کشف و توسعه داروهای ضد چاقی: جلد چهارم

Obesity is a complex health problem, caused by a number of factors such as excessive food intake, lack of physical activity, genetic predisposition, endocrine disorders, medications and psychiatric illnesses. The incidence of obesity among populations in both the developing and the developed world has reached epidemic proportions. In response to this, efforts to control and treat obesity have also been vigorously pursued, ranging from activities focused on raising awareness about lifestyle changes to the discovery and development of safe and effective anti-obesity drugs. Anti-obesity Drug Discovery and Development is a book series focused on this very important area of healthcare research. Each volume presents insightful updates on pharmaceutical research and development for clinical researchers and healthcare professionals involved in obesity treatment programs. The fourth volume of this series covers 6 reviews on anti-obesity treatment strategies including updates on obesity and cancer prevention through dietary modulation, the role of anti-obesity medications in polycystic ovary syndrome, potential anti-obesity strategies targeting mitochondria, calcium silicate based formulations for anti-obesity therapy, and the identification of obesity medications from natural products and plants. Cover 1 Title 2 Biblography 3 End User License Agreement 4 Contents 6 Preface 10 List of Contributors 12 Dietary Modulation, Obesity and Cancer Prevention 13 Jennifer Man Fan Wan1,* and Hiu Yee Kwan2 13 INTRODUCTION 14 HOW DIET RELATES TO CANCERS? 15 Dietary Factors that Promote the Cancer Initiation 15 Ingestion of Powerful, Direct-Acting Carcinogens or their Precursors 16 Ingestion of Carcinogens that are Produced via Food Processing 16 Ingestion of Carcinogens Produced in Stored Food 17 Formation of Carcinogens in the Body 17 DIETARY FACTORS THAT PROMOTE THE CANCER DEVELOPMENT 17 GENERAL MECHANISM OF HOW OBESITY CAN CAUSE AND PROMOTE CANCER 18 DIETARY COMPONENTS WITH CANCER PREVENTION POTENTIAL 21 DIETARY COMPONENTS THAT AFFECT BODY WEIGHT 24 PROSPECTIVE FOR THE ANTI-CANCER STUDY 26 SUMMARY 27 ABBREVIATIONS 28 CONSENT FOR PUBLICATION 30 CONFLICT OF INTEREST 30 ACKNOWLEDGEMENTS 30 REFERENCES 30 The Role of Anti-Obesity Medications in Polycystic Ovary Syndrome 37 Ilgın Turkcuoglu1,* and Rauf Melekoglu2 37 INTRODUCTION 38 Orlistat, Sibutramine, and Rimonabant 43 Insulin-sensitizing Drugs (Metformin, Rosiglitazone, Pioglitazone, and D-chiro-inositol) 46 GLP-1 Agonists (Exenatide, Liraglutide), Phentermine and Topiramate 50 Other Drugs 57 CONSENT FOR PUBLICATION 57 CONFLICT OF INTEREST 57 ACKNOWLEDGEMENTS 58 REFERENCES 58 Sirtuins and Bile Acids: Potential Anti-obesity Strategies Targeting Mitochondria 69 João Alves Amorim1,#, João Soeiro Teodoro1,2,#, Carlos Marques Palmeira1,2 and Anabela Pinto Rolo1,2,* 69 INTRODUCTION 70 SIRTUIN ACTIVATORS AS A NOVEL ANTI-OBESITY STRATEGY 71 Sirtuins 71 Physiological Role of Sirtuins in Metabolism 73 Physiological Role of Sirtuins and Obesity and Metabolic Syndrome 74 Sirtuins Activators for Therapy 79 Sirtuin Activators for Therapy in Obesity 80 NAD+-boosting Compounds 84 BILE ACIDS, OBESITY AND MITOCHONDRIA 86 Bile Acid Receptors Discovery and Properties 86 BA Effects and Mitochondria 88 CONCLUDING REMARKS 90 CONSENT FOR PUBLICATION 90 CONFLICT OF INTEREST 91 ACKNOWLEDGEMENTS 91 REFERENCES 91 Development and Characterization of Calcium Silicate Based Formulations for Anti-Obesity Therapy: Orlistat 110 Sunil K. Jain* 110 INTRODUCTION 110 FLOATING MICROSPHERES 115 Preparation of OT Absorbed CS 115 Preparation of Floating Microspheres 115 Characterization of Floating Microspheres 116 Micromeritic Properties and Morphology 116 Percentage Buoyancy and Drug Entrapment 117 In vivo Drug Release of Floating Microspheres 118 Gamma Scintigraphy 120 Pharmacokinetic Studies 122 FLOATING GRANULES 124 Preparation of Floating Granules 124 Characterization of Floating Granules 124 Drug Content and Floating Ability 124 In vitro Drug Release of Floating Granules 126 CONCLUSION 129 CONSENT FOR PUBLICATION 129 CONFLICT OF INTEREST 129 ACKNOWLEDGEMENTS 129 REFERENCES 129 Multi Targeted Strategies Towards Identification of Potential Drug Candidates from Natural Products in the Management of Obesity 133 Baddireddi Subhadra Lakshmi*, 1,2 and Gopal Thiyagarajan2 133 INTRODUCTION 134 CURRENT TREATMENT STRATEGIES FOR OBESITY 135 MEDICINAL PLANTS AS A SOURCE FOR NOVEL DRUGS 135 MECHANISM AND MOLECULAR TARGETS OF OBESITY 137 INHIBITION OF LIPID ABSORPTION 137 Pancreatic Lipase Inhibitors 137 SUPPRESSION OF APPETITE 140 Glucagon Like Peptide 1 Analogues and Dipeptidyl Peptidase 4 Inhibitors 141 Cholecystokinin Agonists 143 Neuropeptide Y Antagonist 144 Leptin 145 Protein Tyrosine Phosphatase 1B Inhibitors 147 INHIBITION OF ADIPOGENESIS 151 Peroxisome Proliferator Activated Receptor γ (PPARγ) 152 Adiponectin 154 Partial PPARγ Agonists 161 ENERGY EXPENDITURE 165 Thermogenesis 165 MODULATION OF LIPID METABOLISM 167 Lipolysis 167 β-Oxidation 169 Adenosine Monophosphate (AMP) Kinase Activators 170 Sirtuin 1 as a Novel Target of Obesity 173 MULTIFUNCTIONAL ROLE OF NATURAL ANTIOBESITY COMPOUNDS 174 CLINICAL TRIALS STUDY 181 CONCLUSION 184 CONSENT FOR PUBLICATION 185 CONFLICT OF INTEREST 185 ACKNOWLEDGEMENTS 185 REFERENCES 185 Anti-Obesity Molecules from Plants and their Mode of Action 209 Megha Valsaraj, Navaneetha Saseendran, Arun Subash Koorapally and Anu Augustine* 209 GENERAL INTRODUCTION 209 Obesity 210 Definition and Assessment of Obesity 210 Genetic and Environmental Factors Causing Obesity 212 Endocrine and Metabolic Factors 212 Psychological Factors 212 Control of Appetite and Energy Expenditure 213 Obesity Management 213 Role of Medicinal Plants in Obesity Treatment 213 Mechanism of Action of Anti obesity Agents from Plants 214 Modifying Serum Lipoprotein 214 Modifying Serum Apolipoproteins 215 Enzyme Inhibition 215 Inhibitors of Adipogenesis and Adipogenic Factors 216 Blocking Intestinal Absorption 217 Appetite Suppressants 217 Details of Plants Selected for Study 217 Holoptelea Integrifolia 217 Averrhoa bilimbi Linn. 217 Terminalia chebula Retz. 218 Acorus calamus Linn. 218 Picrorhiza kurroa Royle ex Benth 219 Experimental Model and Findings 219 Methodology 219 Animals 219 Acute Oral Toxicity 220 Establishment of Experimental Model 220 Drug Treatment 221 Effect of Plant Extracts on Serum Lipids 221 Effect of Plant Extracts on HDL Cholesterol Levels 221 Effect of Plant Extracts on LDL Cholesterol Levels 223 Effect of Plant Extracts on Apolipoproteins 223 Effect of Different Plant Extracts on Enzymes Involved in Cholesterol Pathway 225 HMG-CoA Reductase 225 Lecithin-Cholesterol Acyltransferase 226 Lipoprotein Lipase 227 Effect of Different Plant Extracts on Intestinal Fat Absorption 228 Effect of Different Plant Extracts on Inhibition of Adipogenesis and Adipogenic Factors 228 CONCLUDING REMARKS 231 CONSENT FOR PUBLICATION 232 CONFLICT OF INTEREST 232 ACKNOWLEDGEMENTS 232 REFERENCES 232 Subject Index 237 Back Cover 245 Content: Cover Title Biblography End User License Agreement Contents Preface List of Contributors Dietary Modulation, Obesity and Cancer Prevention Jennifer Man Fan Wan1,* and Hiu Yee Kwan2 INTRODUCTION HOW DIET RELATES TO CANCERS? Dietary Factors that Promote the Cancer Initiation Ingestion of Powerful, Direct-Acting Carcinogens or their Precursors Ingestion of Carcinogens that are Produced via Food Processing Ingestion of Carcinogens Produced in Stored Food Formation of Carcinogens in the Body DIETARY FACTORS THAT PROMOTE THE CANCER DEVELOPMENT GENERAL MECHANISM OF HOW OBESITY CAN CAUSE AND PROMOTE CANCERDIETARY COMPONENTS WITH CANCER PREVENTION POTENTIAL DIETARY COMPONENTS THAT AFFECT BODY WEIGHT PROSPECTIVE FOR THE ANTI-CANCER STUDY SUMMARY ABBREVIATIONS CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES The Role of Anti-Obesity Medications in Polycystic Ovary Syndrome Ilgın Turkcuoglu1,* and Rauf Melekoglu2 INTRODUCTION Orlistat, Sibutramine, and Rimonabant Insulin-sensitizing Drugs (Metformin, Rosiglitazone, Pioglitazone, and D-chiro-inositol) GLP-1 Agonists (Exenatide, Liraglutide), Phentermine and TopiramateOther Drugs CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Sirtuins and Bile Acids: Potential Anti-obesity Strategies Targeting Mitochondria João Alves Amorim1,#, João Soeiro Teodoro1,2,#, Carlos Marques Palmeira1,2 and Anabela Pinto Rolo1,2,* INTRODUCTION SIRTUIN ACTIVATORS AS A NOVEL ANTI-OBESITY STRATEGY Sirtuins Physiological Role of Sirtuins in Metabolism Physiological Role of Sirtuins and Obesity and Metabolic Syndrome Sirtuins Activators for Therapy Sirtuin Activators for Therapy in ObesityNAD+-boosting Compounds BILE ACIDS, OBESITY AND MITOCHONDRIA Bile Acid Receptors Discovery and Properties BA Effects and Mitochondria CONCLUDING REMARKS CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Development and Characterization of Calcium Silicate Based Formulations for Anti-Obesity Therapy: Orlistat Sunil K. Jain* INTRODUCTION FLOATING MICROSPHERES Preparation of OT Absorbed CS Preparation of Floating Microspheres Characterization of Floating Microspheres Micromeritic Properties and Morphology Percentage Buoyancy and Drug EntrapmentIn vivo Drug Release of Floating Microspheres Gamma Scintigraphy Pharmacokinetic Studies FLOATING GRANULES Preparation of Floating Granules Characterization of Floating Granules Drug Content and Floating Ability In vitro Drug Release of Floating Granules CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Multi Targeted Strategies Towards Identification of Potential Drug Candidates from Natural Products in the Management of Obesity Baddireddi Subhadra Lakshmi*, 1,2 and Gopal Thiyagarajan2 INTRODUCTION Obesity is a complex health problem, caused by a number of factors such as excessive food intake, lack of physical activity, genetic predisposition, endocrine disorders, medications and psychiatric illnesses. The incidence of obesity among populations in both the developing and the developed world has reached epidemic proportions. In response to this, efforts to control and treat obesity have also been vigorously pursued, ranging from activities focused on raising awareness about lifestyle changes to the discovery and development of safe and effective anti-obesity drugs. Anti-obesity Drug Discovery and Development is a book series focused on this very important area of healthcare research. Each volume presents insightful updates on pharmaceutical research and development for clinical researchers and healthcare professionals involved in obesity treatment programs. The fourth volume of this series is a compilation of 6 reviews on anti-obesity treatment strategies including updates on obesity and cancer prevention through dietary modulation, the role of anti-obesity medications in polycystic ovary syndrome, potential anti-obesity strategies targeting mitochondria, calcium silicate based formulations for anti-obesity therapy, and the identification of obesity medications from natural products and plants.

Obesity is a complex health problem, caused by a number of factors such as excessive food intake, lack of physical activity, genetic predisposition, endocrine disorders, medications and psychiatric illnesses. The incidence of obesity among populations in