Mass Spectrometry-Based Metabolomics in Clinical and Herbal Medicines

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