In contrast to existing books which either focus exclusively on the pharmacological properties of plant natural products or cover the secondary metabolism of plants as one section in general plant science book, this is the first to cover all aspects in one volume.
It has all the features of a modern textbook, including color figures, questions and answers and a complimentary website. In addition, the introductory chapters provide sufficient background knowledge in the chemistry and biochemistry of plant natural products and their biotechnological applications to allow its use as a true stand-alone text for student courses.

Table of Contents
Preface XI

1 Biosynthesis and Chemical Properties of Natural Substances in Plants 1

1.1 Selected Classes of Secondary Metabolites 3

1.1.1 Occurrence and Compartmentation 3

1.1.2 Biosynthesis 11

1.1.2.1 Alkaloids 12

1.1.2.2 Phenol Derivatives, Especially Flavonoids 19

1.1.2.3 Betalains 22

1.1.2.4 Cyanogenic Glycosides, Glucosinolates, and other Indole Derivatives 24

1.1.2.5 Terpenes 29

1.1.3 Transcriptional Control 31

1.1.4 Transport of Secondary Metabolites 39

1.2 Evolution of Natural Compounds in Plants 44

1.2.1 Parallel Evolution of Similar Pathways 46

1.2.2 Gene Duplication 48

1.2.3 Gene Clusters 52

1.2.4 Natural Variation 58

1.2.5 Modulation of Different Molecules with Similar Functions 59

1.2.6 Evolution by Stress Factors 60

1.2.6.1 Abiotic Stress 60

1.2.6.2 Biotic Factors 61

1.3 Biotechnological Applications 62

1.3.1 Identification and Quantification of Natural Plant Products 62

1.3.2 Biological Activity 67

1.3.3 Biotechnological Production of Natural Compounds 68

2 Function of Natural Substances in Plants 81

2.1 Secondary Compounds in Primary Metabolism 81

2.2 Development 83

2.2.1 Vegetative Growth 85

2.2.1.1 Structural Polymers 87

2.2.1.2 Flavonoids and Auxin Transport 88

2.2.1.3 Glucosinolates and the Biosynthesis of IAA 90

2.2.1.4 Polar Growth 91

2.2.1.5 Cytoskeleton and Cell Cycle 91

2.2.1.6 Alkaloids and Growth 93

2.2.1.7 Senescence 95

2.2.2 Reproduction: Male Fertility 95

2.2.3 Flower Biology: Pollination 98

2.2.3.1 Nutrients 98

2.2.3.2 Aroma Volatiles 99

2.2.3.3 Color 105

2.2.4 Fruit and Seeds 109

2.2.4.1 Fruit Development 109

2.2.4.2 Seed Formation 112

2.2.4.3 Seed Dispersal 112

2.2.4.4 Seed Dormancy 113

2.3 Abiotic Stress 115

2.3.1 Antioxidative Properties in Plants 116

2.3.2 Light and UV Irradiation 118

2.3.3 High Temperatures 120

2.3.4 Cold, Salt, and Drought Stress 122

2.3.5 Nutrient Deficiency 122

2.3.6 Environmental Pollution 123

2.3.6.1 Heavy Metal Stress 123

2.3.6.2 Air Pollution 124

2.4 Symbioses 124

2.4.1 Rhizobia 125

2.4.2 Mycorrhiza 127

2.4.3 Endophytic Fungi 131

2.4.4 Lichens 131

2.5 Defense 132

2.5.1 Pathogens 134

2.5.1.1 Preformed Defense Response 136

2.5.1.2 Induced-Defense Response 143

2.5.1.3 Systemic Acquired Resistance 153

2.5.2 Antimicrobial Potential in Plant Protection (Biofumigation) 154

2.5.3 Invertebrate Herbivores 154

2.5.3.1 Insects 155

2.5.3.2 Phytopathogenic Fungi Alter the Chemical Defense of Plants Against Insects 163

2.5.3.3 Biological Plant Protection Against Insects with Secondary Metabolites 164

2.5.3.4 Nematodes 164

2.5.3.5 Snails/Slugs 166

2.5.4 Parasitic Plants 166

2.6 Allelopathy 170

3 Biological Effects on Microorganisms and Animals 175

3.1 Coevolution 175

3.1.1 Adaptation Mechanisms of Microbes and Herbivores 179

3.1.1.1 Fungi 182

3.1.1.2 Insects 182

3.1.1.3 Vertebrates 187

3.1.2 Attraction of Insects 189

3.2 Effects on Vertebrates: An Overview 198

3.2.1 Structural and Functional Diversity of Natural Substances: Challenges and Promises 198

3.2.2 Molecular Interactions with Cellular Components 201

3.2.2.1 Protein Targets 201

3.2.2.2 Interaction with Nucleic Acids 206

3.2.2.3 Interaction with Lipids 206

3.2.2.4 Interaction with Carbohydrates 206

3.2.2.5 Metal Chelators 207

3.2.3 Visualization of Natural Substances in Living Cells 209

4 Metabolism and Toxicity of Natural Substances in Mammals 213

4.1 Metabolism of Natural Substances in Mammals 213

4.1.1 Principles of Pharmacokinetics 213

4.1.1.1 Absorption, Distribution, Metabolism, and Excretion 216

4.1.2 Case Studies of Selected Natural Compounds 221

4.1.2.1 Quercetin 221

4.1.2.2 Catechins and Proanthocyanidins 224

4.1.2.3 Resveratrol 224

4.1.2.4 Morphine 226

4.1.2.5 Nicotine 227

4.1.3 Metabolic Bioactivation 229

4.1.4 Effects on Enzymes Controlling Biotransformation and Bioavailability 232

4.1.4.1 Medical Importance 233

4.1.5 Genetic Polymorphisms 235

4.1.5.1 Genetic Polymorphisms of Key Metabolic Enzymes 235

4.1.5.2 Caffeine 237

4.1.5.3 Nicotine 238

4.1.5.4 Codeine and Morphine 238

4.1.5.5 Pharmacogenomics and Personalized Medicine 239

4.2 Toxicity 240

4.2.1 Basic Toxicology 240

4.2.1.1 Cytotoxicity 242

4.2.2 Toxicity of Selected Natural Substances 246

4.2.2.1 Animal Poisons 246

4.2.2.2 Poisons in Plants, Fungi, and Bacteria 247

4.2.2.3 Taxus Alkaloids 250

4.2.2.4 Phallotoxins and Amatoxins 250

4.2.2.5 Ricin 250

4.2.2.6 Bacterial Toxins 252

4.2.3 Strategies and Difficulties in Toxicological Evaluations 253

4.2.3.1 Mutagenicity and Cancerogenicity 254

4.2.3.2 Reprotoxicity and Developmental Toxicity 256

4.2.3.3 Experimental Variables and Limitations of Test Systems 257

5 Examples of Physiological Effects of Natural Substances Present in Food and in Medicinal Plants 261

5.1 Are Antioxidants Good for Health? 261

5.1.1 Generation and Homeostatic Control of Reactive Oxygen and Nitrogen Species 261

5.1.2 Function of ROS/RNS as Signaling Molecules for Cellular Functions 268

5.1.3 Oxidative Stress in Human Diseases and in Aging 271

5.1.4 Natural Substances Affecting Redox Homeostasis 273

5.1.4.1 Reduction of ROS in a Redox Reaction 273

5.1.4.2 Formation of Chelates with Metals 274

5.1.4.3 Inhibition of Enzymes Involved in Stress Defense 275

5.1.4.4 Initiation of an Adaptive Response 276

5.1.5 Hormesis and the Benefits of Temporary Mild Oxidative Stress 278

5.2 Endocrine Effects of Natural Substances 280

5.2.1 Are Endocrine Disruptors a Threat to Animal and Human Health? 280

5.2.2 How Do Phytoestrogens Interfere with the Endocrine System? 285

5.2.2.1 The Estradiol Receptor is a Target of Natural Substances 287

5.2.2.2 Natural Compounds Affecting Steroid Biosynthesis 290

5.2.2.3 Other Activities of Phytoestrogens 292

5.2.3 Evaluation of Risks and Benefits of Phytoestrogens to Treat Common Diseases 292

5.2.3.1 Phytoestrogens and Reproductive Functions 293

5.2.3.2 Do Phytoestrogens Protect Against Breast Cancer? 296

5.2.3.3 Hormone Replacement Therapy 297

5.2.3.4 Other Physiological Effects of Phytoestrogens 298

5.2.3.5 Phytoestrogens Illustrate the Experimental Challenge of a Mechanistic Analysis 299

5.2.4 Transgeneration Effects 299

5.2.5 Natural Substances Interfering with Nonsteroidal Signaling 304

5.3 Interference with Neural Functions 307

5.3.1 Basic Features of the Nervous System and Synaptic Transmission 307

5.3.2 Bioactivity of Cannabinoids 314

5.3.2.1 Effects of Phytocannabinoids on Neural Functions 318

5.3.2.2 Medical Applications of Phytoestrogens 320

5.3.3 Discovery and Bioactivity of Opioids 322

5.3.4 Analgesic Properties of Opioids and Cannabinoids 324

5.3.4.1 Analgesic Effects of Opioids 326

5.3.4.2 Analgesic Activity of Cannabinoids 327

5.3.5 The Hallucinogenic Drugs Psilocin, Psilocybin, and Mescaline 328

5.3.6 Natural Substances Affecting Cholinergic Signaling 330

5.3.6.1 The Cholinergic Synapse 330

5.3.6.2 Cholinergic Signaling is a Target for Natural Substances 332

5.3.6.3 Inhibitors of AChE 333

5.3.6.4 Medical Applications of AChE Inhibitors 336

5.3.7 Sympathomimetic Substances 337

6 Nature's Drugstore for a Healthy Life 341

6.1 Biologically Active Food and Food Components 341

6.1.1 The Quantity of Food Intake Affects Life Expectancy 343

6.1.2 Resveratrol: Longevity and Health with Grapes? 347

6.1.3 Food with Health-Promoting Bioactive Substances 351

6.1.3.1 Grapes (Resveratrol) 351

6.1.3.2 Broccoli (Sulforaphane) 353

6.1.3.3 Hops (Xanthohumol) 354

6.1.3.4 Green Tea (Epigallocatechin 3-Gallate) 355

6.1.3.5 Garlic (Allicin) 356

6.1.3.6 Other Polyphenol-Rich Foods 356

6.1.3.7 Is There a General Mechanistic Principle for Health-Promoting Substances in Food? 357

6.1.4 Functional Food: Does it Hold the Promise? 359

6.2 Natural Compounds in Pharmacological Research 360

6.2.1 Mining for Bioactive Compounds in Marine and Terrestrial Organisms 360

6.2.2 Medicinal Chemistry Inspired by Natural Products 364

6.2.2.1 Lessons from Natural Substances About Relevant Targets 365

6.2.2.2 Natural Chemical Scaffolds and their Pharmacological Optimization 365

6.2.2.3 Systematic Computational Analysis of Natural Scaffolds and Peptide Motifs 368

6.3 The Problem of Complexity: Analysis and Consequences 370

6.3.1 Many Targets: A Problem? 370

6.3.2 From Pharmacology to Polypharmacology 371

6.3.3 Reverse Pharmacology Inspired by Traditional Medicine 375

Further Reading 379

Index 405