.6.4 Clinical Biomarker Discovery 232
16.6.5 Pharmacological Research 232
16.6.6 Toxicology Analysis 232
16.7 Future Perspectives 233
16.8 Conclusions 234
Acknowledgments 234
References 234
17 Potential Application of Mass Spectrometry-Based Lipidomics for Herbal Medicine 245
Ying Cai, Aihua Zhang, Hui Sun, and Xijun Wang
17.1 Introduction 245
17.2 Lipidomics Method 246
17.2.1 Sample Preparation 246
17.2.1.1 Classical Method 246
17.2.1.2 Green Technologies 247
17.2.2 Data Collection and Analysis of Lipidomics 248
17.2.2.1 Untargeted Lipidomics 248
17.2.2.2 Targeted Lipidomics 249
17.2.2.3 Pseudotargeted Lipidomics 249
17.3 Mass Spectrometry Technique in Lipidomics 250
17.3.1 Ionization Technology 250
17.3.2 Mass Analyzer 251
17.3.3 Tandem Mass Spectrometry 252
17.3.4 Ion Mobility-Mass Spectrometry 252
17.3.5 Mass Spectrometry Imaging 253
17.4 Application of Mass Spectrometry-Based Lipidomics for Herbal Medicine 253
17.5 Conclusions 255
Acknowledgments 255
References 255
Index 263
