Poisonous Plants and Phytochemicals in Drug Discovery

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