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- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
Phytoantioxidants and Nanotherapeutics Discover the medicinal importance of antioxidant herbal medicines, phytochemicals, and nanodelivery systems for a wide range of diseases Phytomedicine has been--and continues to be--central to many cultures and societies due to its low toxicity, low cost, accessibility, and efficacy in treating difficult diseases. In fact, many plant-derived bioactive natural products serve as potential sources of drug leads or therapeutic agents in the treatment of a wide range of human diseases. When combined with nanotechnology, phytomedicine has the potential to affect and impact a tissue-specific site, which can reduce drug dosage and side effects while improving activity. Phytoantioxidants and Nanotherapeutics offers a comprehensive look at the significant role that phytomedicine-derived antioxidants play on the field of medicine, particularly when combined with the nanotechnology-derived drug delivery systems. The book thoroughly covers the herbs, plant extracts, and other dietary elements that may be used as sources of natural antioxidants and similarly highlights the use of phytomedicine- derived bioactive compounds including plant polyphenols and flavonoids to reducing the impact of oxidative stress induced human diseases. The text also demonstrates the biochemical and therapeutic targets of nanodrugs and discusses nanostructure toxicity, while emphasizing the challenges and regulatory issues involved with nanophytotherapeutics. Phytoantioxidants and Nanotherapeutics readers will also find: * A helpful bridge between the cutting-edge field of nanotechnology delivery and phytotherapeutics * The potential role of bioactive phytochemicals, particularly polyphenolic compounds and flavonoids, in oxidative stress-induced diseases * Description of the latest developments on nanotherapeutics of phytoantioxidants for the treatment of certain chronic human diseases, such as cancer, inflammations, diabetes, viral, bacterial and parasitic infections, nervous system disorders, cardiovascular disorders, and neurological diseases. Phytoantioxidants and Nanotherapeutics is a useful reference for drug manufacturers and drug developers, formulation scientists, biomedical scientists, medicinal chemists, phytochemists, healthcare providers, and academics and researchers.
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Table of Contents
Cover
Title Page
Copyright Page
Preface
List of Contributors
1 Natural Antioxidants in Oxidative Stress‐Induced Diseases
1.1 Natural Antioxidants: Game Changers in Human Disease Management
1.2 Oxidative Stress: Major Contributor of Human Diseases
1.3 Protective and Restorative Roles of Natural Antioxidants in Various Oxidative Stress‐Induced Diseases
1.4 Protective Mechanisms of Natural Antioxidants at the Molecular Level
1.5 Scope of Natural Antioxidants in Therapeutic Drug Development
1.6 Conclusion
References
2 Phytomedicines as Sources of Natural Antioxidants
2.1 Introduction
2.2 Sources of Phytomedicines
2.3 Role of Oxidative Stress in the Development of Chronic Diseases
2.4 Phytomedicines Along with Antioxidant Potential
2.5 Bioavailability and Metabolism of Phytoantioxidants
2.6 Probable Use of Phytoantioxidants in Prevention and/or Mitigation of Chronic Diseases
2.7 List of Some Marketed Preparations of Phytoantioxidants
2.8 Toxicity and Long‐Term Risk Assessment of Some Phytoantioxidants
2.9 Conclusions
References
3 Herbs, Spices, and Dietary Constituents as Sources of Phytoantioxidants
3.1 Introduction
3.2 Chemical Composition of Herbs and Spices as Potent Antioxidants
3.3 Antioxidant Properties of Herbs and Spices
3.4 Role of Flavonoids in Culinary Herbs and Spices
3.5 Medical Importance of Flavonoids
3.6 Natural Antioxidants
3.7 Role of Indigenous, Culinary Herbs and Spices in Daily Diet
3.8 Role of Antioxidants in Dietary Herbs and Spices – Indian Diet
3.9 Dietary Phytonutrients Phytoantioxidants – Chemical Structure
3.10 Health Benefits of Herbs and Spices
3.11 Traditional and Commercial Value of Herbs and Spices
3.12 Methods for Screening and Determination of Antioxidants
3.13 Conclusion
References
4 Phytoantioxidants and Their Role in Cellular Oxidative Stress
4.1 Introduction
4.2 Oxidative Stress
4.3 Phytoantioxidants
4.4 Role of Phytoantioxidants in Oxidative Stress‐Induced Disease
4.5 Future Scope of Phytoantioxidants as Phytopharmaceuticals
4.6 Conclusion
References
5 Bioactive Flavonoids as Phytoantioxidants
5.1 Introduction
5.2 Structural Features and Natural Sources of Bioactive Flavonoids
5.3 Mechanism of Action as Antioxidants
5.4 Bioavailability and Metabolism
5.5 Semisynthetic Alterations in Bioactive Flavonoids
5.6 Application in Therapeutics
5.7 Conclusion
References
6 Nanoparticulate Delivery Systems for Phytoconstituents
6.1 Natural Product as the Biggest Source of the Drug
6.2 Nanotechnology as a Solution for Delivery of Phytoconstituents
6.3 Nanocarriers for Phytoconstituents
6.4 Polymeric Nanoparticles
6.5 Lipid‐based Nanoparticles
6.6 Metallic Nanoparticles
6.7 Other Particulate Nanocarriers
6.8 Target Specificity and Toxicity Concerns of Nano‐sized Drug Carriers
6.9 Future Prospects
References
7 Nanodelivery of Herbal and Phyto‐Antioxidants
7.1 Introduction
7.2 Natural Antioxidants and Herbal/Phyto‐Antioxidants
7.3 Types of Nanodelivery Systems (Nanoparticles and Others) for Phyto‐Antioxidants
7.4 Nanodelivery of Phyto‐Antioxidant and Therapeutic Applications
7.5 Challenges and Future Perspectives
7.6 Conclusion
References
8 Nanodelivery of Antioxidant Herbal Extracts, Spices, and Dietary Constituents
8.1 Introduction
8.2 Antioxidant Properties of Spices
8.3 Nanodelivery of Herbal Antioxidant Extracts, Spices, and Dietary Constituents
8.4 Conclusion
References
9 Nanophytomedicine in Disease and Therapy
9.1 Introduction
9.2 Nanodelivery/Nanoparticulate Systems in Disease and Therapy
9.3 Nanomedicine as Biomedical Devices for Disease Treatment
9.4 Nanophytomedicine as Therapeutics
9.5 Nanophytomedicine as Nutraceuticals/Functional Foods
9.6 Opportunities, Scopes, and Challenges
9.7 Conclusion
References
10 Biochemical and Therapeutic Targets for Nanophytomedicines
10.1 Introduction
10.2 Biochemical Basis and Metabolic Interrelations of Redox Regulation/Chemistry of ROS‐Based Nanoplatforms
10.3 Nanomedicines in Drug Delivery Systems: Biochemical Pathways and Therapeutic Targets
10.4 Natural Nanotherapeutics on ROS‐Based Platform
10.5 Conclusion and Future Prospects
References
11 Green Approaches for Synthesis of Nanophytopharmaceuticals/Nanophytodelivery Systems
11.1 Introduction
11.2 Synthesis of Nanoparticles
11.3 Green Synthesis
11.4 Nanoparticle Synthesis from Biological Materials
11.5 Conclusion
References
12 Characterization of Nanophytopharmaceuticals
12.1 Introduction
12.2 Polymers Generally Applied in the Fabrication of Nanophytopharmaceuticals
12.3 Eudragit
12.4 Poly Lactic Acid (PLA) and Polylactide‐
co
‐Glycolic Acid (PLGA) – The Polyesters
12.5 Chitosan
12.6 Alginates
References
13 Toxicity of Nanostructures and Nanodrugs
13.1 Introduction
13.2 Causes of Nanotoxicity and Physicochemical Aspects of Nanostructures Responsible for Nanotoxicity
13.3 Different Types of Nanotoxicity
13.4 Mechanisms of Nanotoxicity
13.5 Effect of Nanotoxicity on Different Organs
13.6 Strategies for Making Nontoxic Nano‐Carriers
13.7 Conclusion and Future Perspective
References
14 Nanotherapeutics of Phytoantioxidants for Microbial Infections
14.1 Introduction
14.2 Microbial Diseases – Diagnosis and Progression
14.3 Phytoantioxidants
14.4 Nanodelivery Systems/Nanoformulations for Phytomedicine
14.5 Nano Phytoantioxidants and Their Roles in Microbial Diseases
14.6 Conclusion
References
15 Nanotherapeutics of Phytoantioxidants for Viral Infections
15.1 Introduction
15.2 Types of Viral Infections, Drugs, Plant‐based Drugs, and Phytoantioxidants Available for the Treatments
15.3 Polymeric‐Based Nanophytomedicine Containing Herbal Antioxidants/Phytoantioxidants and Their Antiviral Effects
15.4 Metallic Nanoparticle
15.5 Magnetic Nanoparticles
15.6 Lipid‐Based Nanophytomedicine Containing Phytoantioxidants and Their Antiviral Effects
15.7 Vesicular System‐Based Nanophytomedicine
15.8 Hydrogels
15.9 Dendrimers
15.10 Graphene Oxide Composite
15.11 Self‐Nanoemulsifying Drug Delivery Systems (SNEDDS)
15.12 Some of the Patents for Nanotherapeutics of Phytoantioxidants
15.13 Conclusion and Future Perspective
Acknowledgments
References
16 Nanotherapeutics of Phytoantioxidants for Parasitic Diseases and Neglected Tropical Diseases
16.1 Introduction
16.2 Phytoantioxidants for Parasitic Diseases
16.3 Phytoantioxidants for NTDs
16.4 Nanotherapeutics of Phytoantioxidants for Parasitic Diseases and NTDs
16.5 Future Scope
16.6 Conclusion
Conflict of Interest
List of Abbreviations
References
17 Nanotherapeutics of Phytoantioxidants for Inflammatory Disorders
17.1 Introduction
17.2 Phytoantioxidants and Their Antioxidant Role in Inflammatory Disorders
17.3 Nanodelivery Systems or Nanoformulations, Especially in the Delivery of Herbal Drugs
17.4 Nano‐phytoantioxidants Extending Antioxidant Effects in Inflammatory Disorders
17.5 Nano‐phytoantioxidants and Their Therapeutic Importance in Inflammatory Disorders
17.6 Future Strategies
17.7 Conclusion
References
18 Nanotherapeutics of Phytoantioxidants for Cardiovascular Diseases
18.1 Introduction
18.2 Different Treatment Strategies for CVDs
18.3 The Emergence of Nanomedicine in CVDs
18.4 Nanoparticles as Drug Delivery Agents in the Treatment of CVDs
18.5 Future Scope of Nano‐Based Herbal Formulation in CVDs
18.6 Conclusions
References
19 Nanotherapeutics of Phytoantioxidants for Diabetes Mellitus
19.1 Introduction
19.2 Nanocarried Natural Bioactive Compounds Against Diabetes Mellitus
19.3 Conclusions and Future Perspectives
References
20 Nanotherapeutics of Phytoantioxidants for CNS Disorders
20.1 Introduction
20.2 Etiology and Progression of CNS Disorders
20.3 Current Strategies Developed in the Management of CNS Disorders and Their Limitations
20.4 Phytoantioxidants as Therapeutic Alternatives to CNS Disorders
20.5 Challenges in Administration of Phytoantioxidants in CNS Disorders
20.6 Nanotherapeutics as an Emerging Platform in the Treatment of CNS‐Related Etiologies
20.7 Phytoantioxidants‐Based Nanoformulation for Neuroprotection
20.8 Limitations of Nanotechnology‐Based Drug Delivery to the CNS
20.9 Conclusions and Future Perspectives
References
21 Nanotherapeutics of Phytoantioxidants for Aging and Neurological Disorders
21.1 Introduction
21.2 Reactive Oxygen Species and Oxidative Stress
21.3 Antioxidants
21.4 Phytoantioxidants for Aging and Neurological Disorders
21.5 Nanonization of Phytoantioxidants
21.6 Nanotechnologies Developed for Phytoantioxidants
21.7 Conclusion and Future Perspectives
References
22 Nanotherapeutics of Phytoantioxidants in Cancer
22.1 Introduction
22.2 Phytoantioxidants
22.3 Nanotechnology in Cancer Diagnosis and Target‐Specific Treatment as Phyto‐Nanoformulations
22.4 Recent Advances in Phyto Antioxidant‐Based Nanoformulations in Cancer
22.5 Future Perspective and Conclusion
References
23 Challenges and Regulatory Issues of Nanophytotherapeutics
23.1 Introduction
23.2 Regulatory Issues of Nanophytotherapeutics
23.3 Regulatory Issues of Nanophytotherapeutics in the USA
23.4 Regulatory Issues of Nanophytotherapeutics in Europe
23.5 Regulatory Issues of Nanophytotherapeutics in India
23.6 Conclusions and Future Perspectives
References
Index
End User License Agreement
List of Tables
Chapter 1
Table 1.1 Some fruits and vegetables with their antioxidant compounds.
Chapter 2
Table 2.1 Phytoconstituents with antioxidant potentials.
Chapter 3
Table 3.1 Reactive oxygen species (ROS) and reactive nitrogen species (RNS)...
Table 3.2 Classification of herbs.
Table 3.3 Major chemical compounds in herbs and spices.
Table 3.4 Major antioxidants of herbs and spices.
Table 3.5 Major antioxidants and therapeutic effects of herbs and spices.
Table 3.6 Dietary constituents.
Chapter 4
Table 4.1 List of oxidants and their role in the development of cellular ox...
Table 4.2 ROS‐mediated damage to biomolecules and their leading to cellular...
Table 4.3 Dietary sources of different classes of phytoantioxidants [33–49]...
Table 4.4 Some dietary phytoantioxidants with their reported bioactivities ...
Chapter 5
Table 5.1 Subclasses of flavonoids.
Table 5.2 Dietary sources of some common bioflavonoids with their approxima...
Chapter 6
Table 6.1 Various nanocarriers used for the delivery of phytoconstituents....
Table 6.2 Classification of nanoparticular carrier based on manufacturing c...
Table 6.3 List of polymers commonly used in the preparation of nanoparticle...
Table 6.4 Paclitaxel delivery via polymeric nanoparticles.
Table 6.5 A list of various metallic nanoparticles‐based bioactive marker c...
Table 6.6 List of drugs delivered via carbon nanotube with its therapeutic ...
Table 6.7 Delivery of curcumin in various nanoparticulate carriers with the...
Chapter 8
Table 8.1 Different herbs/spices with antioxidant compounds.
Table 8.2 The major chemical constituents found in spices and herbs which a...
Table 8.3 DPPH and ABTS
+∙
antioxidant assays for garlic and ginger ex...
Table 8.4 Nanocarrier‐based antioxidant potential of some extracts of herbs...
Table 8.5 Some patents on the NPs‐based delivery of extracts of herbs and s...
Chapter 9
Table 9.1 List of FDA‐approved nano‐medicines.
Chapter 10
Table 10.1 A brief summary of certain ROS‐responsive structures and mechani...
Table 10.2 AGEs‐RAGE axis‐induced cytokines and their possible after‐effect...
Table 10.3 Some phytonutrients used in cancer nanomedicines [92].
Table 10.4 List of herbal nanoformulations in wound management.
Chapter 11
Table 11.1 Synthesis of NPs using various biological entities and plant ext...
Chapter 12
Table 12.1 The summary of some grades of Eudragit.
Table 12.2 Recent application of various grades of Eudragit.
Table 12.3 Merits of PLA‐ and PLGA‐based delivery systems.
Table 12.4 Properties of alginate enabling it to be a potential polymer for...
Chapter 13
Table 13.1 Types of nanomaterials and their production procedure.
Chapter 14
Table 14.1 Antimicrobial phytoantioxidants.
Table 14.2 Different green synthesized nanotherapeutics as antimicrobial ag...
Chapter 15
Table 15.1 Some of the phytochemical for antiviral potential.
Table 15.2 Routes of infection and incubation time of some common human vir...
Table 15.3 Some plants and extraction processes for their antiviral efficac...
Table 15.4 Some herbal drug‐loaded nanoformulations for the treatment of vi...
Table 15.5 Patents and recent advances related to nano‐formulations of phyt...
Chapter 16
Table 16.1 Examples of some phytoantioxidants used against parasitic diseas...
Table 16.2 Examples of some phytoantioxidants used against NTDs.
Table 16.3 Nanoformulations of phytoantioxidants used against parasitic dis...
Chapter 17
Table 17.1 Phytoantioxidants and their antioxidant role with special refere...
Table 17.2 Details of nano‐phytoantioxidants extending antioxidant effects ...
Chapter 18
Table 18.1 Various classes of nanotherapeutics and their features for phyto...
Table 18.2 Various nano encapsulated phytoantioxidants containing herbal fo...
Chapter 20
Table 20.1 List of some phytoantioxidants as therapeutic agents against CNS...
Table 20.2 Phytoantioxidant‐based nanoformulation and their beneficial effe...
Chapter 21
Table 21.1 List of phytoantioxidants used for the treatment of aging and ne...
Chapter 22
Table 22.1 Various plant secondary metabolites and their sources.
Table 22.2 Phytoantioxidants in clinical trial.
Table 22.3 Phytochemicals used in cancer [110].
Table 22.4 Various polyphenolic phytoconstituents used in cancer therapy [1...
Chapter 23
Table 23.1 Examples of nanotechnological interventions approved for clinica...
Table 23.2 Contract research organizations in India working on nanomedicine...
Table 23.3 Nano‐based healthcare products in India.
List of Illustrations
Chapter 1
Figure 1.1 Classification of natural antioxidants.
Figure 1.2 Catechin molecule.
Figure 1.3 Proanthocyanin molecule.
Figure 1.4 Leucocyanidin molecule.
Figure 1.5 Influence of antioxidants on human health. Antioxidants can influ...
Figure 1.6 Role of nutraceuticals in the prevention of illness.
Figure 1.7 Schematic representation of dyslipidemia of metabolic syndrome.
Chapter 2
Figure 2.1 Classification of natural antioxidant obtainable from plant and d...
Figure 2.2 Process involved in the development of oxidative stress leads to ...
Chapter 3
Figure 3.1 Different compounds of flavonoids.
Figure 3.2 Application of herbs and spices.
Figure 3.3 Medicinal plants used in ancient Babylonia.
Source:
Pharmapproach...
Chapter 4
Figure 4.1 Cellular events of endogenous antioxidant defense mechanism.
Figure 4.2 ROS‐mediated assault on biomolecules and their related cellular d...
Figure 4.3 Cell signaling pathways involved in oxidative stress.
Figure 4.4 Classification of phytoantioxidants along with their structural d...
Figure 4.5 Molecular pathways involved in phytoantioxidant‐mediated ameliora...
Chapter 5
Figure 5.1 Classification of various natural antioxidants.
Figure 5.2 General structure of flavonoids. (a) Chemical structure of flavon...
Figure 5.3 Pathways through which flavonoids exert their antioxidant action....
Figure 5.4 Mechanisms of antioxidant effect of flavonoids.
Figure 5.5 Structural requirements associated with antioxidant activities of...
Figure 5.6 Structural requirements associated with antioxidant activities of...
Figure 5.7 Metabolism of bioactive flavonoids.
Figure 5.8 Enterohepatic circulation in the metabolism of bioactive flavonoi...
Chapter 6
Figure 6.1 Issues with phytoconstituents need to be handled during delivery....
Figure 6.2 Key benefits of nanocarriers as drug‐delivery vehicles.
Figure 6.3 Various goals to be achieved by nanocarriers.
Figure 6.4 Nanocarrier (a) Polymeric nanoparticles. (b) Solid lipid nanopart...
Figure 6.5 Nanocarrier (a) Carbon nanotube. (b) Nanofibers. (c) Dendrimers. ...
Figure 6.6 Strategy for the treatment of the nanocarriers' approach to skin ...
Figure 6.7 Unsolved issues with nanocarriers.
Chapter 8
Figure 8.1 Reaction mechanism of DPPH with antioxidants.
Figure 8.2 Various nanocarriers for the delivery of herbal antioxidant extra...
Figure 8.3 DPPH radical scavenging activity (%) of chitosan nanoparticles, C...
Figure 8.4 Protective effects of micellar CAPE and pure CAPE in a model of H
Figure 8.5 The scavenging rate for SWCNTs and biohybrids with quercetin and ...
Figure 8.6 (a) Cell cytotoxicity study of neem oil and with nanoemulsion by ...
Chapter 10
Figure 10.1 The broad concept of physiologic and pathologic reactive oxygen ...
Figure 10.2 Biochemical pathway for free radicals in cancer.
Figure 10.3 Biochemical pathway showing ROS in wound healing.
Figure 10.4 Mechanisms involved in ischemia–reperfusion injury and targeting...
Figure 10.5 Pathways of free radicles in Alzheimer’s disease.
Figure 10.6 Pathways of free radicles in Alzheimer’s disease.
Chapter 11
Figure 11.1 Approaches in nanoparticle synthesis.
Figure 11.2 Metal nanoparticle types and biomedical applications of these ty...
Chapter 13
Figure 13.1 Different shapes of nanostructures.
Figure 13.2 Human organs primarily affected by nanotoxicity.
Source:
Crystal...
Chapter 15
Figure 15.1 Various phases of virus infections.
Figure 15.2 Various sources of free radicals/ROS generation.
Figure 15.3 Basic internal structure of nanocapsule.
Figure 15.4 Free radical scavenging effects of T‐NLC and free turmeric extra...
Figure 15.5 Phospolipd bilayer membrane of liposomes.
Figure 15.6 Schematic representation of micelles’ colloidal dispersion.
Figure 15.7
Cymbopogon citratus
volatile oil in vitro release kinetics encap...
Figure 15.8 SEM morphology of gels showed 3D matrix structures (a) blank CS/...
Figure 15.9 (a) The inhibition effects of GSC composite (GSCC) against RSV i...
Chapter 16
Figure 16.1 Classification of phytoantioxidants and chemical structures of s...
Figure 16.2 Overcoming resistance and bioavailability with nanophytoantioxid...
Figure 16.3 Nanophytoantioxidants in parasitic diseases and NTDs with possib...
Chapter 17
Figure 17.1 Nanotherapeutics of phytoantioxidants for inflammatory disorders...
Chapter 18
Figure 18.1 Current strategies for the management of CVDs.
Figure 18.2 Schematic representation of advantages of nanotherapeutics over ...
Figure 18.3 Frequently utilized nanotherapeutics for phytoantioxidant‐mediat...
Figure 18.4 Potential targets for the management of CVDs.
Figure 18.5 Limitations of nanotherapeutics‐mediated drug delivery in CVDs f...
Chapter 20
Figure 20.1 Factors involved in the progression of CNS disorders and the rol...
Figure 20.2 Nanotechnology‐based strategies used for delivering across the C...
Chapter 21
Figure 21.1 Role of reactive oxygen species and oxidative stress in aging an...
Figure 21.2 Commonly used phytotherapeutic compounds with potent antioxidant...
Chapter 22
Figure 22.1 Oxidative stress generation and its biological effect. Environme...
Figure 22.2 The potential molecular mechanism of catechin, lycopene, curcumi...
Figure 22.3 Nutritional genomics.
Chapter 23
Figure 23.1 Different types of nanoformulations in medicine.
Source:
From Re...
Figure 23.2 Different definitions of nanomedicine.
Source:
From Ref. [20]/wi...
Figure 23.3 Nanomedicine and its future course of action.
Source:
From Ref. ...
Figure 23.4 Main areas of nanoparticle translocation and accumulation after ...
Figure 23.5 Major challenges faced in the regulation of nanomaterials.
Figure 23.6 Regulatory issues of nanomedicine.
Source:
From Ref. [27]/with p...
Figure 23.7 Parameters for the nanomedicine innovation landscape.
Guide
Cover Page
Title Page
Copyright Page
Preface
List of Contributors
Table of Contents
Begin Reading
Index
WILEY END USER LICENSE AGREEMENT
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Phytoantioxidants and Nanotherapeutics
Edited by
Mithun Rudrapal
Pune, India
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Library of Congress Cataloging‐in‐Publication DataName: Rudrapal, Mithun, editor.Title: Phytoantioxidants and nanotherapeutics / edited by Mithun Rudrapal.Description: Hoboken, NJ : Wiley, 2022. | Includes bibliographical references and index.Identifiers: LCCN 2022011366 (print) | LCCN 2022011367 (ebook) | ISBN 9781119811770 (cloth) | ISBN 9781119811800 (Adobe PDF) | ISBN 9781119811831 (epub)Subjects: MESH: Antioxidants–therapeutic use | Phytochemicals–therapeutic use | Theranostic Nanomedicine–methodsClassification: LCC QK898.A57 (print) | LCC QK898.A57 (ebook) | NLM QV 325 | DDC 613.2/86–dc23/eng/20220613LC record available at https://lccn.loc.gov/2022011366LC ebook record available at https://lccn.loc.gov/2022011367
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Preface
Phytomedicines, herbal drugs, or dietary components have been widely used all over the world since ancient times and have been recognized by physicians, herbal practitioners, and patients for their better therapeutic effect, as they have fewer adverse effects as compared with modern medicines. Nanodelivery of phyto or herbal constituents has a potential future for enhancing the therapeutic utility and overcoming the problems associated by phytocomponents. In this context, nanodelivery systems or nanocarriers help to treat complex diseases such cancer, viral infections, neurological diseases, central nervous system disorders, and diabetes, just to name a few. Recently, there have been enormous developments in the field of nano‐based drug delivery systems to provide therapeutic agents or natural‐based active components to its target tissue‐specific location for the treatment of various diseases. There are a large number of herbal drug delivery systems successfully employed in recent times. There are still certain challenges that need to be addressed, and therefore, advanced technologies like nanotechnology need to be applied for the successful delivery of phyto and herbal components in the therapeutic management of diseases.
The book entitled Phytoantioxidants and Nanotherapeutics presents a comprehensive review on the medicinal importance of phytomedicine‐derived antioxidants with their development into useful nanodrug delivery systems as nanotherapeutics for potential therapeutic applications as nanobiomedicine in a wide range of oxidative‐stress‐induced chronic human diseases such as cancer, inflammatory disorders, viral infections, bacterial infections, parasitic infections, central nervous system disorders, cardiovascular disorders, diabetes, and neurological diseases. The chapters embedded in the book contain relevant information with latest updates on advanced topics related to the phytomedicine‐derived antioxidants and nanodrug delivery systems. The chapters are presented in a clear and lucid manner in order to aid flow, continuity, and technical presentation. The chapters encompass phytomedicine‐derived bioactive compounds as antioxidants (phytoantioxidants, plant polyphenols, and flavonoids) and their role in oxidative stress‐induced human diseases. Herbs, plant extracts, spices, and dietary constituents as sources of natural antioxidants and their potential medicinal benefits are also covered. Nanostructured or nanoparticulate systems used for the delivery of phytomedicine (including herbal extracts, spices, and dietary constituents) and phytoconstituents are summarized in this book. Biochemical and therapeutic targets of nanodrugs along with the toxicity of nanostructures in the biological matrix are detailed herein. The latest developments on nanotherapeutics of phytoantioxidants for the treatment of certain chronic human diseases such as microbial infections, parasitic diseases, inflammatory disorders, cardiovascular disorders, diabetes, central nervous system disorders, neurological disorders, and cancer are reviewed systematically and comprehensively. Finally, challenges and regulatory issues of nanophytotherapeutics are also highlighted. Some of the key features of this book include:
Presents comprehensive information on the potential role of bioactive phytochemicals, particularly polyphenolic compounds and flavonoids in oxidative‐stress‐induced human diseases.
Illustrates nanostructured or nanoparticulate systems used for the delivery of phytomedicine and/or bioactive phytoconstituents
Highlights biochemical and therapeutic targets of nanodrugs with the toxicity of nanostructures in the biological matrix
Delineates latest developments on nanotherapeutics of phytoantioxidants for the treatment of certain chronic human diseases
This book would be a useful resource for academic and research studies for the development of nanodrug delivery systems using phytomedicine‐derived or herbal phytoantioxidants. It is, therefore, strongly believed that through this book many stakeholders working in pharmaceutical and biomedical sectors will be benefited. This book will be particularly useful to drug developers, drug manufacturers, pharmaceutical scientists (R&D), discovery scientists, biomedical scientists, healthcare professionals, biotechnologists, chemists, biochemists, phytochemists, pharmacologists, toxicologists, researchers, academicians, and students. The exceptional design, well‐defined structure, and the rich content of the proposed book is timely and the need of the hour, and at present, there is no such book available in the market. Additionally, scientists involved in drug delivery research, nanoscience and nanotechnology research, formulation development research, nanobiomedicine research, nanomaterials research, nanodrug formulation research, nanodrug delivery research, and biomedical research are also expected to be the wider audience, users, or readers of this book, regardless if whether they are engaged in basic (chemistry, nanomaterials, nanoscience) or applied (such as pharmaceutical, nanomedicine, or biomedical) research.
List of Contributors
Syed Mohammad AbdullahDepartment of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India
Bhushan A. BhairavDepartment of Pharmaceutical Quality Assurance, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
Vinayak BhatiaDepartment of Glaucoma, ICARE Eye Hospital and Postgraduate Institute, Noida, Uttar Pradesh, India
Swarnali BhattacharjeeLife Sciences Division, Institute of Advanced Study in Science and Technology, Guwahati, Assam, India
Ravi BhushanCentre for Genetic Disorder, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
Debarupa Dutta ChakrabortyDepartment of Pharmaceutical Chemistry, Mata Gujri College of Pharmacy, Mata Gujri University, Kishanganj, Bihar, India
Mainak ChakrabortyDepartments of Pharmaceutical Technology and Pharmacology, NSHM Knowledge Campus, Kolkata, West Bengal, India
Prithviraj ChakrabortyDepartment of Pharmaceutics, Mata Gujri College of Pharmacy, Mata Gujri University, Kishanganj, Bihar, India
Tapash ChakrabortyDepartment of Pharmaceutics, Girijananda Chowdhury Institute of Pharmaceutical Science (GIPS), Guwahati, Assam, India
Joyani DasSarojini Naidu Vanita Pharmacy Maha Vidyalaya, Secunderabad, Telangana, India
Punamjyoti DasDepartment of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh, Assam, India
Prashanta Kumar DebDepartment of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, IndiaandLife Sciences Division, Institute of Advanced Study in Science and Technology, Guwahati, Assam, India
Rajlakshmi DeviLife Sciences Division, Institute of Advanced Study in Science and Technology, Guwahati, Assam, India
Nilayan GuhaDepartment of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh, Assam, India
Tong Thi Thu HoaVNU University of Medicine and Pharmacy, Vietnam National University Hanoi, Cau Giay, Hanoi, Vietnam
N. Shaista JabeenDepartment of Zoology, Dhnabagyam Krishnaswamy Mudaliar College for Women (Autonomous), Vellore, Tamil Nadu, India
Dolly JainOriental College of Pharmacy and Research, Oriental University, Indore, Madhya Pradesh, IndiaandAdina College of Pharmacy, Sagar, Madhya Pradesh, India
Manmohan Singh JangdeShri Balaji College of Pharmaceutical Sciences, Sakti, Chhattisgarh, India
Himadri KalitaDepartment of Zoology, Life Sciences Division, Assam Don Bosco University, Guwahati, Assam, India
Pallabi KashyapDepartment of Pharmaceutical Chemistry, Girijananda Chowdhury Institute of Pharmaceutical Sciences, Guwahati, Assam, India
Gülsen KayaScientific and Technological Research Center, Inonu University, Malatya, Turkey
Merve Keskin Vocational School of Health Services, Bilecik Seyh Edebali University, Bilecik, Turkey
Saban KeskinVocational School of Health Services, Bilecik Seyh Edebali University, Bilecik, Turkey
V. KiruthigaDepartment of Zoology, Dhnabagyam Krishnaswamy Mudaliar College for Women (Autonomous), Vellore, Tamil Nadu, India
Ashwini Kumar MishraDepartment of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research University (DIPSAR), Delhi Pharmaceutical Sciences and Research University, New Delhi, Delhi, India
Siddhartha MajiInstitute of Pharmacy, Ram‐Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, India
Papiya Mitra MazumderDepartment of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India
Santwana PalaiDepartment of Veterinary Pharmacology & Toxicology, College of Veterinary Science & Animal Husbandry, Orissa University of Agriculture & Technology, Bhubaneswar, Odisha, India
Sharad P. PandeyDepartment of Pharmacy, Shri Govindram Seksariya Institute of Technology and Science (SGSITS), Indore, Madhya Pradesh, India
Chandrakantsing V. PardeshiDepartment of Pharmaceutics, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
Vaishali PatelDepartment of Pharmaceutics, Laxminarayan Dev College of Pharmacy, Bharuch, Gujarat, India
Ghanshyam ParmarDepartment of Pharmacy, Sumandeep Vidyapeeth, Vadodara, Gujarat, India
Sabnam ParveenBirbhum Pharmacy School, Birbhum, West Bengal, India
Dipali PatelDepartment of Pharmaceutics, Shri Rawatpura Sarkar University, Raipur, Chhattisgarh, India
Arpita PaulDepartment of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh, Assam, India
Mahendra K. PrajapatiDepartment of Pharmaceutics, School of Pharmacy and Technology Management, SVKM’s NMIMS, Shirpur,Maharashtra, India
Shiv Kumar PrajapatiInstitute of Pharmacy, Ram‐Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, India
Mithun RudrapalDepartment of Pharmaceutical Chemistry, Rasiklal M. Dhariwal Institute of Pharmaceutical Education and Research, Pune, Maharashtra, India
Rakesh SagarDepartment of Pharmacy, Shri Govindram Seksariya Institute of Technology and Science (SGSITS), Indore, Madhya Pradesh, India
Abhishek K. SahDepartment of Pharmacy, Shri Govindram Seksariya Institute of Technology and Science (SGSITS), Indore, Madhya Pradesh, India
Pravat Kumar SahooDepartment of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Delhi Pharmaceutical Sciences and Research University, New Delhi, Delhi, India
Swarnlata SarafUniversity Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India
Anupam SarmaDepartment of Pharmaceutics, Girijananda Chowdhury Institute of Pharmaceutical Science (GIPS), Guwahati, Assam, India
Himangshu SarmaLife Sciences Division, Institute of Advanced Study in Science and Technology, Guwahati, Assam, India
Khomendra Kumar SarwaDepartment of Pharmacy, Government Girls Polytechnic, Raipur, Chhattisgarh, India
Ashish ShahDepartment of Pharmacy, Sumandeep Vidyapeeth, Vadodara, Gujarat, India
Smriti SharmaDepartment of Chemistry, Miranda House, University of Delhi, Delhi, India
Ganesh B. ShevalkarDepartment of Pharmaceutics, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
Vijendra Kumar SuryawanshiDepartment of Pharmaceutics, M J College, Bhilai, Chhattisgarh, India
Bui Thanh TungVNU University of Medicine and Pharmacy, Vietnam National University Hanoi, Cau Giay, Hanoi, Vietnam
Abd. Kakhar UmarDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia
Sonal UpadhyayCentre for Genetic Disorder, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
Dhaneshwar UraonDepartment of Pharmacy, Government Girls Polytechnic, Raipur, Chhattisgarh, India
A. VinodhiniDepartment of Zoology, Dhnabagyam Krishnaswamy Mudaliar College for Women (Autonomous), Vellore, Tamil Nadu, India
Md Kamaruz ZamanDepartment of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh, Assam, India
ZonunmawiiDepartment of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh, Assam, India
James H. ZothantluangaDepartment of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh, Assam, India
1Natural Antioxidants in Oxidative Stress‐Induced Diseases
Himadri Kalita1 and Prashanta Kumar Deb2
1 Department of Zoology, Life Sciences Division, Assam Don Bosco University, Guwahati, Assam, India
2 Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, India
Ayurvedic herbalism is not of the east or the west, of ancient or modern time. It is a science of living that encompasses the whole of life, and which relates the life of the individual to that of the universe. A knowledge that belongs to all living beings.
—Dr. David Frawley and Dr. Vasant Lad, The Yoga of Herbs.
1.1 Natural Antioxidants: Game Changers in Human Disease Management
1.1.1 Types and Sources of Natural Antioxidants
Antioxidants are the compounds acting as a defense system for our body. They neutralize the reactive oxygen species (ROS) generated during various metabolic processes inside our body and during disease conditions. There are various sources of antioxidants such as endogenous antioxidants, which are generated inside our body and exogenous antioxidants from various food sources (Table 1.1) [1]. In recent times, people are more toward natural antioxidant compounds rather than synthetic ones. Polyphenols are a group of compounds with high antioxidant activity. Among the sources of natural antioxidants, the most important are those coming from routinely consuming vegetables and fruits. The classification of natural antioxidants is depicted in Figure 1.1.
1.1.2 Chemical Structures of the Natural Antioxidants
1.1.2.1 Phenolic Compounds and Flavonoids
Phytochemicals, especially phenolics in fruits and vegetables, are the major bioactive compounds known for health benefits [2]. According to Bravo, the presence of polyphenols in fruits and vegetables is greatly influenced by genetic factors, environmental conditions, and degree of ripeness, for instance [3].
Many natural antioxidants exhibit a wide range of biological effects including antibacterial, antiviral, anti‐inflammatory, antiallergenic, antithrombotic, and vasodilatory actions [2]. Medicinal plants basically contain various antioxidants, e.g. vitamins, carotenoids, and phenolic compounds such as catechin, epicatechin, lignin and tannins, and anthocyanins [4].
Table 1.1 Some fruits and vegetables with their antioxidant compounds.
Source: Anwar et al. [1]/IntechOpen/licensed under CC BY 3.0.
No
Fruit/vegetable
Part used
Antioxidant
1.
Banana
Unripe (green) fruit and peel
Phenols and flavonoids
2.
Mango
Peel, kernel
Gallic acid, ellagic acid, gallates, gallotannins, condensed tannins
3.
Watermelon
Peel, rinds
Citrulline, lycopene, flavonoids, and phenols
4.
Cucumber
Peel
Flavonoids and phenols
5.
Potato
Peel
Chlorogenic acid, caffeic acid, ferulic acid, and phenols
6.
Coffee
Coffee ground and residue
Polyphenols, tannins, and gallic acids
7.
Apple
Peel
Epicatechin, catechins, anthocyanins, quercetin glycosides, chlorogenic acid, hydroxycinnamates, phloretin glycosides, and procyanidins
8.
Grapes
Skin and seeds
Coumaric acid, caffeic acid, ferulic acid, chlorogenic acid, cinnamic acid, neochlorogenic acid,
p
‐hydroxybenzoic acid, protocatechuic acid, vanillic acid, gallic acid, proanthocyanidins, quercetin 3‐
o
‐glucuronide, quercetin, and resveratrol
9.
Guava
Skin and seeds
Catechin, cyanidin 3‐glucoside, galangin, gallic acid, homogentisic acid, and kaempferol
10.
Pomegranate
Peel and pericarp
Gallic acid, cyanidin‐3,5‐diglucoside, cyanidin‐3‐diglucoside, and delphinidin‐3,5‐diglucoside
11.
Carrot
Peel
Phenols, β‐carotene
12.
Cucumber
Peel
Phenols, flavonoids, pheophytin, phellandrene, caryophyllene
13.
Potato
Peel
Gallic acid, caffeic acid, vanillic acid, chlorogenic acid, ferulic acid, and phenols
14.
Tomato
Skin and pomace
Carotenoids
In the group of polyphenolic compounds, flavonoids have been extensively studied and include catechins (Figure 1.2), proanthocyanins (Figure 1.3), anthocyanidins, flavones, flavonols, and their glycosides. Studies on the structure–activity relationship have afforded consistent evidence revealing the specific role of structural components and requirements for scavenger radicals, chelating action, and oxidizing activity of flavonoid compounds. In fact, the in vitro antioxidant activity of flavonoids and their metabolites depends on the arrangement of functional groups in the nuclear structure [5]. Most of the beneficial effects of flavonoids on human health are attributed to their antioxidant and chelating properties [5] and also to antimutagenic and antitumoral effects [6]. Flavonoids inhibit a variety of enzyme systems. Among them, there are several oxygenases such as prostaglandin synthase, the key enzyme in eicosanoids biosynthesis. Further, flavonoids also act by inhibiting the hyaluronidase activity helping maintain proteoglycans of connective tissue and preventing the spread of bacterial or tumor metastases [7]. By hindering the oxidation reactions, in which flavonoids are preferentially oxidized, they preserve the body’s natural antioxidants such as ascorbic acid [8].
Figure 1.1 Classification of natural antioxidants.
Source: Anwar et al. [1]/IntechOpen/licensed under CC BY 3.0.
The potential of plant biomasses as a source of bioactive compounds also refers to the by‐products and/or residues of a given production system. For instance, fruit residues (i.e. pomace) are inexpensive, are easily available, and contain bioactive molecules. Consequently, over the past years, research focus has shifted to such residues as a possible source of antioxidant compounds. Shui and Leong reported that antioxidant compounds, such as (−)‐epicatechin and proanthocyanidins, which existed as dimers through pentamers in star fruit (Averrhoa carambola L.) residues, delay oxidative rancidity of soybean oil to a greater extent than butylated hydroxytoluene (BHT) [9].
Figure 1.2 Catechin molecule.
Oxygen free radical processes are involved in both physiological and pathological conditions, which skin tissue repair caused mainly by trauma and burns [10]. The role of antioxidants in the removal of inflammation products is already known and these compounds are also beneficial in wound healing for other reasons. Antioxidants work against the excess of proteases and ROS, protecting protease inhibitors from oxidative damage. In addition, antioxidants can prevent destruction of fibroblasts and other cells caused by ROS over a generation, and therefore may be important in the successful treatment of lesions [11]. Another category of antioxidant leucocyanidin (Figure 1.4), a flavonoid that induces cell proliferation by increased incorporation of thymidine into cellular DNA [12], accelerating the healing of skin wounds [13].
Figure 1.3 Proanthocyanin molecule.
Figure 1.4 Leucocyanidin molecule.
Gallocatechin (GE) consists of the largest groups of naturally occurring phenols with antioxidant potential that is widely distributed in leaves, seeds, bark, and flowers of plants [5]. GE is a good candidate for wound healing and its treatment was able to decrease the epithelization period, healing the lesions in nine days, as well as to increase the hydroxyproline content over the treatment period. Histological analysis of the lesions confirmed the GE healing potential, showing fibroblast proliferation and induction of re‐epithelialization process. On the one hand, ROS are necessary for effective defense against invading pathogens and cell signaling and even in the absence of infection, low levels of ROS are necessary for cell signaling, especially angiogenesis. Consequently, a closer relationship between production and detoxification of ROS is crucial for the normal repair process of an injury.
1.1.2.2 Carotenoids
Carotenoids are also natural antioxidants and they contribute to the stability of foods. Such pigments are not evenly distributed in the food itself as various investigators have found that carotenoids are usually more concentrated in the peel than in the pulp of fruits and vegetables [12]. Three plantain varieties and two dessert banana varieties (Cavendish and Yangambi‐5) were investigated by [14] for pro‐vitamin A carotenoid content. Banana peel has a substantially higher carotenoid. Banana peel (Musa spp., cv. Prata Anã) might be considered a source of carotenes as trans‐β‐carotene, trans‐α‐carotene, and cis‐β‐carotene, which are the major carotenoids from this raw material. Banana peel is a kind of important raw material that might be more exploited regarding its carotenoid concentration as well as in the pulp.
1.1.3 Beneficial Role of Natural Antioxidants in the Management of Human Disease (Illustration and Diagram)
Free radicals are highly reactive species having unpaired electrons in their outermost shell. They react rapidly with the membranes eventually causing cellular damage and finally death. To protect the body from these radicals, the living system should generate or intake various antioxidants as nutraceuticals. Free radicals are generated in the body due to the exposure to various chemicals found in polluted air, water, etc. Most of the diseases including diabetes, hyperlipidemia, Parkinson’s, and Alzheimer’s are the results of the action of these free radicals. They interact with the lipid component of the cell membrane (lipid peroxidation) along with the RNA and DNA [15]. An effective antioxidant complex has different types of radical catching antioxidant sites that seek and destroy free radicals at many cellular sites. There are single specific antioxidants, for example, vitamin E, specific for the protection of an outer fatty layer of cells. A number of scientific studies are going about addressing the varied health benefits of antioxidant supplementation in processes like stress, aging, pathogen infestation, apoptosis, and neurological diseases. Antioxidants reduce the cell‐damaging effects of free radicals. Besides numerous scientifically compelling studies addressing various health benefits of antioxidant supplementation in athletic training with the simple addition of a good antioxidant complex, there are numerous studies addressing the various health benefits of antioxidant supplementation in athletic training with the simple addition of a good antioxidant complex. The brain is uniquely vulnerable to oxidative injury. Due to its high metabolic rate and elevated levels of polyunsaturated lipids, it is the target of lipid peroxidation. Consequently, antioxidants are commonly used as medications to treat various forms of brain injury. Antioxidants are also being investigated as possible treatments for neurodegenerative diseases (NDs) such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis and as a way to prevent noise‐induced hearing loss [15]. People take antioxidant supplements directly from fresh fruits and vegetables. Fruits and vegetables contain a large amount of flavonoids and antioxidant supplements that contribute to protection against different types of cancers and cardiovascular health problems (Figure 1.5) [18].
Figure 1.5 Influence of antioxidants on human health. Antioxidants can influence many aspects of human health such as diabetes, aging, cardiovascular and NDs, cancer, and other illnesses. Antioxidants produce several beneficial effects, promoting a healthy status, and reducing the oxidative stress caused by ROS.
Source: Based on Refs. [16, 17].
1.1.4 Natural Antioxidants as Nutraceuticals in the Prevention of Oxidative Stress‐Associated Diseases (with Suitable Examples)
Antioxidants are substances that retard or prevent deterioration, damage, or destruction by oxidation. Oxidative stress arises by the generation of ROS and ROS are generated in case of a lack of antioxidant defense in the body. Free radicals are a major cause of many degenerative diseases. Many chronic diseases such as diabetes, cardiovascular diseases, NDs, and carcinogenic ailments are related to free radicals [19]. Antioxidants form an integral part of the nutraceutical market. They are the major part of the most commonly occurring nutrients. Antioxidants are quite large in number and diverse in nature and prevent oxidation by neutralizing free radicals at relatively small concentrations. It can prevent the damage at the cellular level by using the following mechanisms: they may ease the energy of the free radical or subdue radical formation or repair the damage and reconstitute the membrane. Dietary intake of antioxidants may exert many potential benefits [20]. Ingestion of antioxidants from fruits and vegetables or administration of synthetic antioxidants decreases certain chronic diseases of aging. For example, intake of vitamin E may prevent Parkinson’s disease [21], many dietary antioxidants can inhibit low‐density lipoprotein‐cholesterol (LDL‐c) oxidation, thus protecting the heart against diseases. Terpenes have unique antioxidant activity as they react with free radicals by partitioning themselves into fatty membranes by virtue of their long carbon side chain and help in the cure of diseases. Thus, polyphenols act as an antioxidant protectant for humans. Phenolic antioxidants such as tocopherols, polyphenols, and phytoestrogens decline oxidative cell injuries and inflammatory reactions improving the brain’s health [22, 23]. Scientific focus on the identification of health‐protectant components within the foodstuff and their mechanism(s) of action needed to be studied properly. Nowadays direct attention should be given to nutraceuticals rather than to the whole‐food concepts implicit in a term such as functional foods [24] (Figure 1.6).
Figure 1.6 Role of nutraceuticals in the prevention of illness.
Source: Jain and Ramawat [25]/ with permission of Springer Nature.
1.2 Oxidative Stress: Major Contributor of Human Diseases
1.2.1 Oxidative Stress in the Development of Human Diseases
Oxidative stress, cellular senescence, and, consequently, various protein factors are involved in several acute and chronic pathological processes, such as metabolic syndrome (MetS), NDs, macular degeneration (MD), biliary diseases, and cancer. MetS‐associated risk factors (i.e. obesity, diabetes, hypertension, and atherosclerosis) are associated with the inflammatory pathway mediated by IL‐1α, IL‐6, and IL‐8, and lead to increased cellular senescence [26, 27]. In many neurodegenerative conditions, including Alzheimer’s disease (AD), brain tissue biopsies show increased levels of p16, matrix metalloproteinase (MMP), and IL‐6 [28, 29]. Chronic obstructive pulmonary disease, biliary cirrhosis, cholangitis, and osteoarthritis share several damaging senescence‐associated secretory phenotype (SASP) profiles including IL‐6, IL‐8, and MMP. The induction of epithelial to mesenchymal transition mediated by ROS promotes cancer metastasis [30]. There is a close relationship between oxidative stress, inflammation, and aging. Aging is a loss of homeostasis due to chronic oxidative stress that affects especially the regulatory systems, such as nervous, endocrine, and immune systems. The consequent activation of the immune system increases the inflammatory responses and, consequently, increases age‐related morbidity and mortality [31].
1.2.1.1 Body Mass Index (BMI)
Previous studies have reported that increased BMI is a strong risk factor for MetS‐associated risk factors [32]. A strong positive association found between obesity and MetS is found in both men [33] and women [34]. Obesity is mainly associated with an increased risk of developing insulin resistance and type 2 diabetes mellitus (T2DM). In obese individuals, a large amount of nonesterified fatty acid (FA) was released by adipose tissue and also other factors responsible for the development of insulin resistance were also released. When insulin resistance is followed by dysfunction of the β‐cells, the downfall of insulin secretion results in an uncontrolled rise in blood glucose levels leading to T2DM. Many genes are responsible for the obesity and pathogenesis of MetS. There are many genes, which determine the range of BMI in the population. Each gene can explain a few gram differences in body weight among the population [33]. Genes that are responsible for obesity and insulin resistance interact with environmental factors such as increased fat/calorie intake and decreased physical activity resulting in the development of obesity and insulin resistance followed ultimately by the development of MetS [35].
1.2.1.2 Hyperglycemia
T2DM is one of the serious endocrine disorders and a major health problem that has been growing in most of the countries today [36]. According to the report of the WHO (2013), about 347 million people suffer from diabetes worldwide. After cancer and cardiovascular disease (CVD), diabetes has become the third “killer” of mankind due to its high prevalence, morbidity, and mortality [29]. A recent report revealed that sales of diabetic drugs have been climbing over the last few years and the maximum sales crossed ₹97 crores since December 2013 in India alone. Type 2 DM is a heterogeneous disorder characterized by a progressive decline in insulin action (insulin resistance), followed by the inability of β‐cells to compensate for insulin resistance (pancreatic β‐cell dysfunction). Insulin resistance is a characteristic metabolic defect that proceeds over β‐cell dysfunction. The β‐cells normally compensate for insulin resistance by secreting more amounts of insulin to maintain glucose homeostasis. In the course of time, however, this β‐cell function gets impaired leading to deterioration in glucose homeostasis and subsequent development of impaired glucose tolerance leading to diabetes [37].
Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. There are mainly two types of diabetes mellitus (DM). Type 1 DM is immune‐mediated and requires daily administration of insulin. The other common type is type 2 DM and characterized by insulin resistance or relative insulin deficiency. T2DM is the most common form and comprises 90% of people with diabetes around the world. The prevalence of T2DM rates continues to increase with increasing number of patients at risk of serious diabetes‐related complications. Having T2DM increases the risk of a myocardial infarction two times and the risk of suffering a stroke two to four times.
Diabetes is a worldwide health problem, due to its high prevalence and because the clinical course of the disease can lead to several impairments, such as vision loss, chronic renal disease, macro‐ and microvascular complications, and eventually result in physical incapacity and death [38]. The American Diabetes Association (ADA) estimates that in 2012, expenditure on the treatment of diabetes and its complications was approximately $245 billion in the United States. Inhibitors of α‐glucosidase, which catalyzes the final step in the digestive process of carbohydrates, can retard the uptake of dietary carbohydrates and suppress postprandial hyperglycemia and may find use in the treatment of diabetic patients. The present generation of drugs used in the treatment of diabetes has certain limitations, and they sometimes lose their effect on glycemic control. Consequently, there is a need for the development of new drugs. Studies have shown that certain plants and phytochemicals have properties that improve the diabetic state. These properties include insulinotropic action on pancreatic β‐cells [39]; enhancement of insulin signaling in the liver [40], adipose tissue [32], and muscle [33]; and reduction in intestinal glucose absorption [34, 41]. Plants containing antioxidant substances have also been shown to have beneficial effects on diabetes, as well as reduce the oxidative stress caused by hyperglycemia [42]. Several α‐glucosidase inhibitors from plants have been screened and shown to be of clinical importance [43].
1.2.1.3 Hyperlipidemia
Hyperlipidemia is a heterogeneous disorder commonly characterized by an increased flux of free fatty acids (FFAs), raised triglycerides (TGs), LDL‐c (bad cholesterol), and apolipoprotein B (apoB) levels, as well as by a reduced plasma high‐density lipoprotein‐cholesterol (HDL‐c) concentration (good cholesterol) because of metabolic effects, or dietary and lifestyle habits (Figure 1.7) [44]. The lipid abnormality in hyperlipidemia is an increase in circulating (nonesterified) FFAs originating from adipose tissue, and inadequate esterification and FFA metabolism [44]. The reduced retention of FAs by adipose tissue leads to an increased flux of FFA returning to the liver, which stimulates hepatic TG synthesis, promoting the production of apoB, whereby deposition and secretion of very low‐density‐lipoprotein‐cholesterol (VLDL‐c). When plasma TG concentration is subsequently increased, TG‐rich HDL particles are formed and undergo catabolism. Elevated VLDL‐c particles are lysed and hence fail to bind efficiently to LDL receptors (LDLr), while the exchange of cholesterol esters with TGs forms TG‐rich lipoproteins, resulting in the formation of small dense LDL‐c particles [45]. A strong association exists between elevated LDL‐c levels and increased incidence of coronary artery disease [46]. The development of atherosclerotic plaques is associated with elevated levels of LDL‐c, reduced receptor‐mediated clearance, increased arterial wall retention, and an increased susceptibility [47]. Cardiovascular risk factors such as hyperlipidemia, hypertension, and thrombosis contribute to the underlying mechanisms of atherosclerotic disease, promoting endothelial dysfunction, oxidative stress, and proinflammatory pathways to peroxidation [47]. Lipid guidelines from the National Heart Foundation of Australia place great emphasis on LDL‐c and HDL‐c as atherogenic and antiatherogenic components, respectively. Indeed, high LDL‐cholesterolemia is considered one of the major modifiable risk factors for coronary heart disease, which continues to be the leading cause of death and morbidity in the United States [44]. Conversely to the Australian lipid guidelines, the Adult Treatment Panel III (ATP III) guidelines of the US National Cholesterol Education Program place greater emphasis on TG levels [44]. According to the National Health and Nutrition Examination Survey III, 24% of individuals aged >20 years had MetS [48]. Dyslipidemia is an independent risk factor for cardiovascular disease [49, 50]. Low HDL‐c and hypertriglyceridemia have been found to be independently and significantly related to myocardial infarction/stroke in patients with MetS [51]. The combination of high fasting glucose and low HDL‐c were shown to have primary predictive ability for coronary heart disease [52]. Dyslipidemia may be caused by a combination of overproduction of VLDL‐c, apoB‐100, decreased catabolism of apoB‐containing particles, and increased catabolism of HDL‐apoA‐I particles. Insulin resistance may be the consequence of this abnormality [53]. Dyslipidemia may arise from genetic components (e.g. mutated LDLr, mutated apoB‐100, mutated proprotein convertase subtilisin/kexintype‐9) [54], with or without environmental components (e.g. improper diet, familial history of hypercholesterolemia, hyperlipidemia, and/or hypertriglyceridemia) [55]. Causes of secondary hyperlipidemia include diabetes, hypothyroidism, obstructive liver disease, chronic renal failure, and drugs that increase LDL‐c and decrease HDL‐c, such as progestins and corticosteroids [56].
Figure 1.7 Schematic representation of dyslipidemia of metabolic syndrome.
1.2.1.4 Hypertension
Previous literature and case‐control studies have revealed that hypertension progression is also a predictor of MetS [57]. There is an association existing between T2DM and hypertension. Endothelial dysfunction could be one of the common pathways explaining the strong association between blood pressure and incident MetS. Studies suggested that endothelial dysfunction is associated with the onset of diabetes [58], and are closely related to blood pressure and hypertension [58]. Also, inflammatory markers such as C‐reactive protein have been consistently related to the incident of T2DM [59], and to increasing blood pressure levels, suggesting that inflammation may be another marker for the association between blood pressure, MetS, and incident T2DM [59]. Thus, insulin resistance may be another link between blood pressure levels and the pathogenesis of MetS [59]. Studies also suggested that blood pressure is linked to MetS. Hence, blood pressure increases with increasing BMI, the potential risk of T2DM associated with hypertension. A causal relationship between hypertension and T2DM is further strengthened by a recent randomized clinical trial study showing a 14% reduction in risk of diabetes in subjects with glucose intolerance by allocation to five‐year treatment with valsartan, an angiotensin II blocker with antihypertensive properties [60].
1.2.1.5 Physical Activity
Studies reported that physical inactivity is a strong risk factor for hyperlipidemia and diabetes. A sedentary lifestyle has been reported to be associated with MetS‐related risk factors like diabetes and obesity for both men and women [61], while moderate and vigorous physical exercise is associated with a lower risk of MetS [62]. Evidence from clinical trials which included physical activity as an integral part of lifestyle interventions suggested that the onset of T2DM can be prevented or delayed as a result of successful lifestyle interventions that included physical activity as a part of these interventions [63]. Physical activity plays an important role in delaying or preventing the development of MetS in those at risk both directly by improving insulin sensitivity and reducing insulin resistance, and indirectly by beneficial changes in body mass and body composition [64].
1.2.1.6 Dietary Pattern
Dietary habit is an important lifestyle risk factor associated with the development of MetS‐related risk factors. There is a positive correlation existing between dietary intake and the risk of developing MetS [65]. Previous literature showed that a higher dietary glycemic index has been consistently associated with an elevated risk of T2DM, which is a risk factor of MetS [66]. Western countries over the past years have shifted toward a more sedentary lifestyle by taking a high‐calorie diet, which is mainly rich in fructose and saturated fatty acid (SFA). Dietary fructose and fat are associated with different MetS‐related risk factors like obesity, insulin resistance, and T2DM. It is of two types, namely SFA and polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA). SFA is deleterious, while PUFA and MUFA have beneficial effects [67]
