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Submit a ProposalPlant-Derived Neurotherapeutics
One Line Description
Unlock the future of brain health with this evidence-based guide that bridges the gap between traditional herbal medicine and modern neuropharmacology, providing the clinical insights needed to develop next-generation neurotherapeutics.
Audience
Researchers, academics, bioengineers, and pharmacy and healthcare professionals across several specialized fields, including neuropharmacology, phytochemistry, and biotechnology.
Researchers, academics, bioengineers, and pharmacy and healthcare professionals across several specialized fields, including neuropharmacology, phytochemistry, and biotechnology.
Description
Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s, and mental health conditions like depression and anxiety, are on the rise due to an aging global population, lifestyle factors, and environmental stressors. These conditions often lack effective and sustainable treatment options, creating an urgent need for innovative therapies. The field of plant-derived neurotherapeutics, at the intersection of traditional herbal medicine and modern neuropharmacology, is rapidly emerging as a promising new area of treatment for these disorders. This book offers a comprehensive exploration of the neurotherapeutic potential of plant secondary metabolites by providing an in-depth look at a broad range of plant-derived compounds, including flavonoids, alkaloids, terpenoids, and polyphenols. Through its detailed exploration of how these compounds support brain health, the book offers a foundational understanding of their therapeutic roles within neuropharmacology. It includes real-world case studies and summaries of preclinical and clinical trials, presenting an evidence-based perspective on plant-derived neurotherapeutics. With contributions from experts across neuropharmacology, phytochemistry, and integrative medicine, the book provides an interdisciplinary audience of researchers, clinicians, and students a glimpse into the future of plant-derived compounds in neurotherapeutics.
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Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s, and mental health conditions like depression and anxiety, are on the rise due to an aging global population, lifestyle factors, and environmental stressors. These conditions often lack effective and sustainable treatment options, creating an urgent need for innovative therapies. The field of plant-derived neurotherapeutics, at the intersection of traditional herbal medicine and modern neuropharmacology, is rapidly emerging as a promising new area of treatment for these disorders. This book offers a comprehensive exploration of the neurotherapeutic potential of plant secondary metabolites by providing an in-depth look at a broad range of plant-derived compounds, including flavonoids, alkaloids, terpenoids, and polyphenols. Through its detailed exploration of how these compounds support brain health, the book offers a foundational understanding of their therapeutic roles within neuropharmacology. It includes real-world case studies and summaries of preclinical and clinical trials, presenting an evidence-based perspective on plant-derived neurotherapeutics. With contributions from experts across neuropharmacology, phytochemistry, and integrative medicine, the book provides an interdisciplinary audience of researchers, clinicians, and students a glimpse into the future of plant-derived compounds in neurotherapeutics.
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Author / Editor Details
Mukul Jain, PhD is a Professor in the Research and Development Cell at Parul University. He has published more than 60 book chapters and articles in international journals and conferences. His research interests include gel electrophoresis, DNA extraction, and cloning.
Mukul Jain, PhD is a Professor in the Research and Development Cell at Parul University. He has published more than 60 book chapters and articles in international journals and conferences. His research interests include gel electrophoresis, DNA extraction, and cloning.
Mohd. Tariq, PhD is a Professor in the Department of Life Sciences at the Parul Institute of Applied Sciences. He has more than 85 publications to his credit. Including two books, book chapters, and articles in international journals and conferences. His research focuses on conservation biology and ecology, biodiversity monitoring, and habitat selection.
Arifullah Mohammed, PhD is an Associate Professor in the Department of Agriculture Science in the School of Agro-Based Industry at the Universiti Malaysia Kelantan. He has published more than 50 book chapters and articles in international journals and conferences. His research interests include plant biotechnology, medicinal plants, and pharmacognosy.
Ayush Madan is a Professor in the Department of Biotechnology in the School of Research and Technology at the People’s University. He has more than 100 publications to his credit, including a patent, five books, book chapters, and articles in international journals and conferences.
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Table of Contents
Preface
1. Introduction to Plant-Derived Neurotherapeutics: An Overview of Secondary Metabolites
Koushik Das, Yukti Mittal, Injamamul Haque and Zuber Khan
1.1 Introduction
1.1.1 Global Burden of Neurological Disorders
1.1.2 Classification of Plant-Derived Secondary Metabolites
1.1.3 Terpenoids and Steroides
1.2 Polyketides and Compounds Generated from Fatty Acids
1.2.1 Fatty Acid Amides
1.2.2 Phytocannabinoids
1.2.3 Polyketides in Neurotherapeutics
1.2.4 Flavonoids
1.2.5 Stilbenes
1.2.6 Anthraquinones
1.3 Alkaloids
1.3.1 Classification of Alkaloids
1.3.2 Mechanisms of Action in Neurotherapeutics
1.3.3 Prominent Alkaloids in Neurotherapeutics
1.3.4 Clinical Applications and Future Perspectives
1.3.5 Biosynthesis of Nonribosomal Polypeptides
1.3.6 Mechanisms of Neuroprotection
1.3.7 Future Prospects and Challenges
1.4 Cofactors for Enzymes
1.4.1 Role of Enzyme Cofactors in Neurotherapeutics
1.5 Phenolic Compounds
1.6 Functions of Secondary Metabolites
1.6.1 Secondary Metabolites as Competitive Weapons
1.6.2 Ecological Roles of Secondary Metabolites
1.6.3 Secondary Metabolites as Carriers of Metals
1.6.4 Secondary Metabolites as Mediators of Symbiotic Relationships
1.6.5 Symbiotic Relations with Other Organisms
1.6.6 Implications for Neurotherapeutics
1.6.7 Secondary Metabolites as a Means of Reproduction
1.6.8 Mechanism of Action
1.6.9 Plant-Derived Neurotherapeutics
1.6.10 Challenges and Future Directions
1.6.11 Secondary Metabolites as Agents of Communication between Organisms
1.7 Studies on Secondary Metabolites in Plants
1.7.1 Neuroprotective Mechanisms of Secondary Metabolites
1.7.2 Promotion of Neurogenesis and Synaptic Plasticity
1.7.3 Mitochondrial Protection
1.7.4 Metal Chelation
1.7.5 Applications in Neurological Disorders
1.7.6 Challenges in Research and Development
1.7.7 Clinical Evidence
1.7.8 Future Directions
1.8 Conclusion
Bibliography
2. Phytochemistry of Neuroprotective Compounds: Key Classes and Their Properties
Baskaran Gunasekaran, Saema Hanafi, Kirtana Devi and Vaidehi Ulaganathan
2.1 Introduction
2.2 Phenolic Compounds
2.2.1 Flavonoids
2.2.2 Phenolic Acids
2.2.3 Stilbenes
2.2.4 Tannins
2.3 Terpenoids
2.3.1 Monoterpenes
2.3.2 Sesquiterpenes
2.3.3 Diterpenes
2.3.4 Triterpenes
2.4 Alkaloids
2.5 Other Neuroprotective Phytochemicals
2.5.1 Polysaccharides
2.5.2 Carotenoids
2.6 Phytochemical Bioavailability and Metabolism
2.7 Conclusion
References
3. Mechanisms of Action: How Plant Metabolites Interact with Neurological Pathways
Nil Patil, Urvi Patil, Mukul Jain, Ayush Madan and Mohd. Tariq
3.1 Introduction
3.1.1 Overview of Plant Metabolites and Their Relevance to Neurological Function
3.1.2 Importance of Understanding Metabolite–Neural Interactions for Brain Health
3.2 The Role of Plant Metabolites in Neuroprotection
3.2.1 Antioxidant Properties
3.2.2 Neurotransmitter Modulation
3.2.3 Signaling Pathway Modulation
3.2.3.1 Environmental Influences and Modulatory Mechanisms
3.2.3.2 Modulation by Biotic and Abiotic Stress
3.2.4 Modulation of Neuro Inflammation
3.2.4.1 Inhibition of Pro-Inflammatory Cytokines
3.2.4.2 Suppression of Microglial Activation
3.2.4.3 Reduction of Oxidative Stress
3.2.4.4 Regulation of Mitogen-Activated Protein Kinase (MAPK) Pathways
3.2.4.5 Modulation of Brain-Derived Neurotrophic Factor (BDNF)
3.3 The Gut–Brain Axis and Plant Metabolites
3.3.1 Gut Microbiota and Neurodegenerative Diseases
3.3.2 Plant Secondary Metabolites and the Gut–Brain Axis
3.3.3 Mechanisms of Action: How Plant Metabolites Modulate the GBA
3.4 Conclusion
References
4. Antioxidant Pathways: Combating Oxidative Stress in the Brain
Annu Verma, D.S.N.B.K. Prasanth and Ashwini Deshpande
4.1 Introduction
4.1.1 Definition and Significance of Oxidative Stress in the Brain
4.2 Mechanisms of Oxidative Stress in the Brain
4.2.1 Sources of ROS
4.2.2 Consequences of Oxidative Stress
4.3 Sources of Oxidative Stress
4.3.1 Mitochondrial Dysfunction
4.3.2 Excitotoxicity
4.3.3 Inflammation
4.3.4 Reactive Oxygen Species (ROS)
4.4 Role of Reactive Oxygen Species
4.5 Importance of Antioxidants
4.6 Brain Vulnerability to Oxidative Damage
4.7 Antioxidant Defense Mechanisms
4.7.1 Enzymatic Antioxidants
4.7.1.1 Superoxide Dismutase
4.7.1.2 Catalase
4.7.1.3 Glutathione Peroxidase
4.7.2 Nonenzymatic Antioxidants
4.7.2.1 Glutathione
4.7.2.2 Vitamins E and C
4.7.2.3 Phytochemicals
4.8 Therapeutic Strategies
4.8.1 Pharmacological Interventions
4.8.1.1 Nrf2 Activation
4.8.1.2 Phytochemical Supplements
4.8.1.3 Antioxidant Therapy
4.9 Lifestyle Modifications
4.9.1 Dietary Interventions
4.9.2 Physical Activity
4.9.3 Cognitive Stimulation
4.10 Innovations and Future Directions
4.10.1 Nanotechnology
4.10.2 Combination Therapies
4.10.3 Personalized Medicine
4.10.4 Dietary Interventions
4.11 Conclusion
References
5. Anti-Inflammatory Effects of Plant Metabolites on Neurological Health
Ahmed H. Elosaily, Ahmed M. El-Dessouki, Riham A. El-Shiekh, Mohamed S. Abd El Hafeez, Ghadir A. Sayed and Noha M. Gamil
5.1 Introduction
5.1.1 Inflammation and Neurological Disorders
5.2 The Pathogenesis of Neuroinflammation
5.2.1 Triggering Events: From Insult to Inflammation
5.2.2 The Dual Role of Microglia: Guardians or Executioners
5.2.3 Astrocytic Response: Amplifiers of Inflammation
5.2.4 Peripheral Immune Invasion: Crossing the Blood–Brain Barrier
5.2.5 Systemic Factors Influencing Neuroinflammation
5.3 Molecular Pathways Driving Neuroinflammation
5.3.1 The NF-κB Pathway: A Central Hub
5.3.2 The COX-2/Prostaglandin Axis: Mediators of Neuronal Sensitization
5.3.3 Reactive Oxygen and Nitrogen Species: The Oxidative Stress Amplifier
5.3.4 Cytokine Signaling: The Proinflammatory Cascade
5.4 Inflammation-Driven Pathogenesis in Specific Neurological Disorders
5.4.1 Alzheimer’s Disease: Chronic Neuroinflammation in the Brain
5.4.2 Parkinson’s Disease (PD): Neuroinflammation Driven by Alpha‑Synuclein
5.4.3 Multiple Sclerosis: Autoimmunity and Inflammation
5.4.4 Stroke: Inflammatory Repercussions of Ischemia
5.5 Preclinical Studies of Plant Extracts or Isolated Compounds Used for Neurological Health
5.5.1 Alzheimer’s Disease
5.5.2 Parkinson’s Disease
5.5.3 Cognitive Decline
5.5.4 Memory Enhancement
5.5.5 Anxiety
5.5.6 Depression
5.5.7 Neurodegeneration
5.5.8 Multiple Sclerosis
5.5.9 Epilepsy
5.5.10 Chronic Pain
5.6 Clinical Studies on Plants for Treating Inflammation in Alzheimer’s Disease
5.7 Clinical Studies on Plants for Treating Inflammation in Parkinson’s Disease
5.8 Clinical Trials Involving Plants with Anti-Inflammatory Activity in the Treatment of MS and NMO
5.9 Conclusion
References
6. Modulating Neurotransmitter Systems: Plant Compounds in Cognitive Enhancement
Reshma Tendulkar and Mugdha Tendulkar,†
6.1 Introduction
6.2 Neuroprotective Phytochemicals and Human Brain Function
6.2.1 Learning and Memory
6.2.2 Influence on the Molecular Level of Brain
6.2.3 Synaptic Plasticity
6.3 Mechanisms of Modulating Neurotransmitter Systems
6.3.1 Pathway of Cholinergic Signaling
6.3.2 Pathway of GABAergic Signaling
6.3.3 Pathway of Glutamergic Signaling
6.3.4 Pathway of Serotonergic Signaling
6.3.5 Pathway of Dopamine Signaling
6.3.6 Modulation by Monoamine Oxidase
6.3.7 Modulation by Catechol-O-Methyltransferase
6.4 Future Implications
6.5 Conclusions
References
7. Promoting Neurogenesis and Neuroplasticity: Potential for Brain Regeneration
Vivek Sharma, Tanuja Sharma, Naveen Singh, Rajnish Srivastava and Naresh Kumar Rangra
7.1 Introduction
7.1.1 Overview of Neuroplasticity and Neurogenesis
7.1.2 Importance of CNS Adaptability
7.2 Mechanisms of Neuroplasticity and Neurogenesis
7.2.1 Cellular and Molecular Basis
7.2.2 Role of Synaptic Plasticity
7.3 Factors Influencing Neuroplasticity and Neurogenesis
7.3.1 Genetic Factors
7.3.2 Environmental Influences
7.4 Impact of Physical Activity
7.4.1 Impact of Physical Activity
7.4.2 Aerobic Exercise and Brain Health
7.4.3 Effects of BDNF on Neurogenesis
7.5 Pharmacological Interventions
7.5.1 Psychedelic Substances (e.g., LSD)
7.5.2 Mechanisms of Action of LSD on Neuroplasticity
7.5.3 Therapeutic Potential in Mental Health
7.6 Nutritional Factors
7.6.1 Impact on Brain Function and Neuroprotection
7.6.2 Dietary Recommendations for Brain Health
7.7 Cognitive and Mental Stimulation
7.7.1 Activities that Promote Neuroplasticity
7.7.2 Benefits of Lifelong Learning and Social Interaction
7.8 Stress and Neuroplasticity
7.8.1 Impact of Chronic Stress on Brain Function
7.8.2 Stress Reduction Techniques (e.g., Meditation, Yoga)
7.9 Future Directions and Challenges in Promoting Neuroplasticity and Neurogenesis
7.10 Conclusion
References
8. Alzheimer’s Disease and Phytochemicals: Mechanisms and Potential Treatments
Shaik Ibrahim Khalivulla, Arifullah Mohammed and Saeed Alshahrani
8.1 Introduction
8.2 Ginkgo biloba
8.3 Crocus sativus
8.4 Ginseng
8.5 Stilbene
8.6 Phenolic Acids
8.7 Carotenoids
8.8 Lignans
8.9 Alkaloids (Huperzine A and Galantamine)
8.10 Terpenoids
8.11 Flavonoids
8.12 Nanoparticle
8.13 Conclusion
References
9. Parkinson’s Disease: Plant Derived Therapeutics and Dopaminergic Support
Naveen Singh, Namita Aggarwal, Nitin Verma and Rajnish Srivastava
9.1 Introduction
9.1.1 Pathological Hallmarks: Dopaminergic Neuron Loss and Alpha-Synuclein Inclusions
9.2 Need for Alternative Therapeutics in PD
9.2.1 Early Interventions and Focus on Natural Products
9.3 Role of Plant-Derived Compounds in PD Therapy
9.3.1 Overview of Phytochemicals with Neuroprotective Properties
9.3.2 Phytochemicals: Multifaceted Pharmacological Effects
9.4 Mechanisms of Action of Plant-Based Therapeutics
9.4.1 Mechanisms of Action of Plant-Based Therapeutics on Regulation of Oxidative Stress
9.4.2 Role of Plant-Based Therapeutics in Neuroinflammation Modulation
9.4.3 Plant-Based Therapeutics in Dopaminergic Neuron Support
9.5 Plant Sources of Antiparkinsonian Compounds with Their Targeted Pathways
9.6 Preclinical Evidence of Plant-Based Therapeutics in PD
9.7 Integrating Natural Products with Dopaminergic Support
9.8 Challenges and Future Directions
9.9 Conclusion
References
10. Huntington’s and Other Neurodegenerative Disorders: Plant-Based Interventions
Mukul Jain, Rupal Dhariwal, Akangsha Lahon, Ritika Bhardwaj and Krishna Thakkar
10.1 Introduction
10.1.1 Genetic Basis and Pathophysiology of Huntington’s Disease
10.1.2 Epidemiology and Prevalence of Huntington’s Disease Globally and in India
10.1.2.1 Geographical Distribution and Prevalence of HD Globally
10.1.2.2 Geographical Distribution and Prevalence of HD in Indian Communities
10.2 Molecular Mechanisms of Huntington’s Disease
10.2.1 Mutation in Huntingtin Gene and the Associated Protein Dysregulation
10.2.2 Oxidative Stress-Induced Mitochondrial Dysfunctioning
10.2.3 Protein Misfolding Promoted by Dysregulated Autophagy
10.2.4 Role of Epigenetic Factors, and Non-Coding RNAs in Promoting Transcriptional Level Dysregulation
10.3 Therapeutic Interventions against Huntington’s Disease
10.3.1 Currently Available Allopathic Interventions, Clinical Trials Phased Medicines Targeting HD
10.3.2 Natural-Therapeutic Approaches for Treatment and Prevention of Huntington’s Disease
10.3.3 Potentials of Natural Options Over Chemical-and Drug-Based Treatments
10.3.4 Integration of the Plant-Based Compounds with the Conventional Therapies
10.3.5 Combinational Therapies Integrating Plant-Based Interventions with Nano Therapy
10.4 Safety Concerns and Regulations of Plant-Based Therapeutics
10.5 Limitations and Drawbacks Associated with Plant-Based Therapeutics
Bibliography
11. Mental Health Disorders: Phytochemical Approaches to Anxiety, Depression, and Stress
Mohd Farhan, Mohd Faisal, Asim Rizvi, Ghazala Muteeb, Mohammad Aatif and Mir Waqas Alam
11.1 Introduction
11.2 Overview of Phytochemicals
11.3 Role and Mechanisms of Phytochemicals in the Treatment of Mental Health Disorders
11.3.1 Anxiety Disorders
11.3.1.1 In Vivo Studies
11.3.1.2 Clinical Trials
11.3.2 Depression
11.3.2.1 In Vivo Studies
11.3.2.2 Clinical Studies
11.4 Studies on the Effects of Phytochemicals on Anxiety and Depression in Animals and Humans
11.5 Phytochemical Bioavailability in Brain Tissue
11.6 Nanotechnology-Based Approaches to Enhancing Phytochemical Bioavailability in Brain
11.6.1 Nanoencapsulation
11.6.2 Natural Nanocarriers
11.6.3 Solid Lipid Nanoparticles
11.6.4 Polymeric Nanoparticles
11.6.5 Liposomes
11.7 Adverse Effects of Phytochemicals
11.8 Restrictions on the Study
11.9 Conclusion and Future Perspectives
References
12. Bioavailability and Pharmacokinetics of Plant Metabolites in Neurotherapeutics
Himanshu Jain and Neeraj K. Aggarwal
12.1 Introduction to Bioavailability and Pharmacokinetics
12.1.1 Physiological Barriers to Effective Neurotherapeutic Delivery
12.1.2 Gastrointestinal and Hepatic Constraints on Phytochemical Absorption
12.1.3 Pharmacokinetic Limitations of Plant-Derived Neurotherapeutics
12.1.4 Strategies to Overcome Pharmacokinetic Barriers
12.2 Absorption of Plant Metabolites
12.2.1 Solubility: A Critical Barrier for Absorption
12.2.2 Permeability: Crossing the Intestinal Epithelium
12.2.3 Gastrointestinal Stability: Protecting Bioactive Compounds
12.2.4 Gut Microbiota and Biotransformation: Modulating Metabolic Fate
12.2.5 Strategies for Enhancing Absorption and Bioavailability
12.3 Distribution and Brain Penetration of Plant-Derived Neurotherapeutics
12.3.1 Physiological Barriers and the Selective Nature of the Blood–Brain Barrier
12.3.2 Passive and Carrier-Mediated Transport across the Blood–Brain Barrier
12.3.3 Efflux Transporters as a Barrier to CNS Accumulation
12.3.4 Metabolic Transformations and Their Impact on Brain Distribution
12.3.5 Advanced Delivery Strategies to Enhance Brain Penetration
12.4 Metabolism of Phytochemicals
12.4.1 Phase I Metabolism: Functionalization and Its Influence on Phytochemical Activity
12.4.2 Phase II Metabolism: Conjugation, Clearance, and Neurotherapeutic Implications
12.4.3 Gut Microbiota as a Key Modulator of Phytochemical Metabolism
12.5 Excretion and Elimination
12.5.1 Routes of Elimination and Their Impact on Pharmacokinetic
12.5.2 Importance of Systemic Clearance in Determining Therapeutic Efficacy
12.6 Challenges in Bioavailability and Pharmacokinetics
12.6.1 Poor Solubility and Stability
12.6.2 First-Pass Metabolism and Rapid Systemic Clearance
12.6.3 Efflux Transporters Limiting Brain Penetration
12.7 Enhancing Bioavailability and Brain Targeting
12.7.1 Nanotechnology-Based Delivery Systems
12.7.2 Structural Modifications to Increase Stability and Bioavailability
12.7.3 Prodrug Approaches and Inhibitors to Modulate Metabolic Pathways
12.8 Future Perspectives
12.8.1 Integration of Advanced Drug Delivery Technologies
12.8.2 Metabolic Engineering and Personalized Medicine
12.8.3 Advancing In Vivo Models for Evaluation
12.8.4 Exploring the Gut–Brain Axis and Microbiome Interactions
12.8.5 Artificial Intelligence and Machine Learning in Drug Design
12.9 Conclusion
References
13. Formulation and Delivery Systems for Brain-Targeted Phytochemicals
Unmesh Gulabrao Bhamare, Prakash Pannalal Muleva, Deepali Dattatray Bhandari, Ramanlal Narayan Kachave, Sunil Vishvnath Amrutkar and Dattatraya Manohar Shinkar
13.1 Introduction
13.2 Phytochemicals with Brain-Targeting Potential
13.2.1 Neuroprotective Phytochemicals
13.2.2 Mechanisms of Action
13.2.3 Applications in Neurological Diseases
13.3 Barriers to Brain Delivery
13.3.1 Physiological Barriers
13.3.2 Phytochemical Limitations
13.3.3 Mechanisms Exacerbating Barriers
13.4 Formulation Strategies for Brain-Targeted Phytochemicals
13.4.1 Nanocarriers
13.4.2 Lipid-Based System
13.4.3 Inorganic Nanoparticles
13.4.4 Conjugates and Prodrugs
13.4.5 Biomaterials and Hydrogels
13.5 Delivery Systems for Brain Targeting
13.5.1 Routes of Administration
13.5.2 Active Targeting Strategies
13.5.3 Passive Targeting
13.5.4 Stimuli-Responsive Systems
13.5.5 Emerging Technologies
13.6 Challenges and Solutions in Brain-Targeted Delivery of Phytochemicals
13.6.1 Challenges
13.6.2 Solutions
13.7 Case Studies and Examples of Brain-Targeted Phytochemical Delivery Systems
13.7.1 Successful Formulations
13.7.2 Clinical Trials Involving Phytochemicals
13.7.3 Future Directions and Lessons from Case Studies
13.8 Future Prospects and Research Directions
13.8.1 Innovations in Delivery Systems
13.8.2 Multifunctional Approaches
13.8.3 Personalized Medicine
13.8.4 Future Challenges and Considerations
13.9 Conclusion
References
14. Preclinical and Clinical Studies: Evidence Supporting Plant Neurotherapeutics
Nisha Vijayan Kalayil, Sahaya Nadar, Ekta Thakor and Jegan Nadar
14.1 The Importance of Neurotherapeutics in Managing Neurological Disorders
14.2 Overview of Plant-Derived Compounds as Therapeutic Agents
14.3 Scope and Objectives of the Chapter
14.4 Mechanisms of Plant-Derived Neurotherapeutics
14.4.1 Neuroprotective Mechanisms of Plant-Derived Compounds
14.4.1.1 Antioxidant Properties
14.4.1.2 Anti-Inflammatory Effects
14.4.2 Modulation of Neurotransmitter Systems
14.4.2.1 Cholinergic System
14.4.2.2 Dopaminergic System
14.4.2.3 Serotonergic and GABAergic Systems
14.4.3 Neurogenesis and Synaptic Plasticity
14.5 Preclinical Studies: Evidence Supporting Plant Neurotherapeutics
14.5.1 Parkinson’s Disease (PD)
14.5.2 Alzheimer’s Disease (AD)
14.5.3 Ischemic Stroke
14.5.4 Depression
14.5.5 Multiple Sclerosis (MS)
14.6 Clinical Evidence Evaluating Plant-Derived Neurotherapeutics
14.7 Challenges
14.7.1 Bioavailability and Pharmacokinetics
14.7.2 Standardization of Plant Extracts
14.7.3 Lack of Large-Scale Clinical Trials
14.8 Future Directions
14.8.1 Advances in Drug Delivery Systems
14.8.2 Integration of Multi-Omics Approaches
14.8.3 Ethical and Regulatory Considerations
14.9 Conclusion
Bibliography
15. Plant-Based Brain Therapies: Challenges and Future Prospects Along with Molecular Mechanism Aided in Cognitive Protection
K.R. Padma, K.R. Don, M. Sankari, K. Harathi and N. Sandhya
15.1 Background of the Study
15.1.1 Natural Remedies from Plants Include Substances That Protect Nerve Cells
15.2 Nootropics Derived from Plants and Their Impact on Cognitive Performance
15.2.1 These are Well-Known Plant-Based Substances That Serve as Cognitive Enhancers
15.2.2 Ginkgo biloba
15.2.3 About Panax ginseng
15.2.4 The Rhodiola rosea
15.2.5 Ashwagandha and Its Impact on Cognitive Function
15.3 Natural Products Could Be Potential Targets for Neurodegenerative Disease Treatment
15.3.1 Nutrition and Cognitive Well-Being: An Exciting New Frontier
15.3.2 Trends in Consumer Preferences for Functional Foods
15.3.3 Vegetables and Fruits as a Researcher Topic
15.3.4 A Plant-Based Approach for Treating Spinal Muscular Atrophy
15.3.5 Medicinal Plants Have Neuroprotective Properties against Alzheimer’s Disease
15.3.6 Herbal Therapy for Alzheimer’s Disease
15.3.6.1 Main Insights
15.4 Plant-Derived Neuroprotective Compounds and the Role of Fiber in Cognitive Function Mechanisms
15.4.1 Fiber and Neuroprotection Engagement
15.5 Molecular Pathways and Disease-Associated Objectives of Medicinal Plants in the Management of Motor Neuron Disorders
15.6 Constraints
15.6.1 Prospective Possibilities
15.6.2 Challenges
15.6.3 Final Thoughts
Acknowledgments
References
16. Traditional and Modern Uses of Plants in Neurotherapy—A Comparative Perspective
Laxmi, Rahul Sharma, Shriyansh Srivastava, Izaz Hussain and Rakesh Sahu
16.1 Introduction
16.2 Historical Perspectives on Plant-Based Neurotherapy
16.2.1 Ancient Medicinal Traditions (Ayurveda, Traditional Chinese Medicine, Indigenous Healing System)
16.2.2 Early Documentation of Plant-Based Neurotherapeutics
16.2.3 Evolution of Herbal Remedies Over Time
16.3 Traditional Plant-Based Approaches in Neurotherapy
16.3.1 Commonly Used Plants in Ancient Healing (e.g., Ginkgo biloba, Ashwagandha, Bacopa monnieri)
16.3.1.1 Ginkgo biloba
16.3.1.2 Ashwagandha (Withania somnifera)
16.3.1.3 Brahmi (Bacopa monnieri)
16.3.2 Cultural Perspectives and Healing Philosophies
16.4 Modern Scientific Approaches to Plant-Based Neurotherapy
16.4.1 Advances in Phytochemistry and Neuropharmacology
16.4.2 Clinical Studies on Herbal Neuroprotectants
16.4.3 Synergistic Effects and Bioavailability Challenges
16.5 Comparative Analysis: Traditional vs. Modern Use
16.5.1 Effectiveness and Limitations of Traditional Remedies
16.5.2 Standardization and Regulatory Challenges in Modern Applications
16.5.3 Integrative Approaches: Bridging Traditional Wisdom with Modern Science
16.6 Emerging Trends and Future Prospects
16.6.1 Innovations in Herbal Neurotherapy (Nanotechnology, Personalized Medicine)
16.6.2 Potential for Plant-Based Drugs in Neurological Disorders
16.7 Conclusion
Abbreviations List
References
17. Case Studies of Plant Extracts in Neurotherapeutics Formulations
Erum Khalid, Sudhair Alam, Feroza Hamid wattoo, Muhammad Javaid Asad, Saima Amin and Muhammad Gulfaraz
17.1 Introduction
17.2 The Growing Role of Plant-Derived Compounds in Neurotherapeutics
17.3 Bioactive Compounds and Their Role in Brain Regeneration
17.3.1 Phenols
17.3.2 Flavonoids
17.3.3 Alkaloids
17.3.4 Terpenoids and Saponins
17.4 Plant Extracts’ Mechanisms of Action in Neurotherapeutics
17.4.1 Activity of Antioxidants and Free Radical Scavenging
17.5 Case Studies on Specific Plant Extracts
17.5.1 Ginkgo biloba in Cognitive Enhancement
17.5.2 Case Studies: Plant-Based Therapies in Parkinson’s Disease
17.5.2.1 Important Historical Events
17.5.3 Case Studies on Plant Extracts in Neurotherapeutics
17.5.3.1 Alzheimer’s Disease with Polygonum multiflorum (P. multiflorum)
17.5.3.2 Sorbus Commixta in AD
17.5.3.3 The Role of Rehmannia glutinosa (R. glutinosa) in AD
17.5.4 Case Study—Neuroprotective Effect of Grewia tiliaefolia
17.5.4.1 Phytochemical Composition and Bioactive Identification
17.5.4.2 Anti-Amyloidogenic Properties and Alzheimer’s Disease Model
17.5.4.3 Neuroprotection and Cell Viability in Neuronal Cells
17.5.4.4 Molecular Docking and Computational Analysis
17.6 Formulation Strategies for Neurotherapeutics
17.7 Preclinical and Clinical Evidence
17.8 Challenges in Neurotherapeutic Formulations
17.9 Future Directions
17.10 Conclusion
References
18. Future Trends in Plant-Derived Neurotherapeutics: From Lab to Clinic
Ananda Kumar Chettupalli, Mustapha, S.K. Abdual Rahaman, Neha Gupta, Garlapati Vijay Kumar and Sarad Pawar Naik Bukke
List of Abbreviations
18.1 Introduction to Plant-Derived Neurotherapeutics
18.1.1 An Overview of Neurotherapeutics: Definition, Importance, and Scope
18.1.2 Historical Perspective: Traditional Use of Plants in Treating Neurological Disorders
18.1.3 Modern Relevance: Bridging Traditional Medicine with Modern Pharmacology
18.1.4 Challenges in Neurotherapeutic Development: Complexity of Neurological Diseases and Drug Development Hurdles
18.2 Neuropharmacological Potential of Phytochemicals
18.2.1 Key Phytochemicals and Their Mechanisms: Alkaloids, Flavonoids, Terpenoids, and Polyphenols
18.2.2 Targeted Neurological Pathways: Antioxidative, Anti-Inflammatory, and Neuroprotective Pathways
18.2.3 Examples of Prominent Neuroprotective Plants
18.3 Advances in Preclinical Research
18.3.1 In Vitro Studies: Cellular Models for Studying Neurotoxicity and Protection
18.3.2 In Vivo Studies: Animal Models of Neurodegenerative Diseases
18.3.3 Biotechnology Integration: Genomic and Proteomic Approaches to Identify Active Compounds
18.4 Clinical Development and Translational Challenges
18.4.1 Phases of Clinical Trials: From Safety to Efficacy Studies
18.4.2 Phytochemical Standardization: Ensuring Consistency and Potency
18.4.3 Ethical Considerations: Balancing Traditional Knowledge and Intellectual Property
18.5 Emerging Technologies in Neurotherapeutics
18.5.1 Nanotechnology for Drug Delivery: Enhancing Bioavailability and Targeting
18.5.2 Artificial Intelligence and Drug Discovery: Predicting Efficacy and Toxicity of Plant Compounds
18.5.3 CRISPR and Genetic Engineering: Unlocking Plant-Derived Compounds Through Biosynthesis
18.6 Case Studies of Success and Failure
18.6.1 Success Stories: Plant-Based Drugs Currently in Use for Neurological Conditions
18.6.2 Lessons from Failures: Identifying Gaps in Research and Development
18.6.3 Insights for Future Endeavors: Best Practices in Drug Development Pipelines
18.7 The Role of Traditional Medicine and Ethnopharmacology
18.7.1 Indigenous Knowledge Systems: Contributions to Modern Neurotherapeutics
18.7.2 Global Integration: Bridging Traditional Practices with Scientific Rigor
18.7.3 Sustainability and Biodiversity: Ethical Sourcing and Conservation Efforts
18.8 Future Perspectives and Trends in Neurotherapeutics
18.8.1 Personalized Medicine: Phytochemicals Tailored to Genetic Profiles
18.8.2 Hybrid Therapies: Combining Plant-Derived Compounds with Synthetic Drugs
18.8.3 Global Collaboration: Collaborative Efforts in Research and Funding
18.9 Conclusion and Recommendations
References
About the Editors
Index
Back to Top
Preface
1. Introduction to Plant-Derived Neurotherapeutics: An Overview of Secondary Metabolites
Koushik Das, Yukti Mittal, Injamamul Haque and Zuber Khan
1.1 Introduction
1.1.1 Global Burden of Neurological Disorders
1.1.2 Classification of Plant-Derived Secondary Metabolites
1.1.3 Terpenoids and Steroides
1.2 Polyketides and Compounds Generated from Fatty Acids
1.2.1 Fatty Acid Amides
1.2.2 Phytocannabinoids
1.2.3 Polyketides in Neurotherapeutics
1.2.4 Flavonoids
1.2.5 Stilbenes
1.2.6 Anthraquinones
1.3 Alkaloids
1.3.1 Classification of Alkaloids
1.3.2 Mechanisms of Action in Neurotherapeutics
1.3.3 Prominent Alkaloids in Neurotherapeutics
1.3.4 Clinical Applications and Future Perspectives
1.3.5 Biosynthesis of Nonribosomal Polypeptides
1.3.6 Mechanisms of Neuroprotection
1.3.7 Future Prospects and Challenges
1.4 Cofactors for Enzymes
1.4.1 Role of Enzyme Cofactors in Neurotherapeutics
1.5 Phenolic Compounds
1.6 Functions of Secondary Metabolites
1.6.1 Secondary Metabolites as Competitive Weapons
1.6.2 Ecological Roles of Secondary Metabolites
1.6.3 Secondary Metabolites as Carriers of Metals
1.6.4 Secondary Metabolites as Mediators of Symbiotic Relationships
1.6.5 Symbiotic Relations with Other Organisms
1.6.6 Implications for Neurotherapeutics
1.6.7 Secondary Metabolites as a Means of Reproduction
1.6.8 Mechanism of Action
1.6.9 Plant-Derived Neurotherapeutics
1.6.10 Challenges and Future Directions
1.6.11 Secondary Metabolites as Agents of Communication between Organisms
1.7 Studies on Secondary Metabolites in Plants
1.7.1 Neuroprotective Mechanisms of Secondary Metabolites
1.7.2 Promotion of Neurogenesis and Synaptic Plasticity
1.7.3 Mitochondrial Protection
1.7.4 Metal Chelation
1.7.5 Applications in Neurological Disorders
1.7.6 Challenges in Research and Development
1.7.7 Clinical Evidence
1.7.8 Future Directions
1.8 Conclusion
Bibliography
2. Phytochemistry of Neuroprotective Compounds: Key Classes and Their Properties
Baskaran Gunasekaran, Saema Hanafi, Kirtana Devi and Vaidehi Ulaganathan
2.1 Introduction
2.2 Phenolic Compounds
2.2.1 Flavonoids
2.2.2 Phenolic Acids
2.2.3 Stilbenes
2.2.4 Tannins
2.3 Terpenoids
2.3.1 Monoterpenes
2.3.2 Sesquiterpenes
2.3.3 Diterpenes
2.3.4 Triterpenes
2.4 Alkaloids
2.5 Other Neuroprotective Phytochemicals
2.5.1 Polysaccharides
2.5.2 Carotenoids
2.6 Phytochemical Bioavailability and Metabolism
2.7 Conclusion
References
3. Mechanisms of Action: How Plant Metabolites Interact with Neurological Pathways
Nil Patil, Urvi Patil, Mukul Jain, Ayush Madan and Mohd. Tariq
3.1 Introduction
3.1.1 Overview of Plant Metabolites and Their Relevance to Neurological Function
3.1.2 Importance of Understanding Metabolite–Neural Interactions for Brain Health
3.2 The Role of Plant Metabolites in Neuroprotection
3.2.1 Antioxidant Properties
3.2.2 Neurotransmitter Modulation
3.2.3 Signaling Pathway Modulation
3.2.3.1 Environmental Influences and Modulatory Mechanisms
3.2.3.2 Modulation by Biotic and Abiotic Stress
3.2.4 Modulation of Neuro Inflammation
3.2.4.1 Inhibition of Pro-Inflammatory Cytokines
3.2.4.2 Suppression of Microglial Activation
3.2.4.3 Reduction of Oxidative Stress
3.2.4.4 Regulation of Mitogen-Activated Protein Kinase (MAPK) Pathways
3.2.4.5 Modulation of Brain-Derived Neurotrophic Factor (BDNF)
3.3 The Gut–Brain Axis and Plant Metabolites
3.3.1 Gut Microbiota and Neurodegenerative Diseases
3.3.2 Plant Secondary Metabolites and the Gut–Brain Axis
3.3.3 Mechanisms of Action: How Plant Metabolites Modulate the GBA
3.4 Conclusion
References
4. Antioxidant Pathways: Combating Oxidative Stress in the Brain
Annu Verma, D.S.N.B.K. Prasanth and Ashwini Deshpande
4.1 Introduction
4.1.1 Definition and Significance of Oxidative Stress in the Brain
4.2 Mechanisms of Oxidative Stress in the Brain
4.2.1 Sources of ROS
4.2.2 Consequences of Oxidative Stress
4.3 Sources of Oxidative Stress
4.3.1 Mitochondrial Dysfunction
4.3.2 Excitotoxicity
4.3.3 Inflammation
4.3.4 Reactive Oxygen Species (ROS)
4.4 Role of Reactive Oxygen Species
4.5 Importance of Antioxidants
4.6 Brain Vulnerability to Oxidative Damage
4.7 Antioxidant Defense Mechanisms
4.7.1 Enzymatic Antioxidants
4.7.1.1 Superoxide Dismutase
4.7.1.2 Catalase
4.7.1.3 Glutathione Peroxidase
4.7.2 Nonenzymatic Antioxidants
4.7.2.1 Glutathione
4.7.2.2 Vitamins E and C
4.7.2.3 Phytochemicals
4.8 Therapeutic Strategies
4.8.1 Pharmacological Interventions
4.8.1.1 Nrf2 Activation
4.8.1.2 Phytochemical Supplements
4.8.1.3 Antioxidant Therapy
4.9 Lifestyle Modifications
4.9.1 Dietary Interventions
4.9.2 Physical Activity
4.9.3 Cognitive Stimulation
4.10 Innovations and Future Directions
4.10.1 Nanotechnology
4.10.2 Combination Therapies
4.10.3 Personalized Medicine
4.10.4 Dietary Interventions
4.11 Conclusion
References
5. Anti-Inflammatory Effects of Plant Metabolites on Neurological Health
Ahmed H. Elosaily, Ahmed M. El-Dessouki, Riham A. El-Shiekh, Mohamed S. Abd El Hafeez, Ghadir A. Sayed and Noha M. Gamil
5.1 Introduction
5.1.1 Inflammation and Neurological Disorders
5.2 The Pathogenesis of Neuroinflammation
5.2.1 Triggering Events: From Insult to Inflammation
5.2.2 The Dual Role of Microglia: Guardians or Executioners
5.2.3 Astrocytic Response: Amplifiers of Inflammation
5.2.4 Peripheral Immune Invasion: Crossing the Blood–Brain Barrier
5.2.5 Systemic Factors Influencing Neuroinflammation
5.3 Molecular Pathways Driving Neuroinflammation
5.3.1 The NF-κB Pathway: A Central Hub
5.3.2 The COX-2/Prostaglandin Axis: Mediators of Neuronal Sensitization
5.3.3 Reactive Oxygen and Nitrogen Species: The Oxidative Stress Amplifier
5.3.4 Cytokine Signaling: The Proinflammatory Cascade
5.4 Inflammation-Driven Pathogenesis in Specific Neurological Disorders
5.4.1 Alzheimer’s Disease: Chronic Neuroinflammation in the Brain
5.4.2 Parkinson’s Disease (PD): Neuroinflammation Driven by Alpha‑Synuclein
5.4.3 Multiple Sclerosis: Autoimmunity and Inflammation
5.4.4 Stroke: Inflammatory Repercussions of Ischemia
5.5 Preclinical Studies of Plant Extracts or Isolated Compounds Used for Neurological Health
5.5.1 Alzheimer’s Disease
5.5.2 Parkinson’s Disease
5.5.3 Cognitive Decline
5.5.4 Memory Enhancement
5.5.5 Anxiety
5.5.6 Depression
5.5.7 Neurodegeneration
5.5.8 Multiple Sclerosis
5.5.9 Epilepsy
5.5.10 Chronic Pain
5.6 Clinical Studies on Plants for Treating Inflammation in Alzheimer’s Disease
5.7 Clinical Studies on Plants for Treating Inflammation in Parkinson’s Disease
5.8 Clinical Trials Involving Plants with Anti-Inflammatory Activity in the Treatment of MS and NMO
5.9 Conclusion
References
6. Modulating Neurotransmitter Systems: Plant Compounds in Cognitive Enhancement
Reshma Tendulkar and Mugdha Tendulkar,†
6.1 Introduction
6.2 Neuroprotective Phytochemicals and Human Brain Function
6.2.1 Learning and Memory
6.2.2 Influence on the Molecular Level of Brain
6.2.3 Synaptic Plasticity
6.3 Mechanisms of Modulating Neurotransmitter Systems
6.3.1 Pathway of Cholinergic Signaling
6.3.2 Pathway of GABAergic Signaling
6.3.3 Pathway of Glutamergic Signaling
6.3.4 Pathway of Serotonergic Signaling
6.3.5 Pathway of Dopamine Signaling
6.3.6 Modulation by Monoamine Oxidase
6.3.7 Modulation by Catechol-O-Methyltransferase
6.4 Future Implications
6.5 Conclusions
References
7. Promoting Neurogenesis and Neuroplasticity: Potential for Brain Regeneration
Vivek Sharma, Tanuja Sharma, Naveen Singh, Rajnish Srivastava and Naresh Kumar Rangra
7.1 Introduction
7.1.1 Overview of Neuroplasticity and Neurogenesis
7.1.2 Importance of CNS Adaptability
7.2 Mechanisms of Neuroplasticity and Neurogenesis
7.2.1 Cellular and Molecular Basis
7.2.2 Role of Synaptic Plasticity
7.3 Factors Influencing Neuroplasticity and Neurogenesis
7.3.1 Genetic Factors
7.3.2 Environmental Influences
7.4 Impact of Physical Activity
7.4.1 Impact of Physical Activity
7.4.2 Aerobic Exercise and Brain Health
7.4.3 Effects of BDNF on Neurogenesis
7.5 Pharmacological Interventions
7.5.1 Psychedelic Substances (e.g., LSD)
7.5.2 Mechanisms of Action of LSD on Neuroplasticity
7.5.3 Therapeutic Potential in Mental Health
7.6 Nutritional Factors
7.6.1 Impact on Brain Function and Neuroprotection
7.6.2 Dietary Recommendations for Brain Health
7.7 Cognitive and Mental Stimulation
7.7.1 Activities that Promote Neuroplasticity
7.7.2 Benefits of Lifelong Learning and Social Interaction
7.8 Stress and Neuroplasticity
7.8.1 Impact of Chronic Stress on Brain Function
7.8.2 Stress Reduction Techniques (e.g., Meditation, Yoga)
7.9 Future Directions and Challenges in Promoting Neuroplasticity and Neurogenesis
7.10 Conclusion
References
8. Alzheimer’s Disease and Phytochemicals: Mechanisms and Potential Treatments
Shaik Ibrahim Khalivulla, Arifullah Mohammed and Saeed Alshahrani
8.1 Introduction
8.2 Ginkgo biloba
8.3 Crocus sativus
8.4 Ginseng
8.5 Stilbene
8.6 Phenolic Acids
8.7 Carotenoids
8.8 Lignans
8.9 Alkaloids (Huperzine A and Galantamine)
8.10 Terpenoids
8.11 Flavonoids
8.12 Nanoparticle
8.13 Conclusion
References
9. Parkinson’s Disease: Plant Derived Therapeutics and Dopaminergic Support
Naveen Singh, Namita Aggarwal, Nitin Verma and Rajnish Srivastava
9.1 Introduction
9.1.1 Pathological Hallmarks: Dopaminergic Neuron Loss and Alpha-Synuclein Inclusions
9.2 Need for Alternative Therapeutics in PD
9.2.1 Early Interventions and Focus on Natural Products
9.3 Role of Plant-Derived Compounds in PD Therapy
9.3.1 Overview of Phytochemicals with Neuroprotective Properties
9.3.2 Phytochemicals: Multifaceted Pharmacological Effects
9.4 Mechanisms of Action of Plant-Based Therapeutics
9.4.1 Mechanisms of Action of Plant-Based Therapeutics on Regulation of Oxidative Stress
9.4.2 Role of Plant-Based Therapeutics in Neuroinflammation Modulation
9.4.3 Plant-Based Therapeutics in Dopaminergic Neuron Support
9.5 Plant Sources of Antiparkinsonian Compounds with Their Targeted Pathways
9.6 Preclinical Evidence of Plant-Based Therapeutics in PD
9.7 Integrating Natural Products with Dopaminergic Support
9.8 Challenges and Future Directions
9.9 Conclusion
References
10. Huntington’s and Other Neurodegenerative Disorders: Plant-Based Interventions
Mukul Jain, Rupal Dhariwal, Akangsha Lahon, Ritika Bhardwaj and Krishna Thakkar
10.1 Introduction
10.1.1 Genetic Basis and Pathophysiology of Huntington’s Disease
10.1.2 Epidemiology and Prevalence of Huntington’s Disease Globally and in India
10.1.2.1 Geographical Distribution and Prevalence of HD Globally
10.1.2.2 Geographical Distribution and Prevalence of HD in Indian Communities
10.2 Molecular Mechanisms of Huntington’s Disease
10.2.1 Mutation in Huntingtin Gene and the Associated Protein Dysregulation
10.2.2 Oxidative Stress-Induced Mitochondrial Dysfunctioning
10.2.3 Protein Misfolding Promoted by Dysregulated Autophagy
10.2.4 Role of Epigenetic Factors, and Non-Coding RNAs in Promoting Transcriptional Level Dysregulation
10.3 Therapeutic Interventions against Huntington’s Disease
10.3.1 Currently Available Allopathic Interventions, Clinical Trials Phased Medicines Targeting HD
10.3.2 Natural-Therapeutic Approaches for Treatment and Prevention of Huntington’s Disease
10.3.3 Potentials of Natural Options Over Chemical-and Drug-Based Treatments
10.3.4 Integration of the Plant-Based Compounds with the Conventional Therapies
10.3.5 Combinational Therapies Integrating Plant-Based Interventions with Nano Therapy
10.4 Safety Concerns and Regulations of Plant-Based Therapeutics
10.5 Limitations and Drawbacks Associated with Plant-Based Therapeutics
Bibliography
11. Mental Health Disorders: Phytochemical Approaches to Anxiety, Depression, and Stress
Mohd Farhan, Mohd Faisal, Asim Rizvi, Ghazala Muteeb, Mohammad Aatif and Mir Waqas Alam
11.1 Introduction
11.2 Overview of Phytochemicals
11.3 Role and Mechanisms of Phytochemicals in the Treatment of Mental Health Disorders
11.3.1 Anxiety Disorders
11.3.1.1 In Vivo Studies
11.3.1.2 Clinical Trials
11.3.2 Depression
11.3.2.1 In Vivo Studies
11.3.2.2 Clinical Studies
11.4 Studies on the Effects of Phytochemicals on Anxiety and Depression in Animals and Humans
11.5 Phytochemical Bioavailability in Brain Tissue
11.6 Nanotechnology-Based Approaches to Enhancing Phytochemical Bioavailability in Brain
11.6.1 Nanoencapsulation
11.6.2 Natural Nanocarriers
11.6.3 Solid Lipid Nanoparticles
11.6.4 Polymeric Nanoparticles
11.6.5 Liposomes
11.7 Adverse Effects of Phytochemicals
11.8 Restrictions on the Study
11.9 Conclusion and Future Perspectives
References
12. Bioavailability and Pharmacokinetics of Plant Metabolites in Neurotherapeutics
Himanshu Jain and Neeraj K. Aggarwal
12.1 Introduction to Bioavailability and Pharmacokinetics
12.1.1 Physiological Barriers to Effective Neurotherapeutic Delivery
12.1.2 Gastrointestinal and Hepatic Constraints on Phytochemical Absorption
12.1.3 Pharmacokinetic Limitations of Plant-Derived Neurotherapeutics
12.1.4 Strategies to Overcome Pharmacokinetic Barriers
12.2 Absorption of Plant Metabolites
12.2.1 Solubility: A Critical Barrier for Absorption
12.2.2 Permeability: Crossing the Intestinal Epithelium
12.2.3 Gastrointestinal Stability: Protecting Bioactive Compounds
12.2.4 Gut Microbiota and Biotransformation: Modulating Metabolic Fate
12.2.5 Strategies for Enhancing Absorption and Bioavailability
12.3 Distribution and Brain Penetration of Plant-Derived Neurotherapeutics
12.3.1 Physiological Barriers and the Selective Nature of the Blood–Brain Barrier
12.3.2 Passive and Carrier-Mediated Transport across the Blood–Brain Barrier
12.3.3 Efflux Transporters as a Barrier to CNS Accumulation
12.3.4 Metabolic Transformations and Their Impact on Brain Distribution
12.3.5 Advanced Delivery Strategies to Enhance Brain Penetration
12.4 Metabolism of Phytochemicals
12.4.1 Phase I Metabolism: Functionalization and Its Influence on Phytochemical Activity
12.4.2 Phase II Metabolism: Conjugation, Clearance, and Neurotherapeutic Implications
12.4.3 Gut Microbiota as a Key Modulator of Phytochemical Metabolism
12.5 Excretion and Elimination
12.5.1 Routes of Elimination and Their Impact on Pharmacokinetic
12.5.2 Importance of Systemic Clearance in Determining Therapeutic Efficacy
12.6 Challenges in Bioavailability and Pharmacokinetics
12.6.1 Poor Solubility and Stability
12.6.2 First-Pass Metabolism and Rapid Systemic Clearance
12.6.3 Efflux Transporters Limiting Brain Penetration
12.7 Enhancing Bioavailability and Brain Targeting
12.7.1 Nanotechnology-Based Delivery Systems
12.7.2 Structural Modifications to Increase Stability and Bioavailability
12.7.3 Prodrug Approaches and Inhibitors to Modulate Metabolic Pathways
12.8 Future Perspectives
12.8.1 Integration of Advanced Drug Delivery Technologies
12.8.2 Metabolic Engineering and Personalized Medicine
12.8.3 Advancing In Vivo Models for Evaluation
12.8.4 Exploring the Gut–Brain Axis and Microbiome Interactions
12.8.5 Artificial Intelligence and Machine Learning in Drug Design
12.9 Conclusion
References
13. Formulation and Delivery Systems for Brain-Targeted Phytochemicals
Unmesh Gulabrao Bhamare, Prakash Pannalal Muleva, Deepali Dattatray Bhandari, Ramanlal Narayan Kachave, Sunil Vishvnath Amrutkar and Dattatraya Manohar Shinkar
13.1 Introduction
13.2 Phytochemicals with Brain-Targeting Potential
13.2.1 Neuroprotective Phytochemicals
13.2.2 Mechanisms of Action
13.2.3 Applications in Neurological Diseases
13.3 Barriers to Brain Delivery
13.3.1 Physiological Barriers
13.3.2 Phytochemical Limitations
13.3.3 Mechanisms Exacerbating Barriers
13.4 Formulation Strategies for Brain-Targeted Phytochemicals
13.4.1 Nanocarriers
13.4.2 Lipid-Based System
13.4.3 Inorganic Nanoparticles
13.4.4 Conjugates and Prodrugs
13.4.5 Biomaterials and Hydrogels
13.5 Delivery Systems for Brain Targeting
13.5.1 Routes of Administration
13.5.2 Active Targeting Strategies
13.5.3 Passive Targeting
13.5.4 Stimuli-Responsive Systems
13.5.5 Emerging Technologies
13.6 Challenges and Solutions in Brain-Targeted Delivery of Phytochemicals
13.6.1 Challenges
13.6.2 Solutions
13.7 Case Studies and Examples of Brain-Targeted Phytochemical Delivery Systems
13.7.1 Successful Formulations
13.7.2 Clinical Trials Involving Phytochemicals
13.7.3 Future Directions and Lessons from Case Studies
13.8 Future Prospects and Research Directions
13.8.1 Innovations in Delivery Systems
13.8.2 Multifunctional Approaches
13.8.3 Personalized Medicine
13.8.4 Future Challenges and Considerations
13.9 Conclusion
References
14. Preclinical and Clinical Studies: Evidence Supporting Plant Neurotherapeutics
Nisha Vijayan Kalayil, Sahaya Nadar, Ekta Thakor and Jegan Nadar
14.1 The Importance of Neurotherapeutics in Managing Neurological Disorders
14.2 Overview of Plant-Derived Compounds as Therapeutic Agents
14.3 Scope and Objectives of the Chapter
14.4 Mechanisms of Plant-Derived Neurotherapeutics
14.4.1 Neuroprotective Mechanisms of Plant-Derived Compounds
14.4.1.1 Antioxidant Properties
14.4.1.2 Anti-Inflammatory Effects
14.4.2 Modulation of Neurotransmitter Systems
14.4.2.1 Cholinergic System
14.4.2.2 Dopaminergic System
14.4.2.3 Serotonergic and GABAergic Systems
14.4.3 Neurogenesis and Synaptic Plasticity
14.5 Preclinical Studies: Evidence Supporting Plant Neurotherapeutics
14.5.1 Parkinson’s Disease (PD)
14.5.2 Alzheimer’s Disease (AD)
14.5.3 Ischemic Stroke
14.5.4 Depression
14.5.5 Multiple Sclerosis (MS)
14.6 Clinical Evidence Evaluating Plant-Derived Neurotherapeutics
14.7 Challenges
14.7.1 Bioavailability and Pharmacokinetics
14.7.2 Standardization of Plant Extracts
14.7.3 Lack of Large-Scale Clinical Trials
14.8 Future Directions
14.8.1 Advances in Drug Delivery Systems
14.8.2 Integration of Multi-Omics Approaches
14.8.3 Ethical and Regulatory Considerations
14.9 Conclusion
Bibliography
15. Plant-Based Brain Therapies: Challenges and Future Prospects Along with Molecular Mechanism Aided in Cognitive Protection
K.R. Padma, K.R. Don, M. Sankari, K. Harathi and N. Sandhya
15.1 Background of the Study
15.1.1 Natural Remedies from Plants Include Substances That Protect Nerve Cells
15.2 Nootropics Derived from Plants and Their Impact on Cognitive Performance
15.2.1 These are Well-Known Plant-Based Substances That Serve as Cognitive Enhancers
15.2.2 Ginkgo biloba
15.2.3 About Panax ginseng
15.2.4 The Rhodiola rosea
15.2.5 Ashwagandha and Its Impact on Cognitive Function
15.3 Natural Products Could Be Potential Targets for Neurodegenerative Disease Treatment
15.3.1 Nutrition and Cognitive Well-Being: An Exciting New Frontier
15.3.2 Trends in Consumer Preferences for Functional Foods
15.3.3 Vegetables and Fruits as a Researcher Topic
15.3.4 A Plant-Based Approach for Treating Spinal Muscular Atrophy
15.3.5 Medicinal Plants Have Neuroprotective Properties against Alzheimer’s Disease
15.3.6 Herbal Therapy for Alzheimer’s Disease
15.3.6.1 Main Insights
15.4 Plant-Derived Neuroprotective Compounds and the Role of Fiber in Cognitive Function Mechanisms
15.4.1 Fiber and Neuroprotection Engagement
15.5 Molecular Pathways and Disease-Associated Objectives of Medicinal Plants in the Management of Motor Neuron Disorders
15.6 Constraints
15.6.1 Prospective Possibilities
15.6.2 Challenges
15.6.3 Final Thoughts
Acknowledgments
References
16. Traditional and Modern Uses of Plants in Neurotherapy—A Comparative Perspective
Laxmi, Rahul Sharma, Shriyansh Srivastava, Izaz Hussain and Rakesh Sahu
16.1 Introduction
16.2 Historical Perspectives on Plant-Based Neurotherapy
16.2.1 Ancient Medicinal Traditions (Ayurveda, Traditional Chinese Medicine, Indigenous Healing System)
16.2.2 Early Documentation of Plant-Based Neurotherapeutics
16.2.3 Evolution of Herbal Remedies Over Time
16.3 Traditional Plant-Based Approaches in Neurotherapy
16.3.1 Commonly Used Plants in Ancient Healing (e.g., Ginkgo biloba, Ashwagandha, Bacopa monnieri)
16.3.1.1 Ginkgo biloba
16.3.1.2 Ashwagandha (Withania somnifera)
16.3.1.3 Brahmi (Bacopa monnieri)
16.3.2 Cultural Perspectives and Healing Philosophies
16.4 Modern Scientific Approaches to Plant-Based Neurotherapy
16.4.1 Advances in Phytochemistry and Neuropharmacology
16.4.2 Clinical Studies on Herbal Neuroprotectants
16.4.3 Synergistic Effects and Bioavailability Challenges
16.5 Comparative Analysis: Traditional vs. Modern Use
16.5.1 Effectiveness and Limitations of Traditional Remedies
16.5.2 Standardization and Regulatory Challenges in Modern Applications
16.5.3 Integrative Approaches: Bridging Traditional Wisdom with Modern Science
16.6 Emerging Trends and Future Prospects
16.6.1 Innovations in Herbal Neurotherapy (Nanotechnology, Personalized Medicine)
16.6.2 Potential for Plant-Based Drugs in Neurological Disorders
16.7 Conclusion
Abbreviations List
References
17. Case Studies of Plant Extracts in Neurotherapeutics Formulations
Erum Khalid, Sudhair Alam, Feroza Hamid wattoo, Muhammad Javaid Asad, Saima Amin and Muhammad Gulfaraz
17.1 Introduction
17.2 The Growing Role of Plant-Derived Compounds in Neurotherapeutics
17.3 Bioactive Compounds and Their Role in Brain Regeneration
17.3.1 Phenols
17.3.2 Flavonoids
17.3.3 Alkaloids
17.3.4 Terpenoids and Saponins
17.4 Plant Extracts’ Mechanisms of Action in Neurotherapeutics
17.4.1 Activity of Antioxidants and Free Radical Scavenging
17.5 Case Studies on Specific Plant Extracts
17.5.1 Ginkgo biloba in Cognitive Enhancement
17.5.2 Case Studies: Plant-Based Therapies in Parkinson’s Disease
17.5.2.1 Important Historical Events
17.5.3 Case Studies on Plant Extracts in Neurotherapeutics
17.5.3.1 Alzheimer’s Disease with Polygonum multiflorum (P. multiflorum)
17.5.3.2 Sorbus Commixta in AD
17.5.3.3 The Role of Rehmannia glutinosa (R. glutinosa) in AD
17.5.4 Case Study—Neuroprotective Effect of Grewia tiliaefolia
17.5.4.1 Phytochemical Composition and Bioactive Identification
17.5.4.2 Anti-Amyloidogenic Properties and Alzheimer’s Disease Model
17.5.4.3 Neuroprotection and Cell Viability in Neuronal Cells
17.5.4.4 Molecular Docking and Computational Analysis
17.6 Formulation Strategies for Neurotherapeutics
17.7 Preclinical and Clinical Evidence
17.8 Challenges in Neurotherapeutic Formulations
17.9 Future Directions
17.10 Conclusion
References
18. Future Trends in Plant-Derived Neurotherapeutics: From Lab to Clinic
Ananda Kumar Chettupalli, Mustapha, S.K. Abdual Rahaman, Neha Gupta, Garlapati Vijay Kumar and Sarad Pawar Naik Bukke
List of Abbreviations
18.1 Introduction to Plant-Derived Neurotherapeutics
18.1.1 An Overview of Neurotherapeutics: Definition, Importance, and Scope
18.1.2 Historical Perspective: Traditional Use of Plants in Treating Neurological Disorders
18.1.3 Modern Relevance: Bridging Traditional Medicine with Modern Pharmacology
18.1.4 Challenges in Neurotherapeutic Development: Complexity of Neurological Diseases and Drug Development Hurdles
18.2 Neuropharmacological Potential of Phytochemicals
18.2.1 Key Phytochemicals and Their Mechanisms: Alkaloids, Flavonoids, Terpenoids, and Polyphenols
18.2.2 Targeted Neurological Pathways: Antioxidative, Anti-Inflammatory, and Neuroprotective Pathways
18.2.3 Examples of Prominent Neuroprotective Plants
18.3 Advances in Preclinical Research
18.3.1 In Vitro Studies: Cellular Models for Studying Neurotoxicity and Protection
18.3.2 In Vivo Studies: Animal Models of Neurodegenerative Diseases
18.3.3 Biotechnology Integration: Genomic and Proteomic Approaches to Identify Active Compounds
18.4 Clinical Development and Translational Challenges
18.4.1 Phases of Clinical Trials: From Safety to Efficacy Studies
18.4.2 Phytochemical Standardization: Ensuring Consistency and Potency
18.4.3 Ethical Considerations: Balancing Traditional Knowledge and Intellectual Property
18.5 Emerging Technologies in Neurotherapeutics
18.5.1 Nanotechnology for Drug Delivery: Enhancing Bioavailability and Targeting
18.5.2 Artificial Intelligence and Drug Discovery: Predicting Efficacy and Toxicity of Plant Compounds
18.5.3 CRISPR and Genetic Engineering: Unlocking Plant-Derived Compounds Through Biosynthesis
18.6 Case Studies of Success and Failure
18.6.1 Success Stories: Plant-Based Drugs Currently in Use for Neurological Conditions
18.6.2 Lessons from Failures: Identifying Gaps in Research and Development
18.6.3 Insights for Future Endeavors: Best Practices in Drug Development Pipelines
18.7 The Role of Traditional Medicine and Ethnopharmacology
18.7.1 Indigenous Knowledge Systems: Contributions to Modern Neurotherapeutics
18.7.2 Global Integration: Bridging Traditional Practices with Scientific Rigor
18.7.3 Sustainability and Biodiversity: Ethical Sourcing and Conservation Efforts
18.8 Future Perspectives and Trends in Neurotherapeutics
18.8.1 Personalized Medicine: Phytochemicals Tailored to Genetic Profiles
18.8.2 Hybrid Therapies: Combining Plant-Derived Compounds with Synthetic Drugs
18.8.3 Global Collaboration: Collaborative Efforts in Research and Funding
18.9 Conclusion and Recommendations
References
About the Editors
Index
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