Phytochemical Drug Discovery for Central Nervous System Disorders

Contributors xv Preface xxi 1 Central Nervous System Disorders and Food and Drug Administration–Approved Drugs 1 Estella U. Odoh, Chukwuebuka Egbuna, Chukwuma M. Onyegbulam, Diovu E. Obioma, Linda A. Onugwu, Obinna S. Onugwu, and Mithun Rudrapal 1.1 Incidence and Prevalence of Major Neurologic Disorders 2 1.2 Etiology 2 1.3 Pathogenesis 3 1.4 Central Nervous System Disorders and Drugs Approved by the Food and Drug Administration 3 1.4.1 Attention-Deficit/Hyperactivity Disorder 4 1.4.2 Migraine 8 1.4.3 Parkinson’s Disease 9 1.4.4 Multiple Sclerosis 11 1.4.5 Alzheimer’s Disease 11 1.4.6 Muscular Dystrophy 12 1.4.7 Epilepsy/Seizure 12 1.5 Conclusion 13 References 13 2 Drug Discovery from Medicinal Plants against Parkinson’s Disease 17 Dunya Al-Duhaidahawi 2.1 Pathogenesis of Parkinson’s Disease 17 2.1.1 Misfolding and Aggregation of Proteins 17 2.1.2 Mitochondrial Dysfunction 18 2.1.3 Neuroinflammation 18 2.1.4 Metal Ion Imbalance in the Brain 18 2.1.5 Protease-Mediated Degradation Inhibition 18 2.1.6 Oxidative Stress 19 2.2 Natural Dopaminergic Neuroprotective Compounds 19 2.2.1 Polyphenols 19 2.2.1.1 Resveratrol 19 2.2.1.2 Sesamin 19 2.2.1.3 Curcumin 19 2.2.1.4 6-Shogaol 20 2.2.1.5 Fustin 20 2.2.1.6 Biochanin A 20 2.2.1.7 Acacetin 20 2.2.1.8 Baicalein 20 2.3 Nitrogenated Phytochemicals 21 2.3.1 Alkaloids 21 2.3.1.1 Tetrahydro Berberine 21 2.3.1.2 Berberine 21 2.3.1.3 Celastrol 21 2.3.2 Saponins 21 2.3.2.1 Astragaloside IV 21 2.3.2.2 Ginseng 21 2.4 Chinese Herbal Medications and Parkinson’s Disease 22 2.4.1 Acanthopanax 22 2.4.2 Alpinia 22 2.4.3 Camellia 22 2.4.4 Cassia 23 2.4.5 Chrysanthemum 23 2.4.6 Cistanche 23 2.4.7 Gastrodia 23 2.4.8 Ginkgo 24 2.4.9 Gynostemma 24 2.4.10 Paeonia 24 2.4.11 Panax 25 2.4.12 Polygala 25 2.4.13 Polygonum 25 2.4.14 Psoralea 26 2.5 Herbal Medicines from India and Parkinson’s Disease 26 2.5.1 Withania somnifera 26 2.5.2 Tinospora cordifolia 26 2.5.3 Mucuna pruriens 26 2.6 European Plants 27 2.7 α-Synuclein as a Potential Therapeutic Target 27 2.7.1 Phytochemicals Targeting the α-Synuclein Cascade 27 2.8 Conclusion 28 References 39 3 Drug Discovery from Medicinal Plants against Alzheimer’s Disease 43 Mona M. Marzouk, Mai M. Farid, Nesrine M. Hegazi, and Shahira M. Ezzat 3.1 Pathogenesis 44 3.1.1 Amyloid Plaques 44 3.1.2 Neurofibrillary Tangles 45 3.1.3 Synaptic Damage 45 3.1.4 Cholinergic Functions 45 3.1.5 Oxidative Stress 45 3.1.6 Neuroinflammation 45 3.2 Treatment Strategies for Alzheimer’s Disease 46 3.2.1 Amyloid Hypothesis 46 3.2.2 Tau Proteins Hypothesis 46 3.2.3 Dendritic Hypothesis 54 3.2.4 Cholinergic Hypothesis 55 3.2.5 Strategies for 5-HT 6 Obstruction 55 3.2.6 Metabolic Hypothesis 55 3.3 Medicinal Plants Having Effects against Alzheimer’s Disease 56 3.3.1 Medicinal Plants Targeting the Cholinergic System 56 3.3.2 Medicinal Plants Targeting Amyloid Beta 61 3.3.3 Medicinal Plants Targeting Tau-Related Pathways 65 3.4 Natural Products with Proven Anti-Alzheimer’s Activity 66 3.5 Conclusion 66 References 70 4 Effects of Medicinal Plants and Phytochemicals on Schizophrenia 81 Nithya Rani Raju, S.V. Rashmitha, S. Pavithra, Erika Amparo Torres, M. Kishor, and Raghu Ram Achar 4.1 Mechanisms of Action Related to Schizophrenia 81 4.1.1 Vesicular Monoamine Transporters 82 4.1.2 Dopamine Receptors/Transporters 82 4.1.3 Serotonin Receptors/Transporters 83 4.1.4 Glutamate Transporters 84 4.1.5 Gamma-Aminobutyric Acid Level/Receptors 84 4.1.6 Genes Related to Schizophrenia 87 4.2 Ayurvedic Plants Used as Treatment for Schizophrenia and Related Psychoses 88 4.2.1 Allium cepa 88 4.2.2 Acorus calamus. Linn 88 4.2.3 Bacopa monnieri 89 4.2.4 Carum carvi 89 4.2.5 Celastrus panicutalus 90 4.2.6 Centella asiatica 90 4.2.7 Convolvulus pluricaulis 91 4.2.8 Coriandrum sativum 91 4.2.9 Cuminum cyminum L. 91 4.2.10 Cyperus Rotundus Linn. 92 4.2.11 Eclipta alba 92 4.2.12 Ficus religiosa 92 4.2.13 Glycyrrhiza glabra 93 4.2.14 Moringa oleifera 93 4.2.15 Nigella sativa 93 4.2.16 Piper longum 94 4.2.17 Rauwolfia serpentina 94 4.2.18 Sesbania grandiflora 95 4.2.19 Sphaeranthus indicus 95 4.2.20 Tinospora cordifolia 96 4.2.21 Valeriana wallichii 96 4.2.22 Withania somnifera 97 4.2.23 Ziziphus mauritiana 97 4.3 Conclusion 97 References 122 5 Drug Discovery from Medicinal Plants and Phytochemicals against Neuropathic Pain 137 Santwana Palai, Shyam S. Kesh, and Mithun Rudrapal 5.1 Mechanisms of Neuropathic Pain 138 5.2 Animal Models for Studying Neuropathic Pain 139 5.2.1 Streptozotocin-Induced Diabetes 139 5.2.2 High-Fat Diet 139 5.2.3 Sciatic Nerve Injury 139 5.2.4 Chemotherapy-Induced Peripheral Neuropathy 139 5.3 Medicinal Plants and Phytochemicals against Neuropathic Pain 139 5.4 Role of Plants and Phytochemicals in Different Neuropathic Pain Models 140 5.4.1 Diabetic Neuropathy 140 5.4.2 Chemotherapy-Induced Peripheral Neuropathy 153 5.4.3 Sciatic Nerve Chronic Constriction Injury 154 5.4.4 Other Neuropathic Pain Signaling Pathways 154 5.5 Future Perspectives 155 5.6 Conclusion 155 References 155 6 Brain Function, Stroke, and Medicinal Herbs 161 Shahira M. Ezzat, Rana Marghany, Nehal El Mahdi, and Mohamed A. Salem 6.1 Brain Function and Stroke 161 6.2 Strategies for Treatment of Ischemic Stroke 162 6.2.1 Neuroprotective Strategy 162 6.2.1.1 Oxidative Stress Targeting 162 6.2.1.2 Excitotoxicity Targeting 162 6.2.1.3 Apoptosis Targeting 162 6.2.2 Neurorestorative Strategy 162 6.2.2.1 Angiogenesis Targeting 162 6.2.2.2 Neurogenesis Targeting 163 6.3 Medicinal Plants for the Treatment of Stroke 163 6.4 Natural Products for the Treatment of Stroke 165 6.5 Recent Applications of Nanomedicine for Treatment of Stroke 165 6.6 Conclusion 174 References 174 7 Plant-Based Analgesics 181 Gabriel O. Anyanwu and Dorathy O. Anzaku 7.1 Current Analgesic Drugs and Their Mechanisms of Action 182 7.2 Plant-Derived Lead Compounds with Analgesic Activities 182 7.2.1 Saponins and Terpenoids 184 7.2.2 Flavonoids 184 7.2.3 Alkaloids 184 7.2.4 Glycosides 185 7.3 Analgesic Effects of Medicinal Plants Found in Nigeria 185 7.4 Limitations of Plant-Based Analgesics 194 7.5 Future Directions and Perspective for Plant-Based Analgesics 194 7.6 Conclusion 194 References 195 8 Medicinal Plants and Phytochemicals against Depression 203 Neelma Munir, Ayesha Qamar, Maria Hasnain, Huma Waqif, Maria Hanif, Zirwa Sarwar, and Shagufta Naz 8.1 Causes of Depression 203 8.1.1 Genetic Factors 204 8.1.2 Environmental Factors 204 8.1.3 Risk Factors for Depression 204 8.2 Symptoms of Depression 204 8.2.1 Symptoms of Depression in Men 204 8.2.2 Symptoms of Depression in Women 205 8.2.3 Symptoms of Depression in Children 205 8.3 Diagnosis of Depression 205 8.4 Types of Depression 205 8.4.1 Major Depressive Disorder 206 8.4.2 Persistent Depressive Disorder 206 8.4.3 Depression with Psychosis 206 8.4.4 Depression in Pregnancy 207 8.5 Treatment of Depression 207 8.5.1 Natural Treatment for Depression 208 8.5.2 Medicinal Plants as Antidepressants 208 8.5.2.1 Lavandula officinalis 209 8.5.2.2 Kaempferia parviflora 210 8.5.2.3 Asparagus racemosus 211 8.5.2.4 Passiflora foetida 211 8.5.2.5 Momordica charantia 212 8.5.2.6 Bacopa monniera 212 8.5.2.7 Valeriana officinalis 212 8.5.2.8 Rhodiola rosea 212 8.5.2.9 Withania somnifera 212 8.5.2.10 Matricaria recutita 213 8.5.2.11 Ginkgo biloba 213 8.6 Conclusion 213 References 214 9 Anti-inflammatory Agents from Medicinal Plants 219 Bui T. Tung, Tran V. Linh, Trinh P. Thao, and Nguyen D. Thuan 9.1 Role of Neuroinflammation in Neurodegenerative Diseases 220 9.2 Neuroinflammatory Drugs 222 9.3 Medicinal Plants as Sources of Anti-inflammatory Agents 231 9.3.1 Allium sativum 232 9.3.2 Azadirachta indica 233 9.3.3 Cassia tora 233 9.3.4 Euphorbia hirta 233 9.3.5 Garcinia mangostana 234 9.3.6 Punica granatum 235 9.3.7 Ricinus communis 235 9.3.8 Scutellaria baicalensis 236 9.3.9 Solanum melongena 237 9.4 Bioactive Compounds as Anti-inflammatory Agents 237 9.4.1 Curcumin 238 9.4.2 Eugenol 238 9.4.3 Epigallocatechin 3-Gallate 239 9.4.4 Guggulsterone 240 9.4.5 Resveratrol 240 9.4.6 Thymoquinone 241 9.5 Conclusion 241 References 242 10 Plant-Based Products and Phytochemicals against Viral Infections of the Central Nervous System 251 Santwana Palai, Shyam S. Kesh, and Mithun Rudrapal 10.1 Viral Infections of the Central Nervous System 252 10.2 Plant and Phytochemicals as Antiviral Agents for Central Nervous System Viral Infections 252 10.2.1 SARS Cov-2 Virus 252 10.2.2 Japanese Encephalitis Virus 262 10.2.3 West Nile Virus 263 10.2.4 Tick-Borne Encephalitis Virus 264 10.2.5 Herpes Simplex Virus 264 10.2.6 Rabies Virus 265 10.2.7 Varicella Zoster Virus 266 10.2.8 Poliomyelitis Virus 266 10.2.9 Human Immunodeficiency Virus 267 10.3 Controlling Vectors of Viral Diseases of the Central Nervous System 268 10.4 Future Perspectives 269 10.5 Conclusion 269 References 270 11 Fruits and Nutraceuticals for the Prevention and Treatment of Central Nervous System Disorders 273 Abeer M. A. El Sayed and Chukwuebuka Egbuna 11.1 Fruits for Cognition and Brain Health 274 11.1.1 Aegle marmelos 274 11.1.2 Citrullus lanatus 274 11.1.3 Citrus grandis 274 11.1.4 Phoenix sylvestris 274 11.1.5 Phyllanthus emblica 274 11.1.6 Emblica officinalis 275 11.1.7 Solanum torvum 275 11.1.8 Terminalia chebula 275 11.1.9 Blackberries 275 11.1.10 Blueberries 276 11.1.11 Strawberries 276 11.1.12 Raspberries 276 11.1.13 Cherries 276 11.1.14 Oranges 277 11.1.15 Plums 277 11.1.16 Prunes 277 11.1.17 Red Grapes 277 11.1.18 Pomegranates 278 11.2 Nutraceuticals in Ameliorating Neurodegeneration 278 11.2.1 Quercetin and Kaempferol 278 11.2.2 Withanine 278 11.2.3 Asiatic Acid 279 11.2.4 Bhilavanol A and B 279 11.3 Nutraceuticals in Alzheimer’s Disease 279 11.3.1 Flavonoids 279 11.3.2 Apigenin 280 11.3.3 Genistein, Daidzein, Glycitin 280 11.3.4 Resveratrol 280 11.3.5 Curcumin 280 11.3.6 Carotenoids 280 11.3.7 Crocin 281 11.3.8 Carnosic Acid and Rosmarinic Acid 281 11.3.9 Alkaloids 281 11.4 Nutraceuticals in Parkinson’s Disease 281 11.4.1 Vitamins: Folate, Cobalamin, Pyridoxin 281 11.5 Nutraceuticals in Depression 283 11.6 Nutraceuticals in Psychotic Disorders 283 11.7 Conclusion 283 References 284 12 Neurorestorative Potential of Medicinal Plants and Their hytochemicals 291 Babatunde O. Adetuyi, Kehinde A. Odelade, Grace O. Odine, Oluwatosin A. Adetuyi, Semiloore O. Omowumi, Olubanke O. Ogunlana, and Chukwuebuka Egbuna 12.1 Therapeutic Value of Some Medicinal Plants and their Importance 292 12.2 Types of Medicinal Plants and Their Uses 293 12.3 Phytochemicals 293 12.4 Phytochemical Constituents in Some Medicinal Plants 295 12.4.1 Onions 295 12.4.1.1 Phytochemical Constituents in Onions 295 12.4.2 Turmeric 296 12.4.2.1 Phytochemical Constituents in Turmeric 296 12.4.3 Ginger 297 12.4.3.1 Phytochemical Constituents in Ginger 297 12.4.4 Garlic 297 12.4.4.1 Phytochemical Constituents in Garlic 298 12.5 The Brain 298 12.5.1 Brain Physiology 299 12.5.1.1 Neurotransmitters and Receptors 299 12.5.1.2 Electrical Activity 300 12.5.1.3 Metabolism 300 12.5.2 Functions of the Brain 300 12.5.2.1 Perception 300 12.5.3 Motor Control 300 12.5.4 Homeostasis 301 12.5.5 Motivation 301 12.5.6 Learning and Memory 302 12.6 Brain Conditions 302 12.7 Protective Effects of Medicinal Plants on the Brain 303 12.7.1 Crocus sativus 303 12.7.1.1 Medicinal Properties of Crocus sativus 303 12.7.2 Nigella sativa 304 12.7.2.1 Medicinal Properties of Nigella sativa 304 12.7.3 Coriandrum sativum 304 12.7.3.1 Medicinal Properties of Coriandrum sativum 304 12.7.4 Ferula assafoetida 304 12.7.4.1 Medicinal Properties of Ferula assafoetida 304 12.7.5 Thymus vulgaris 305 12.7.5.1 Medicinal Properties of Thymus vulgaris 305 12.7.6 Curcuma longa 305 12.7.6.1 Medicinal Properties of Curcuma longa 305 12.8 Conclusion 305 References 306 13 Neurotransmitter Modulation by Phytochemicals 311 Prachee Dubey and Kanti Bhooshan Pandey 13.1 Sources, Structures, and Classifications of Phytochemicals 311 13.2 Neurotransmitters and Their Functions 316 13.3 Modulation of Cholinergic Signaling by Phytochemicals 317 13.3.1 Effect of Phytochemicals on Acetylcholinesterase 318 13.4 Effect of Phytochemicals on GABAergic Signaling 318 13.5 Effect of Phytochemicals on Glutamatergic Signaling 319 13.6 Modulation of Serotonergic and Dopaminergic Signaling by Phytochemicals 320 13.7 Conclusion 321 Acknowledgments 321 References 321 14 Antipyretic Agents from Plant Origins 327 Kamoru A. Adedokun, Sikiru O. Imodoye, Akeem O. Busari, Malik A. Sanusi, Abdullah Olawuyi, and Maroof G. Oyeniyi 14.1 Pyrexia Development, Its Mechanisms, and the Roles of Plant Metabolites as Antipyretics 328 14.1.1 Fever Development 328 14.1.2 Mechanisms of Fever Development 328 14.1.2.1 Humoral Pathway 328 14.1.2.2 Neural Pathway 330 14.1.3 Roles of Plant Metabolites as Antipyretics 331 14.2 Antipyretic Agents of Plant Origin 341 14.2.1 Arbutus andrachne (Family Ericaceae) 341 14.2.2 Berberis spp. (Family Berberidaceae) 343 14.2.3 Cassia fistula Linn. (Family Caesalpiniaceae) 343 14.2.4 Crataeva magma (Family Capparidaceae) 344 14.2.5 Echinops kebericho M. (Family Asteraceae) 345 14.2.6 Enicostema littorale (Family Gentianaceae) 346 14.2.7 Piper nigrum (Family Piperaceae) 346 14.2.8 Viola betonicifolia (Family Violaceace) 347 14.3 Conclusion and Future Perspectives 348 References 349 15 Medicinal Herbs against Central Nervous System Disorders 359 Ahmed Olatunde, Neelma Munir, Godwin Anywar, Maria Hanif, Huma Waqif, Habibu Tijjani, Barbara Sawicka, and Akram Muhammad 15.1 Medicinal Plants as Interventions for Central Nervous System Disorders 360 15.2 Some Medicinal Plants with Neuroprotective Action on Central Nervous System Disorders 362 15.2.1 Desmodium adscendens, Cleome rutidosperma, Withania somnifera, and Panax ginseng 362 15.2.2 Baccopa monnieri and Rauvolfia serpentina 363 15.2.3 Avena sativa and Annona squamosa 364 15.2.4 Acorus calamus, Emblica officinalis, and Strychnos nux-vomica 365 15.3 Some Central Nervous System Disorders and Medicinal Plant Interventions 366 15.3.1 Depression 366 15.3.1.1 Family Amaryllidaceae – Allium cepa 366 15.3.1.2 Family Plantaginaceae – Bacopa monnieri 367 15.3.1.3 Family Fabaceae – Glycyrrhiza glabra 368 15.3.1.4 Family Lamiaceae – Rosmarinus officinalis 368 15.3.1.5 Family Zingiberaceae – Zingiber officinale 369 15.3.2 Epilepsy 369 15.3.2.1 Family Hypoxidaceae – Hypoxis hemerocallidea 370 15.3.2.2 Family Piperaceae – Piper methysticum 371 15.3.2.3 Family Caprifoliaceae – Valeriana officinalis 372 15.3.2.4 Family Phyllanthaceae – Bridelia micrantha 372 15.3.2.5 Family Rubiaceae – Sarcocephalus latifolius 372 15.3.3 Huntington’s Disease 372 15.3.3.1 Family Ginkgoaceae – Ginkgo biloba 373 15.3.3.2 Family Araliaceae – Panax ginseng 373 15.3.3.3 Family Asteraceae – Calendula officinalis 373 15.3.3.4 Family Primulaceae – Embelia ribes 374 15.3.3.5 Family Theaceae – Camellia sinensis 374 15.4 Some Mechanistic Actions of Medicinal Herbs against Central Nervous System Disorders 374 15.4.1 In Vitro Studies 375 15.4.2 In Vivo Studies 375 15.5 Conclusion 376 References 376 16 Important Antihistaminic Plants and Their Potential Role in Health 385 Salwa Bouabdallah, Hagar A. Sobhy, Babatunde O. Adetuyi, Omayma A. Eldahshan, and Chukwuebuka Egbuna 16.1 Antihistaminic Plants 386 16.1.1 Family Acanthaceae 386 16.1.2 Family Amaranthaceae 386 16.1.3 Family Amaryllidaceae 387 16.1.4 Family Asclepiadaceae 387 16.1.5 Family Asteraceae 387 16.1.6 Family Caesalpiniaceae 387 16.1.7 Family Casuarinaceae 387 16.1.8 Family Cruciferae 388 16.1.9 Family Cucurbitacea 388 16.1.10 Family Euphorbiaceae 388 16.1.11 Family Fabaceae 388 16.1.12 Family Lamiaceae 388 16.1.13 Family Moraceae 388 16.1.14 Family Myricaceae 388 16.1.15 Family Myrtaceae 389 16.1.16 Family Olacaceae 389 16.1.17 Family Piperaceae 389 16.1.18 Family Poaceae 389 16.1.19 Family Polygalaceae 390 16.1.20 Family Scrophulariaceae 390 16.1.21 Family Verbenaceae 390 16.1.22 Family Zygophylaceae 390 16.2 Bioactive Compounds with Antihistaminic Activities 390 16.3 Conclusion 394 References 394 17 Effect of Plant-Based Anticonvulsant Products and Phytochemicals 397 Muhammad Akram, Sadia Zafar, Hassan Shah, Zerfishan Riaz, Khawaja S. Ahmad, Muhammad Riaz, Naveed Munir, Muhammad Jahangeer, Imtiaz M. Tahir, Michael P. Okoh, Muhammad A. Ishfaq, David Pérez-Jorge, Vanessa de Andrade Royo, Muhammad M. Aslam, Chukwuebuka Egbuna, and Chukwunonso O. Igboekwe 17.1 Types of Epileptic Seizures 398 17.2 Basic Mechanisms of Epilepsy 398 17.3 Epilepsy and Oxidative Stress 400 17.4 Epilepsy and Inflammation 401 17.5 Tests for Seizure Induction 402 17.6 Medicinal Plants Used to Treat Epilepsy 402 17.7 Conclusion 403 References 407 18 Application of Nanophytomedicine for the Treatment of Central Nervous System Disorders 413 Nilesh Rarokar, Nilambari Gurav, and Shailendra Gurav 18.1 Neurodegenerative Disease and the Blood–Brain Barrier 414 18.1.1 Problems Associated with Treatment of Central Nervous System Disorders 414 18.1.2 Role of the Blood–Brain Barrier 415 18.1.3 Blood–Brain Barrier Crossing Mechanism 415 18.1.4 Phytomedicine/Neuroprotective Drugs Reported for Central Nervous System Disorders 416 18.2 Nano Approaches to Central Nervous System Drug Delivery 418 18.2.1 Types of Nanocarriers 418 18.2.1.1 Liposomes 418 18.2.1.2 Micelles 418 18.2.1.3 Solid Lipid Nanoparticles 418 18.2.1.4 Phytosomes 419 18.2.1.5 Nanosponges 419 18.2.1.6 Nanoemulsions 419 18.2.1.7 Dendrimers 420 18.2.1.8 Nanoparticles 420 18.2.2 Techniques/Preparation/Methods 420 18.2.3 Mechanism of Action of Drug Release 421 18.3 Nanophytomedicine for Treatment of Central Nervous System Disorders 422 18.3.1 Alzheimer’s Disease 422 18.3.2 Parkinson’s Disease 422 18.3.3 Epilepsy 423 18.3.4 Stroke 423 18.3.5 Huntington’s Disease 424 18.3.6 Multiple Necrosis 425 18.3.7 Tumors/Gliomas/Glioblastomas 425 18.4 Challenges in Nanophytomedicine 425 18.5 Conclusion 426 References 426 Index 431