Nutraceuticals and Natural Product Derivatives Disease Prevention & Drug Discovery

Introduces readers to the growing applications of nutraceuticals and other natural product derivatives

This comprehensive book presents a prophylactic and therapeutic approach to chronic disease prevention strategy by highlighting the translational potential of plant-derived dietary and non-dietary factors from epidemiological, laboratory, and clinical studies. It also shares the experiences of highly reputed experts working in the area of phytomedicine and nutraceutical agents in chemoprevention, to promote the significance of natural products and dietary factors as an elite priority for containing chronic diseases in the human population.

Nutraceuticals and Natural Product Derivatives: Disease Prevention & Drug Discovery starts by examining natural food sources for the control of glycemia and the prevention of diabetic complications. It then looks at the anti-aging effects of sulfur-containing amino acids and nutraceuticals, and the potential of garcinia fruits to combat metabolic syndrome. Other topics covered include honey- and propolis-mediated regulation of protein networks in cancer cells; recent trends in drug discovery against Alzheimer?s disease; the therapeutic potential of metalloherbal nanoceuticals; and much more.

• Offers an alternative, natural approach to the prevention of chronic diseases
• Emphasizes the potential of plant-derived dietary and non-dietary factors from epidemiological, laboratory, and clinical studies
• Features contributions from world-renowned experts in the field of phytomedicine and nutraceutical agents in chemoprevention
• Includes prevention strategies in normal/risk populations through routine inclusion of specific dietary regimens and as therapeutic strategy for better management through adjuvant interventions with conventional treatment protocols

Nutraceuticals and Natural Product Derivatives: Disease Prevention & Drug Discovery will appeal to graduate students and professionals in cell and molecular biology, translational research, pharmacology/drug discovery, medicinal chemistry, and clinical nutrition.

List of Contributors xvii

Foreword xxi

Preface xxv

Books Description xxix

Expert Commentary xxxi

1 Natural Food Sources for the Control of Glycemia and the Prevention of Diabetic Complications 1
Carlo Pesce, Carla Iacobini, and Stefano Menini

1.1 Introduction: Obesity, Metabolic Syndrome, and Type 2 Diabetes Epidemics: The Role of Nutrition 1

1.2 Phytochemicals of Nutraceutical Importance and Functional Foods of Plant Origin 3

1.2.1 Dietary Oils 3

1.2.2 Vegetables and Fruits 4

1.3 Nutraceuticals and Functional Foods of Animal Origin 8

1.3.1 The Case of Carnosine 8

1.4 Nutraceuticals of Both Plant and Animal Origin 9

1.5 Probiotics, Prebiotics, and Symbiotics 12

1.6 Conclusion 15

References 17

2 Anti‐Aging Effects of Sulfur‐Containing Amino Acids and Nutraceuticals 25
Geetika Garg, Abhishek Kumar Singh, Sandeep Singh, and Syed Ibrahim Rizvi

2.1 Aging and Nutrition 25

2.2 Natural Antioxidants 26

2.2.1 Sulfur‐Containing Amino Acids and Their Role as Antioxidants 26

2.2.2 Anti‐Aging Effects of L‐Cysteine 27

2.3 N‐Acetyl‐L‐Cysteine 28

2.3.1 Neuroprotective Effects of N‐Acetyl‐L‐Cysteine 29

2.3.2 N‐Acetyl‐L‐Cysteine in Combination with Other Antioxidants 29

2.4 Methionine 30

2.4.1 Methionine Restriction 30

2.5 Sulfur‐Containing Nutraceuticals and Foods Rich in Sulfur‐Containing Amino Acids 31

2.5.1 Whey Protein 32

2.5.2 Anti‐Aging Effects of Whey Protein 32

2.6 Conclusion 33

Acknowledgments 33

Conflict of Interest 33

References 33

3 Garcinia Fruits: Their Potential to Combat Metabolic Syndrome 39
Oliver John, Lindsay Brown, and Sunil K. Panchal

3.1 Introduction 39

3.2 Overview of Compounds in Garcinia Species 40

3.2.1 Garcinia mangostana 44

3.2.1.1 Chemical Properties 51

3.2.1.2 Biological Activities of G. mangostana 51

3.2.1.3 Toxicity 55

3.2.2 Garcinia cambogia 56

3.2.2.1 Chemical Properties 56

3.2.2.2 Biological Activities 57

3.2.2.3 Toxicity 59

3.2.2.4 Future Research 59

3.2.3 Garcinia humilis 59

3.2.3.1 Chemical Properties 59

3.2.3.2 Biological Activities 60

3.2.4 Garcinia dulcis 61

3.2.4.1 Chemical Properties 61

3.2.4.2 Biological Properties 61

3.2.4.3 Potential Research 62

3.3 Limitations 62

3.4 Conclusion 64

References 64

4 Pro‐Angiogenic and Anti‐Angiogenic Effects of Small Molecules from Natural Products 81
Jingyi Ma and Xuelin Zhou

4.1 Biological mechanisms of Angiogenesis 81

4.2 Pharmacological Models for Angiogenesis Study 82

4.3 Pro‐Angiogenic Effects of Small Molecules from Natural Products 83

4.3.1 Natural Products as Sources for Screening Pro‐Angiogenic Stimulators 83

4.3.2 Flavonoids 84

4.3.3 Saponins 84

4.3.4 Salvianolic Acids 85

4.3.5 Other Small Molecules 85

4.3.5.1 Ferulic Acid 85

4.3.5.2 Aloe vera–Derived Compounds 85

4.3.6 Summary 86

4.4 Anti‐Angiogenic Effects of Small Molecules from Natural Products 86

4.4.1 Natural Products as Sources for Screening Angiogenic Inhibitors 87

4.4.2 Flavonoids 87

4.4.3 Diterpenoids 89

4.4.4 Polyphenol 90

4.4.5 Saponins 92

4.4.6 Alkaloids 93

4.4.7 Chalcone 93

4.4.8 Anthraquinone 93

4.4.9 Carotenoids 94

4.4.10 Other Small Molecules 94

4.4.10.1 Cucurbitacin B 94

4.4.10.2 Honokiol 95

4.4.10.3 Shikonin 95

4.4.10.4 Hyperforin 95

4.4.10.5 Glyceollins 95

4.4.10.6 Sulforaphane 99

4.4.11 Summary 99

4.5 Conclusion 99

Acknowledgment 99

Conflict of Interest 99

References 100

5 Nutraceuticals and Natural Product Derivatives in the Premises of Disease Prevention 111
Mohammad Fahad Ullah, Showket Hussain Bhat, and Faisel M. Abu‐Duhier

5.1 Introduction: How Significant Is the Role of Natural Molecules in Disease Prevention? 111

5.2 Natural Products in Cancer Chemoprevention 113

5.3 Natural Products in the Management of Diabetes 117

5.4 Natural Products as Therapeutic Agents against Gout Disease 122

5.5 Herbal Derivatives in Prevention of Alzheimer’s Disease 124

5.6 Conclusion 127

Acknowledgments 127

References 127

6 Honey‑ and Propolis‐Mediated Regulation of Protein Networks in Cancer Cells 137
Ammad Ahmad Farooqi, Mirna Azalea Romero, Aliye Aras,Muhammad Zahid Qureshi, and Lara Hanna Wakim

6.1 Introduction 137

6.2 Honey‐Mediated Targeting of Signal Transducer and Activator of Transcription (STAT) Proteins 138

6.3 Reactive Oxygen Species (ROS) Production in Cancer Cells 138

6.4 Apoptosis 139

6.5 Regulation of DNA Damage 139

6.6 Combinatorial Strategies: It Takes Two to Tango 139

6.7 Bioactive Propolis Chemicals as Tumor Necrosis Factor (TNF)‐Related Apoptosis‐Inducing Ligand (TRAIL) Sensitizers 141

6.8 Bioactive Chemicals of Propolis Target Different Proteins of Cell‐Signaling Pathways 142

6.9 Conclusion 142

References 142

7 Antiproliferative Effects and Mechanism of Action of Phytosterols Derived from Bioactive Plant Extracts 145
Gabriel Lopez‐Garcia, Amparo Alegria, Reyes Barbera, and Antonio Cilla

7.1 Introduction 145

7.2 Mechanisms of the Anticancer Actions of Phytosterols 146

7.3 Anticancer Effects of Phytosterols 147

7.3.1 Plant Extracts Containing Phytosterols 148

7.3.2 Isolated Phytosterols from Plant Extracts 155

7.4 Conclusions 161

Acknowledgments 162

References 162

8 Yerba Mate (Ilex paraguariensis A. St. Hil.): A Promising Adjuvant in the Treatment of Diabetes, Obesity, and Metabolic Syndrome 167
Vanesa Gesser Correa, Rubia Carvalho Gomes Correa, Tatiane Francielli Vieira, Adelar Bracht, Rosane Marina Peralta, and Eloa Angelica Koehnlein

8.1 Introduction 167

8.2 Nutritional Composition of Ilex paraguariensis 169

8.3 Composition in Bioactive Compounds 170

8.4 Yerba Mate: Research Trends and Main Findings over 20 Years 171

8.5 Biological Activities of Yerba Mate Related to Diabetes, Obesity,and Metabolic Syndrome 172

8.5.1 In Vitro Studies 172

8.5.2 Animal Studies 174

8.5.3 Clinical Trials 176

8.6 Summarizing Conclusion and Perspectives 177

References 178

9 Role of Natural Antioxidants from Selected Plants Belonging to the Scrophulariaceae and Buddlejaceae Families in the Prevention and Treatment of Neurodegenerative Diseases 183
Cigdem Kahraman, Zeliha S. Akdemir, and I. Irem Tatli

9.1 Introduction 183

9.2 Natural Antioxidants from Verbascum Species (Mullein) for Their Therapeutic Activities against Neurodegenerative Diseases 188

9.3 Natural Antioxidants from Scrophularia Species (Figwort) for Their Therapeutic Activities against Neurodegenerative Diseases 200

9.4 Natural Antioxidants from Buddleja Species (Butterfly Bush) for Their Therapeutic Activities against Neurodegenerative Diseases 209

9.5 Secondary Metabolites and Their Therapeutic Activities against Neurodegenerative Diseases 221

9.6 Conclusions 225

Acknowledgments 226

References 226

10 Recent Trends in Drug Discovery against Alzheimer’s Disease: Use of Natural Products and Nutraceuticals from Botanicals 237
Sudatta Maity, Samapika Nandy, and Abhijit Dey

10.1 Introduction 237

10.2 Symptoms 237

10.3 Etiopathogenesis 238

10.4 Conventional Therapy 239

10.5 Complementary and Alternative Therapies (CATs) for AD 239

10.6 Research Methodology 240

10.7 Neuroprotective Biomolecules: Possible Roles against AD Pathogenesis 241

10.7.1 1‐O‐acetyllycorine 241

10.7.2 α‐Iso‐cubebenol 245

10.7.3 α‐Onocerin 245

10.7.4 Acteoside 256

10.7.5 Apigenin 256

10.7.6 β‐Asarone 256

10.7.7 Baicalein and Baicalin 256

10.7.8 Bellidin, Bellidifolin, Bellidin 8‐O‐β‐Glucopyranoside and Bellidifolin 8‐O‐β‐Glucopyranoside 256

10.7.9 Catalpol 257

10.7.10 Cryptotanshinone 257

10.7.11 Curcuminoids 257

10.7.12 Cynatroside B 258

10.7.13 Galantamine 258

10.7.14 Genistein 258

10.7.15 Huperzine A 258

10.7.16 Icariin 259

10.7.17 Isorhynchophylline 259

10.7.18 Luteolin 259

10.7.19 Melatonin 259

10.7.20 Naringenin 260

10.7.21 Piceatannol 260

10.7.22 p‐coumaric acid 260

10.7.23 Piperine 260

10.7.24 Quercetin 261

10.7.25 Salidroside 261

10.7.26 Silibinin 261

10.7.27 Stepharanine, Cyclanoline, and N‐Methyl Stepholidine 262

10.7.28 Tripchlorolide (T4) 262

10.7.29 Triptexanthoside C 262

10.7.30 Ursolic Acid 262

10.7.31 Xanthoceraside 262

10.7.32 Xylocoside G 263

10.7.33 Zeatin 263

10.7.34 z‐Ligustilide 263

10.8 Conclusion 263

Abbreviations 264

References 266

11 Therapeutic Potential of Metalloherbal Nanoceuticals: Current Status and Future Perspectives 279
Shazia Usmani, Muhammad Arif, and Syed Misbah Hasan

11.1 Historical Background of Indian Herbal Medicine 279

11.2 Concept of Herbalism 280

11.3 Positive Correlation between Phytopharmacology and Phytochemistry: Need of the Hour 280

11.4 Validation of Herbal Therapeutics: An Indispensable Boon for Ayurveda 281

11.4.1 Reverse Pharmacology–Based Validation of Herbal Drugs [14] 281

11.4.2 Amplifying Approaches for Validation of Traditional Medicine 282

11.4.3 Scientific Integration of Traditional Herbals in Clinical Practice 282

11.4.3.1 Evidence‐Based Benefits of Herbs 282

11.4.4 Bhasmas: The Metal‐Based Ayurvedic Medicine 283

11.4.4.1 Preparation of Bhasmas 283

11.4.5 Steps Involved in the Preparation of Bhasmas 284

11.4.5.1 Characterization of Bhasma 285

11.5 Metals Commonly Employed for Preparation of Bhasmas 286

11.5.1 Swarna (Gold) 286

11.5.2 Parada (Mercury) 287

11.5.2.1 Tamra (Copper) 287

11.5.2.2 Lauha (Iron) 288

11.5.2.3 Rajata (Silver) 288

11.5.2.4 Yashada (Zinc) 289

11.5.2.5 Naga (Lead) 289

11.5.2.6 Vanga (Tin) 290

11.6 Toxicity Aspect: An Issue of Concern in the Use of Herbomineral Formulations 290

11.6.1 Conflictive Opposition by Western Medicine Philosophy 291

11.6.2 Conclusive Statements Supported by Varied Research Works 292

11.6.3 Future Prospects in Light of Knowledge within Ayurvedic Texts and Its Application as Nanomedicine 298

References 298

12 Green Tea Polyphenols: A Putative Mechanism for Cytotoxic Action against Cancer Cells 305
Mohd Farhan, Uzma Shamim, and S.M. Hadi

12.1 Dietary Constituents and Their Role in Prevention of Cancer 305

12.2 Cancer Chemoprevention by Dietary Polyphenols 306

12.3 Polyphenolic Compounds and Their Chemical Classification 308

12.4 Dietary Sources of Plant‐Derived Polyphenolic Compounds 311

12.5 Metabolism of Polyphenolic Compounds in Humans 314

12.6 Polyphenols and Their Therapeutic Potential 316

12.6.1 Anticancer Properties 316

12.6.2 Prospective Anticancer Mechanisms of Plant‐Derived Dietary Polyphenols 318

12.6.2.1 Antioxidant Action 319

12.6.2.2 Pro‐Oxidant Action 319

Acknowledgments 321

References 321

13 Nature’s Armamentarium against Malaria: Antimalarials and Their Semisynthetic Derivatives 333
Fyaz M.D. Ismail

13.1 Introduction 333

13.2 Synthetic Drugs Allow Mass Prophylaxis of Malarial Infections 336

13.3 The Cooperative World War II Wartime Program 338

13.4 The Post‐Chloroquine Era: A Return to Finding Drugs from Nature 340

13.5 Compounds from Plant Sources 340

13.5.1 South America 342

13.5.1.1 Quassinoids 342

13.5.1.2 Amazonia Plants 344

13.5.1.3 Plants Deserving Further Investigation 345

13.5.2 Promising Antimalarials Native to Africa 347

13.5.2.1 Burkina Faso 347

13.5.2.2 Congo 347

13.5.2.3 Ethiopia 349

13.5.2.4 Kenya 350

13.5.2.5 Madagascar 351

13.5.3 North America and Europe 351

13.5.3.1 Helanin 352

13.5.4 India and East Asia 353

13.5.4.1 China 354

13.5.4.2 Japan and Korea 359

13.5.5 Australia 359

13.6 The Future 361

13.7 Conclusion 363

References 363

14 Nutraceutical‐Based Pharmacological Intervention in the Management of Liver Diseases 375
Aaliya Shah and Syed Mudassar

14.1 Liver: A Multifunctional Organ 375

14.2 Biomarkers of Hepatic Injury 377

14.3 Nutraceutical Intervention in the Management of Liver Diseases 377

14.3.1 Vitamins 378

14.3.1.1 Vitamin D 378

14.3.1.2 Vitamin C 379

14.3.1.3 Vitamin E 379

14.3.2 Dietary Polyphenols 380

14.3.2.1 Flavonoids 380

14.3.3 Anthocyanins, Isoflavones, and Flavanones 380

14.3.4 Stilbenes 381

14.3.5 Curcuminoids 381

14.3.6 Silymarin 381

14.3.7 Beverages (Coffee and Tea) 381

14.3.8 Polyunsaturated Fatty Acids (PUFAs) 382

14.3.8.1 Short‐Chain, Medium‐Chain, and Long‐Chain Fatty Acids (SCFAs, MCFAs, and LCFAs) 382

14.3.8.2 Polyunsaturated Fatty Acids 382

14.3.9 Probiotics 383

14.3.10 Fruits 384

14.3.10.1 Grape 384

14.3.10.2 Black Currant 384

14.3.10.3 Plum 384

14.3.10.4 Pomegranate 384

14.3.10.5 Gac Fruit 385

14.3.11 Vegetables 385

14.3.11.1 Celery Seeds 385

14.3.11.2 Spices 385

14.3.11.3 Saffron 385

14.3.11.4 Soy 386

14.3.11.5 Cereals 386

14.4 Conclusion 386

References 386

Index 395ftoc.

About the Editors

Mohammad Fahad Ullah, is an Assistant Professor of Biochemistry in the Department of Medical Laboratory Technology (FAMS) and a Research Scientist at Prince Fahd Research Chair, University of Tabuk, Saudi Arabia.

Aamir Ahmad, is an Assistant Professor of Oncologic Sciences at University of South Alabama's Mitchell Cancer Institute, Mobile, AL, USA.