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Drug Discovery from Plants A.A. Salim Y.-W. Chin A.D. Kinghorn
The Role of Plants in Human History 1
The Role of Plant-Derived Compounds in Drug Development 4
Plant Secondary Metabolites as Drug Precursors 4
Plant Secondary Metabolites as Drug Prototypes 6
Plant Secondary Metabolites as Pharmacological Probes 8
Recent Developments in Drug Discovery from Plants 9
New Plant-Derived Drugs Launched Since 2001 9
Examples of Plant-Derived Compounds Currently Involved in Clinical Trials 11
Plant Extracts Currently Involved in Clinical Trials 15
Recent Trends and Future Directions 18
Grapevine Stilbenes and Their Biological Effects P. Waffo-Teguo S. Krisa T. Richard J.-M. Merillon
Introduction 25
Epidemiology 26
Chemistry of Stilbenes 27
Characterisation 27
Monomers 27
Oligomers 29
Biosynthetic Pathway 32
Distribution in Vitis vinifera 33
Determination of Stilbenes in Wine 33
Biological and Pharmacological Activities 35
Bioavailability andMetabolism 35
Cardiovascular Protection 39
Antioxidant Activity 39
Antithrombotic and Vasoprotective Properties 41
Biological Activities after Ingestion of Polyphenols or Wine 42
Cancer Chemoprevention 43
Neurodegenerative Diseases 46
Conclusion 49
Research into Isoflavonoid Phyto-oestrogens in Plant Cell Cultures M.T. Luczkiewicz
Introduction 56
The Influence of the Basic Experimental Media on the Biosynthesis of Isoflavones in In Vitro Cultures 57
The Influence of Physical Factors on the Biosynthesis and Accumulation of Isoflavonoids in In Vitro Cultures 59
The Effect of Technological Procedures on the Biosynthesis and Accumulation of Isoflavonoids in In Vitro Cultures 60
Elicitation 61
Supplementation with Biosynthesis Precursors 70
Biotransformation 71
Genetic Modifications 73
In Vitro Cultures of Legume Plants Oriented for Selective Production of Phyto-oestrogens 77
Secondary Metabolite Production from Plant Cell Cultures: the Success Stories of Rosmarinic Acid and Taxol S. Kintzios
Introduction: Cell Factories at the Cross Point 86
Rosmarinic Acid 87
General Information 87
Historical Development of In Vitro RA Production - a Brief Overview 87
Stimulation of Biosynthetic Pathways Leads to Enhanced RA Accumulation In Vitro 88
Is RA Biosynthesis Growth Dependent? 89
Is RA Accumulation Related to Culture Differentiation? 90
Recent Attempts to Scale Up RA Production 91
RA Production in Immobilized Cell Cultures 92
Taxol 92
General Information 92
Historical Development of In Vitro Taxol Production - a Brief Overview 93
Stimulation of Biosynthetic Pathways Leads to Enhanced Taxol Accumulation In Vitro 94
Is Taxol Biosynthesis Growth and Differentiation Dependent? 96
Recent Attempts to Scale Up Taxol Production 97
Taxol Production in Immobilized Cell Cultures 97
Conclusions 98
Guggulsterone: a Potent Natural Hypolipidemic Agent from Commiphora wightii - Problems, Perseverance, and Prospects K. G. Ramawat M. Mathur S. Dass S. Suthar
Introduction 102
Distribution 102
Biology 102
Gum-Resin Production 103
Chemistry 104
Methods of Analysis 104
Thin-Layer Chromatography 104
High-Performance Liquid Chromatography 109
Traditional Therapeutic Uses 109
Pharmacology 110
Animal and Clinical Trials 110
Mechanism of Action 111
Other Potential Activities 112
Toxicity 113
Biotechnological Approaches 113
Micropropagation 113
Somatic Embryogenesis 114
Resin Canal Formation 115
Guggulsterone Production 115
Future Prospects 119
Silybum marianum (L.) Gaertn: the Source of Silymarin P. Corchete
Introduction 124
Botany 125
Chemical Composition of S. marianum Fruits 126
Pharmacology of Silymarin 130
Mechanisms of Action 131
Antioxidant Activity 131
Effects on Hepatocyte Membranes and Cellular Permeability 131
Effects on Receptor Binding of Toxins and Drugs 131
Stimulation of Protein Synthesis 132
Inhibition of Cell Proliferation in Hepatic Fibrosis 132
Anti-inflammatory Activity 132
Pharmacological Applications 132
Hepatoprotective Action 132
Hypocholesterolemic Action 134
Chemopreventive and Anticarcinogenic Effects 134
Anti-inflammatory Action 136
Other Actions 137
Bioavailability 138
Toxicology 139
Therapeutics 139
Biotechnology 140
The Production of Dianthrones and Phloroglucinol Derivatives in St. John's Wort A. Kirakosyan D.M. Gibson P.B. Kaufman
Introduction 149
Dianthrone and Phloroglucinol Derivatives Family of Compounds in Hypericum perforatum 150
Botany of Hypericum 152
Medicinal Uses of Hypericin and Hyperforin 152
Biotechnology for the Production of Hypericin and Hyperforin 154
Biosynthesis of Hypericin and Hyperforin in Mature Plants 154
Plant Cell Biotechnology 156
Influences on Hypericin and Hyperforin Productivity by Other Factors 159
New Directions for Hypericin and Hyperforin Production 161
Conclusions 162
Production of Alkaloids in Plant Cell and Tissue Cultures D. Laurain-Mattar
Introduction 165
Correlation Between Organogenesis, Somatic Embryogenesis and Isoquinoline Alkaloid Accumulation 168
Hairy Roots and Tropane and Morphinan Alkaloid Accumulation 170
Conclusion and Perspective 171
Bacopa monnieri, a Nootropic Drug M. Rajani
Introduction 175
Chemical Constituents 176
Analysis of Saponins of B. monnieri 184
Pharmacological Studies 184
Clinical Studies 188
Concluding Remarks 189
Biotechnology and Tissue Culture Studies on B. monniera 190
Chemical Profiling of Nothapodytes nimmoniana for Camptothecin, an Important Anticancer Alkaloid: Towards the Development of a Sustainable Production System R. Uma Shaanker B.T. Ramesha G. Ravikanth R.P. Gunaga R. Vasudeva K.N. Ganeshaiah
Introduction 198
N. nimmoniana: Ecology and Distribution 201
Basic Patterns of Accumulation of CPT in N. nimmoniana 203
Chemical Profiling of Populations of N. nimmoniana for CPT 204
Modeling Habitat Suitability for CPT Production 207
Development of a Sustainable Extraction Approach 209
Conclusions 210
Colchicine - an Overview for Plant Biotechnologists S. Ghosh S. Jha
Introduction 216
The Alkaloid Colchicine 218
Toxicity of Colchicine 218
Biological Effects of Colchicine 219
Colchicine as a Medicine 222
Botanical Use of Colchicine 222
Chemistry of Colchicine 223
Occurrence 225
Biotechnological Approaches for the Production of Colchicine 225
Conclusion 228
In Vitro Azadirachtin Production S. Srivastava A.K. Srivastava
Introduction 234
Chemistry of Azadirachtin 236
Mode of Action of Azadirachtin 237
Biosynthetic Pathway for Azadirachtin 238
Qualitative and Quantitative Analysis of Azadirachtin 238
Availability of Azadirachtin 242
Plant Cell/Tissue Culture: an Alternative for Azadirachtin Production 243
Azadirachtin Production from Plant Cell/Tissue Cultures of Azadirachta indica 243
Yield Improvement Strategies 244
Strain Improvement and Selection 245
Media Compositions and Culture Conditions 245
Application of Elicitors, Precursors and Permeabilising Agents 246
Genetic Engineering Approach 247
Somatic Embryogenesis and Regeneration 248
Two-Phase (Stage) Systems 248
Immobilisation 248
Stability of Azadirachtin 249
Scale-up of In Vitro Azadirachtin Production 249
Conclusion 250
Arabinogalactan Protein and Arabinogalactan: Biomolecules with Biotechnological and Therapeutic Potential A. Pal
Introduction 256
Biological Activities of AGP 259
Role of AGPs in Reproductive Organ Development 261
Signaling Role of AGP 262
Abiotic Stress Tolerance Conferred by AGP 263
Probable Role in PCD 263
Commercial Uses of Gum Arabic 264
AG as Dietary Fiber and Prebiotics 264
AG as Immunomodulators and Immunity Enhancers 265
Echinacea-AG as a Nutraceutical 266
Other Uses of AG 266
Scope of Exploiting the Potentials of AGP and AG in Plant Biotechnology and Therapeutics 267
Concluding Remarks 267
Hairy Roots: a Powerful Tool for Plant Biotechnological Advances S. Guillon J. Tremouillaux-Guiller P.K. Pati P. Gantet
Introduction 272
Hairy Roots Are on the Way to towards an Experimental Model 272
Improvement in the Productivity of Hairy Roots: Biotic and Abiotic Treatments or Metabolite Trapping 275
Potential Discovery of Metabolic Genes from Transcriptome Analysis of T-DNA Activation Tagging or Elicited Hairy Roots 277
RNA Silencing via Hairy Root: a Powerful Tool for Loss-of-Function Analyses of Genes 277
Metabolic Engineering of the Hairy Root System 278
Hairy Roots: A Novel System for Molecular Farming 279
Phytoremediation Process for Cleaning up the Environment and More Knowledge on Root Adsorption 279
Scale up and Technological Integration into Industry 280
Perspectives 281
Hairy Roots of Catharanthus roseus: Efficient Routes to Monomeric Indole Alkaloid Production S. Guillon P. Gantet M. Thiersault M. Rideau J. Tremouillaux-Guiller
Introduction 286
Materials and Methods 286
Bacterial Strain 286
Plant Material 287
Hairy Root Induction 287
Liquid Hairy Root Culture 287
Methyl Jasmonate Treatment 287
Alkaloid Identification by Ceric Ammonium Sulphate Reagent 288
Serpentine and Ajmalicine Content Determination by Spectrofluorometry 288
Catharanthine Content Determination by High-Performance Liquid Chromatography Analysis 288
Statistical Analysis 289
Results and Discussion 289
Genetic Transformation of Catharanthus Leaves 289
Alkaloid Profiles 291
Alkaloid Contents 292
Conclusion 294
Roseroot (Rhodiola rosea L.): Effect of Internal and External Factors on Accumulation of Biologically Active Compounds Z. Weglarz J.L. Przybyl A. Geszprych
Introduction 298
Plant Characteristics 298
Intraspecific Variability 300
Distribution of Phenolic Compounds in Rhizomes and Roots 300
Quality of Raw Material of Different Origin 303
Individual Variation 304
Accumulation of Biomass and Biologically Active Compounds in the Underground Organs of Roseroot During Plant Development 305
Effect of Ecological Factors on the Accumulation of Biomass and Biologically Active Compounds in the Underground Organs of Roseroot 308
Effect of Post-harvest Treatment on the Quality of Raw Material and Extracts 310
Apoptosis and Plant-Derived Pharmaceuticals L.F. Brisson
Introduction 317
Molecular Regulation of Apoptosis 317
Plant Antitumoral Substances 318
Plant Substances 318
Chemotherapeutic Drugs 319
Taxanes 319
Vinca Alkaloids 320
Chemopreventive Agents: Catechin and its Derivatives 321
Conclusion 322
The Indian Herbal Drugs Scenario in Global Perspectives K.G. Ramawat S. Goyal
Introduction 325
Indian System of Medicine 328
World-Wide Use of Medicinal Aromatic Plants 336
Supply and Demand of Medicinal Plants 337
Medicinal Plant Biodiversity 338
Traditional Medicine in Healthcare 340
Indian Pharmaceutical Industries 341
Quality of Herbal Drugs 342
Concluding Remarks 343
Phytochemical Standardization of Herbal Drugs and Polyherbal Formulations M. Rajani N.S. Kanaki
Introduction 349
Herbal drugs 349
Trade Scenario 350
Bottlenecks and Steps to be Taken 350
Strategy 351
Status of Herbal Drugs in Pharmacopoeias 351
Official 352
Others 352
Phytochemical Standardization 352
Sample Preparation 353
Preliminary Screening for Chemical Groups and Quantification of Chemical Groups 354
Phytochemical Profiles - Fingerprinting 354
Multiple Marker-Based Fingerprinting 355
Marker Compound Analysis 357
Marker Compounds 357
Quantification of Marker Compounds 357
Multiple Marker-Based Evaluation 358
Polyherbal Formulations 359
Hyphenated Techniques 361
Reference Compounds 364
Some Examples 364
Raw Material 364
Ammoniacum Gum 364
Cinchona officinalis Stem Bark 365
Formulation 366
Chandraprabhavati 366
Conclusion 366
Subject Index 371
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