Dietary Polyphenols in Human Diseases: Advances and Challenges in Drug Discovery

Cover
Half Title
Title Page
Copyright Page
Table of Contents
Preface
About the Editor
Contributors
1 Dietary Polyphenols, Antioxidant Effects, and Human Diseases
	1.1 Introduction
	1.2 Dietary Polyphenols
		1.2.1 General Chemistry, Structure and Sources of Polyphenols
	1.3 Dietary Polyphenols as Antioxidants
		1.3.1 Antioxidant Mechanisms of Dietary Polyphenols
		1.3.2 Metabolism and Bioavailability of Dietary Polyphenols
	1.4 Role of Polyphenols in Human Disease Management
		1.4.1 Protective Role of Dietary Polyphenols in Metabolic Syndrome (MetS)
		1.4.2 Protective Role of Dietary Polyphenols in CVDs
		1.4.3 Hepatoprotective Effects of Dietary Polyphenols
		1.4.4 The Chemopreventive Role of Dietary Antioxidant Polyphenols
		1.4.5 Protective Role of Dietary Antioxidant Polyphenols in Neurodegenerative Disorders
		1.4.6 Dietary Phytochemicals in Gastrointestinal Disease and Microbial Infections
		1.4.7 Interaction of Polyphenols With Gut Microbiota, Neurodegeneration and Cognition
		1.4.8 Dietary Polyphenols in Arthritis and Inflammations
	1.5 Future Perspectives and Conclusion
	References
2 Biochemical, Molecular, Pharmacokinetic, and Toxicological Aspects of Dietary Polyphenols
	2.1 Introduction
	2.2 Chemistry and Biological Importance
		2.2.1 Classification
		2.2.2 Chemical Structure
			2.2.2.1 Flavonoids
			2.2.2.2 Non-Flavonoids
			2.2.2.3 Polyphenol Amides
		2.2.3 Medicinal Importance
	2.3 Polyphenols and OS
		2.3.1 Biochemistry of OS
		2.3.2 Biochemical/molecular Markers as Targets for Polyphenols
		2.3.3 Molecular Mechanisms of Polyphenols in OS
	2.4 Anti-Inflammatory Activities
		2.4.1 Regulation of NF-.B
		2.4.2 Mitogen-Activated Protein Kinases (MAPKs) Regulation
		2.4.3 Arachidonic Acid Regulation
	2.5 Anti-Oxidant Activities
	2.6 Anti-Tumor Activity
	2.7 Antiaging Activities
	2.8 Cardio-Protecting Effects
	2.9 Neuro-Protective Effects
	2.10 Pharmacokinetics Profile
		2.10.1 Polyphenol Interaction With Saliva
		2.10.2 Polyphenol Transit in Small Intestine
			2.10.2.1 Protein Transporters Mediated Polyphenol Transit
		2.10.3 Gut Microbiota-Mediated Polyphenol Transit
		2.10.4 Conjugation and Nature of Metabolites
		2.10.5 Plasma Transport and Lipid Structural Partitioning
		2.10.6 Plasma Concentrations
		2.10.7 Tissue Uptake
		2.10.8 Elimination
	2.11 Toxicity of the Polyphenol
		2.11.1 Intestinal and Kidney Dysfunctions
		2.11.2 Thyroid Dysfunction
		2.11.3 Anti-Nutritional Effects
			2.11.3.1 Low Iron Absorption
			2.11.3.2 Low Protein Digestion Absorption
	2.12 Drug Pharmacokinetics and Bioavailability
	2.13 Conclusion and Future Prospective
	References
3 Dietary Polyphenols in Aging, Neurological, and Cognitive Disorders
	3.1 Introduction
		3.1.1 Parkinson’s Disease (PD)
		3.1.2 Alzheimer Disease (AD)
		3.1.3 Depression
		3.1.4 Schizophrenia
	3.2 Bioavailability of Dietary Polyphenols
	3.3 Polyphenols Beyond Blood–brain Barrier
	3.4 Evidence-Based Utility of Dietary Polyphenolics in Clinical Trials
	3.5 Conclusion and Future Perspective
	References
4 Dietary Polyphenols in Cancer
	4.1 Introduction
		4.1.1 Oxidative Stress in Cancer
		4.1.2 What Are Antioxidants?
	4.2 Dietary Polyphenolics
		4.2.1 Classification of Polyphenolics (Zhou Et Al., 2016)
			4.2.1.1 Phenolic Acids
			4.2.1.2 Flavonoids
			4.2.1.3 Polyphenoleic Amides
			4.2.1.4 Other Polyphenols
		4.2.2 Potential Health Effects of Polyphenols
		4.2.3 Antioxidant Activity of Polyphenols
			4.2.3.1 Catechin
			4.2.3.2 Lycopene
			4.2.3.3 Curcumin
			4.2.3.4 Resveratrol
			4.2.3.5 Genistein
		4.2.4 ADME Profile of Polyphenols
	4.3 Polyphenols in Cancer
		4.3.1 Modification of Redox Status
		4.3.2 Interference With Cancer Cell Functions
			4.3.2.1 Cell Cycle
			4.3.2.2 Apoptosis
			4.3.2.3 Invasion and Metastasis
			4.3.2.4 Angiogenesis
	4.4 Use of Polyphenols in Various Types of Cancer
		4.4.1 Prostate Cancer
		4.4.2 Colon Cancer
		4.4.3 Breast Cancer
		4.4.4 Lung Cancer
		4.4.5 Bladder Cancer
		4.4.6 Skin Cancer
		4.4.7 Pancreatic Cancer
		4.4.8 Leukemia
	4.5 Polyphenolics in Cancer Targeted Drug Delivery Systems
		4.5.1 Liposomes
		4.5.2 Solid Lipid Nanoparticles
		4.5.3 Nano Micelles
		4.5.4 Dendrimers
		4.5.5 Gold Nanoparticles
	4.6 Clinical Evidence of Polyphenols
	4.7 Conclusion
	References
5 Dietary Polyphenols in Cardiovascular Diseases (CVDs)
	5.1 Introduction
	5.2 Effect of Polyphenol On Hypertension
		5.2.1 Effect of Phytoestrogens On Hypertension
	5.3 Polyphenols as Inhibitors of Low-Density Lipoproteins (LDL)
		5.3.1 Polyphenols From Fruits and Vegetables
		5.3.2 Effect of Polyphenols On Vasodilation
	5.4 Conclusion
	References
6 Dietary Polyphenols in Arthritis and Inflammatory Disorders
	6.1 Introduction
	6.2 Dietary Polyphenols Used in Treatment of Arthritis
		6.2.1 Quercetin
			6.2.1.1 Source
			6.2.1.2 Chemistry
			6.2.1.3 Pharmacology
			6.2.1.4 Pharmacokinetics and Toxicity
		6.2.2 Gallic Acid
			6.2.2.1 Source
			6.2.2.2 Chemistry
			6.2.2.3 Pharmacology
			6.2.2.4 Pharmacokinetics and Toxicity
		6.2.3 Kaempferol
			6.2.3.1 Source
			6.2.3.2 Chemistry
			6.2.3.3 Pharmacology
			6.2.3.4 Pharmacokinetics and Toxicity
		6.2.4 Naringenin
			6.2.4.1 Source
			6.2.4.2 Pharmacology
			6.2.4.3 Pharmacokinetics and Toxicity
		6.2.5 Ferulic Acid
			6.2.5.1 Source
			6.2.5.2 Pharmacology
			6.2.5.3 Pharmacokinetics and Toxicity
		6.2.6 Epigallocatechin-3-Gallate
			6.2.6.1 Source
			6.2.6.2 Pharmacology
			6.2.6.3 Pharmacokinetics and Toxicity
		6.2.7 Luteolin
			6.2.7.1 Source
			6.2.7.2 Pharmacology
			6.2.7.3 Pharmacokinetics and Toxicity
		6.2.8 Cumaric Acid
			6.2.8.1 Source
			6.2.8.2 Chemistry
			6.2.8.3 Pharmacology
			6.2.8.4 Pharmacokinetics and Toxicity
		6.2.9 Chlorogenic Acid
			6.2.9.1 Source
			6.2.9.2 Chemistry
			6.2.9.3 Pharmacology
			6.2.9.4 Pharmacokinetics and Toxicity
		6.2.10 Butein
			6.2.10.1 Source
			6.2.10.2 Pharmacology
		6.2.11 Shogaol
			6.2.11.1 Source
			6.2.11.2 Pharmacology
			6.2.11.3 Pharmacokinetics and Toxicity
		6.2.12 Myricetin
			6.2.12.1 Source
			6.2.12.2 Pharmacology
		6.2.13 6-Gingerol
			6.2.13.1 Source
			6.2.13.2 Pharmacology
			6.2.13.3 Pharmacokinetics and Toxicity
		6.2.14 Puerarin
			6.2.14.1 Source
			6.2.14.2 Pharmacology
	6.3 Dietary Polyphenols Under Clinical Trials for the Treatment of Arthritis and Inflammatory Diseases
	6.4 Conclusion and Future Perspective
	References
7 Dietary Polyphenols in Diabetes
	7.1 Introduction
	7.2 Dietary Polyphenols
		7.2.1 Structure, Classification, and Sources
		7.2.2 Flavonoids
			7.2.2.1 Flavonols
			7.2.2.2 Flavanols
			7.2.2.3 Isoflavone
			7.2.2.4 Flavone
			7.2.2.5 Flavanone
			7.2.2.6 Anthocyanins and Anthocyanidins
		7.2.3 Nonflavonoids
			7.2.3.1 Phenolic Acids
			7.2.3.2 Stilbenes
			7.2.3.3 Lignans
	7.3 The Biological and Biochemical Function of Polyphenols
		7.3.1 Anti-Hypertensive Effect
		7.3.2 Pro-Oxidant Activity
		7.3.3 Anti-Atherosclerotic Effect
		7.3.4 Anti-Metabolic Effect
		7.3.5 Anti-Obesity Effect
		7.3.6 Microbial Suppression Effect
		7.3.7 Immunomodulatory Effect
		7.3.8 Anti-Oxidant Activity
		7.3.9 Anti-Cancer Effect
		7.3.10 Hypoglycemic Effect
	7.4 Antidiabetic Polyphenols
		7.4.1 Curcumin
		7.4.2 Resveratrol
		7.4.3 Catechins
		7.4.4 Procyanidin
		7.4.5 Anthocyanidins
		7.4.6 Caffeoylquinic Acids
		7.4.7 Isoflavones
	7.5 Antidiabetic Polyphenols in Clinical Trials and Marketed Products
	7.6 Conclusion
	References
8 Dietary Polyphenols in Bacterial and Fungal Infections
	8.1 Introduction
	8.2 Polyphenols in the Prevention of Bacterial and Fungal Infections
		8.2.1 Absorption of Dietary Polyphenols
			8.2.1.1 Flavonoids
			8.2.1.2 Lignans
			8.2.1.3 Tannins
			8.2.1.4 Phenolic Acids
		8.2.2 Antimicrobial Effects of Dietary Polyphenols
		8.2.3 Mechanism of Action of Polyphenols On Bacteria and Fungus
			8.2.3.1 Anti-Bacterial Mechanisms of Polyphenols
			8.2.3.2 Antifungal Mechanisms of Polyphenols
		8.2.4 Synergism
	8.3 Polyphenols in Immunology
		8.3.1 Role of Polyphenols in Innate and Adaptive Immunity
			8.3.1.1 Effect of Polyphenols On Innate Immune System
			8.3.1.2 Effect of Polyphenols On Adaptive Immune System
		8.3.2 Immunobiotics and Their Interactions With Polyphenols
		8.3.3 Polyphenols as Immune Boosters in Viral Infections
	8.4 Implications of Food Safety Systems and Policy
		8.4.1 Food Processing
		8.4.2 Marketing and Regulation
		8.4.3 Fortification and Supplementation
	8.5 Conclusion and Future Prospective
	References
9 Dietary Polyphenols in Viral Infections
	9.1 Introduction
	9.2 Structure and Classes of Polyphenols
		9.2.1 Phenolic Acids
		9.2.2 Flavonoids
		9.2.3 Tannins
		9.2.4 Stilbenes
		9.2.5 Lignans
	9.3 Significant Dietary Sources of Polyphenolic Compounds
	9.4 Bioavailability and Pharmacokinetics of Polyphenols
	9.5 Biological Activity of Polyphenolic Compounds
		9.5.1 Antimicrobialactivity
		9.5.2 Anti-SARS-CoV-2
		9.5.3 Anti-HIV Activity
			9.5.3.1 Anti HSV Activity
			9.5.3.2 Activity Against Influenza Virus
			9.5.3.3 Other Antiviral Activity of Polyphenolic Compounds
	9.6 Conclusion and Future Perspectives
	Acknowledgement
	References
10 Dietary Polyphenols in Parasitic Diseases and Neglected Tropical Diseases (NTDs)
	10.1 Introduction
	10.2 Dietary Polyphenols Against Parasitic Diseases
		10.2.1 Malaria
		10.2.2 Dengue
		10.2.3 Chikungunya
		10.2.4 Leishmaniasis
		10.2.5 Zika Virus
	10.3 Dietary Polyphenols Against NTDs
		10.3.1 Chagas Disease
		10.3.2 Fascioliasis
		10.3.3 Human African Trypanosomiasis
		10.3.4 Leprosy
		10.3.5 Lymphatic Filariasis
		10.3.6 Trachoma
		10.3.7 Schistosomiasis
	10.4 Current Challenges and Future Scopes
	10.5 Conclusions
	References
11 Dietary Polyphenols for the Management of Skin Diseases and Wound Healing
	11.1 Introduction
	11.2 Classification and Sources of Dietary Polyphenols
		11.2.1 Phenolic Acids
		11.2.2 Flavonoids
		11.2.3 Tannins
		11.2.4 Stilbenes
	11.3 Dietary Polyphenols in Skin Diseases and Wound Infections
		11.3.1 Anti-Aging
		11.3.2 Topical Allergies
		11.3.3 Skin Cancer
		11.3.4 Wound Healing
	11.4 Nanocarrier-Based Delivery of Dietary Polyphenols in the Management of Skin Diseases/wound Healing
		11.4.1 Lipid-Based Nanocarriers
		11.4.2 Polymeric Nanoparticles
		11.4.3 Nanogel
		11.4.4 Hydrogel
		11.4.5 Miscellaneous NPs
	11.5 Conclusion
	Conflicts of Interest
	References
12 Dietary Polyphenols From Spices and Their Impact On Human Health
	12.1 Introduction
	12.2 Spices
		12.2.1 Classification and Types
		12.2.2 Spices in Functional Foods/culinary Preparation
	12.3 Polyphenols: An Important Secondary Metabolite
		12.3.2 Structure and Derivatives of Polyphenols
		12.3.3 Pathways and Distribution of Polyphenols in the Spices
		12.3.4 Leading Polyphenols From Spices: Analysis and Drug Discovery
	12.4 Potential Mechanisms
		12.4.1 Absorption and Interaction Inside the Body
		12.4.2 Significant Signaling Pathways
	12.5 Polyphenols and the Potential Health Effects
		12.5.1 Health Assistances: Therapeutic and Pharmacological Properties
			12.5.1.1 Antioxidant Activity and Their Impression On Human Health
			12.5.1.2 Anti-Inflammatory Activity
			12.5.1.3 Anticancer Effect
			12.5.1.4 Cardio-Protective Effects
			12.5.1.5 Effects Against Cognitive and Neurodegenerative Disease
			12.5.1.6 Anti-Diabetic Property
		12.5.2 As Dietary Supplements: Overlook for Health Benefits
		12.5.3 Futuristic Approaches: Opportunities for Food and Pharmaceuticals
	12.6 Conclusion and Future Prospective
	Acknowledgments
	Author Disclosure Statement
	References
13 Dietary Polyphenols in Drug Discovery By Drug Repurposing and Computational Screening
	13.1 Introduction
	13.2 Structural Classification and Chemistry of Polyphenols
		13.2.1 Flavonoids
		13.2.2 Tannins
		13.2.3 Phenolic Acids
		13.2.4 Lignans
		13.2.5 Stilbenes
	13.3 Computational-Based Approaches for Repurposing Dietary Polyphenol
		13.3.1 Virtual Screening
		13.3.2 Pharmacophore Modeling
		13.3.3 Molecular Docking
		13.3.4 QSAR Approaches
			13.3.4.1 Case Study 1
			13.3.4.2 Case Study 2
	13.4 Dietary Polyphenols as Leads in Drug Design and Discovery
		13.4.1 Curcumin
		13.4.2 Resveratrol
		13.4.3 Catechins
		13.4.4 Rutin
		13.4.5 Quercetin
		13.4.6 Kaempferol
	13.5 Conclusion and Future Perspectives
	References
Index