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Submit a ProposalRole of Flavonoids in Chronic Metabolic Diseases
 | From Bench to Clinic Edited by Neeraj Mishra, Sumel Ashique, B.H. Jaswanth Gowda, Arshad Farid, Ashish Garg Copyright: 2024 | Status: Published ISBN: 9781394238040 | Hardcover | 624 pages Price: $225 USD  |
One Line Description
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.
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.
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.
Description
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.
Back to Top
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.
Back to Top
Author / Editor Details
Neeraj Mishra is a professor at the Amity Institute of Pharmacy, Uttar Pradesh, India. He has published more than 100 articles on novel drug delivery systems, localized drug delivery, and targeted and controlled drug delivery on nanocarriers in international and national journals, as well as 15 books. He has been granted three international and three Indian patents.
Neeraj Mishra is a professor at the Amity Institute of Pharmacy, Uttar Pradesh, India. He has published more than 100 articles on novel drug delivery systems, localized drug delivery, and targeted and controlled drug delivery on nanocarriers in international and national journals, as well as 15 books. He has been granted three international and three Indian patents.
Sumel Ashique is an assistant professor at the Bengal College of Pharmaceutical Sciences & Research, West Bengal, India. Research interests include drug delivery, nanotechnology, and target treatment strategies. Ashique has published more than 60 articles in international and national-reputed journals and has been granted four patents from India and Australia.
B.H. Jaswanth Gowda is a senior research fellow at Yenopya (deemed to be a university), Mangalore, India. His research primarily focuses on developing varieties of nano- and micro-based transdermal and ocular drug delivery systems, including microneedles, for the treatment of various disease conditions. He has authored 40+ research and review articles and book chapters.
Arshad Farid is an assistant professor at the Gomal Center of Biochemistry and Biotechnology, Gomal University, Pakistan. He has more than 90 international and national publications and 15 international patents.
Ashish Garg is an assistant professor in the Department of Pharmaceutics, Guru Ramdas Khalsa Institute of Science and Technology (Pharmacy), Jabalpur, Madhya Pradesh, India. He has published over 80 articles in national and international journals, authored 15 book chapters, and edited 6 books. Garg has been granted three international patents and published three Indian patents.
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Table of Contents
Preface
1. Exploring the Therapeutic Power of Flavonoids on Chronic Disease: Unraveling the Mechanisms of Action Especially by Following MAPKs/NF-KB Signaling Pathways
Habab Ali Ahmad, Fazal Wahab, Mujib Ullah and Muhammad Imran Khan
1.1 Introduction
1.1.1 Structure and Classification of Flavonoids
1.1.2 Sources and Origins of Flavonoids
1.1.3 Flavonoid Bioavailability and Metabolism
1.2 Chronic Diseases and Inflammation
1.2.1 Understanding Chronic Diseases
1.2.2 Role of Inflammation in Chronic Disease
1.2.3 MAPKs and NF-κB Mediated Inflammatory Signaling Pathways
1.2.4 Flavonoids as a Potent Modulator of MAPKs/NF-κB Signaling
1.2.5 Antioxidant Properties
1.3 Interplay between Flavonoids and Inflammatory Mediators
1.4 Estrogenic Activities of Flavonoids
1.5 Chronic Diseases and Role of Flavonoids
1.5.1 Cardiovascular Diseases: Effects of Flavonoids on Heart Health
1.5.1.1 Antioxidant Activities
1.5.1.2 Anti-Inflammatory Effects
1.5.1.3 Antiplatelet Activities
1.5.1.4 Vasodilatory Effects
1.5.1.5 Lipid-Lowering Actions
1.5.2 Neurological Disorders: Neuroprotective Role of Flavonoids
1.5.2.1 Antioxidant Activities
1.5.2.2 Anti-Inflammatory Effects
1.5.2.3 Modulating Neuronal Signaling
1.5.2.4 Enhancing Neurogenesis
1.5.3 Metabolic Syndrome: Flavonoids and Insulin Sensitivity
1.5.3.1 Alleviating Inflammation
1.5.3.2 Reducing Oxidative Stress
1.5.3.3 Preserving Pancreatic Beta Cell Function
1.5.3.4 Regulating Glucose Uptake and Metabolism
1.5.3.5 Improving Dyslipidemia
1.5.4 Cancer: Anticancer Potential of Flavonoids
1.5.4.1 Anticancer Effect of Flavonoids Induced by MAPK Pathway
1.5.4.2 Targeting NF-κB Pathway in Cancer
1.5.4.3 Dual Targeting of MAPK and NF-κB Pathway
1.5.4.4 Antioxidant and Anti-Inflammatory Effect in Cancer
1.5.4.5 Regulating Carcinogen Metabolism
1.5.4.6 Cell Cycle Arrest by Flavonoids
1.5.4.7 Anti-Proliferative Activities of Flavonoids
1.5.4.8 Inhibiting Angiogenesis and Metastasis
1.5.4.9 Enhancing Apoptosis
1.6 Flavonoids’ Role in Neurodegenerative Disorders
1.7 Mechanisms of Action
1.7.1 MAPK and NF-κB Pathway in Neurodegeneration
1.7.2 Various Key Research Findings in Neurodegenerative Diseases Versus Flavonoids
1.8 In Vitro Experimental Approaches
1.8.1 Use of Cell Culture Models for Assessment of Flavonoid Activity
1.8.2 Western Blotting for Protein Dynamics
1.8.3 PCR for Analysis of the Transcriptional Effects of Flavonoids
1.8.4 Reporter Assays
1.8.5 High-Throughput Screening
1.9 In Vitro Studies on Flavonoid-Mediated Signaling Modulation
1.9.1 NF-κB Pathway Modulation
1.9.2 MAPK Signaling Effects
1.9.3 Modulating Apoptosis and Survival Pathways
1.10 Animal Models and Preclinical Investigations
1.11 Animal Models and Methodologies
1.11.1 Significance of Animal Models
1.11.2 Inflammation and Oxidative Stress Models
1.11.3 Quercetin in Rat Models of Arthritis
1.11.4 Naringenin in Mice Models of Obesity-Induced Inflammation
1.11.4.1 Cancer Models
1.11.4.2 Neurodegeneration Models
1.12 Human Clinical Trials: Efficacy and Safety of Flavonoid Interventions
1.12.1 Cardiovascular Disease
1.12.2 Cancer
1.12.3 Memory and Cognition
1.13 Mechanism of Action
1.13.1 Modulation of MAPK Signaling Pathways
1.13.2 NF-κB Inhibition
1.13.3 Regulation of Pro-Inflammatory Cytokines
1.13.4 Alteration of Oxidative Stress Pathways
1.13.5 Effects on Apoptosis and Cell Proliferation
1.14 Future Research Directions for Improved Flavonoids Use
1.14.1 Improving Bioavailability of Flavonoids
1.14.2 Elucidating Mechanisms of Action
1.14.3 Exploring Synergistic Effects with Other Compounds
1.14.4 Further Epidemiological and Intervention Studies
1.14.5 Emphasis on the Therapeutic Potential of Flavonoids
1.14.6 Importance of Continued Research in the Field
1.15 Conclusion
References
2. Structure–Activity Relationship Between Flavonoids and Chronic Metabolic Diseases
Bhavesh Deore and Richa Vartak
2.1 Introduction
2.2 Chemistry of Flavonoids Associated with Metabolic Disorders
2.2.1 Characteristic of SAR between Flavonoids and Antioxidant Activity
2.2.2 Characteristic of SAR Between Flavonoids and Glucose Regulation
2.2.3 Characteristic of SAR Between Flavonoids and Lipid Peroxidation (LPO)
2.2.4 Structure–Activity Relationship of Flavonoids and Cardiovascular Diseases (CVD)
2.3 Current Advancements
2.4 Conclusion
References
3. Dietary Sources, Classification, Biosynthesis, and Mechanism of Action of Flavonoids in Combating Oxidative Stress
Muhammad Sirab Khan, Sadaf Khan, Nida Khan and Amir Sada Khan
3.1 Introduction
3.2 Dietary Source
3.3 Classification of Flavonoids
3.3.1 Flavones
3.3.1.1 Apigenin
3.3.1.2 Luteolin
3.3.2 Flavanones
3.3.2.1 Hesperetin
3.3.2.2 Naringenin
3.3.3 Flavonols
3.3.3.1 Quercetin
3.3.4 Flavanols
3.3.4.1 Catechins
3.3.4.2 Epicatechin
3.3.5 Isoflavones
3.3.5.1 Genistein
3.3.5.2 Daidzein
3.3.6 Anthocyanidins
3.3.6.1 Cyanidin
3.4 Biosynthesis of Flavonoids
3.4.1 Shikimate Pathway
3.4.2 Phenylpropanoid Pathway
3.4.3 Flavonoid Pathway
3.5 Mechanism of Flavonoids in Combating Oxidative Stress Against Chronic Diseases
3.5.1 Cancer
3.5.2 Cardiovascular Disease (CVD)
3.5.3 Diabetes Mellitus
3.5.4 Alzheimer’s Disease (AD)
References
4. Role of Flavonoids and Probiotics for Maintaining Healthy Gut Microbiota in Response to Chronic Metabolic Diseases
Habab Ali Ahmad, Neelum Gul Qazi, Nasir Jalal and Muhammad Imran Khan
4.1 Introduction
4.1.1 Mechanisms of Action of Flavonoids in the Human Body
4.1.1.1 Antioxidant Properties
4.1.1.2 Modulation of Cellular Signaling Pathways
4.1.1.3 Anti-Inflammatory Properties
4.1.1.4 Cardiovascular Protective Effects
4.1.1.5 Modulation of Enzyme Activity
4.1.1.6 Anti-Cancer Effects
4.2 Interaction with Gut Microbiota
4.3 Role of Flavonoids in the Gut Microbiota
4.3.1 Direct Effects on Microbial Composition
4.3.2 Bacterial Species Promoted by Flavonoids
4.3.2.1 Bifidobacterium spp.
4.3.2.2 Lactobacillus spp.
4.3.2.3 Akkermansia muciniphila
4.3.2.4 Faecalibacterium prausnitzii
4.3.3 Bacterial Species Inhibited by Flavonoids
4.3.3.1 Staphylococcus aureus
4.3.3.2 Escherichia coli
4.3.3.3 Salmonella typhimurium
4.3.3.4 Helicobacter pylori
4.3.3.5 Pseudomonas aeruginosa
4.3.3.6 Clostridium species
4.3.4 Impact on Gut Barrier Function and Integrity
4.3.4.1 Direct Impact on Epithelial Tight Junctions (TJs)
4.3.4.2 Anti-Inflammatory Properties
4.3.4.3 Antioxidant Activity
4.3.5 Interactions with Gut Microbiota
4.3.6 Anti-Inflammatory and Antioxidative Effects in the Gut
4.3.6.1 Flavonoids: Anti-Inflammatory Agents
4.3.6.2 Antioxidative Properties of Flavonoids
4.3.6.3 Probiotics and Gut Health
4.3.6.4 Probiotics as Antioxidants
4.4 Overview of Probiotics
4.4.1 Classification of Probiotics
4.4.1.1 Genus and Species
4.4.1.2 Strain Specificity
4.4.1.3 Source of Origin
4.4.1.4 Functionality
4.4.2 Sources and Common Strains of Probiotics
4.4.3 Mechanisms of Probiotics Effects in Humans
4.4.3.1 Restricting Pathogens through Colonization Resistance
4.4.3.2 Gut Barrier Function Enhancement
4.4.3.3 Immune System Modulation
4.4.3.4 Production of Beneficial Bioactive Metabolites
4.4.3.5 Influence on Other Members of the Gut Microbiota
4.5 Role of Probiotics in the Gut Microbiota
4.5.1 Colonization Resistance and Competitive Exclusion
4.5.2 Reinforcing the Gut Barrier Function
4.5.2.1 Structure and Function of the Gut Barrier
4.5.2.2 Role of Probiotics in Enhancing Gut Barrier Function
4.6 Flavonoids and Gut Barrier Protection
4.6.1 Anti-Inflammatory Properties
4.6.2 Direct Enhancement of Barrier Function
4.6.3 Antioxidative Actions
4.7 Implications for Health
4.8 Immune System Modulation
4.8.1 Direct Interaction with Immune Cells
4.8.2 Cytokine Production
4.8.3 Promotion of Regulatory T Cells (Tregs)
4.8.4 Strengthening the Intestinal Barrier
4.8.5 Competition with Pathogenic Microorganisms
4.8.6 Production of Bioactive Compounds
4.9 Production of Bioactive Metabolites Beneficial for Gut Health
4.10 Synergistic Effects of Flavonoids and Probiotics on Gut Health
4.10.1 Combined Benefits for Microbiota Diversity
4.10.2 Enhancement of Beneficial Bacterial Growth
4.10.3 Crosstalk on How Flavonoids Can Enhance Probiotic Effectiveness and Vice Versa
4.10.4 Flavonoids Enhancing the Effectiveness of Probiotics
4.10.5 Probiotics Augmenting the Bioavailability and Function of Flavonoids
4.11 Potential in Alleviating Symptoms of Chronic Metabolic Diseases
4.11.1 Chronic Metabolic Diseases
4.11.1.1 Overview of Chronic Metabolic Diseases Influenced by Gut Health
4.11.2 Type 2 Diabetes (T2D)
4.11.3 Obesity
4.11.4 Nonalcoholic Fatty Liver Disease (NAFLD)
4.11.5 Cardiovascular Diseases (CVDs)
4.11.6 Inflammatory Responses and Metabolic Endotoxemia
4.12 Potential Therapeutic Strategies Using Flavonoids and Probiotics
4.12.1 Targeted Flavonoid and Probiotic Combinations
4.12.2 Sequential Administration
4.12.3 Personalized Therapies
4.12.4 Flavonoid and Probiotic-Enhanced Foods
4.12.5 Addressing Bioavailability
4.13 Current Limitations and Challenges
4.14 Potential Side Effects and Interactions
4.14.1 Potential Side Effects and Interactions
4.14.2 Probiotics: Potential Side Effects and Interactions
4.14.3 Variability in Human Response to Flavonoids and Probiotics
4.15 Future Directions
4.15.1 Novel Delivery Methods to Increase Effectiveness
4.15.2 Potential for Personalized Gut Health Strategies
4.15.3 Integration of Flavonoids and Probiotics into Standard Treatment Plans for Metabolic Diseases
4.15.3.1 Therapeutic Implications
4.16 Conclusion
References
5. Correlation Between Gut Microbiota and Chronic Metabolic Diseases
Aneela Nawaz, Sabeena Zafar, Muqaddas Shahzadi, Mehmoona Sharif, Umme Habiba Saeeda, Nauman Ahmed Khalid and Samiullah Khan
5.1 Introduction
5.2 Normal Gut Microbiota
5.3 Role of Gut Microbiota
5.3.1 Metabolism and Signaling
5.3.2 Immunity
5.3.3 Regulation of Gut Microbiota
5.3.4 Antimicrobial Protection
5.4 The GIT’s Structure and Function
5.5 Outside of GIT
5.6 Nutrition and Metabolism
5.7 Human Gut Microbiota Homeostasis and Its Roles in Intestinal Health
5.8 Variables Influencing Microbial Homeostatic Balance
5.8.1 Age and Delivery Pattern
5.8.2 Diet
5.8.3 Antibiotics
5.9 Metabolic Disorders Associated with Dysbiosis of Gut Microbiota
5.9.1 The Impact of Obesity on Intestinal Microbiota Composition
5.9.2 Metabolic Products of Bacteria and Dyslipidemia
5.9.3 Inflammation and Insulin Resistance
5.9.4 Intestinal Barrier Permeability and Metabolic Endotoxemia
5.9.5 Irritable Bowel Syndrome
5.9.6 Inflammatory Bowel Diseases
5.9.7 Colorectal Cancer
5.10 Treating Gut Microbiome Dysbiosis
5.10.1 Fecal Microbial Transplant (FMT)
5.10.2 Diet Intervention
5.10.3 Small Molecules
5.10.4 Interactions between Gut Microbiota and Pharmaceuticals
5.11 Conclusion
References
6. Impact of Dietary Flavonoid Metabolism on Gut Microbiome: A Key Therapeutic Approach for the Management of Type 2 Diabetes Mellitus
Mehmoona Sharif, Mohammad Ejaz, Aneela Nawaz, Umme Habiba Saeeda, Shayan Naeem and Samiullah Khan
6.1 Introduction
6.2 Food-Based Flavonoids
6.3 Flavonoid Metabolism within the Gut
6.3.1 Deglycosylation Reaction
6.3.2 Demethylation and Dehydroxylation Reactions
6.3.3 Deketomethylation Reaction
6.3.4 Reduction and Cleavage of C-Ring Reactions
6.4 Flavonoids and Gut Microbiota
6.5 The Influence of Flavonoids on Gut Microbiota
6.5.1 Regulation of the Arrangement and Intensity of Gut Microflora
6.5.2 Stability of Gut Barrier Integrity
6.5.3 Impact on the Body’s Defenses
6.5.4 Effects on Gut Microflora Metabolites
6.6 Gut Microbiota and T2DM
6.7 Mechanism of Action of Flavonoids on Type 2 Diabetes Mellitus
6.7.1 Flavonoids Ameliorate T2DM by Reducing Insulin Resistance
6.7.2 Flavonoids Improve T2DM by Decreasing Oxidative Damage
6.7.3 Flavonoids Reduce T2DM by Controlling Glycolipid Metabolism Disorders
6.7.4 Flavonoids Regulate T2DM through Controlling Glucose Biosynthesis
6.7.5 Flavonoids Improve T2DM by Blocking α-Glucosidase
6.8 Impact of Flavonoids on Gut Microflora Against Diabetes Complication
6.8.1 Animal Study Evidence
6.8.2 Clinical Evidence
6.9 Conclusion
6.10 Future Prospects
References
7. Impact of Dietary Plant Flavonoids on Obesity and Autophagy
Phool Chandra, Zeeshan Ali, Nishat Fatma and Neetu Sachan
7.1 Introduction
7.2 The Role of Autophagy and Obesity
7.3 Dietary Flavonoids: A Diverse Class of Plant Compounds
7.4 Mechanisms of Dietary Plant Flavonoids in Obesity and Autophagy
7.4.1 Regulation of Adipocyte Differentiation and Modulation of Lipolysis
7.4.2 Activation of Thermogenesis
7.4.3 Modulation of Lipid Absorption and Metabolism in the Gut
7.4.4 Regulation of Gene Expression and Signaling Pathways
7.4.5 Antioxidant and Anti-Inflammatory Effects
7.4.6 Activation of AMPK
7.4.7 Inhibition of mTOR Signaling
7.4.8 Modulation of Sirtuin Activity
7.5 Flavonoids and Obesity-Associated Metabolic Disorders
7.5.1 Type 2 Diabetes Mellitus
7.5.2 Non-Alcoholic Fatty Liver Disease
7.5.3 Cardiovascular Diseases
7.6 Biosynthesis and Bioavailability of Dietary Plant Flavonoid
7.7 Conclusion
References
8. Flavonoids and Nanotechnology in Insulin Resistance Diabetic Complications
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
8.2 Insulin Resistance Diabetic Complications
8.2.1 Pathophysiology
8.2.2 Symptoms
8.3 Classification of Flavonoids
8.4 Current Treatment Approaches for Insulin Resistance Diabetic Complications
8.5 Types and Mechanisms of Nanocarrier Encapsulated Flavonoids in Insulin Resistance Diabetic Complications
8.6 Advantages and Limitations of Nanotechnology in Diabetic Complications
8.7 Toxicity of Flavonoids
8.8 Conclusion
Acknowledgments
References
9. The Effect and Mechanisms of Flavonoids on Inflammation and Chronic Metabolic Diseases
Sagnik Nag, Janardhan Pallavi, Ushasi Das Bose, Sana Jalili, Nayanika Pramanik, Sourav Mohanto and Mohammed Gulzar Ahmed
9.1 Introduction
9.2 Overview of Flavonoid Biosynthesis and Biomedical Significance
9.3 Flavonoids as Anti-Inflammatory Agent
9.4 Flavonoids against Chronic Inflammatory Metabolic Disorders
9.4.1 Cancer Management
9.4.2 Inflammatory Bowel Disorder
9.4.3 Cardiovascular Diseases
9.4.4 Neuroinflammatory and Neurological Disorders
9.4.5 Diabetic Management
9.5 Challenges to Using Flavonoid as a Therapeutic Agent
9.6 Future Perspectives and Conclusion
References
10. Flavonoids and Their Metabolites: Impact on Gut Microbiota in Connection with Chronic Metabolic Diseases
Priyanka Chakraborty, Koyel Kar, Sailee Chowdhury and Kamalika Mazumder
10.1 Introduction
10.2 Classification of Flavonoids
10.2.1 Anthocyanins
10.2.2 Chalcones
10.2.3 Flavanones
10.2.4 Flavones
10.2.5 Flavonols
10.2.6 Isoflavonoids
10.3 Effects of Flavonoids and Their Metabolites on Gut Microbiota
10.3.1 The Modification of the Intestinal Flora and Structure
10.3.2 Defense of Abdominal Wall Purpose
10.3.3 Mucosal Immunity System Influence
10.3.4 Metabolites Affected by the Gut Microbiota
10.3.5 Changing Signaling Molecule Expression
10.4 Metabolic Effects of Gut Microbiota on Flavonoids and Their Metabolites
10.4.1 The Impact of Abdominal Microbiota Happening Flavonoids’ Metabolic Process
10.4.1.1 Metabolism of Flavonoids and Their Metabolites
10.4.1.2 The Function of Gut Microbiota in Flavonoid Metabolism and Biotransformation
10.4.2 Intestinal Microorganisms’ Mechanism of Biotransformation and Flavonoids Formation
10.4.3 The Role of Gut Microbiota in Dictating Bioavailability and Bioactivity of Flavonoids
10.5 Flavonoids, Microbiota, and Metabolic Diseases
10.5.1 Flavonoid and Its Interaction with the Microbiota of the Gut
10.5.2 Effect of Flavonoids on Metabolic Diseases
10.5.2.1 Obesity
10.5.2.2 Type II and Insulin-Resistant Diabetes Mellitus
10.6 Future Prospect
10.7 Conclusion
References
11. Polyphenol-Encapsulated Nanoparticles for the Treatment of Chronic Metabolic Diseases
Popat Mohite, Abhijeet Puri, Deepak Bharati and Sudarshan Singh
11.1 Introduction
11.2 Nanodrug Delivery System
11.2.1 Types of Nanodrug Delivery Systems
11.2.1.1 Metallic Nanoparticles
11.2.1.2 Nanocrystals
11.2.1.3 Inorganic Nanoparticles
11.2.1.4 Dendrimers
11.2.1.5 Polymeric Nanoparticles
11.3 Medicinal Plant Extract: Polyphenols
11.4 Nanoencapsulation of Polyphenolics
11.5 Plant Extracted Nano-Systems for Prevention and Treatment of Different Metabolic Disorders
11.5.1 Oxidative Stress
11.5.1.1 Oxidative Stress and Inflammation
11.5.1.2 Oxidative Stress and Its Role in the Development of Cardiovascular Diseases
11.6 Delivery of Polyphenols to the Targets
11.6.1 Nanoparticle Formulations
11.6.2 Microencapsulation
11.6.3 Cyclodextrin-Based Complexation
11.6.4 Self-Emulsifying Drug Delivery Systems
11.6.5 Coating and Encapsulation
11.6.6 Conjugation and Modification
11.6.7 Prodrug Strategies
11.7 Polyphenol Activity and Chemical Structure Correlation
11.7.1 Hydroxyl Group Placement and Count
11.7.2 Distinct Flavonoid Categories
11.7.3 Metal Chelation and Binding
11.7.4 Aromatic Rings and Cyclic Arrangement
11.7.5 Glycosylation and Conjugation
11.7.6 Stereochemistry’s Impact
11.8 Challenging Issues in Applications of Polyphenol-Encapsulated Nanoparticles
11.9 Conclusion
References
12. Role of Flavonoids in ROS-Mediated Cardiovascular Disorders
Santenna Chenchula, Kuttiappan Anitha, Ashish Garg, Sumel Ashique, Mohan Krishna Ghanta and Neeraj Mishra
12.1 Introduction: General Flavonoids and Cardiovascular Disorders
12.2 Role of Flavonoids in Different Ailments
12.2.1 Coronary Heart Disease (CHD)
12.2.2 Atherosclerosis
12.2.3 Hypertension
12.2.4 Stroke
12.2.5 Role of Antioxidants
12.2.5.1 Major Characteristics of Flavonoids’ Role as ROS Scavengers
12.2.5.2 Role of Flavonoids to Regulate Superoxide Dismutase (SOD)
12.3 Pathophysiology of Cardiovascular Disorders and Oxidative Stress Contribution
12.3.1 Oxidative Stress and Endothelial Dysfunction
12.3.2 The Significance of Oxidative Stress and Inflammation in Cardiovascular Diseases
12.4 Mechanism of Flavonoids in ROS-Mediated Cardiovascular Disorders
12.4.1 Mechanisms of Antioxidants
12.4.2 Mechanisms of Antioxidants
12.4.3 Antiplatelet Mechanisms
12.4.4 Anti-Inflammatory Mechanisms
12.4.5 Anti-Hypertensive Mechanisms
12.4.6 Antiatherogenic Effects of Flavonoids
12.4.7 Anti-Ischemic Effects of Flavonoids
12.5 Strategies of Antioxidant Therapy in CV Disorders
12.5.1 Supplementation with Exogenous Antioxidants
12.5.2 Phytochemical-Rich Diets
12.5.3 Modulation of Endogenous Antioxidant Systems
12.5.3.1 Formation of Oxidative Stress Inhibitors
12.5.3.2 Mitochondrial-Targeted Antioxidants
12.5.3.3 Compounds That Facilitate Functional Repair of ROS-Induced Damage
12.5.4 Antioxidant Role of Clinical Drugs
12.6 Safety and Toxicity Concerns Associated with the Consumption of Flavonoids in the Human Body
12.7 Conclusion and Future Prospects
References
13. Advancement of Nanoengineered Flavonoids for Chronic Metabolic Diseases
Himanshu Sharma, Amit Anand, Praveen Halagali, Aparna Inamdar, Rashmi Pathak, Farzad Taghizadeh-Hesary and Sumel Ashique
13.1 Introduction
13.1.1 Chronic Metabolic Diseases: Prevalence and Challenges
13.1.2 Need for Novel Therapeutic Approaches
13.2 Flavonoids: Nature Therapeutic Compounds
13.2.1 Potential Role of Flavonoids in Chronic Metabolic Diseases
13.2.2 Challenges in the Clinical Application of Flavonoids
13.2.3 Nanotechnology: A Solution for Enhancing Flavonoid Delivery
13.3 Nanoengineering Strategies for Flavonoid Delivery
13.3.1 Liposomes’ Versatile Nanoformulations
13.3.2 Solid Lipid Nanoparticles Enhancing Stability and Bioavailability
13.3.3 Phytosomes
13.3.4 Other Nanostructured Delivery Systems for Flavonoids
13.3.5 Niosomes
13.3.5.1 Polymeric Nanoparticles
13.3.5.2 Nanoemulsion
13.3.5.3 Nanocrystal-Loaded Wafers
13.4 Optimization of Nanoengineered Flavonoids
13.4.1 Surface Modification Strategies for Enhanced Targeting and Stability
13.4.2 Controlled Release Systems for Sustained Therapeutic Effect
13.4.3 Combination Therapies and Synergistic Effects
13.5 Enhanced Bioavailability and Stability of Flavonoids
13.5.1 Overcoming Gastrointestinal Barriers
13.5.1.1 Lesser Molecular Weight
13.5.1.2 Reduce Metabolic Conversion
13.5.2 Targeted Delivery Strategies for Site-Specific Action
13.5.2.1 Improving the Intestinal Absorption
13.5.2.2 Changing the Site of Absorption
13.5.3 Approaches to Improve Flavonoid Stability and Prevent Degradation
13.6 Nanoengineered Flavonoids for Chronic Metabolic Diseases
13.6.1 Obesity and Flavonoid Therapy
13.6.1.1 Mechanisms of Anti-Obesity Effects
13.6.1.2 Role of Nanoengineered Delivery Systems
13.6.2 Role of Flavonoids in Diabetes Mellitus Therapy
13.6.2.1 Mechanisms of Anti-Diabetic Effects
13.6.2.2 Enhancing Efficacy through Nanotechnology
13.6.3 Cardiovascular Disorders and Flavonoid Therapy
13.6.3.1 Mitigating Inflammation and Oxidative Stress
13.6.3.2 Nanoengineered Approaches for Improved Delivery
13.7 Preclinical, Clinical Studies, and Recent Progress
13.8 Challenges
13.9 Conclusion and Future Prospective
References
14. Flavonoid Intake and Risk of Toxicity in Chronic Metabolic Disease
Sanzia Mehjabin, Md. Khokon Miah Akanda, Nazia Hoque, A. H. M. Nazmul Hasan, G. M. Masud Parvez and Ashik Mosaddik
14.1 Introduction
14.2 Dose and Intake
14.3 Delivery System
14.3.1 Nanotechnology
14.3.1.1 Lipid-Based Delivery System
14.3.1.2 Polymer-Based Nanoparticles
14.3.2 Structural Modifications
14.4 How to Develop the Disease by Taking Flavonoids in Excessive Amounts
14.5 Risk of Toxicity
14.5.1 Quercetin
14.5.2 Catechins
14.5.3 Rutin
14.5.4 Isoflavones
14.5.5 Citrus Flavonoids
14.5.6 Flavan-3-ols
14.5.7 Nutrient Interaction (Iron)
14.5.8 Osteoporotic Fracture
14.5.9 Cancer
14.5.10 Chronic Prostatitis
14.5.11 Cardiovascular Disease
14.5.12 Renal Toxicity
14.5.13 Liver Damage
14.5.14 Rheumatoid Arthritis
14.6 Toxicity Measurement
14.6.1 Cell Viability Assays
14.6.2 Animal Studies
14.6.3 Acute Toxicity Studies
14.6.4 Genotoxicity Assays
14.6.5 Chronic Toxicity Studies
14.6.6 Human Clinical Trials
14.7 Remedies
14.7.1 Discontinue Flavonoid-Rich Foods
14.7.2 Increase Fluid Intake
14.7.3 Supportive Care
14.7.4 Medical Intervention
14.7.5 Symptomatic Treatment
14.7.6 Variety of Sources
14.7.7 Consider Supplements Cautiously
14.8 Conclusion
References
15. Molecular Mechanisms of Flavonoids in Chronic Metabolic Diseases and Path to Clinical Trials
Mahnoor Zafar, Neelum Gul Qazi, Waqas Nawaz and Muhammad Imran Khan
15.1 Introduction
15.1.1 Molecular Mechanisms
15.2 The Complex Interplay of Flavonoids and Metabolic Pathways
15.2.1 Insulin Sensitivity and Flavonoids
15.2.1.1 Molecular Interactions in Insulin Signaling
15.2.2 Modulation of Mitochondrial Function
15.2.3 Endoplasmic Reticulum Stress and Unfolded Protein Response
15.2.4 Crosstalk with Adipokines
15.2.5 Interaction with Hormonal Pathways
15.2.6 MicroRNA (miRNA) Regulation
15.2.6.1 Quercetin and miRNA Modulation
15.2.6.2 Fisetin and miRNA Interactions
15.3 Angiogenesis, Vascular Health, and Hepatic Enzyme Modulation
15.3.1 Angiogenesis and Vascular Health
15.3.2 Anti-Angiogenic Properties in Cancer
15.3.3 Vascular Endothelial Function and Atherosclerosis
15.3.4 Anti-Inflammatory Effects on Vasculature
15.3.5 Vascular Protection in Diabetes
15.4 Neurohormonal Mechanisms
15.4.1 Interaction with Serotonin Receptors
15.4.2 Modulation of Dopamine Pathways
15.4.3 Impact on Neuroendocrine Stress Response
15.4.4 Influence on Melatonin Production
15.4.5 Interplay with Norepinephrine
15.4.6 G Protein-Coupled Receptors (GPCRs)
15.5 Inhibition of Advanced Glycation End-Products
15.6 Fatty Acid Synthase, Lipid Metabolism, and Flavonoids
15.6.1 Flavonoids’ Effect on Cholesterol Levels
15.7 Clinical Studies (Animal and Human Studies)
15.7.1 Preclinical Studies: The Backbone of Clinical Trials
15.7.1.1 Animal Models
15.7.1.2 Cellular Models: The Microscopic View
15.7.2 Clinical Trials: From Bench to Bedside
15.7.2.1 Human Clinical Trials
15.7.3 Current Clinical Trials on Flavonoids
15.8 Dose Delivery Systems
15.8.1 Dose Delivery Systems: Strategies for Optimal Formulation
15.8.2 Pharmacokinetics
15.8.3 Safety Concerns of Flavonoids
15.8.4 Balancing Therapeutic Benefits and Toxicity Risks
15.8.4.1 In Vitro Screening
15.8.4.2 In Vivo Models
15.8.4.3 Strategies for Mitigation
15.8.5 Ethical and Regulatory Settings
15.9 Barriers and Challenges in Clinical Trials
15.9.1 Financial and Logistical Constraints
15.9.2 Issues in Sample Size and Placebo Effects
15.10 Improving Study Design and Use of Advanced Technology for Data Compilation
15.10.1 Improvement in Study Design
15.10.2 Use of Advanced Technology for Data Collection
15.10.2.1 Electronic Health Records (EHRs)
15.10.2.2 Artificial Intelligence (AI)
References
16. Flavonoid Associated with Preclinical and Clinical Trials Involved in Insulin Resistance/Hyperglycemia, Obesity, Liver Intoxication, Aging, and Cardiovascular Diseases
Junaid Qayum, Abida Bibi, Gagan Preet and Arshad Farid
16.1 Introduction to Flavonoids
16.1.1 Flavonoids in Clinical Trials for the Treatment of Insulin Resistance
16.1.2 Molecular Mechanisms Involved in Insulin Resistance
16.2 Obesity and Treatment via Flavonoids
16.2.1 Role of Flavonoids in the Regulation of Obesity
16.3 Risk of Liver Intoxication and the Protective Role of Flavonoids
16.4 Flavonoids and Cardiovascular Diseases: Role of NF-κB Signaling Pathway
16.5 Conclusion
References
Index
Back to Top
Preface
1. Exploring the Therapeutic Power of Flavonoids on Chronic Disease: Unraveling the Mechanisms of Action Especially by Following MAPKs/NF-KB Signaling Pathways
Habab Ali Ahmad, Fazal Wahab, Mujib Ullah and Muhammad Imran Khan
1.1 Introduction
1.1.1 Structure and Classification of Flavonoids
1.1.2 Sources and Origins of Flavonoids
1.1.3 Flavonoid Bioavailability and Metabolism
1.2 Chronic Diseases and Inflammation
1.2.1 Understanding Chronic Diseases
1.2.2 Role of Inflammation in Chronic Disease
1.2.3 MAPKs and NF-κB Mediated Inflammatory Signaling Pathways
1.2.4 Flavonoids as a Potent Modulator of MAPKs/NF-κB Signaling
1.2.5 Antioxidant Properties
1.3 Interplay between Flavonoids and Inflammatory Mediators
1.4 Estrogenic Activities of Flavonoids
1.5 Chronic Diseases and Role of Flavonoids
1.5.1 Cardiovascular Diseases: Effects of Flavonoids on Heart Health
1.5.1.1 Antioxidant Activities
1.5.1.2 Anti-Inflammatory Effects
1.5.1.3 Antiplatelet Activities
1.5.1.4 Vasodilatory Effects
1.5.1.5 Lipid-Lowering Actions
1.5.2 Neurological Disorders: Neuroprotective Role of Flavonoids
1.5.2.1 Antioxidant Activities
1.5.2.2 Anti-Inflammatory Effects
1.5.2.3 Modulating Neuronal Signaling
1.5.2.4 Enhancing Neurogenesis
1.5.3 Metabolic Syndrome: Flavonoids and Insulin Sensitivity
1.5.3.1 Alleviating Inflammation
1.5.3.2 Reducing Oxidative Stress
1.5.3.3 Preserving Pancreatic Beta Cell Function
1.5.3.4 Regulating Glucose Uptake and Metabolism
1.5.3.5 Improving Dyslipidemia
1.5.4 Cancer: Anticancer Potential of Flavonoids
1.5.4.1 Anticancer Effect of Flavonoids Induced by MAPK Pathway
1.5.4.2 Targeting NF-κB Pathway in Cancer
1.5.4.3 Dual Targeting of MAPK and NF-κB Pathway
1.5.4.4 Antioxidant and Anti-Inflammatory Effect in Cancer
1.5.4.5 Regulating Carcinogen Metabolism
1.5.4.6 Cell Cycle Arrest by Flavonoids
1.5.4.7 Anti-Proliferative Activities of Flavonoids
1.5.4.8 Inhibiting Angiogenesis and Metastasis
1.5.4.9 Enhancing Apoptosis
1.6 Flavonoids’ Role in Neurodegenerative Disorders
1.7 Mechanisms of Action
1.7.1 MAPK and NF-κB Pathway in Neurodegeneration
1.7.2 Various Key Research Findings in Neurodegenerative Diseases Versus Flavonoids
1.8 In Vitro Experimental Approaches
1.8.1 Use of Cell Culture Models for Assessment of Flavonoid Activity
1.8.2 Western Blotting for Protein Dynamics
1.8.3 PCR for Analysis of the Transcriptional Effects of Flavonoids
1.8.4 Reporter Assays
1.8.5 High-Throughput Screening
1.9 In Vitro Studies on Flavonoid-Mediated Signaling Modulation
1.9.1 NF-κB Pathway Modulation
1.9.2 MAPK Signaling Effects
1.9.3 Modulating Apoptosis and Survival Pathways
1.10 Animal Models and Preclinical Investigations
1.11 Animal Models and Methodologies
1.11.1 Significance of Animal Models
1.11.2 Inflammation and Oxidative Stress Models
1.11.3 Quercetin in Rat Models of Arthritis
1.11.4 Naringenin in Mice Models of Obesity-Induced Inflammation
1.11.4.1 Cancer Models
1.11.4.2 Neurodegeneration Models
1.12 Human Clinical Trials: Efficacy and Safety of Flavonoid Interventions
1.12.1 Cardiovascular Disease
1.12.2 Cancer
1.12.3 Memory and Cognition
1.13 Mechanism of Action
1.13.1 Modulation of MAPK Signaling Pathways
1.13.2 NF-κB Inhibition
1.13.3 Regulation of Pro-Inflammatory Cytokines
1.13.4 Alteration of Oxidative Stress Pathways
1.13.5 Effects on Apoptosis and Cell Proliferation
1.14 Future Research Directions for Improved Flavonoids Use
1.14.1 Improving Bioavailability of Flavonoids
1.14.2 Elucidating Mechanisms of Action
1.14.3 Exploring Synergistic Effects with Other Compounds
1.14.4 Further Epidemiological and Intervention Studies
1.14.5 Emphasis on the Therapeutic Potential of Flavonoids
1.14.6 Importance of Continued Research in the Field
1.15 Conclusion
References
2. Structure–Activity Relationship Between Flavonoids and Chronic Metabolic Diseases
Bhavesh Deore and Richa Vartak
2.1 Introduction
2.2 Chemistry of Flavonoids Associated with Metabolic Disorders
2.2.1 Characteristic of SAR between Flavonoids and Antioxidant Activity
2.2.2 Characteristic of SAR Between Flavonoids and Glucose Regulation
2.2.3 Characteristic of SAR Between Flavonoids and Lipid Peroxidation (LPO)
2.2.4 Structure–Activity Relationship of Flavonoids and Cardiovascular Diseases (CVD)
2.3 Current Advancements
2.4 Conclusion
References
3. Dietary Sources, Classification, Biosynthesis, and Mechanism of Action of Flavonoids in Combating Oxidative Stress
Muhammad Sirab Khan, Sadaf Khan, Nida Khan and Amir Sada Khan
3.1 Introduction
3.2 Dietary Source
3.3 Classification of Flavonoids
3.3.1 Flavones
3.3.1.1 Apigenin
3.3.1.2 Luteolin
3.3.2 Flavanones
3.3.2.1 Hesperetin
3.3.2.2 Naringenin
3.3.3 Flavonols
3.3.3.1 Quercetin
3.3.4 Flavanols
3.3.4.1 Catechins
3.3.4.2 Epicatechin
3.3.5 Isoflavones
3.3.5.1 Genistein
3.3.5.2 Daidzein
3.3.6 Anthocyanidins
3.3.6.1 Cyanidin
3.4 Biosynthesis of Flavonoids
3.4.1 Shikimate Pathway
3.4.2 Phenylpropanoid Pathway
3.4.3 Flavonoid Pathway
3.5 Mechanism of Flavonoids in Combating Oxidative Stress Against Chronic Diseases
3.5.1 Cancer
3.5.2 Cardiovascular Disease (CVD)
3.5.3 Diabetes Mellitus
3.5.4 Alzheimer’s Disease (AD)
References
4. Role of Flavonoids and Probiotics for Maintaining Healthy Gut Microbiota in Response to Chronic Metabolic Diseases
Habab Ali Ahmad, Neelum Gul Qazi, Nasir Jalal and Muhammad Imran Khan
4.1 Introduction
4.1.1 Mechanisms of Action of Flavonoids in the Human Body
4.1.1.1 Antioxidant Properties
4.1.1.2 Modulation of Cellular Signaling Pathways
4.1.1.3 Anti-Inflammatory Properties
4.1.1.4 Cardiovascular Protective Effects
4.1.1.5 Modulation of Enzyme Activity
4.1.1.6 Anti-Cancer Effects
4.2 Interaction with Gut Microbiota
4.3 Role of Flavonoids in the Gut Microbiota
4.3.1 Direct Effects on Microbial Composition
4.3.2 Bacterial Species Promoted by Flavonoids
4.3.2.1 Bifidobacterium spp.
4.3.2.2 Lactobacillus spp.
4.3.2.3 Akkermansia muciniphila
4.3.2.4 Faecalibacterium prausnitzii
4.3.3 Bacterial Species Inhibited by Flavonoids
4.3.3.1 Staphylococcus aureus
4.3.3.2 Escherichia coli
4.3.3.3 Salmonella typhimurium
4.3.3.4 Helicobacter pylori
4.3.3.5 Pseudomonas aeruginosa
4.3.3.6 Clostridium species
4.3.4 Impact on Gut Barrier Function and Integrity
4.3.4.1 Direct Impact on Epithelial Tight Junctions (TJs)
4.3.4.2 Anti-Inflammatory Properties
4.3.4.3 Antioxidant Activity
4.3.5 Interactions with Gut Microbiota
4.3.6 Anti-Inflammatory and Antioxidative Effects in the Gut
4.3.6.1 Flavonoids: Anti-Inflammatory Agents
4.3.6.2 Antioxidative Properties of Flavonoids
4.3.6.3 Probiotics and Gut Health
4.3.6.4 Probiotics as Antioxidants
4.4 Overview of Probiotics
4.4.1 Classification of Probiotics
4.4.1.1 Genus and Species
4.4.1.2 Strain Specificity
4.4.1.3 Source of Origin
4.4.1.4 Functionality
4.4.2 Sources and Common Strains of Probiotics
4.4.3 Mechanisms of Probiotics Effects in Humans
4.4.3.1 Restricting Pathogens through Colonization Resistance
4.4.3.2 Gut Barrier Function Enhancement
4.4.3.3 Immune System Modulation
4.4.3.4 Production of Beneficial Bioactive Metabolites
4.4.3.5 Influence on Other Members of the Gut Microbiota
4.5 Role of Probiotics in the Gut Microbiota
4.5.1 Colonization Resistance and Competitive Exclusion
4.5.2 Reinforcing the Gut Barrier Function
4.5.2.1 Structure and Function of the Gut Barrier
4.5.2.2 Role of Probiotics in Enhancing Gut Barrier Function
4.6 Flavonoids and Gut Barrier Protection
4.6.1 Anti-Inflammatory Properties
4.6.2 Direct Enhancement of Barrier Function
4.6.3 Antioxidative Actions
4.7 Implications for Health
4.8 Immune System Modulation
4.8.1 Direct Interaction with Immune Cells
4.8.2 Cytokine Production
4.8.3 Promotion of Regulatory T Cells (Tregs)
4.8.4 Strengthening the Intestinal Barrier
4.8.5 Competition with Pathogenic Microorganisms
4.8.6 Production of Bioactive Compounds
4.9 Production of Bioactive Metabolites Beneficial for Gut Health
4.10 Synergistic Effects of Flavonoids and Probiotics on Gut Health
4.10.1 Combined Benefits for Microbiota Diversity
4.10.2 Enhancement of Beneficial Bacterial Growth
4.10.3 Crosstalk on How Flavonoids Can Enhance Probiotic Effectiveness and Vice Versa
4.10.4 Flavonoids Enhancing the Effectiveness of Probiotics
4.10.5 Probiotics Augmenting the Bioavailability and Function of Flavonoids
4.11 Potential in Alleviating Symptoms of Chronic Metabolic Diseases
4.11.1 Chronic Metabolic Diseases
4.11.1.1 Overview of Chronic Metabolic Diseases Influenced by Gut Health
4.11.2 Type 2 Diabetes (T2D)
4.11.3 Obesity
4.11.4 Nonalcoholic Fatty Liver Disease (NAFLD)
4.11.5 Cardiovascular Diseases (CVDs)
4.11.6 Inflammatory Responses and Metabolic Endotoxemia
4.12 Potential Therapeutic Strategies Using Flavonoids and Probiotics
4.12.1 Targeted Flavonoid and Probiotic Combinations
4.12.2 Sequential Administration
4.12.3 Personalized Therapies
4.12.4 Flavonoid and Probiotic-Enhanced Foods
4.12.5 Addressing Bioavailability
4.13 Current Limitations and Challenges
4.14 Potential Side Effects and Interactions
4.14.1 Potential Side Effects and Interactions
4.14.2 Probiotics: Potential Side Effects and Interactions
4.14.3 Variability in Human Response to Flavonoids and Probiotics
4.15 Future Directions
4.15.1 Novel Delivery Methods to Increase Effectiveness
4.15.2 Potential for Personalized Gut Health Strategies
4.15.3 Integration of Flavonoids and Probiotics into Standard Treatment Plans for Metabolic Diseases
4.15.3.1 Therapeutic Implications
4.16 Conclusion
References
5. Correlation Between Gut Microbiota and Chronic Metabolic Diseases
Aneela Nawaz, Sabeena Zafar, Muqaddas Shahzadi, Mehmoona Sharif, Umme Habiba Saeeda, Nauman Ahmed Khalid and Samiullah Khan
5.1 Introduction
5.2 Normal Gut Microbiota
5.3 Role of Gut Microbiota
5.3.1 Metabolism and Signaling
5.3.2 Immunity
5.3.3 Regulation of Gut Microbiota
5.3.4 Antimicrobial Protection
5.4 The GIT’s Structure and Function
5.5 Outside of GIT
5.6 Nutrition and Metabolism
5.7 Human Gut Microbiota Homeostasis and Its Roles in Intestinal Health
5.8 Variables Influencing Microbial Homeostatic Balance
5.8.1 Age and Delivery Pattern
5.8.2 Diet
5.8.3 Antibiotics
5.9 Metabolic Disorders Associated with Dysbiosis of Gut Microbiota
5.9.1 The Impact of Obesity on Intestinal Microbiota Composition
5.9.2 Metabolic Products of Bacteria and Dyslipidemia
5.9.3 Inflammation and Insulin Resistance
5.9.4 Intestinal Barrier Permeability and Metabolic Endotoxemia
5.9.5 Irritable Bowel Syndrome
5.9.6 Inflammatory Bowel Diseases
5.9.7 Colorectal Cancer
5.10 Treating Gut Microbiome Dysbiosis
5.10.1 Fecal Microbial Transplant (FMT)
5.10.2 Diet Intervention
5.10.3 Small Molecules
5.10.4 Interactions between Gut Microbiota and Pharmaceuticals
5.11 Conclusion
References
6. Impact of Dietary Flavonoid Metabolism on Gut Microbiome: A Key Therapeutic Approach for the Management of Type 2 Diabetes Mellitus
Mehmoona Sharif, Mohammad Ejaz, Aneela Nawaz, Umme Habiba Saeeda, Shayan Naeem and Samiullah Khan
6.1 Introduction
6.2 Food-Based Flavonoids
6.3 Flavonoid Metabolism within the Gut
6.3.1 Deglycosylation Reaction
6.3.2 Demethylation and Dehydroxylation Reactions
6.3.3 Deketomethylation Reaction
6.3.4 Reduction and Cleavage of C-Ring Reactions
6.4 Flavonoids and Gut Microbiota
6.5 The Influence of Flavonoids on Gut Microbiota
6.5.1 Regulation of the Arrangement and Intensity of Gut Microflora
6.5.2 Stability of Gut Barrier Integrity
6.5.3 Impact on the Body’s Defenses
6.5.4 Effects on Gut Microflora Metabolites
6.6 Gut Microbiota and T2DM
6.7 Mechanism of Action of Flavonoids on Type 2 Diabetes Mellitus
6.7.1 Flavonoids Ameliorate T2DM by Reducing Insulin Resistance
6.7.2 Flavonoids Improve T2DM by Decreasing Oxidative Damage
6.7.3 Flavonoids Reduce T2DM by Controlling Glycolipid Metabolism Disorders
6.7.4 Flavonoids Regulate T2DM through Controlling Glucose Biosynthesis
6.7.5 Flavonoids Improve T2DM by Blocking α-Glucosidase
6.8 Impact of Flavonoids on Gut Microflora Against Diabetes Complication
6.8.1 Animal Study Evidence
6.8.2 Clinical Evidence
6.9 Conclusion
6.10 Future Prospects
References
7. Impact of Dietary Plant Flavonoids on Obesity and Autophagy
Phool Chandra, Zeeshan Ali, Nishat Fatma and Neetu Sachan
7.1 Introduction
7.2 The Role of Autophagy and Obesity
7.3 Dietary Flavonoids: A Diverse Class of Plant Compounds
7.4 Mechanisms of Dietary Plant Flavonoids in Obesity and Autophagy
7.4.1 Regulation of Adipocyte Differentiation and Modulation of Lipolysis
7.4.2 Activation of Thermogenesis
7.4.3 Modulation of Lipid Absorption and Metabolism in the Gut
7.4.4 Regulation of Gene Expression and Signaling Pathways
7.4.5 Antioxidant and Anti-Inflammatory Effects
7.4.6 Activation of AMPK
7.4.7 Inhibition of mTOR Signaling
7.4.8 Modulation of Sirtuin Activity
7.5 Flavonoids and Obesity-Associated Metabolic Disorders
7.5.1 Type 2 Diabetes Mellitus
7.5.2 Non-Alcoholic Fatty Liver Disease
7.5.3 Cardiovascular Diseases
7.6 Biosynthesis and Bioavailability of Dietary Plant Flavonoid
7.7 Conclusion
References
8. Flavonoids and Nanotechnology in Insulin Resistance Diabetic Complications
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
8.2 Insulin Resistance Diabetic Complications
8.2.1 Pathophysiology
8.2.2 Symptoms
8.3 Classification of Flavonoids
8.4 Current Treatment Approaches for Insulin Resistance Diabetic Complications
8.5 Types and Mechanisms of Nanocarrier Encapsulated Flavonoids in Insulin Resistance Diabetic Complications
8.6 Advantages and Limitations of Nanotechnology in Diabetic Complications
8.7 Toxicity of Flavonoids
8.8 Conclusion
Acknowledgments
References
9. The Effect and Mechanisms of Flavonoids on Inflammation and Chronic Metabolic Diseases
Sagnik Nag, Janardhan Pallavi, Ushasi Das Bose, Sana Jalili, Nayanika Pramanik, Sourav Mohanto and Mohammed Gulzar Ahmed
9.1 Introduction
9.2 Overview of Flavonoid Biosynthesis and Biomedical Significance
9.3 Flavonoids as Anti-Inflammatory Agent
9.4 Flavonoids against Chronic Inflammatory Metabolic Disorders
9.4.1 Cancer Management
9.4.2 Inflammatory Bowel Disorder
9.4.3 Cardiovascular Diseases
9.4.4 Neuroinflammatory and Neurological Disorders
9.4.5 Diabetic Management
9.5 Challenges to Using Flavonoid as a Therapeutic Agent
9.6 Future Perspectives and Conclusion
References
10. Flavonoids and Their Metabolites: Impact on Gut Microbiota in Connection with Chronic Metabolic Diseases
Priyanka Chakraborty, Koyel Kar, Sailee Chowdhury and Kamalika Mazumder
10.1 Introduction
10.2 Classification of Flavonoids
10.2.1 Anthocyanins
10.2.2 Chalcones
10.2.3 Flavanones
10.2.4 Flavones
10.2.5 Flavonols
10.2.6 Isoflavonoids
10.3 Effects of Flavonoids and Their Metabolites on Gut Microbiota
10.3.1 The Modification of the Intestinal Flora and Structure
10.3.2 Defense of Abdominal Wall Purpose
10.3.3 Mucosal Immunity System Influence
10.3.4 Metabolites Affected by the Gut Microbiota
10.3.5 Changing Signaling Molecule Expression
10.4 Metabolic Effects of Gut Microbiota on Flavonoids and Their Metabolites
10.4.1 The Impact of Abdominal Microbiota Happening Flavonoids’ Metabolic Process
10.4.1.1 Metabolism of Flavonoids and Their Metabolites
10.4.1.2 The Function of Gut Microbiota in Flavonoid Metabolism and Biotransformation
10.4.2 Intestinal Microorganisms’ Mechanism of Biotransformation and Flavonoids Formation
10.4.3 The Role of Gut Microbiota in Dictating Bioavailability and Bioactivity of Flavonoids
10.5 Flavonoids, Microbiota, and Metabolic Diseases
10.5.1 Flavonoid and Its Interaction with the Microbiota of the Gut
10.5.2 Effect of Flavonoids on Metabolic Diseases
10.5.2.1 Obesity
10.5.2.2 Type II and Insulin-Resistant Diabetes Mellitus
10.6 Future Prospect
10.7 Conclusion
References
11. Polyphenol-Encapsulated Nanoparticles for the Treatment of Chronic Metabolic Diseases
Popat Mohite, Abhijeet Puri, Deepak Bharati and Sudarshan Singh
11.1 Introduction
11.2 Nanodrug Delivery System
11.2.1 Types of Nanodrug Delivery Systems
11.2.1.1 Metallic Nanoparticles
11.2.1.2 Nanocrystals
11.2.1.3 Inorganic Nanoparticles
11.2.1.4 Dendrimers
11.2.1.5 Polymeric Nanoparticles
11.3 Medicinal Plant Extract: Polyphenols
11.4 Nanoencapsulation of Polyphenolics
11.5 Plant Extracted Nano-Systems for Prevention and Treatment of Different Metabolic Disorders
11.5.1 Oxidative Stress
11.5.1.1 Oxidative Stress and Inflammation
11.5.1.2 Oxidative Stress and Its Role in the Development of Cardiovascular Diseases
11.6 Delivery of Polyphenols to the Targets
11.6.1 Nanoparticle Formulations
11.6.2 Microencapsulation
11.6.3 Cyclodextrin-Based Complexation
11.6.4 Self-Emulsifying Drug Delivery Systems
11.6.5 Coating and Encapsulation
11.6.6 Conjugation and Modification
11.6.7 Prodrug Strategies
11.7 Polyphenol Activity and Chemical Structure Correlation
11.7.1 Hydroxyl Group Placement and Count
11.7.2 Distinct Flavonoid Categories
11.7.3 Metal Chelation and Binding
11.7.4 Aromatic Rings and Cyclic Arrangement
11.7.5 Glycosylation and Conjugation
11.7.6 Stereochemistry’s Impact
11.8 Challenging Issues in Applications of Polyphenol-Encapsulated Nanoparticles
11.9 Conclusion
References
12. Role of Flavonoids in ROS-Mediated Cardiovascular Disorders
Santenna Chenchula, Kuttiappan Anitha, Ashish Garg, Sumel Ashique, Mohan Krishna Ghanta and Neeraj Mishra
12.1 Introduction: General Flavonoids and Cardiovascular Disorders
12.2 Role of Flavonoids in Different Ailments
12.2.1 Coronary Heart Disease (CHD)
12.2.2 Atherosclerosis
12.2.3 Hypertension
12.2.4 Stroke
12.2.5 Role of Antioxidants
12.2.5.1 Major Characteristics of Flavonoids’ Role as ROS Scavengers
12.2.5.2 Role of Flavonoids to Regulate Superoxide Dismutase (SOD)
12.3 Pathophysiology of Cardiovascular Disorders and Oxidative Stress Contribution
12.3.1 Oxidative Stress and Endothelial Dysfunction
12.3.2 The Significance of Oxidative Stress and Inflammation in Cardiovascular Diseases
12.4 Mechanism of Flavonoids in ROS-Mediated Cardiovascular Disorders
12.4.1 Mechanisms of Antioxidants
12.4.2 Mechanisms of Antioxidants
12.4.3 Antiplatelet Mechanisms
12.4.4 Anti-Inflammatory Mechanisms
12.4.5 Anti-Hypertensive Mechanisms
12.4.6 Antiatherogenic Effects of Flavonoids
12.4.7 Anti-Ischemic Effects of Flavonoids
12.5 Strategies of Antioxidant Therapy in CV Disorders
12.5.1 Supplementation with Exogenous Antioxidants
12.5.2 Phytochemical-Rich Diets
12.5.3 Modulation of Endogenous Antioxidant Systems
12.5.3.1 Formation of Oxidative Stress Inhibitors
12.5.3.2 Mitochondrial-Targeted Antioxidants
12.5.3.3 Compounds That Facilitate Functional Repair of ROS-Induced Damage
12.5.4 Antioxidant Role of Clinical Drugs
12.6 Safety and Toxicity Concerns Associated with the Consumption of Flavonoids in the Human Body
12.7 Conclusion and Future Prospects
References
13. Advancement of Nanoengineered Flavonoids for Chronic Metabolic Diseases
Himanshu Sharma, Amit Anand, Praveen Halagali, Aparna Inamdar, Rashmi Pathak, Farzad Taghizadeh-Hesary and Sumel Ashique
13.1 Introduction
13.1.1 Chronic Metabolic Diseases: Prevalence and Challenges
13.1.2 Need for Novel Therapeutic Approaches
13.2 Flavonoids: Nature Therapeutic Compounds
13.2.1 Potential Role of Flavonoids in Chronic Metabolic Diseases
13.2.2 Challenges in the Clinical Application of Flavonoids
13.2.3 Nanotechnology: A Solution for Enhancing Flavonoid Delivery
13.3 Nanoengineering Strategies for Flavonoid Delivery
13.3.1 Liposomes’ Versatile Nanoformulations
13.3.2 Solid Lipid Nanoparticles Enhancing Stability and Bioavailability
13.3.3 Phytosomes
13.3.4 Other Nanostructured Delivery Systems for Flavonoids
13.3.5 Niosomes
13.3.5.1 Polymeric Nanoparticles
13.3.5.2 Nanoemulsion
13.3.5.3 Nanocrystal-Loaded Wafers
13.4 Optimization of Nanoengineered Flavonoids
13.4.1 Surface Modification Strategies for Enhanced Targeting and Stability
13.4.2 Controlled Release Systems for Sustained Therapeutic Effect
13.4.3 Combination Therapies and Synergistic Effects
13.5 Enhanced Bioavailability and Stability of Flavonoids
13.5.1 Overcoming Gastrointestinal Barriers
13.5.1.1 Lesser Molecular Weight
13.5.1.2 Reduce Metabolic Conversion
13.5.2 Targeted Delivery Strategies for Site-Specific Action
13.5.2.1 Improving the Intestinal Absorption
13.5.2.2 Changing the Site of Absorption
13.5.3 Approaches to Improve Flavonoid Stability and Prevent Degradation
13.6 Nanoengineered Flavonoids for Chronic Metabolic Diseases
13.6.1 Obesity and Flavonoid Therapy
13.6.1.1 Mechanisms of Anti-Obesity Effects
13.6.1.2 Role of Nanoengineered Delivery Systems
13.6.2 Role of Flavonoids in Diabetes Mellitus Therapy
13.6.2.1 Mechanisms of Anti-Diabetic Effects
13.6.2.2 Enhancing Efficacy through Nanotechnology
13.6.3 Cardiovascular Disorders and Flavonoid Therapy
13.6.3.1 Mitigating Inflammation and Oxidative Stress
13.6.3.2 Nanoengineered Approaches for Improved Delivery
13.7 Preclinical, Clinical Studies, and Recent Progress
13.8 Challenges
13.9 Conclusion and Future Prospective
References
14. Flavonoid Intake and Risk of Toxicity in Chronic Metabolic Disease
Sanzia Mehjabin, Md. Khokon Miah Akanda, Nazia Hoque, A. H. M. Nazmul Hasan, G. M. Masud Parvez and Ashik Mosaddik
14.1 Introduction
14.2 Dose and Intake
14.3 Delivery System
14.3.1 Nanotechnology
14.3.1.1 Lipid-Based Delivery System
14.3.1.2 Polymer-Based Nanoparticles
14.3.2 Structural Modifications
14.4 How to Develop the Disease by Taking Flavonoids in Excessive Amounts
14.5 Risk of Toxicity
14.5.1 Quercetin
14.5.2 Catechins
14.5.3 Rutin
14.5.4 Isoflavones
14.5.5 Citrus Flavonoids
14.5.6 Flavan-3-ols
14.5.7 Nutrient Interaction (Iron)
14.5.8 Osteoporotic Fracture
14.5.9 Cancer
14.5.10 Chronic Prostatitis
14.5.11 Cardiovascular Disease
14.5.12 Renal Toxicity
14.5.13 Liver Damage
14.5.14 Rheumatoid Arthritis
14.6 Toxicity Measurement
14.6.1 Cell Viability Assays
14.6.2 Animal Studies
14.6.3 Acute Toxicity Studies
14.6.4 Genotoxicity Assays
14.6.5 Chronic Toxicity Studies
14.6.6 Human Clinical Trials
14.7 Remedies
14.7.1 Discontinue Flavonoid-Rich Foods
14.7.2 Increase Fluid Intake
14.7.3 Supportive Care
14.7.4 Medical Intervention
14.7.5 Symptomatic Treatment
14.7.6 Variety of Sources
14.7.7 Consider Supplements Cautiously
14.8 Conclusion
References
15. Molecular Mechanisms of Flavonoids in Chronic Metabolic Diseases and Path to Clinical Trials
Mahnoor Zafar, Neelum Gul Qazi, Waqas Nawaz and Muhammad Imran Khan
15.1 Introduction
15.1.1 Molecular Mechanisms
15.2 The Complex Interplay of Flavonoids and Metabolic Pathways
15.2.1 Insulin Sensitivity and Flavonoids
15.2.1.1 Molecular Interactions in Insulin Signaling
15.2.2 Modulation of Mitochondrial Function
15.2.3 Endoplasmic Reticulum Stress and Unfolded Protein Response
15.2.4 Crosstalk with Adipokines
15.2.5 Interaction with Hormonal Pathways
15.2.6 MicroRNA (miRNA) Regulation
15.2.6.1 Quercetin and miRNA Modulation
15.2.6.2 Fisetin and miRNA Interactions
15.3 Angiogenesis, Vascular Health, and Hepatic Enzyme Modulation
15.3.1 Angiogenesis and Vascular Health
15.3.2 Anti-Angiogenic Properties in Cancer
15.3.3 Vascular Endothelial Function and Atherosclerosis
15.3.4 Anti-Inflammatory Effects on Vasculature
15.3.5 Vascular Protection in Diabetes
15.4 Neurohormonal Mechanisms
15.4.1 Interaction with Serotonin Receptors
15.4.2 Modulation of Dopamine Pathways
15.4.3 Impact on Neuroendocrine Stress Response
15.4.4 Influence on Melatonin Production
15.4.5 Interplay with Norepinephrine
15.4.6 G Protein-Coupled Receptors (GPCRs)
15.5 Inhibition of Advanced Glycation End-Products
15.6 Fatty Acid Synthase, Lipid Metabolism, and Flavonoids
15.6.1 Flavonoids’ Effect on Cholesterol Levels
15.7 Clinical Studies (Animal and Human Studies)
15.7.1 Preclinical Studies: The Backbone of Clinical Trials
15.7.1.1 Animal Models
15.7.1.2 Cellular Models: The Microscopic View
15.7.2 Clinical Trials: From Bench to Bedside
15.7.2.1 Human Clinical Trials
15.7.3 Current Clinical Trials on Flavonoids
15.8 Dose Delivery Systems
15.8.1 Dose Delivery Systems: Strategies for Optimal Formulation
15.8.2 Pharmacokinetics
15.8.3 Safety Concerns of Flavonoids
15.8.4 Balancing Therapeutic Benefits and Toxicity Risks
15.8.4.1 In Vitro Screening
15.8.4.2 In Vivo Models
15.8.4.3 Strategies for Mitigation
15.8.5 Ethical and Regulatory Settings
15.9 Barriers and Challenges in Clinical Trials
15.9.1 Financial and Logistical Constraints
15.9.2 Issues in Sample Size and Placebo Effects
15.10 Improving Study Design and Use of Advanced Technology for Data Compilation
15.10.1 Improvement in Study Design
15.10.2 Use of Advanced Technology for Data Collection
15.10.2.1 Electronic Health Records (EHRs)
15.10.2.2 Artificial Intelligence (AI)
References
16. Flavonoid Associated with Preclinical and Clinical Trials Involved in Insulin Resistance/Hyperglycemia, Obesity, Liver Intoxication, Aging, and Cardiovascular Diseases
Junaid Qayum, Abida Bibi, Gagan Preet and Arshad Farid
16.1 Introduction to Flavonoids
16.1.1 Flavonoids in Clinical Trials for the Treatment of Insulin Resistance
16.1.2 Molecular Mechanisms Involved in Insulin Resistance
16.2 Obesity and Treatment via Flavonoids
16.2.1 Role of Flavonoids in the Regulation of Obesity
16.3 Risk of Liver Intoxication and the Protective Role of Flavonoids
16.4 Flavonoids and Cardiovascular Diseases: Role of NF-κB Signaling Pathway
16.5 Conclusion
References
Index
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