Role of Flavonoids in Chronic Metabolic Diseases: From Bench to Clinic

Preface xxv

1 Exploring the Therapeutic Power of Flavonoids on Chronic Disease: Unraveling the Mechanisms of Action Especially by Following MAPKs/NF-KB Signaling Pathways 1
Habab Ali Ahmad, Fazal Wahab, Mujib Ullah and Muhammad Imran Khan

1.1 Introduction 2

1.2 Chronic Diseases and Inflammation 7

1.3 Interplay between Flavonoids and Inflammatory Mediators 12

1.4 Estrogenic Activities of Flavonoids 12

1.5 Chronic Diseases and Role of Flavonoids 14

1.6 Flavonoids’ Role in Neurodegenerative Disorders 24

1.7 Mechanisms of Action 25

1.8 In Vitro Experimental Approaches 27

1.9 In Vitro Studies on Flavonoid-Mediated Signaling Modulation 29

1.10 Animal Models and Preclinical Investigations 30

1.11 Animal Models and Methodologies 30

1.12 Human Clinical Trials: Efficacy and Safety of Flavonoid Interventions 35

1.13 Mechanism of Action 36

1.14 Future Research Directions for Improved Flavonoids Use 39

1.15 Conclusion 41

2 Structure--Activity Relationship Between Flavonoids and Chronic Metabolic Diseases 51
Bhavesh Deore and Richa Vartak

2.1 Introduction 52

2.2 Chemistry of Flavonoids Associated with Metabolic Disorders 52

2.3 Current Advancements 61

2.4 Conclusion 62

3 Dietary Sources, Classification, Biosynthesis, and Mechanism of Action of Flavonoids in Combating Oxidative Stress 67
Muhammad Sirab Khan, Sadaf Khan, Nida Khan and Amir Sada Khan

3.1 Introduction 68

3.2 Dietary Source 68

3.3 Classification of Flavonoids 70

3.4 Biosynthesis of Flavonoids 77

3.5 Mechanism of Flavonoids in Combating Oxidative Stress Against Chronic Diseases 82

4 Role of Flavonoids and Probiotics for Maintaining Healthy Gut Microbiota in Response to Chronic Metabolic Diseases 115
Habab Ali Ahmad, Neelum Gul Qazi, Nasir Jalal and Muhammad Imran Khan

4.1 Introduction 116

4.2 Interaction with Gut Microbiota 119

4.3 Role of Flavonoids in the Gut Microbiota 119

4.4 Overview of Probiotics 127

4.5 Role of Probiotics in the Gut Microbiota 132

4.6 Flavonoids and Gut Barrier Protection 134

4.7 Implications for Health 135

4.8 Immune System Modulation 135

4.9 Production of Bioactive Metabolites Beneficial for Gut Health 137

4.10 Synergistic Effects of Flavonoids and Probiotics on Gut Health 139

4.11 Potential in Alleviating Symptoms of Chronic Metabolic Diseases 142

4.12 Potential Therapeutic Strategies Using Flavonoids and Probiotics 145

4.13 Current Limitations and Challenges 147

4.14 Potential Side Effects and Interactions 148

4.15 Future Directions 151

4.16 Conclusion 154

5 Correlation Between Gut Microbiota and Chronic Metabolic Diseases 161
Aneela Nawaz, Sabeena Zafar, Muqaddas Shahzadi, Mehmoona Sharif, Umme Habiba Saeeda, Nauman Ahmed Khalid and Samiullah Khan

5.1 Introduction 162

5.2 Normal Gut Microbiota 164

5.3 Role of Gut Microbiota 165

5.4 The GIT’s Structure and Function 168

5.5 Outside of GIT 170

5.6 Nutrition and Metabolism 171

5.7 Human Gut Microbiota Homeostasis and Its Roles in Intestinal Health 172

5.8 Variables Influencing Microbial Homeostatic Balance 173

5.9 Metabolic Disorders Associated with Dysbiosis of Gut Microbiota 175

5.10 Treating Gut Microbiome Dysbiosis 178

5.11 Conclusion 181

6 Impact of Dietary Flavonoid Metabolism on Gut Microbiome: A Key Therapeutic Approach for the Management of Type 2 Diabetes Mellitus 189
Mehmoona Sharif, Mohammad Ejaz, Aneela Nawaz, Umme Habiba Saeeda, Shayan Naeem and Samiullah Khan

6.1 Introduction 190

6.2 Food-Based Flavonoids 192

6.3 Flavonoid Metabolism within the Gut 193

6.4 Flavonoids and Gut Microbiota 200

6.5 The Influence of Flavonoids on Gut Microbiota 200

6.6 Gut Microbiota and T2DM 208

6.7 Mechanism of Action of Flavonoids on Type 2 Diabetes Mellitus 208

6.8 Impact of Flavonoids on Gut Microflora Against Diabetes Complication 214

6.9 Conclusion 217

6.10 Future Prospects 218

7 Impact of Dietary Plant Flavonoids on Obesity and Autophagy 227
Phool Chandra, Zeeshan Ali, Nishat Fatma and Neetu Sachan

7.1 Introduction 228

7.2 The Role of Autophagy and Obesity 230

7.3 Dietary Flavonoids: A Diverse Class of Plant Compounds 232

7.4 Mechanisms of Dietary Plant Flavonoids in Obesity and Autophagy 234

7.5 Flavonoids and Obesity-Associated Metabolic Disorders 241

7.6 Biosynthesis and Bioavailability of Dietary Plant Flavonoid 246

7.7 Conclusion 247

8 Flavonoids and Nanotechnology in Insulin Resistance Diabetic Complications 259
Sanjesh Kumar, Mansi Singh, Pooja S. Murkute, Ananya Chakraborty, Arshad Farid, Hafiza Sehrish Kiani, Farzad Taghizadeh-Hesary, Mithun Bhowmick and Sumel Ashique

8.1 Introduction 260

8.2 Insulin Resistance Diabetic Complications 261

8.3 Classification of Flavonoids 273

8.4 Current Treatment Approaches for Insulin Resistance Diabetic Complications 284

8.5 Types and Mechanisms of Nanocarrier Encapsulated Flavonoids in Insulin Resistance Diabetic Complications 293

8.6 Advantages and Limitations of Nanotechnology in Diabetic Complications 301

8.7 Toxicity of Flavonoids 306

8.8 Conclusion 309

9 The Effect and Mechanisms of Flavonoids on Inflammation and Chronic Metabolic Diseases 317
Sagnik Nag, Janardhan Pallavi, Ushasi Das Bose, Sana Jalili, Nayanika Pramanik, Sourav Mohanto and Mohammed Gulzar Ahmed

9.1 Introduction 318

9.2 Overview of Flavonoid Biosynthesis and Biomedical Significance 322

9.3 Flavonoids as Anti-Inflammatory Agent 326

9.4 Flavonoids against Chronic Inflammatory Metabolic Disorders 328

9.5 Challenges to Using Flavonoid as a Therapeutic Agent 336

9.6 Future Perspectives and Conclusion 338

10 Flavonoids and Their Metabolites: Impact on Gut Microbiota in Connection with Chronic Metabolic Diseases 347
Priyanka Chakraborty, Koyel Kar, Sailee Chowdhury and Kamalika Mazumder

10.1 Introduction 348

10.2 Classification of Flavonoids 349

10.3 Effects of Flavonoids and Their Metabolites on Gut Microbiota 352

10.4 Metabolic Effects of Gut Microbiota on Flavonoids and Their Metabolites 357

10.5 Flavonoids, Microbiota, and Metabolic Diseases 363

10.6 Future Prospect 367

10.7 Conclusion 368

11 Polyphenol-Encapsulated Nanoparticles for the Treatment of Chronic Metabolic Diseases 375
Popat Mohite, Abhijeet Puri, Deepak Bharati and Sudarshan Singh

11.1 Introduction 376

11.2 Nanodrug Delivery System 378

11.3 Medicinal Plant Extract: Polyphenols 384

11.4 Nanoencapsulation of Polyphenolics 388

11.5 Plant Extracted Nano-Systems for Prevention and Treatment of Different Metabolic Disorders 391

11.6 Delivery of Polyphenols to the Targets 401

11.7 Polyphenol Activity and Chemical Structure Correlation 402

11.8 Challenging Issues in Applications of Polyphenol-Encapsulated Nanoparticles 404

11.9 Conclusion 405

12 Role of Flavonoids in ROS-Mediated Cardiovascular Disorders 417
Santenna Chenchula, Kuttiappan Anitha, Ashish Garg, Sumel Ashique, Mohan Krishna Ghanta and Neeraj Mishra

12.1 Introduction: General Flavonoids and Cardiovascular Disorders 418

12.2 Role of Flavonoids in Different Ailments 419

12.3 Pathophysiology of Cardiovascular Disorders and Oxidative Stress Contribution 425

12.4 Mechanism of Flavonoids in ROS-Mediated Cardiovascular Disorders 430

12.5 Strategies of Antioxidant Therapy in CV Disorders 439

12.6 Safety and Toxicity Concerns Associated with the Consumption of Flavonoids in the Human Body 444

12.7 Conclusion and Future Prospects 445

13 Advancement of Nanoengineered Flavonoids for Chronic Metabolic Diseases 459
Himanshu Sharma, Amit Anand, Praveen Halagali, Aparna Inamdar, Rashmi Pathak, Farzad Taghizadeh-Hesary and Sumel Ashique

13.1 Introduction 460

13.2 Flavonoids: Nature Therapeutic Compounds 465

13.3 Nanoengineering Strategies for Flavonoid Delivery 470

13.4 Optimization of Nanoengineered Flavonoids 478

13.5 Enhanced Bioavailability and Stability of Flavonoids 480

13.6 Nanoengineered Flavonoids for Chronic Metabolic Diseases 483

13.7 Preclinical, Clinical Studies, and Recent Progress 491

13.8 Challenges 491

13.9 Conclusion and Future Prospective 491

14 Flavonoid Intake and Risk of Toxicity in Chronic Metabolic Disease 511
Sanzia Mehjabin, Md. Khokon Miah Akanda, Nazia Hoque, A. H. M. Nazmul Hasan, G. M. Masud Parvez and Ashik Mosaddik

14.1 Introduction 512

14.2 Dose and Intake 514

14.3 Delivery System 514

14.4 How to Develop the Disease by Taking Flavonoids in Excessive Amounts 516

14.5 Risk of Toxicity 517

14.6 Toxicity Measurement 524

14.7 Remedies 526

14.8 Conclusion 528

15 Molecular Mechanisms of Flavonoids in Chronic Metabolic Diseases and Path to Clinical Trials 535
Mahnoor Zafar, Neelum Gul Qazi, Waqas Nawaz and Muhammad Imran Khan

15.1 Introduction 536

15.2 The Complex Interplay of Flavonoids and Metabolic Pathways 537

15.3 Angiogenesis, Vascular Health, and Hepatic Enzyme Modulation 540

15.4 Neurohormonal Mechanisms 542

15.5 Inhibition of Advanced Glycation End-Products 544

15.6 Fatty Acid Synthase, Lipid Metabolism, and Flavonoids 545

15.7 Clinical Studies (Animal and Human Studies) 548

15.8 Dose Delivery Systems 555

15.9 Barriers and Challenges in Clinical Trials 559

15.10 Improving Study Design and Use of Advanced Technology for Data Compilation 562

16 Flavonoid Associated with Preclinical and Clinical Trials Involved in Insulin Resistance/Hyperglycemia, Obesity, Liver Intoxication, Aging, and Cardiovascular Diseases 571
Junaid Qayum, Abida Bibi, Gagan Preet and Arshad Farid

16.1 Introduction to Flavonoids 572

16.2 Obesity and Treatment via Flavonoids 575

16.3 Risk of Liver Intoxication and the Protective Role of Flavonoids 579

16.4 Flavonoids and Cardiovascular Diseases: Role of NF-kB Signaling Pathway 581

16.5 Conclusion 584

References 584

Index 591