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 1Habab 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 51Bhavesh 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 67Muhammad 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 115Habab 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 161Aneela 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 189Mehmoona 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 227Phool 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 259Sanjesh 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 317Sagnik 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 347Priyanka 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 375Popat 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 417Santenna 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 459Himanshu 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 511Sanzia 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 535Mahnoor 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 571Junaid 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

This comprehensive volume covers the entire field of flavonoids by explaining their complex functions in reducing chronic metabolic illnesses, from the early stages of laboratory research to the development of therapeutic uses. Flavonoids are plant-based substances proven to have potential medical benefits in managing chronic metabolic disorders. This book explores concepts in laboratory research and therapeutic capabilities to enhance awareness of flavonoids in a medical context. The book begins with a thorough examination of the basic biochemical and molecular processes that underlie long-term metabolic disorders. It looks into these bioactive substances, from their natural origins to the synthesis of innovative derivatives. Analyzing both lab research and preclinical trials critically, it provides a solid basis for understanding the exciting opportunities flavonoids bring in treating metabolic diseases. The scope of this work extends beyond theoretical domains into clinical environments. It closes the gap between bench-side findings and bedside applications by revealing the translational potential of flavonoids. It is possible to understand the practical implications and future directions of flavonoid-based therapeutics through the synthesis of evidence-based clinical studies, therapeutic approaches, and possible healthcare issues. Readers will find the book: contains cutting-edge insights into metabolic disease research and delves into recent discoveries on the molecular mechanisms of flavonoids; facilitates a viewpoint into the findings of practical clinical implementations and the progression of flavonoid investigations from controlled experimental environments to prospective therapeutic interventions;explores the scientific effects of flavonoids on chronic metabolic disorders;presents evidence from human trials and epidemiological research on flavonoid clinical processes;encompasses various aspects of preventive measures for managing widespread metabolic diseases, containing dietary recommendations, lifestyle interventions, and the potential involvement of flavonoids;offers a comprehensive guide on how to effectively utilize flavonoids for therapeutic purposes. Audience This book is intended for researchers, scientists, clinicians/physicians, and public health professionals who work in pharmacology settings. The book is a vital tool for clinicians, nutritionists, and other healthcare professionals who are concerned about cutting-edge methods for dietary guidelines to gain an understanding of flavonoids and long-term metabolic disorders.