The nuclear factor erythroid 2-related factor 2 (Nrf2) was described as a master regulator of the cellular antioxidant response. Moreover, many critical biological functions linked to cell viability, metabolism, autophagy, inflammation, immunity, and differentiation have been attributed to Nrf2, which regulates over 600 genes. It is well known that oxidative stress, which Nrf2 can ameliorate, plays a key role in many pathologic processes such as aging, obesity, diabetes, cancer, and neurodegenerative diseases.
Flavonoids, on the other hand, through their ability to activate and upregulate Nrf2, can have anti-oxidative, anti-inflammatory, anti-mutagenic, and anti-carcinogenic properties. Flavonoids are an essential ingredient in nutraceuticals, functional foods, and pharmaceuticals. The present book Flavonoids and Anti-Aging: The Role of Transcription Factor Nuclear Erythroid 2-Related Factor2 focuses on the interaction between Nrf2 and flavonoids and their applications in various conditions such as aging, osteoporosis, cardiovascular diseases, and neurodegenerative disease and many other areas.
Key Features
Focuses on the mechanisms and use of flavonoids in activating Nrf2 as an anti-aging and "WELLNESS" molecule
Provides a specific approach to flavonoid activation of Nrf2 and its implications in aging and various disease conditions and its applications as nutraceuticals
Presents flavonoid-based functional foods
Discusses the flavonoid nutraceuticals market and future trends
Written by experts in the field, this book provides a unique approach to understanding the flavonoid activation of the transcription factor Nrf2, which is responsible for many different disease conditions due to increased reactive oxidative species in the body caused by some physiological triggers.
Author(s): Karam F.A. Soliman, Yashwant V. Pathak
Series: Nutraceuticals: Basic Research and Clinical Applications
Publisher: CRC Press
Year: 2023
Language: English
Pages: 292
City: Boca Raton
Cover
Half Title
Series Page
Title Page
Copyright Page
Dedication
Table of Contents
Preface
Editors
Contributors
1 Flavonoids: Sources, Chemical Classification, and Pharmacological Activities
Introduction
Flavonols
Flavanones
Isoflavonoids
Flavanols
Flavones
Neoflavonoids
Anthocyanidin
Chalcones
Flavonoid Sources
Synthesis of Flavonoids
The Pharmacological Activities of Flavonoids
Antioxidant Activity
Anti-Inflammatory Activity
Anticancer Activity
Antimicrobial Activity
Antifungal Activity
Cardioprotective Effects
Antiviral Activity
Hepatoprotective Activity
Antidiabetic Effects
Antiatheroscleroitc Effects
Antiulcer Activity
Conclusion
References
2 Flavonoids' Classification and their Applications as Nutraceuticals
Introduction
Classification and Structure of Flavonoids
Nutraceuticals
Bridging the Gap Between Food and Medicine
Classification of Nutraceuticals
The Health Benefits of Flavonoid-Rich Nutraceuticals
Flavonoid-Rich Nutraceuticals as Antioxidants
Flavonoids-Rich Nutraceuticals and Anti-Inflammation
Flavonoid-Rich Nutraceuticals and Brain Function
Flavonoid-Rich Nutraceuticals and Cardiovascular Diseases
Flavonoid-Rich Nutraceuticals and Metabolic Syndrome-Related Diseases
Biotechnology Application to Scale Up Flavonoid-Rich Nutraceuticals
Conclusion
References
3 The Role of Nrf2 in Flavonoids' Anticancer Activity
Introduction
Tumor Microenvironment and Chemopreventive Compounds
Oxidative Stress and Inflammation as Molecular Mechanisms of Cancer
The Role of Nuclear Factor E2–Related Factor-2 in Modulating Oxidative Stress
Nrf2 as the Target for Chemopreventive Phytochemicals
Polyphenols That Induce Nrf2 Activation
Resveratrol
Curcumin
Epigallocatechin Gallate
Quercetin
Hesperidin
Luteolin, Baicalin, Apigenin, and Naringenin
Conclusion
References
4 Role of Flavonoid Activation of Nrf2 in Neurodegenerative Disease and Brain Aging
Introduction
Neurodegenerative Diseases and Brain Aging
Biological Process Implicated in the Progression and Pathogenesis of Neurodegenerative Diseases
Oxidative Stress
Neuroinflammation
Mitochondrial Dysfunction
Apoptosis
Excitotoxicity
Flavonoids Alter Multiple Pathways Implicated in Brain Aging and Neurodegenerative
Role of Flavonoids in Oxidative Stress
Role of Flavonoids in Inflammation
Role of Flavonoids in Glutathione Increase
Role of Flavonoids in Nrf2 Modulation
Role of Nrf2 in Neurodegenerative Diseases
Antioxidant Role of Nrf2
Anti-Inflammatory Role of Nrf2
Role of Nrf2 in Mitochondrial Function
Role of Nrf2 in Brain Aging
Neuroprotective Activities of Flavonoid Targeting Nrf2
Flavonoid Targeting Nrf2 in Alzheimer's Disease
Flavonoid Targeting Nrf2 in Parkinson's Disease
Flavonoid Targeting of Nrf2 in Huntington's Disease
Flavonoid Targeting Nrf2 in Amyotrophic Lateral Sclerosis
Flavonoids That Activate the Expression of Nrf2
7, 8-Dihydroxyflavone
Luteolin
Myricetin
Sulforaphane
Epigallocatechin Gallate
Curcumin
Conclusion
Funding
Institutional Review Board Statement
Informed Consent Statement
Author Contributions
Conflict of Interest
References
5 Aging-Related Hearing Loss and Nrf2
Ototoxic Compounds
Cisplatin
Noise-Induced Hearing Loss
Aging and Hearing Loss
Molecular Injury Pathways in Aging-Related Hearing Loss
Nrf2 and the Prevention of Hearing Loss
References
6 Nrf2 and Ocular Aging: Flavonoid and Nutraceuticals Use
Introduction
Oxidative Stress and Age-Related Eye Diseases
Oxidative Stress and Age-Related Macular Degeneration
Oxidative Stress and Diabetic Retinopathy
Oxidative Stress and Glaucoma
Oxidative Stress and Cataracts
Nrf2 and Age-Related Eye Diseases
Nrf2 and Age-Related Macular Degeneration
Nrf2 and Diabetic Retinopathy
Nrf2 and Glaucoma
Nrf2 and Cataracts
Polyphenols as Potential Therapies for Age-Related Eye Diseases
Resveratrol
Curcumin
Quercetin
Epigallocatechin Gallate
Anthocyanins
Conclusion
References
7 Role of Nrf2 in Obesity and Flavonoid Action
Introduction
Adipogenesis
Determination
Differentiation
Pathophysiology of Obesity
Reactive Oxygen Species and Obesity
Inflammation and Obesity
Inflammation and Oxidative Stress in Obesity
Nuclear Factor Erythroid 2-Related Factor
Role of Nrf2 Pathway in Adipogenesis
Nrf2, Adipocyte Function, and Metabolism
Role of Nrf2 Pathway in Obesity
Effect of Nrf2 Gene Deletion on Obesity
Role of Nrf2 Overexpression in Obesity
Pharmacological Activators of Nrf2
Flavonoids
Role of Flavonoids in Nrf2 Signaling and Obesity
Conclusion
References
8 Flavonoids Activation of Nrf2 and Osteoporosis
Introduction
Bone Formation
Osteoblasts
Bone Lining Cells
Osteocytes
Osteoclasts
Bone Remodeling/Metabolism
Osteoporosis
Nrf2 and Bone Formation
Nrf2 and Bone Homeostasis
Nrf2 and Osteoblastogenesis
Nrf2 and Osteoclastogenesis
Nrf2 and Fracture Healing Mechanism
Traditional Osteoporosis Treatment
Flavonoid and Osteoporosis Treatment
Quercetin
Genistein
Kaempferol
Myricetin
Icariin
Luteolin
Hesperidin
Apigenin
Daidzein
Other Flavonoids
Abbreviation
References
9 Role of Nrf2 in Cardiovascular Diseases and Flavonoid Action
The Cellular Antioxidant Defense System
Transcription Factor Nuclear Factor Erythroid 2–Related Factor (Nrf2)
Nrf2 and Cardiovascular Diseases
Role of Nrf2 in Endothelial Dysfunction
Flavonoids
Effect of Flavonoids on Nrf2
References
10 Nrf2 and the Aging Liver
Introduction
Hallmarks of the Aging Liver: Morphological, Physiological, and Functional
Morphological Changes
Physiological and Functional Changes
Mechanisms of the Free Radical Generation in the Aging Liver
Role of Nrf2 in the Regulation of Free Radicals in the Aging Liver
Mechanisms of Nrf2 Regulation in Aging Liver Suffering From
Non-Alcoholic Fatty Liver Disease
Non-Alcoholic Steatohepatitis
Alcoholic Liver Disease
Viral Hepatitis B and C
Hepatocellular Carcinoma
Acute Liver Failure
Ischemia-Reperfusion Damage to the Liver
Current Therapeutic Advances Targeting Nrf2 Pathways in Aging Liver
Drugs From the Natural Source
Resveratrol
Curcumin
Quercetin
Drugs From a Non-Natural Source
Conclusions
Acknowledgments
Conflict of Interest
References
11 Nrf2 Flavonoid-Based Functional Foods
Introduction
What Are Flavonoids?
Role of Nrf2?
What Are Functional Foods?
Dark Chocolate
Flavonoid Properties
Nrf2 Activation
Cancer
Neuroprotection
Green Tea
Flavonoid Properties
Nrf2 Activation
Liver Disease
Cardiovascular Diseases
Red Raspberries
Flavonoid Properties
Nrf2 Activation
Anti-Aging
Cardiovascular Diseases
Cabbage
Flavonoid Properties
Nrf2 Activation
Diabetes
Blueberry
Flavonoid Properties
Nrf2 Activation
Anti-Inflammation
Diabetes Retinopathy
Red Wine
Flavonoid Properties
Nrf2 Activation
Neuroprotection
Soybeans
Flavonoid Properties
Nrf2 Activation
Cardiovascular Diseases
Conclusion and Future Trends
References
12 The Role of Nrf2 Activation and Autophagy in Aging and Neurodegenerative Diseases
The Defense System: Keap1-Nrf2-ARE
Mechanistic Controls on Nrf2-ARE
Mechanistic Controls on Keap1
Age-Related Loss of Nrf2/Keap1ARE
Overview of Nrf2-Related Autophagy
Nrf2 SQSTM1/p62 Autophagy Age-Related Shutdown
Age-Related Nrf2/SQSTM1/p62 Shutdown and Neurodegenerative Diseases (Alzheimer's Disease, Parkinson's Disease)
Alzheimer's Disease
Preventing the Formation of Aggregates (Gnt-III)
Parkinson's Disease
Anti-Aging Druggable Nrf2/SQSTM1/p62 Targets: Nutraceuticals
Nrf2 Activators/False Positives and Methodological Concerns
Normalization of Nrf2 p62/SQSTM1 Axis: Effective Nutraceuticals in Animal Models
Data Interpretation Concerns
Conclusion
References
Index
