List of Contributors xvii
List of Figures xxi
List of Tables xxiii
Preface xxv
Editors xxvii
1 Historical Use of Toxic Plants 1
Godwin Anywar
1.1 Introduction to Toxic Plants 1
1.2 Poisonous Plants as Sources of Traditional and Modern Medicines 2
1.3 Toxic Plants and Justice 4
1.3.1 Toxic Plants in Capital Punishment 4
1.3.2 Trial by Ordeal 4
1.4 Toxic Plants in Poisoned Weapons 6
1.4.1 Arrow Poisons 6
1.5 Plant Fishing Poisons/Piscicides/Ichthyotoxins 6
1.6 Poisonous Plants as Food 7
1.7 Poisonous Plants as Biopesticides 9
1.8 Toxic Psychoactive Plants for Recreational and Religious Purposes 9
1.9 Poisonous Plants in Warfare and Bioterrorism 10
1.10 Poisonous Plants as Carcinogens and Teratogens 11
1.11 Conclusion 12
References 12
2 Classification of Phytotoxins and their Mechanisms of Action 19
Andrew G. Mtewa, Chukwuebuka Egbuna, Kennedy J. Ngwira, Fanuel Lampiao, Umang Shah, and Thokozani Kachulu Mtewa
2.1 Introduction 20
2.1.1 Endophytic Phytotoxins 20
2.1.2 Secondary Metabolites 21
2.2 Possible Categorization 21
2.2.1 Biological Characteristics 21
2.2.2 Chemical Characteristics 22
2.3 Currently Available Classification Tools 24
2.4 Role of Phytotoxin Classification 25
2.4.1 Drug Discovery 25
2.4.2 Environmental Monitoring 25
2.4.3 Phytotoxins, Aquatic Life, and Water Quality 26
2.4.4 Air Contamination 26
2.4.5 Food Contamination 26
2.4.6 Security and Safety Services 27
2.4.7 Agricultural 27
2.5 Brief Mechanisms of Action 27
2.6 Conclusion 28
References 28
3 Poisonous Plants as Sources of Anticancer and Other Drugs 31
Félicien Mushagalusa Kasali, Andrew G. Mtewa, and Gaétan Tabakam
3.1 Introduction 31
3.2 Poisonous Plants in the Treatment of Cancer and Other Diseases 32
3.3 Poisonous Plant-Based Anticancer Drugs that are on the Market 33
3.4 Poisonous Plant-Based Drugs Against Other Diseases that are on the Market 33
3.5 Conclusion 33
References 75
4 Drugs in Clinical Practice from Toxic Plants and Phytochemicals 79
Tadele Mekuriya Yadesa, Patrick Engeu Ogwang, and Casim Umba Tolo
4.1 Introduction 80
4.2 Drugs in Clinical Practice from Toxic Plants 81
4.2.1 Curare 81
4.2.2 Drugs Acting on the Central Nervous System 81
4.2.2.1 Morphine 81
4.2.2.2 Cocaine 82
4.2.2.3 Ergot Alkaloids 83
4.2.3 Atropine, Scopolamine, and Hyoscyamine 84
4.2.4 Physostigmine and Other Acetylcholinesterase Inhibitors 85
4.2.5 Antitumor Agents 85
4.2.5.1 Podophyllotoxin and Etoposide 85
4.2.5.2 Taxanes 86
4.2.5.3 Vincristine and Vinblastine 87
4.2.6 Other Drugs 88
4.2.6.1 Cardiac Glycosides 88
4.2.6.2 Colchicine 89
4.2.6.3 Coumarins 89
4.2.6.4 Nicotine and the Neonicotinoids 90
References 90
5 Toxicology and Health Benefits of Plant Alkaloids 95
Ibrahim Chikowe, Andrew G. Mtewa, and Duncan C. Sesaazi
5.1 Introduction 95
5.2 Pharmacological Properties of Alkaloids 97
5.3 Toxicological Properties of Alkaloids 100
5.4 Acute and Chronic Toxicities 100
5.4.1 Genotoxicity and Tumorigenicity 101
5.4.2 Lung Toxicity, Neurotoxicity, and Teratogenicity 102
5.5 Factors that Influence the Toxicological Profile of Alkaloids 102
5.6 Conclusion 103
References 103
6 Chemical and Pharmacological Mechanisms of Plant-Derived Neurotoxins 109
Amanjot Annu, Reuben S. Maghembe, Andrew G. Mtewa, and G.M. Narasimha Rao
6.1 Introduction 110
6.2 Nerve Agents 110
6.3 Chemical Mechanisms of Neurotoxicity Induced by Organophosphate Nerve Agents 111
6.4 Mustards 112
6.4.1 Effect of HD on Skin 113
6.4.2 Effect of HD on Other Organs 113
6.4.3 The Activation of HD 114
6.4.4 Mechanism of Action 115
6.5 Plant Natural Neurotoxins 116
6.6 Plant Glycosides 118
6.7 Conclusion 119
References 119
7 Phytosedatives for Drug Discovery 123
Shahira M. Ezzat, Ahmed Zayed, and Mohamed A. Salem
7.1 Introduction 123
7.2 Treatment of Neuropsychological Disorders: The Current Scenario 124
7.3 Phytosedatives: Desirable Alternatives to Synthesized Drugs 125
7.4 Different Classes of Phytosedatives 125
7.4.1 Flavonoids 126
7.4.2 Alkaloids 128
7.4.3 Essential Oils 129
7.4.4 Other Classes of Phytosedatives 130
7.5 Plants with Reported Sedative Actions 130
7.6 Conclusion 152
References 152
8 Mushroom Species and Classification: Bioactives in Poisonous and Edible Mushrooms 163
Sadia Zafar, Farhat Jabeen, Muhammad Akram, Zarfishan Riaz, and Naveed Munir
8.1 Introduction 163
8.2 Classification of Mushrooms 164
8.2.1 Edible Mushrooms 165
8.2.2 Non-Edible Mushrooms 165
8.3 Bioactive Agents in Mushroom Species 165
8.4 Bioactive Agents in Non-Edible Mushroom Species 166
8.4.1 Polysaccharides 166
8.4.2 Glucans 166
8.4.3 Polysaccharide-Protein Complexes 174
8.4.4 Terpenes 174
8.4.5 Phenolic Compounds 175
8.4.6 Peptides and Proteins 176
8.5 Other Bioactive Compounds of Mushroom Species 176
8.6 Conclusion 176
References 177
9 Toxicity Protocols for Natural Products in the Drug Development Process 189
Tamirat Bekele Beressa, Amanjot Annu, and Andrew G. Mtewa
9.1 Introduction 190
9.2 In Vitro Toxicity Testing for Natural Products 190
9.2.1 Cell Culture Method for Toxicity Testing 191
9.2.2 Cell Culture for Acute Toxicology Testing 192
9.3 Methods Used for In Vitro Toxicity Studies 193
9.3.1 MTT Assay 193
9.3.2 Neutral Red Uptake Assay 193
9.3.3 Lactate Dehydrogenase Assay 194
9.4 In Vitro Models for Liver Toxicity 194
9.5 In Vitro Models for Nephrotoxicity Studies 194
9.6 In Vitro Model for Dermal Toxicity Testing 195
9.7 Mutagenicity Testing In Vitro 195
9.7.1 Bacterial Cell System 196
9.8 Reproductive and Teratogenicity Studies In Vitro 196
9.8.1 H295R Steroidogenesis Assay 197
9.8.2 Embryonic Stem Cell Test 197
9.8.3 Whole Rat Embryo Cultures 197
9.9 In Vivo Toxicity Testing of Natural Products 198
9.9.1 Acute Toxicity Testing 198
9.9.2 Subchronic Toxicity Testing 200
9.9.3 Chronic Toxicity Testing 201
9.9.4 Dermal and Ocular Toxicity 203
9.9.5 Toxicity Testing for Fertility and Reproduction 204
9.9.6 Combined Repeated Dose Toxicity Study with Reproduction/Developmental Testing 206
9.9.7 In Vivo Carcinogenicity Testing 207
9.10 Conclusion 208
References 208
10 Quality Control for the Safety of Natural Products 213
Tadele Mekuriya Yadesa, Patrick Engeu Ogwang, and Casim Umba Tolo
10.1 Introduction 214
10.2 Quality Assurance of Herbal Products 215
10.3 Methods of Quality Control for Herbal Products 216
10.3.1 DNA-Based Technologies 216
10.3.2 Good Practice Guidelines 216
10.3.3 Chemoprofiling 217
10.3.4 Toxicology 217
10.3.5 Monographs and Pharmacopeias 217
10.3.6 Preclinical Evidence of Safety and Efficacy 217
10.3.7 Systems Biology 218
10.3.8 Animal Experimentation 218
10.3.9 Clinical Evidence of Safety and Efficacy 218
10.4 WHO Guidelines for Quality Standardization of Herbal Formulations 219
10.4.1 Quality Control of Crude Material 219
10.4.2 Identity of Plant Material 219
10.4.3 Safety Assessment and Documentation 220
10.5 Concept of Validation in Herbal Products 220
10.6 Challenges Related to Quality Control and Monitoring the Safety of Herbal Products 221
References 222
11 Secondary Metabolites and Toxins of Microbial Origin for the Treatment of Diseases 225
Dharmandra Baria, Umang Shah, Chukwuebuka Egbuna, and Andrew G. Mtewa
11.1 Introduction 226
11.2 Antimicrobial Agents from Microbial Sources 227
11.3 Antifungal Agents from Microbial Sources 229
11.4 Anticancer Agents from Microbial Sources 230
11.5 Hypocholesterolemic Agents from Microbial Sources 235
11.6 Immunosuppressants from Microbial Sources 237
11.7 Enzyme Inhibitors from Microbial Sources 239
11.8 Antiparasitic Agents from Microbial Sources 240
11.9 Recent Advances in Drug Discovery from Microbial Sources 241
References 243
12 Development of Phyto-Antidotes Against Adverse Chemical Agents 249
Roman Lysiuk, Petro Oliynyk, Halyna Antonyak, and Dmytro Voronenko
12.1 Introduction 249
12.2 Heavy Metals and their Effects on the Body 251
12.3 Detoxification Properties of Biologically Active Substances of Plant-Based Foods 253
12.3.1 Pectins 253
12.3.2 Phytin 254
12.3.3 Betalains 255
12.3.4 Phytochelatins 256
12.3.5 Ellagic Acid 257
12.3.6 Miscellaneous 258
12.4 Current State of Clinical Application of Phyto-Antidotes 259
12.5 Further Prospects in the Search for Promising Phyto-Antidotes 260
12.6 Conclusions 261
References 262
13 Nanoformulated Herbal Drug Delivery as Efficient Antidotes Against Systemic Poisons 269
Prabir Kumar Kulabhusan, Shailaja Agrawal, Jaison Jeevanandam, and Michael K. Danquah
13.1 Introduction 269
13.2 Herbal Phytochemicals as Antidotes for Systemic Poisons 271
13.2.1 Herbal Phytochemicals as Antidotes for Heavy Metal Poisoning 272
13.2.2 Herbal Phytochemicals as Antidotes for Snake Venom Poisoning 275
13.3 Nanoformulated Herbal Phytochemicals as Antidotes 276
13.3.1 Inorganic Nanoparticles 278
13.3.2 Micelles and Liposomes 279
13.3.3 Polymeric Nanoparticles 281
13.4 Mechanism of Nanoformulated Herbal Phytochemicals against Systemic Poisoning 281
13.5 Future Perspectives 283
13.6 Conclusion 285
References 285
14 Phytochemical-Based Nanoparticles as Foes and Friends 295
Charles Oluwaseun Adetunji, Oluwaseyi Olaniyan, Juliana Bunmi Adetunji, and Itoan Roli
14.1 Introduction 295
14.2 Phytochemicals Used in the Synthesis of Nanoparticles 297
14.3 Anti-Inflammatory Effects of Nanoparticles 297
14.4 Wound-Healing Effects of Nanoparticles 299
14.5 Antiparasitic, Antifungal, and Antibacterial Activities of Nanoparticles 300
14.6 Neuroprotective Effects of Nanoparticles 304
14.7 Cardioprotective Effects of Nanoparticles 307
14.8 Anticancer Effects of Nanoparticles 308
14.9 Advantages of Nanoparticles 311
14.10 Disadvantages of Nanoparticles 311
14.11 Conclusion and Future Directions 312
References 313
15 Application of Metabolomics in Emergency Phytochemical Poisoning and Remediation 323
Mohamed A. Salem, Ahmed Zayed, and Shahira M. Ezzat
15.1 Introduction 324
15.2 Traditional Use of Medicinal Plants 325
15.3 Natural Products: Safety and Toxicity 328
15.3.1 Safety 328
15.3.2 Toxicity and Natural Killers 329
15.4 Biological Systems in Phytochemical Poisoning and Remediation 330
15.5 Metabolomics: An Important Functional Genomics Tool 332
15.5.1 Essential Components of a Metabolomics Workflow 333
15.5.2 Sample Preparation 334
15.5.3 Analytical Methods in Metabolomics 334
15.5.4 Metabolite Identification 335
15.5.5 Data Processing and Analysis 335
15.5.6 Pathway Analysis 335
15.6 Assessment of Toxicity of Herbal Medicines Using Metabolomics 335
15.7 Application of Metabolomics in Emergency Phytochemical Poisoning and Remediation 336
15.7.1 Hepatotoxicity of Triptolide 337
15.7.2 Hepatotoxicity of Noscapine 337
15.8 Conclusion 338
References 338
16 Methods for the Detection and Identification of Phytotoxins 349
Senyo Botchie and Andrew G. Mtewa
16.1 Introduction 350
16.2 Phytotoxins 350
16.2.1 Importance of Toxins 351
16.3 Methods Generally Used for Phytotoxin Detection 352
16.3.1 Biological Method Review of Detecting Phytotoxins 352
16.3.2 Chemical and Microbiological Reagents 352
16.4 Protease Inhibition Detection Protocol 354
16.4.1 Exposure of the Protease Detection Plate to a Protease Inhibitor or Bacterial Growth (Step 1) 354
16.4.2 Exposure to a Protease-Containing Solution (Step 2) 355
16.4.3 Detecting Zones of Protease Inhibition (Step 3) 355
16.5 Isolation of Phytotoxins from Microorganisms 355
16.5.1 Detection of Phytotoxins Isolated from Fungi 356
16.5.2 Purification of the Extracted Phytotoxins 356
16.6 Conclusion 356
References 357
17 Categorization, Management, and Regulation of Potentially Weaponizable Toxic Plants 359
Muhammad Akram and Rabia Zahid
17.1 Introduction 359
17.2 Management of Weaponized Natural Food Agents 360
17.3 Techniques Used for Extraction, Segregation, and Decontamination of Phytochemicals 361
17.3.1 Solvent-Based Extraction of Phenolic Compounds 361
17.3.2 Microwave-Associated Extraction 361
17.3.3 Ultrasound-Assisted Extraction 362
17.4 Techniques for Identification of Bioactive Compounds 362
17.4.1 Ultraviolet-Visible Spectroscopy 362
17.4.2 Infrared Spectroscopy 363
17.4.3 Nuclear Magnetic Resonance Spectroscopy 363
17.4.4 Mass Spectrometry 363
17.5 Types of Natural Phytotoxins 363
17.5.1 Aquatic Biotoxins 363
17.5.2 Glycosides 364
17.5.3 Other Common Phytotoxins 364
17.6 Conclusion 365
References 365
18 In Silico Modeling as a Tool to Predict and Characterize Plant Toxicity 367
Charles Oluwaseun Adetunji, William Peter Mitembo, Chukwuebuka Egbuna, and G.M. Narasimha Rao
18.1 Introduction 368
18.2 Components of In Silico Toxicity Methods 368
18.2.1 Databases 369
18.2.2 Molecular Descriptors 369
18.2.3 Toxicity Models and Modeling Software 369
18.2.4 Simulation Packages 369
18.3 Modeling Methods 371
18.4 Structural Alerts/Rule Based 371
18.5 Statistical Structure-Based Activity Relationship Models 373
18.5.1 Read-Across 373
18.6 Conclusion 374
References 375
Index 379
