PHARMACODYNAMIC BASIS OF

HERBAL MEDICINESECOND EDITION

Manuchair Ebadi, Ph.D., F.A.C.C.P.Chester Fritz Distinguished Professor of Pharmacology and of Clinical Neuroscience

Associate Vice President for Medical ResearchSchool of Medicine and Health Sciences

University of North DakotaGrand Forks, North Dakota

@ Taylor &. FrancisTaylor & Francis Croup

Boca Raton London New York

CRC is an imprint of the Taylor & Francis Croup,an informa business

ContentsChapter 1 The Pharmacokinetic Basis of Therapeutics 1

Introduction 1Administration of Drugs 2

Duration of Action 2Nature of the Drugs 2Special Circumstances 3Drug Delivery by Iontophoresis or Phonophoresis 3Liposomal Drug Delivery System 3Bioavailability 3

Absorption of Drugs 3Drug Particle Size 4Buccal and Sublingual Absorption 4Intranasal Delivery 4Rectal Administration 5

Transport Mechanisms 5Passive Diffusion 5Carrier-Mediated Transport 5Facilitated Transport 6Ion Pair Transport 6Pinocytosis 6Receptor-Mediated Endocytosis 6

Other Factors Controlling the Rate of Absorption of Drugs 6Degree of Ionization 7Surface Area 8Blood Flow 8Gastric Emptying Time 8

Hepatic First-Pass Effect 9Distribution of Drugs 9Binding of Various Drugs to Plasma Proteins 10

Albumin 10Alpha,-Acid Glycoprotein 10Other Glycoproteins 10Lipoproteins 11

Tissue Localization of Drugs 11Apparent Volume of Distribution of Drugs 12The Blood-Brain Barrier 12The Placental Barrier 12Drugs in Pregnancy and the Newborn 13

Drug Therapy in Pregnancy 13Drug Therapy in the Newborn 13

The Site of Action of Drugs 13Nature and Type of Pharmacologic Receptor Sites 13Dose-Response Relationship 14Potency and Efficacy 14

Physiologic and Pharmacologic Antagonism 16Enhancement of Drug Action 16Therapeutic Index 16Biotransformation 17

Hepatic Drug Metabolism 17Nonhepatic Metabolism 17

Plasma 17Lung 18Intestinal Epithelium 18

Molecular Biology of Multiple Isoenzymes of P-450 18Scheme of the Mixed-Function Oxidation Reaction Pathway 18Consequence of Biotransformation Reactions 19

Precursor Activation 19Metabolic Activation of Drugs 19

Conversion to Metabolites with Dissimilar Actions 19Conversion to More Active Products 19Lethal Synthesis 19

Drug Metabolite Kinetics 19Factors That Modify the Metabolism of Drugs 20

Pharmacogenetics 20Liver Disease 20The Influence of Age 20Enzyme Induction and Inhibition 20Clinical Implications of Enzyme Induction and Inhibition 21

Renal Excretion of Drugs 21Rate of Excretion of Drugs by the Kidneys 21Significance of Blood Flow for Drug Clearance 22Half-Life of a Drug 23

Chapter 2 Pharmacodynamics 25

Introduction ~rSite of Action ~cMode of Action 25Mechanism of Action 25Structure-Activity Relationship 25Drug Actions Unrelated to Structures 26Drug Receptor-Specific Interaction ' "^ 26Cellular Sites of Actions of Drugs 27

Drug-Coenzyme Interactions 27Isoniazid and Pyridoxal Phosphate 27Folk Acid and Trimethoprim-Sulfamethoxazole.... 27

Drug-Enzyme Interactions 27Allopurinol, Xanthine Oxidase, and Hyperuremk States 28Drugs and Bronchial Asthma 28

Drug-Nucleic Acid Interactions 28

The Interactions of Drugs with Neuronal Elements. 29Interaction of Drugs with the Endocrine System ".'~Z. 29

Alpha-Methyldopa and Renin 29Drugs and Prolactin «g

Chapter 3 Adverse Reactions and Drug-Drug Interactions 31

Introduction 31Definitions 31

Iatrogenic Reactions 31Allergic Reactions 31Idiosyncratic Reactions 32Tolerance and Tachyphylaxis 32Supersensitivity 33Pharmacokinetic Interactions 33Interaction at the Site of Absorption 33

Alteration of Gastric pH 33Formation of Complex 34Alteration in Gastric Emptying Time 34

Interactions at the Plasma-Protein Binding Sites 34Interactions at the Stage of Drug Biotransformation 35Interactions at the Site of Excretion 36

Chapter 4 Herb-Drug Interactions 37

Herbs and Drug Effects 37Potential Interactions between Alternative Therapies and Warfarin 38Anticoagulants and Thrombolytic Agents 38Aggregin and Platelet Aggregation 42Vitamin E and Platelet Aggregation 42Platelet-Activating Factor 42Platelet-Inhibiting Drugs 42Fibrinolysis 43Hirudin and Thrombin 43Agents that Interfere with Coagulation 43Oral Anticoagulants 44Herbs with Coumarin, SalicyJate, or Antiplatelet Drugs 44

Feverfew 44Garlic 45Ginger 45Ginkgo 45Coenzyme Ql0 45Danshen 45Devil's Claw 46Ginseng 46Green Tea 46Papain 46Vitamin E 46

Chapter 5 Natural Products as a Resource for Established and New Drugs 49

The Role of Herbal Medicines in Health Care 49Drug Therapy in Chinese Traditional Medicine 50

Prescription of Multiple Herbs in CTM 50Pharmacological Classification of Herbs According to CTM 51

Classic Plant Substances 53Caffeine 53

Capsaicin 53P-Carotene 53Colchicine 53Nordihydroguaiaretic Acid 53Pilocarpine 56Quinine 56Scopolamine (Hyoscine) 56Tetrahydrocannabinol 56Theophylline 56

Antimalarial Agents 56Cardiovascular Drugs 57CNS Drugs 57Antibiotics 58Antineoplastic Agents 59Cholesterol-Lowering Agents (Hypolipemics) 60Immunomodulators .61Recently Evaluated Herbal Products 61

Aloe Vera Gel (Aloe vera) 61American Dwarf Palm (Serenoa repens) 61Cranberry juice (Vaccinium spp.) 61Evening Primrose Oil (Oenothera biennis) 61Feverfew Leaf (Tanacetum parthenium) 62Garlic (Allium sativum) 62Ginger Root (Zingiber officinale) 62Ginkgo Leaf (Ginkgo biloba) 62Hawthorn {Crataegus monogyna and C. laevigata) 62Horse Chestnut (Aesculus hippocastanum) 62Ipecacuanha (Cephaelis ipecacuanha and C. acuminata) 62Ispaghula Husk (Plantago ovato) 63Kava-Kava (Piper methysticum) 63Marijuana (Cannabis sativa) 63St. John's Wort (Hypericum perforatum) 63Tea Tree Oil (Melaleuca alternifolia) ZZZZZZ. ......(AWheat Bran (Triticum spp.) 53

New Uses for "Old" Drugs 53

Chapter 6 Alternative Therapies 55

Introduction ,,

Why Patients Use Alternative Medicine ".'.'.'.'.'.'.'.'.. 65Acupressure , ,Acupuncture „Aromatherapy , ,Auricular Therapy \ , .Ayurveda ,Biodynamic Massage ^Bioenergetic Therapy ZZZZ. 67Chi Kung Medicine , ?

Chinese Herbalism , g

Chiropractic Medicine , g

Crystal and Gem Therapies ZZZ 68

Cupping Therapy 68Dietary and Nutritional Therapies 69Eastern Herbal Medicine 69Environmental Therapies 70Flower and Tree Remedies 70Food and Diet Therapy 71Geopathic Therapy 72Gestalt Therapy 72Herbal Medicine 72Homeopathy 74Hydrotherapy 74Hypnosis and Hypnotherapy 74Iridology 74Japanese Medicine 75Light Therapy 75Massage Therapy 75

Shiatsu 75Therapeutic Massage 75Reflexology 76Sports Massage 76Baby Massage 76Biodynamic Massage 76

Moxibustion 76Myotherapy 76Native American Herbal Medicine 76Naturopathy (Medicatrix Naturae) 77Osteopathy 77Persian Medicine 77Polarity Therapy 78Psychic Healing 78Psychological Therapies 78

Analytical Therapy 78Behavioral Therapy 79Humanistic Therapy 79Integrative Therapy 79Meditation Therapy 79Sound Therapy 79

Reflexology (Reflex Zone Therapy) 79Reiki Therapy 80Relaxation Therapies 80

Rolfing Medicine 80Shamanistic Medicine 80T'ai Chi Chuan Medicine 81Therapeutic Diets 81

Exclusion Diet 81Vegetarian Diet 81Vegan Diet 81Food Combining Diet 81Anti-Candida Diet 81Liver Diet 81

Low Blood Sugar Diet 81

Macrobiotic Diet ^2Tibetan Medicine 82Transcendental Meditation (TM) 82Transpersonal Therapies <"Visualization Therapy 83Yoga 8 3

Chapter 7 Herbal Therapeutics Then and Now 85

Introduction °5Agnus Castus 85Agrimony 85Alfalfa 85Aloe 85Aloe Vera 86Angelica 86Aniseed 86Apricot 86Arnica 86Artichoke 86Asafoetida 86Avens 86Bayberry 87Black Cohosh 87Bloodroot 87Blue Cohosh 87Blue Hag 87Bogbean 87Boldo 87Boneset 87Borage 88Broom 88Buchu 88Burdock 88Burnet 88Calamus 88Calendula 88Capsicum g9Cascara g9Cascara Sagrada g9Cassia g9Cat's Claw g9

Celery ZZZZZZZZZZZZZZ. ZZZZ.&9Centaury ogCereus 09Chamomile OQChamomile (German) 90Chamomile (Roman) QQChaparral OQCinnamon on

Clivers 90Clove 90Cola 91Coltsfoot 91Comfrey 91Corn Silk 91Couchgrass 91Cowslip 91Cranberry 91Damiana 92Dandelion 92Devil's Claw 92Dong Quai 92Drosera 92Echinacea 92Elder 92Elecampane 93Eucalyptus 93Euphorbia 93Evening Primrose 93Eyebright 93False Unicorn 93Fenugreek 93Feverfew 93Figwort 94Frangula 94Fucus 94Fumitory 94Garlic 94Gentian 94Ginger 94Ginkgo 95Ginkgo biloba 95Ginseng (Eleuthemcoccus) 95Ginseng (Panax) 95Golden Seal 95Gravel Root 95Ground Ivy 96Guaiacum 96Hawthorn 96Holy Thistle 96Hops 96Horehound (Black) 96Horehound (White) 96Horse Chestnut 96Horseradish 97Hydrangea 97Hydrocotyle 97Ispaghula 97Jamaica Dogwood 97Juniper 97

Kava 97Lady's Slipper 97Lemon Verbena 97Licorice 98Liferoot 98Lime Flower 98Lobelia 98Ma Huang and the Ephedra Alkaloids 98Marshmallow 98Mate 99Meadowsweet 99Mistletoe 99Motherwort 99Myrrh 99Nettle 99Panax ginseng 99Parsley 99Parsley Piert 100Passionflower 100Pennyroyal 100Pilewort 100Plantain JQOPleurisy Root 100Pokeweed JQOp °p l a r ZZZZZZZZZZZZ^. ZZZZZZZ.100Prickly Ash (Northern) 101Prickly Ash (Southern) IQIPulsatilla ,QJQuassia .QJQueen's Delight JQJ

Raspberry ZZZZZZZZZZZZZZ 101Red Clover ] 0 ,Rhubarb ]ft2Rosemary m

1U/^ 102Sarsapanlla 1 0 2

Sassafras -Saw Palmetto ft2

"""^"IIIIII:::::: \? • • • • • • • • • • ^ I I I I I I : : : : : : \ v aSenna

Shepherd's Purse.ZZZZ ]? ,Skullcap... m

» 1 n-2

Skunk Cabbage .... l

Slippery Elm ZZ1 | j£Squill 1 0 3

St. John's Wort Z. 1 0 3

Stone Root... 1 0 3

Tansy.... 104Thyme 1 0 4

Uva-Ursi.... 1 0 4

Valerian I 0 4

104

Vervain 104Wild Carrot 104Wild Lettuce 105Willow 105Witch Hazel 105Yarrow 105Yellow Dock 105Yucca 105

Chapter 8 Dietary Antioxidants 107

Introduction 107The Role of Diet in Curing and Preventing Diseases 107Antioxidant Capacity of Vegetables and Fruits 107Antioxidant Activity in Cereal Grains 108Antioxidant Actions of Du-Zhong 108Oxidative Stress and Chemotherapeutic Effectiveness 110Principle of Cancer Therapy 110Chemotherapy 110Alkylating Agents 112

Nitrogen Mustards 112Chlorambucil 112Cyclophosphamide 112Alkyl Sulfonate 112Nitrosoureas 113Triazenes 113Antimetabolites 113

1313141515151616161616161717171717171718181919

P-Carotene 120

Folic Acid AnalogsPyrimidine AnalogsDeoxycytidine Analogs

Purine Antimetabolites.Natural Products

Vinca Alkaloids..DactinomycinMithramycinDaunorubicin and Doxorubicin.Bleomycin

Miscellaneous Antineoplastic Agents.AsparaginaseHydroxyureaCis-PlatinumCarboplatinProcarbazineEtoposideCancer-Chemotherapy-Induced Emesis.

Oxidative Stress and Interference with the Cytotoxic Effects of Antineoplastic Agents....Antioxidant Effects on Antineoplastic Activity and Chemotherapy-Induced Side Effects.

Vitamin EVitamin CCoenzyme Q10 (Ubiquinone).

Glutathione (GSH) and Glutathione Esters 120jV-Acetylcysteine 121Glutamine 121Selenium 121Genistein and Daidzein 122Quercetin 122

Conclusions 123

Chapter 9 Herbal Drugs and Their High Demand in Treating Diseases 125

Introduction 125Laws Regulating Herbs and Dietary Supplements 126

Food, Drug, and Cosmetic Act 126Nutrition Labeling and Education Act of 1990 126Dietary Supplement Health and Education Act of 1994 127Food and Drug Administration Modernization Act 127

Scientists Who Pioneered Herbal Medicine 128

Chapter 10 Algae 139

Introduction 139Kainic Acid 140Domoic Acids 141Toxicity of Caulerpa 142Toxicity of Gracilaria 142

Chapter 11 Alkaloids 143

Introduction 143Classification J44

The Group Containing Aliphatic Bases with an Aromatic Nucleus... 144The Pyrrolidine Group 144The Pyridine Group 144The Glyoxaline Group 145Alkaloids with Condensed Pyrrolidine and Piperidine Rings 146Derivatives of Quinoline 1 4 7

Derivatives of Isoquinoline 147Phenanthrene ,47Indole Derivatives ,47The Purine Bases ]4gAlkaloids of Unknown Constitution j49

Chapter 12 Aloe and Colon Function 151

IntroductionAloe Preparations

Chemical Composition of Aloe Plants ] 5 2

The Therapeutic Uses of Aloe ,~Aloe and Cancer J.

Aloe and AIDS ZZ. tAloe and Asthma ZZZZZZZ^ «

Aloe and Diabetes 153Aloe Gel and Skin Ailments 153Aloe and Constipation 153

Movements of the Colon 154Mixing Movements: Haustrations 154Propulsive Movements: "Mass Movements" 154Initiation of Mass Movements by the Gastrocolic and Duodenocolic Reflexes 155

Defecation 155The Defecation Reflexes 155

Other Autonomic Reflexes Affecting Bowel Activity 157Constipation 157

Definition 157Causes 158

Cathartics 158Emodin or Anthraquinone Cathartics 159Cascara Sagrada 160Senna 160Rhubarb 160Aloe 160Castor Oil 161Ricin 161Abrin 161CrotonOil 161Resin of Podophyllum 162Jalap, Scammonium, Ipomea 162Colocynth, Elaterin, and Bryonia 162

Chapter 13 Banisterine, Selegiline, and Parkinson's Disease 163

Introduction 163The Actions of Acetylcholine and Dopamine 163History 164Selegiline 164Clinical Pharmacokinetics of Selegiline 165Lack of Adverse Interaction between Selegiline and Citalopram or between Selegiline

and Cabergoline 166Distribution of Monoamine Oxidases A and B mRNAs in the Rat Brain by In Situ

Hybridization 167Inhibition of Monoamine Oxidase B by Banisterine and Selegiline and the Initial

Rationale of Using Them in Parkinson's Disease 168Protection of Dopaminergic Neurons by Rasagiline 169Protection against MPTP-Induced Neurotoxicity by Selegiline 171Protection by Selegiline of Dopaminergic Neurons in Culture from Toxic Factors 172Protection by Selegiline of Dopaminergic Neurons from Glutamate-Induced

Excitotoxicity 173Selegiline: A Calmodulin Antagonist 175Induction by Selegiline of Dopamine Release through an ATP-Sensitive Potassium

Channel 176Neurotrophic-Like Action of Selegiline: Rescue of Axotomized Motorneurons

Independent of Monoamine Oxidase Inhibition 177Restoration by Selegiline of Serum Insulin-Like Growth Factor-I in Aged Rats 181

Protection by Selegiline of Dopaminergic Neurons from Toxicity Induced byGlutathione Depletion 182

Increase by Selegiline of the Striatal Superoxide Dismutase 185Protection by Selegiline against Peroxynitrite- and Nitric-Oxide-Induced Apoptosis 186Antiapoptotic Actions of Selegiline in a Variety of Neurons 187Stimulation by Selegiline of Biosynthesis of Cytokines Interleukin-1 p and Interleukin-6 188Interleukin 1 189Interleukin 6 189Banisterine and Selegiline for the Treatment of Parkinson's Disease 190

Rigidity 191Hypokinesia 191Abnormal Gait and Posture 191Other Clinical Features 191

Summary and Conclusions 193

Chapter 14 Belladonna Alkaloids: Autonomic Drugs 195

Introduction 195Solanaceae or Nightshade Family 195

Occurrence 196History 196Chemistry 197Botany of Solanaceae 198

Pharmacognosy of Belladonna 198Preparation of the Leaves 199Preparations of the Root 199Atropine and Its Derivatives 199

Belladonna Alkaloids and the Autonomic Nervous System 199Comparison of the Somatic and Autonomic Nervous Systems 199Neurochemical Basis of Cholinergic Transmission 200Division and Functions of the Autonomic Nervous System 200Classification of Cholinergic Receptors 202Cholinergic Receptor Blocking Agents " I "1.203Dose-Dependent Effects of Atropine ZZZZZ. ""203The Historical Uses of Belladonna Alkaloids ZZZZZZZZ^. I"203The Modern Uses of Synthetic Muscarinic Receptor Antagonists!!" ZZZZ.2MContraindications to Anticholinergic Agents 205Hyoscyamine 205Scopolamine ~orSynthetic and Semisynthetic Substitutes for Belladonna Alkaloids 206

Quaternary Ammonium Muscarinic Receptor Antagonists 206Ipratropium _o6Methoscopolamine 2o7Homatropine Methylbromide 207Methantheline o 7

Propantheline „-Other Compounds -nQ™ . J\)o

lertiary-Amine Muscarinic Receptor Antagonists ZZZZZZZZZZZZ ZZZZZZZ.MChapter 15 Blueberry (Vaccinium) 2 0 9

Chapter 16 Botulinum Toxin 213

Introduction 213Botulinum Toxin Type A (Oculinum) 213Botulism Antitoxin, Trivalent (ABE) Equine 213Uses of Botulinum Toxin Injection in Medicine Today 213Rationale for Treatment with Botulinum Neurotoxin 214

Ophthalmic Disorders 214Movement Disorders 215Spasticity 215Neuromuscular Disorders 215Pain 216Ear, Nose, and Throat Disorders 216Disorders of Pelvic Floor 216Overactivity of Smooth Muscles 216Hypersecretion of Glands Supplied by Cholinergic Sympathetic or

Parasympathetic Neurons 216

Chapter 17 Brussels Sprouts 217

Introduction 217Effects of Brussels Sprouts on Oxidative DNA Damage 217

Chapter 18 Cannabis 221

Introduction 221The Psychoactive Effects of Cannabis 221Marijuana in History 223Botanical Properties of Cannabis indica or Indian Cannabis (Indian Hemp) 224Marijuana-Induced Inebriation 225Cannabinoid Receptor Subtypes 226

Cannabinoid Receptor (CB,) 227Cannabinoid Receptor (CB2) 227

Cannabinoid Receptors and Their Endogenous Agonist, Anandamide 227Central Nervous System Cannabinoid Receptors 228Therapeutic Potential of Cannabinoid Ligands 228

Movement Disorders 228Multiple Sclerosis 229Huntington's Chorea 229Neuroprotection 229Cannabis for Migraine 230

Antiemetic Effects of Cannabis 230The Physiology of Vomiting 230The Central Control of Vomiting 230Drugs to Control the Vomiting Caused by Cancer Therapy 231Ondansetron 231Dexamethasone 231Metoclopramide 232Phenothiazines 233

Cannabinoids 233Benzodiazepines 233

Anticipatory Nausea and Vomiting 233

Delayed Emesis 233Multiple-Day Cisplatin Chemotherapy 233Summary 233

Cannabis for Dyskinesia 234Conclusion 236

Chapter 19 Capsicum, Rosemary, and Turmeric 237

Chapter 20 Carotenoids 239

Introduction 239Prostate Cancer 240Breast Cancer 240Cancer of the Head and Neck 240Cardiovascular Disease 240Age-Related Macular Degeneration 241

Chapter 21 Chocolate 243

Chapter 22 Cinchona Tree 245

Introduction 245Cinchona: A Peruvian Bark 245Varieties of Cinchona 245Composition of Cinchona 245Quinine for Treatment of Malaria "". 247Blood Schizonticides 248Quinine Sulfate: A Classic Drug " 248Other Actions of Quinine ' 250

Colloids and Surface Phenomena 250Local Actions 251Ulcers " 25iSunburn Prophylaxis [[ 251Quinine as Anesthetic 251Antiseptic Action , , ,Effect on Digestion ^ 251Antipyretic Action 251

^ ^Skeletal Muscle .Cinchonism "_ J.

Skin Eruptions and Idiosyncrasy " 252

Chapter 23 Coca253

Introduction....

coca ZZZZZZZZZZZZ 253

Habitat ZZZZZZZZZ'. 253

Synonym ^Er-y-throx'y-lon L 2 ^

Co'ca 253History 253

253

Plant 254Commercial Properties 255Botanical Properties 255Chemical Composition 256

Cocaine as a Local Anesthetic 256General Pharmacology of Local Anesthesia 257

Vascular Supply at the Site of Injection 257Systemic Reactions 258

Cardiovascular Effects 258Central Nervous System Effects 258Allergic Reactions 258Effect of Cocaine 259

Mechanism of Local Anesthetic Action of Cocaine 259Detailed Pharmacology of Cocaine as a Local Anesthetic 259

Selective Action on Motor and Sensory Fiber 260Peripheral Paralysis of Special Sense Nerves 261Site of Action 261Combination of Anesthetics 261Potassium Synergism 261Alkalinization 261Other Synergisms 262Epinephrine Anesthetic Combinations 262Local Vascular Action 262Practical Application of Local Anesthetics 262Local Ischemia 263Surface Anesthesia 263Ophthalmic Anesthesia 263Actions of Cocaine on the Eye 263Insoluble Anesthetics for Open Wounds and Ulcers 263Conduction and Infiltration Anesthesia 264Spastic Rigidity of Skeletal Muscles 264Spinal Anesthesia 264Sympathetic Stimulation 264Circulation 265Cerebral Stimulation 265Incoordination, Narcosis, and Convulsions 265Emesis 265Temperature 265

Examples of Currently Used Local Anesthetics 265Procaine 265Chloroprocaine 265Tetracaine 266Lidocaine 266Mepivacaine 266Prilocaine 266Bupivacaine 266Etidocaine 266

Clinical Uses of Local Anesthetics 266Infiltration Anesthesia 266Field Block Anesthesia 266Nerve Block Anesthesia 267

Intravenous Regional Anesthesia (Bier's Block) 267Spinal Anesthesia 267Epidural Anesthesia 268Epidural and Intrathecal Opiate Analgesia 268

Safe and Toxic Dosage of Local Anesthetics 268Destruction of Cocaine In Vitro: Sterilization 269Cocaine, A "Nerve Stimulant" 269

Cocaine Addiction 270Uses of Cocaine in the 18th Century 270Cocaine: A Psychostimulant 270Cocaine Blocks Dopamine Transporter 271Biosynthesis of Dopamine 271Cocaine Withdrawal Symptoms and Signs 272Pharmacological Interventions 272

Chapter 24 Colchicine and Gout 275

Introduction 275History 275Gout and Hyperuricemia ....275Allopurinol 276Uricosuric Agents 276Treatment with Colchicine for Gout .277

Pharmacological Properties 277Effect in Gout 277Effect on Cell Division 277Other Effects 277Pharmacokinetics and Metabolism 278Toxic Effects 278Therapeutic Uses 278Acute Attacks 278Prophylactic Uses 279

Other Uses of Colchicine 279

Chapter 25 Compositae 2 8 1

IntroductionSesquiterpene Lactones ^p,

Sesquiterpene-InducedNeurotoxicity ZZZZZZZZZZ. 282Tanacetum Parthenium (Feverfew) 282

Other Asteraceae Groups. 8 ,;;;;;;;;;; f*; ; ; ; ; ; fArtemisia ,,Baccharis ,

Tg4Elephantopus

Helenium ZZZZZMontanoaPackera ZZ^. 285

Parthenium 2 8 5

Tithonia 2 8 5

285

Chapter 26 Curare and Neuromuscular Blockade 287

Introduction 287Curare 287Skeletal Muscle Relaxants 288

The Neuromuscular Junction 289Nicotinic Cholinergic Receptors 289Mechanism of Action of Neuromuscular Blocking Agents 289

Phase I: Blockade (Depolarization) 289Phase II: Blockade (Desensitization) 290

Sequence and Onset of Neuromuscular Blockade 290Factors Affecting Neuromuscular Blockade 292

Drug Interactions 292Electrolytes 293Acid-Base Balance 293Hypothermia 293Disease States 294Age 294

Side Effects of Neuromuscular Blocking Agents 294Cardiovascular Effects 294Ocular and Muscular Effects 294Histamine Release 294

Erythrina Alkaloids 294Methonium Compounds 295

Chapter 27 Daffodil and Alzheimer's Disease 297

Introduction 297History and General Effects 297Compounds Found in Daffodils 297

Lycorine (Formerly Narcissine) 299Galanthamine 299

Chemistry of Galanthamine 299Pharmacological Mechanisms of Galanthamine Activity 299Pharmacokinetics of Galanthamine 299Use of Galanthamine to Treat Depression 300Specific Studies Showing Antinociceptive Effects of Galanthamine 300Summary 300

The Treatment of Cognitive Impairment in Alzheimer's Disease 301Therapeutic Objectives in Alzheimer's Disease 301The Cholinergic Hypothesis of Alzheimer's Disease and Cholinergic Enhancement

Strategies 301Acetylcholinesterase Inhibitors 302

Tetrahydroaminoacridine 302Pharmacology 302Pharmacokinetics 303Clinical Applications 303Side Effects 303Drug-Drug Interactions 303Overdosage 303

Physostigmine and Its Derivatives 303Limitations of AChE-Inhibitor Therapy in Alzheimer's Disease 303

Cholinergic Agonists 305Acetylcholine Precursors 305Acetylcholine-Releasing Agent 305Noncholinergic Neurotransmitter Replacement Strategies 305

Monoaminergic Drugs 305Neuropeptides 305Drugs Affecting Glutamate Receptor Sites 305Nootropics 305Antioxidants 305Desferrioxamine: An Iron-Chelating Agent 306Nerve Growth Factor 306Anti-Inflammatory Agents 306

Chapter 28 Eggplant 309

Chapter 29 Ephedrine (Ma Huang): A Decongestant and Vasopressor 311

The Actions of Ephedrine 311History 311Ephedra 312Ephedrine 312Pharmacological Properties of Ephedrine 313Effect on Organ Systems 313

Cardiovascular 313Bronchi 314Eye " 314Other Smooth Muscle ....314Glands 314Central Nervous System 315Skeletal Muscle 315

Routes of Administration 315Absorption, Fate, and Excretion 315Therapeutic Uses of Ephedrine 315

Bronchial Asthma 315Allergic Disorders 316Spinal Anesthesia 316Heart Block 3 ^Mydriasis ^Enuresis -,,7Myasthenia Gravis 3j7

Miscellaneous Actions of Ephedrine ZZZZZ. 317Signs and Symptoms of Ephedrine Toxkhy ..ZZZZZZZZZZZ 317

Chapter 30 Ergot, Its Alkaloids, and Headache ....319

Introduction 19

Ergot and the Ergot Alkaloids ZZZZZ. 319Source ZZ.ZZZZZ 319Constituents of Ergot 3 l 9

History 320Chemistry 321

The Efficacy of Ergotamine in Headache 321Introduction 322Classification of Headaches 323Precipitating Factors of Headache Symptoms 323Migraine: The Involvement of Serotonin and the Effectiveness of Sumatriptan in

Migraine Headache 324Metabolism of Serotonin 324Actions of Serotonin 324Serotonergic Abnormalities 325Other Hypotheses 325Serotonin Receptors and Their Subtypes 325Serotonin Receptor Antagonists 325Clinical Efficacy of Sumatriptan 325Side Effects of Sumatriptan 326Mechanisms of Antimigraine Action of Sumatriptan 326

Prevention and Treatment of Migraine 326Methysergide 326

Calcium and Calcium-Channel Blockers 328Calcium Antagonists 328Other Preventative Agents 328

Cranial Neuralgias 328Trigeminal and Glossopharyngeal Neuralgias 328Ergoloid Mesylates (Dihydrogenated Ergot Alkaloids; Dihydroergotoxine) 329

Chapter 31 Flavonoids 331

Introduction 331The Pharmacodynamics of Flavonoids 332

Protein Kinase C Inhibition 332Phospholipase A2 Inhibition 333Na+-and K+-ATPase Inhibition 333Lipoxygenase and Cyclooxygenase Inhibition 333Cyclic Nucleotide Phosphodiesterase Inhibition 333Reverse Transcriptase Inhibition 333HIV-1 Proteinase Inhibition 334Ornithine Decarboxylase Inhibition 334Topoisomerase Inhibition 334Xanthine Oxidase Inhibition 334Aromatase Inhibition 334Aldose Reductase Inhibition 335FAD-Containing Monoamine Oxidase Inhibition 335Carbonyl Reductase Inhibition (Aldo-Keto-Reductase Family of Enzymes) 335Hyaluronidase Inhibition 335Histidine Decarboxylase and DOPA Decarboxylase Inhibition 335Aldehyde and Alcohol Dehydrogenase Inhibition 335RNA and DNA Polymerase Inhibition 336Human DNA Ligase I Inhibition 336Sialidase Inhibition 337

Antioxidant Properties of Flavonoids 337

Mutagenicity and Genotoxicity of Excessive Flavonoid Intake 337Characteristics and Content of Flavonoids in Common Foods 333

Safe Flavonoid Intake 310

Chapter 32 Flaxseed 341

Chapter 33 Folate in Fruit 343

Introduction ».,Functions of Vitamin B l 2 -,.Bioavailability of Vitamin B l 2 343

Food Sources of Vitamin B12 for Elderly People ZZZZZZZ. 344Factors Contributing to Declining Vitamin B12 Status with Aging 344Prevalence of Vitamin B l 2 Deficiency in Elderly People 344

Effects of Deficiency V7.Neurological Effects of Deficiency ZZZZZZZZZ. 344Hematological Effects of Deficiency ..." 344

Gastrointestinal Effects of Deficiency ."..' 344

Indicators of Hematological Status ' m

Replacement Therapy V7Function of Folic Acid in Gestation....!...".." \ZFunction in Cardiovascular Disease ZZZ ™<Antioxidant Vitamins..

between Vitamin Bl2 and Folic Acid 34 6

Chapter 34 Food-Drug Interactions.347

IntroductionBiotransformation 347Hepatic Drug Metabolism [ 3 4 7

Nonhepatic Metabolism 347Plasma 347Lung ^ 347

Intestinal Epithelium 3 4 8

Molecular Biology of M u l t i p k k o ^ z ^ ' o f p ^ o ' 3

Precursor Activation 349Metabolic Activation of Drugs 3 4 9

r : : s : ° ^ e t ^ :::^, h »n ,0 More Ac,,,e t ^ ™ ' " ^ * 'Lethal Synthesis 350

Drug Metabolite KineticsFactors That Modify the Metabolism "JiZZ

350350' : ' n a t M o d l t y t h e Metabolism of Drugs 3 5 °

Pharmacogenetics 8 350Liver Disease 350The Influence of Age 351Enzyme Induction and'lnhibition ZZZZZZZZZ..351

Chapter 35 Foxglove, Cardiac Glycosides, and Congestive Heart Failure 355

Digitalis 355The Digitalis Series 355Chemistry 356Cardiac Glycosides in the Treatment of Congestive Heart Failure 358Biochemical Basis of Myocardial Contraction 359The Positive Inotropic Action of Cardiac Glycosides 360

The Modes of Action of Cardiac Glycosides 360Electrophysiological Effects of Cardiac Glycosides 360Digitalis Toxicity 361

Symptoms of Digitalis Toxicity 361Cardiac Effects 361Gastrointestinal Effects 362Visual Effects 362Neuropsychiatric Symptoms 362

Treatment of Digitalis Toxicity 362General Treatment 362Specific Treatment 362Antidigoxin Antibodies 362

Drugs Acting on Peripheral Dopamine Receptors 362Dopamine Receptors 362

Drugs Inhibiting Phosphodiesterase 363Vasodilators and Angiotensin Antagonists 363

Receptor-Dependent Vasodilation 364Endothelium-Dependent vs. Independent Vasodilators 364

Chapter 36 Ginkgo biloba 367

Introduction 367Ginkgo biloba Extract and Inhibition of Monoamine Oxidase A and B in Living

Human Brain 367Ginkgo biloba and Nitric Oxide 368

Chapter 37 Ginseng and Cholinergic Transmission 371

Introduction 371Cholinergic Transmission 372

Division and Functions of the Autonomic Nervous System 372Neurochemical Basis of Cholinergic Transmission 373Classification of Cholinergic Receptors 373Cholinergic (Cholinomimetic) Receptor Agonists 374Anticholinesterase Agents 374

Structure of Acetylcholinesterase 374Classification of Cholinesterase Inhibitors 374Antidote to Irreversible Cholinesterase Inhibitors 375Cholinergic Receptor Blocking Agents 375Dose-Dependent Effects of Atropine 376Synthetic Muscarinic Receptor Antagonists 376

Ophthalmology 376Preoperative Uses 376Cardiology 376

Gastroenterology 376Neurology 377

Contraindication to Anticholinergic Agents 377Other CNS Actions of Ginseng 377

Antineoplastic and Immunomodulatory Effects of Ginseng 377

Chapter 38 Green, White, and Black Teas 379

Introduction 379Antioxidant Properties 379The Efficacy of Tea in Attenuating Skin Cancer 380Anticariogenic Effects of Tea 381

Pathogenesis of Dental Caries 381Potential Anticariogenic Actions of Tea 381Benefits of White Tea 381

Chapter 39 Herbal Plants and Tuberculosis 383

Antituberculosis Efficacy of Natural Products 383Mycobacterial Diseases 384

Tuberculosis 384Leprosy 384Other Diseases 385Antimicrobial Activity of Plants 385

Chapter 40 Herbal Products for the Chemotherapy of Human ImmunodeficiencyVirus Infection 387

Introduction 387Herbal Products Used in HIV Therapy 387Etiological Agent 388Life Cycle of HIV 388Immunopharmacology 390Immune System Components 390Cyanovirin-N 391Sulfated Polysaccharides 392Ingenol Derivatives 392Flavonoids 392Glycyrrhizin 393Mannose-Specific Plant Lectins 393Siamycins 393Betulinic Acids 393Polyphemusins 394Baicalin 394Avarol, Avarone, Psychotrine, and Phloroglucinol Derivatives (i.e., Mallotojaponin) 3^4

Calanolides and Inophyllums 395Illimaquinone 395Curcumin, Curcumin Analogs, Dicaffeoylquinic Acid, and L-Chicoric Acid 395Equisetin 396Melittin ZZZZZZZZZZZZZZZZZ. 396

Trichosantin, MAP30, GAP31, DAP31, and DAP32 396

Bellenamine 396Hypericin and Pseudohypericin 397

Chapter 41 Honey: The Nectar of Life 399

Introduction 399Wonder of Honey 399Curative Properties of Honey 400Common Kinds of Honey 400Honey: An Antioxidant 403Honey Enhances Memory Formation 403Neurochemical Basis of Cholinergic Transmission 403

Classification of Cholinergic Receptors 403Honey and the Treatment of Wounds and Burns 404Honey for the Treatment of Peptic Ulcers 405Honey for the Treatment of Gastroenteritis 405Honey in Inflammatory Bowel Disease 406Honey Protects against Carcinogenesis 406Honey in the Treatment of Herpes Simplex Lesions 407Treatment of Bullous Keratopathy with Honey 407

Chapter 42 Horseradish and Antiplatelet Actions 409

Introduction 409Antiplatelet Drugs 409

Aspirin 409Dipyridamole 411Ticlopidine 411

Therapeutic Uses of Anticoagulant, Thrombolytic, and Antiplatelet Drugs 412Venous Thromboembolism 412Myocardial Infarction 412Unstable Angina 412Saphenous Vein Bypass Grafts 412Percutaneous Transluminal Coronary Angioplasty 412Atrial Fibrillation 412Prosthetic Heart Valves 412Valvular Heart Disease 413Cerebrovascular Disease 413Peripheral Vascular Disease 413Primary Prevention of Arterial Thromboembolism 413

Chapter 43 Hypericum (St. John's Wort) and Depression 415

Introduction 415St. John's Wort 416

Botanical Name 416Family 416Synonyms 416

Common Names 416Commercial Products 416Active Ingredients 416

Hypericum (St. John's Wort) in Folk Medicine and Traditional Systems of Medicine 417Antidepressants 417Neurotransmitters and Their Role in Depression 419Classification of Antidepressants 419Dibenzapine Derivatives 419

Conversion to Pharmacologically Active Metabolites 420Various Properties of the Tricyclic Antidepressants 420The Sites of Action of Antidepressants 420Side Effects of Antidepressants 422Therapeutic Indications 422Fatal Overdoses 423

Monoamine Oxidase Inhibitors 424Indications for Monoamine Oxidase Inhibitors 424

Newer, Novel, or Atypical Antidepressants 424Control of Manic Episodes in Manic-Depressive Psychosis Using Lithium 425

Pharmacokinetics 425Side Effects 425Pharmacodynamics of Lithium 426Therapeutic Uses of Lithium 426Regulatory Status of Hypericum 426

Chapter 44 Ipecac 427

Ipecacuanha and Emetine 427Ipecac 427

History 427Active Principles 427Status and Use 427

Drugs That Produce Vomiting (Emetics) 429Source, Nature, and Preparations 429Nature of Emetic Action of Ipecac 430Clinical Effects 431

Prevention of Further Absorption of Poison 431Emesis 431Syrup of Ipecac 432Monitoring 432

Amebiasis 433Treatment of the Asymptomatic Carrier 433Treatment of Acute Amebic Dysentery 433Treatment of Amebic Hepatitis and Abscess 433

Chapter 45 Manuka and Fungal Disease 435

Tea Tree Oils from Australia and New Zealand 435Fungal Diseases 436Antifungal Agents 436Systemic Antifungal Agents 436

Amphotericin B 436Pharmacodynamics 437Pharmacokinetics and Proper Usage 43?

Flucytosine 438

Ketoconazole 438Fluconazole 438Griseofulvin 438Ny statin 439

Topical Antifungal Agents 439Clotrimazole 439Econazole 439Miconazole 439Terconazole and Butoconazole 439Ciclopirox Olamine 440Haloprogin 440Tolnaftate 440Naftifine 440Undecylenic Acid 440Benzoic Acid and Salicylic Acid 440

Aromatherapy Cautions 440

Chapter 46 Marine Therapeutics 441

Chapter 47 Morphine: Papaver somniferum 445

Introduction 445Opioid Analgesics in History 445Friedrich Wilhelm Adam Serturner and Opium 446Opium 446Cultivation, Collection, and Commerce 447Morphine and Other Narcotic Analgesics 448Multiple Medications to Treat Painful Conditions 448Endogenous Opioid Peptides 449Opioid Receptors 449

The Evidence for Multiple Opioid Receptors 449Distribution of Opioid Receptors 450Proposed Functions of the Opioid Receptor Subtypes 450

Morphine and Related Compounds 452Morphine: A Naturally Occurring Analgesic 452

Effects on the Central Nervous System 452Analgesic Effects 455Therapeutic Uses of Morphine 456Sedation and Sleep 458Side Effects of Morphine 459Morphine-Induced Addiction 460Withdrawal Symptoms 462Antidiarrheal Effects 463Oliguric Effect 463Morphine-Induced Tolerance 464

Natural Opium Alkaloids 464Codeine 464Papaverine 464Noscapine 465

Synthetic Derivatives of the Opium Alkaloids 465Heroin (Diamorphine) 465

Dihydrocodeinone 466Dihydromorphinone 466Dextromethorphan Hydrobromide 466Levorphanol Tartrate 467Ethylmorphine 467Apomorphine 467

Symptoms 467Nonopiate Addicting Analgesics 468

Meperidine (Pethidine) 468Action 468Undesirable Side Effects 469Metabolism 469Therapeutic Use 469

Methadone 469Action 470Mechanism of Action 470Therapeutic Uses 470

Alphaprodine Hydrochloride 470Anileridine 471Phenazocine 471Piminodine Ethanesulfonate 471Dextropropoxyphene 471

Opioids with Mixed Actions: Agonists-Antagonists and Partial Agonists 472Opioid Receptor Antagonists 472

Antitussive Preparations 472

Chapter 48 Oats (Avena sativa L.) and Their Antioxidant Activity 473

Introduction 473

Chapter 49 Olives and Olive Oil .475

Chapter 50 Onion and Garlic .477

,477Introduction

Active Ingredients in Onion and Garlic 4 7 7

Inh,bition of Platelet Aggregation by Onion andGarlic' 478

Anticoagulants and Thrombolytic Agents 478Aggregin and Platelet Aggregation.... ! 7 8

Vitamin E and Platelet Aggregation \ 470Platelet-Activating Factor qPlatelet-Inhibiting D r u g s . " " ! fl

Eicosanoids 4/9

PharmacokineticPropertiesofmeEicosanoids' 479Phys.ology of the Eicosanoids '1The Pharmacodynamics of Eicosanoids" ZThe Therapeutic Uses of Eicosanoids To,

Agents That Alter Metabolism of Eicosanoids' 4Effect of Garhc and Onions on Eicosanoid Metaoo ism 4

G a ? T a"d LiPid-L™ering Effects of Cart 4Garhc and Cancer Prevention....

...483

Anticlastogenic Effects of Garlic and Onion 483Antimicrobial Effects of Garlic and Onion 483The Antioxidant Actions and Other Therapeutic Effects of Garlic 484Cardioprotective Actions of Wild Garlic (Allium ursinum) in Ischemia and Reperfusion 484ACE Inhibitors 484

Myocardial Infarction 485Progressive Renal Impairment 485Scleroderma Renal Crisis 486

Antioxidant Activity of Allicin, an Active Principle in Garlic 486Attenuation of Ischemic Brain Damage by Aged Garlic Extracts 487Inhibition of Free-Radical Generation and Augmentation of Antioxidant Enzyme

Activity in Vascular Endothelial Cells by Garlic 488Attenuation of Renal Oxidative Stress with Garlic Oil 489Amelioration of Hyperlipidemia in Chronic Aminonucleoside Nephrosis by Garlic 490Amelioration of Gentamicin Nephrotoxicity by Garlic: Relation to Antioxidant Enzymes 491

Chapter 51 Immunoenhancing Actions of Plantain 493

Introduction 493Immunopharmacology 494Therapies That Enhance or Suppress the Immune System 494

Radioimmunotherapy 494Cell Transfer Therapy and Cancer 494Immunosuppressive Agents 494Corticosteroids 496Cytotoxic Compounds as Alkylating Agents 496

Antimetabolites 497Cyclosporin A and Dihydrocyclosporin C 497Antilymphocyte Globulin 497Rho (D) Immune Globulin 497Immunomodulating Agents 498

Summary 498

Chapter 52 Plants and Diabetes 499

Introduction 499Antidiabetic Agents 499Effects of Food on Insulin Release 500Effects of Fasting on Insulin Release 500Metabolic Consequences of Diabetes Mellitus 500Diabetes Mellitus and Pregnancy 501Classes of Diabetes Mellitus 502Signs and Symptoms of Diabetes 502Complications of Diabetes 502

Vascular Complications 502Neuropathy 502

The Insulin Receptor 502Structure and Function 502Termination of Insulin Signal 503Clinical Syndromes Associated with Cellular Defects in Insulin Receptor 503

Treatment of Diabetes Mellitus 503Dietary Treatment 503Drug Treatment 504

Insulin 504Oral Hypoglycemic Agents 505

Receptors for Sulfonylurea and Their Mechanism of Action 506Treatment of Diabetic Ketoacidosis 506

Chapter 53 Pomegranate 507

Chapter 54 Pycnogenol 509

Introduction 509Antioxidant Activity of Pycnogenol 509Vasorelaxant Activity 510Inhibition of Platelet Aggregation 510Enhancement of Microcirculation 510Inhibition of Elastase Activity 511Regulation of Inflammatory Response 511Modulation of Macrophage Activity 511Summary 511

Chapter 55 Pygeum qfricanum and Permixon for the Treatment of Patients with BenignProstatic Hyperplasia 513

Introduction 513Urinary Symptoms and Flow Measures ...514Permixon in the Treatment of Symptomatic Benign Prostatic Hyperplasia 514

Chapter 56 Reserpine 515

Introduction c^The Rauwolfia Alkaloids 515Chemistry ^15Pharmacology <-,£Mechanism of Action ^17

Prevention of the Storage of Norepinephrine by Reserpine 518Neurochemical Basis of Adrenergic Transmission ...518Catecholamine Metabolism 519

Adrenergic Neuronal-Blocking Drugs 519Side Effects ]Q

Chapter 57 Rhubarb , 2 1

Introduction .

Rhubarb and Its Laxative Properties «21Constipation .Laxatives and Cathartics ,23

Irritants ZZZZZZZ. 523Bulk Saline Laxatives ,23Lubricants „-

Other Uses of Laxatives 524Antioxidant Properties of Rhubarb 524

Chapter 58 Saffron 525

Introduction 525Antioxidant Effect of Saffron 525Effect of Saffron on Learning and Memory 525Possible Molecular Target of Crocin 526

Chapter 59 Salicylate 529

Introduction 529Source 529Official Salicylates Used in the Early 20th Century 529Analgesics-Antipyretics and Anti-Inflammatory Agents 530Mechanism of Action of Aspirin 531Aspirin and Its Uses 531

Aspirin-Induced Analgesia 531Aspirin-Induced Antipyresis 532Uricosuric Effects of Aspirin 532Anti-Inflammatory Effects of Aspirin 532Aspirin and Cardiovascular Disease 532Aspirin and the Premenstrual Syndrome 532

Side Effects of Aspirin 532Effects of Salicylate on Respiration 532Treatment of Aspirin Poisoning 533The Gastrointestinal Effect of Aspirin 533The Hematopoietic Effect of Aspirin 533

New Uses of Aspirin 533Salicylate Protects against MPTP-Induced Parkinsonism 534Health Effects of Salicylates in Foods 535Aspirin-Induced Asthma 535Aspirin and Other Natural Inhibitors of Tumor Necrosis Factor-cc Production, Secretion,

and Function 540Inhibition of TNF Production and Secretion 540

Inhibitors of TNF-Mediated Cytotoxicity 542

Chapter 60 Sex Herbs 545

Introduction 545Impotence 545Normal Sexual Function 546Failure of Erection 547Therapy 547

Drugs That Stimulate Sexual Behavior 549Levodopa 549Amyl Nitrite 549Vitamin E 550Sildenafil (Viagra) 550

Emerging Pharmacological Therapies for Erectile Dysfunction 550

Chapter 61 Sponges and Steroids 553

Introduction 553Examples of Steroids Found in Sponges 553

Polyoxygenated Steroids 553Steroid Sulfates 553

Steroids with Unconventional Side Chains 554Adrenal Steroids 554

The Synthesis of Cholesterol 555Classification of Adrenal Steroids 555

The Glucocorticoids 555The Mineralocorticoids 556The Sex Hormones 557

Regulation of Adrenal Steroid Biosynthesis 557Adrenocorticotropic Hormones 558Actions and Pharmacological Applications of Glucocorticoids 558

Central Nervous System Effects 559Calcium Metabolism 560Contraindications to Glucocorticoid Therapy 561

Adrenal Disorders — Cushing's Syndrome 561Reproductive Pharmacology 561

Steroid Hormones 561Receptors 561Receptor Antagonists 561Estrogens 562

Progesterone 564Antifertility Agents 566

Androgens 566

Chapter 62 Taxol (Paclitaxel) and Cancer Chemotherapy 571

Introduction 571

Chemical Groups of Natural Products with Anticancer Properties!!!ZZZZZZZZZZZZZZZZ.SllCancer Chemotherapy 574Alkylating Agents 575

Nitrogen Mustards 575Chlorambucil 576Cyclophosphamide 576Alkyl Sulfonate 576Nitrosoureas 575Triazenes eyg

Antimetabolites ,75Folic Acid Analogues 576Pyrimidine Analogs 577Deoxycytidine Analogs 578Purine Antimetabolites 578

Natural Products ,-79Vinca Alkaloids 579Dactinomycin ^79Mithramycin cjg

Daunorubicin and Doxorubicin 58O

Bleomycin 580Paclitaxel and Docetaxel 580

Miscellaneous Antineoplastic Agents 581Asparaginase 581Hydroxyurea 581Cis-Platinum 581Carboplatin 581Procarbazine 581Etoposide 582

Cancer Chemotherapy-Induced Emesis 582

Chapter 63 Tomatoes and Medicine 583

Lycopene and Prostate Cancer 583History of Carotenoids 584Physicochemical Nature of Carotenoids 584Lycopene: An Important Carotenoid in Tumor Suppression 584Carotenoid Content of Fruits and Vegetables 584Distribution of Lycopene in Humans 585Concentrations of Carotenoids in Human Organs 585Tomatoes, Lycopene, and Cancer Risk 587

Lung andPleural Cancers 587Quenching of Reactive Oxygen by Lycopene 588

Chapter 64 Ulcer Therapy with Herbal Medicine 591

Introduction 591Acid-Pepsin Disease 591Pathogenesis of Peptic Ulcer 591Physiology of Gastric Acid Secretion 591Drug Therapy 592

Antacids 592Anticholinergic Drugs 592Histamine-Receptor Antagonists 593Inhibitors of H+K+-ATPase 593

Active Herbal Products with Antiulcer Activity 593Flavonoids 593Quercetin 594Naringin 595Anthocyanosides 595Sophoradin Derivatives 595Saponins 595Tannins 596Gums and Mucilages 597

Herbal Drugs with Antiulcer Activity 597Licorice 597Aloe Gel 598Capsicum (Chili) 598

Chapter 65 Valerian 599

Introduction 599Valerian in the Management of Insomnia 599The Use of Valerian in Folk Medicine and Traditional Systems of Medicine 600Valerian 600y-Aminobutyric Acid 600Basic Mechanisms of Epilepsy 601The Anxiolytic Agents 602Pharmacodynamics of Benzodiazepines 602GABA Receptors 603Benzodiazepine-Binding Sites 603Mode of Action of Benzodiazepine Derivatives 604

Antianxiety Effects 604Muscle Relaxant Activity 604Sedative Effects 605Anticonvulsant Activity 605

Mode of Actions of the General Anesthetics 605Glycine 606Sedatives and Hypnotics 606

The Barbiturates 606Classification 606Pharmacokinetics 607Acute Toxicity 607Addiction 608Selection of Drugs ....608

Nonbarbiturate Sedatives and Hypnotics — Benzodiazepine Derivatives 608Regulatory Status 609

Chapter 66 Vitamins and Diet 611

Introduction 611Nutritional Actions of Vitamins 611

Part One: Fat-Soluble Vitamins [ .611Vitamin A 611Retinols 611Beta Carotene 611Vitamin K 613

Vitamin K Derivatives 613Vitamin D (Calciferol) ' 613Vitamin E (Tocopherols) Z. 614

Part Two: Water-Soluble Vitamins 614B i o t i n ! ! ! ! '.6UFolate (Folic Acid, Folacin) 614Niacin (Vitamin B3, Nicotinic Acid"Nicotinamide) Z.6UPantothenic Acid (Vitamin B5) 615Riboflavin (Vitamin B2) 615Thiamine (Vitamin B,) 615

Vitamin B6 (Pyridoxine, Pyridoxamine"'pyridoxal) ^615Vitamin B12 (Cobalamins) 6l5Vitamin C (Ascorbic Acid) 615

The Importance of Vitamin A in Human Nutrition!: 616Dietary Sources of Vitamin A 6 l 6

Action of Vitamin A 617Vitamin A and Carcinogenesis 617Vitamin A and Immune Function 617Symptoms of Deficiency 618

Eye 619Bronchorespiratory Tract 619Skin 619Genitourinary System 619Gastrointestinal Tract 619Sweat Glands 619Bone 619Miscellaneous 619

Therapeutic Uses 620Vitamin A Deficiency Diseases 620Dermatological Diseases 620Cancer and Other Uses 620

Excessive Vitamin A Intake (Hypervitaminosis A) 620Vitamin A (Retinol) (Aquasol A) 621

Aging and Diet 621Basic Dietary Recommendations 621Antioxidants, Protective Plant Chemicals, Preventing Diseases 621

Essential Trace Minerals 622Foods That Help 623

Apples 623Apricots 623Artichokes 624Asparagus 624Avocados 624Bananas 624Beans 624Bean Sprouts 624Beef and Veal 624Beer 624Beets 624Bioflavonoids 624Blackberries 625Blueberries 625Bread 625Brussels Sprouts 625Buckwheat 625Butter and Margarine 625Cabbage 625Caffeine 625Cakes, Cookies, and Pastries 626Carrots 626Cauliflower 626Celeriac 626Celery 626Cereals 626Cheese 626Cherries 627

Chestnuts 627Chilies 627Chocolate and Candy 627Coconuts 627Coffee 627Corn 627Cranberries 627Cucumbers 628Currants 628D a t e s 628Eggplants 628E gg s 628F e n n e l 628F i b e r 628

628F r u i t s 628F i s h ....629

Gooseberries

629629629

Grapefruit

° r a p e s ••••—ZZZZZZZZZZZZZZZZZZZZZZZZZZZZ !!!629H 630Honey 630

Ice Cream ,,„

Z Z Z Z Z Z ZKiwi FruitsKohlrabi

630;;;LeeksLegumes .' fLemons bil

Limes... 631

z-11

Malted Milk, Malt Extracts .' %\MangoesMayonnaise

" ! 631

6?JMelons !Milk and Milk P r o d u c t s ! !ts!!.Mushrooms and Truffles....!Nectarines ^3

632

632632

Nuts and SeedsOilsOkra ! !Olives ! " 632Onions 633Oranges 633Organ Meats 633Papayas 633Parsnips. 633

ZZZZZZZZZZZ 633

Pasta 633Peaches 633Pears 634Peas and Pea Pods 634Peppers 634Pickles and Other Condiments 634Pineapples 634Plums 634Pork 634Poultry 634Prunes 635Pumpkins 635Quinces 635Quinoa 635Radishes 635Raspberries 635Rhubarb 635Rice 636Salad Dressings 636Salt and Sodium 636Sauces and Gravies 636Seaweed 636Shellfish 636Smoked, Cured, and Pickled Meats 637Snacks and Dips 637Soft Drinks 637Soups 637Spinach 637Squash 638Strawberries 638Tangerines 638Tea 638Tomatoes 638Turnips 638Vinegar 639Watercress 639Wine 639Yams and Sweet Potatoes 639Yogurt 639Zucchini 639Zwieback 639

Chapter 67 Wheat Germ 641

Introduction 641Mitochondrial Dysfunction in Neurodegeneration 642

Toxin Models of Parkinson's Disease 644Toxin Models of Huntington's Disease 644Alzheimer's Disease 644

Increase in Brain Mitochondrial Concentrations and Exertion of Neuroprotective Effects byCoenzymeQ,,, 645

Neuroprotective and Neurorestorative Strategies for Parkinson's Disease 645Efficacy of Coenzyme Q10 in Parkinson's Disease 645The Neuroprotective Role of Vitamin E 646

Chapter 68 Wine 647

Introduction 647Effects of Red Wine 647Alcohol 647

The Pharmacology of Alcohol 649Effects of Ethyl Alcohol 649

Central Nervous System 649Acute Intake of Alcohol 649Cardiovascular System 649Gastrointestinal Effects 649Liver 650Endocrine Glands 650Fetal Alcohol Syndrome 651

Pharmacokinetics of Ethanol .651Poisoning and Toxicity 652

Acute Poisoning 652Delirium Tremens 652Chronic Toxicity 652

Treatment of Alcoholism 652

Disulfiram: An Alcohol Sensitizing Agent [ [ 653

Chapter 69 Yogurt and the Immune System 655

Introduction.... ,ce

, ...OJJ

Immune System Functions 655In Vitro Indexes of Immune F u n c t i o n . . . ! ! 656Phagocytic Activity 656

Lymphocyte Proliferation Assay ZZZZZ. 656Cytokine Production 6 5 7

Yogurt Components with Potential ^ ^ ^ ^ ^ ^ Z Z Z I Z Z Z

Specific References. , , ,661

General References ^

Index....673