Preface
Page: ii-ii (1)
Author: Surya Pratap Singh, Hareram Birla and Chetan Keswani
DOI: 10.2174/9789815040197123010002
Parkinson's Disease: A Phytotherapeutic Prospective
Page: 1-23 (23)
Author: Bhargab Deka, Bedanta Bhattacharjee, Naveen Shivavedi, Gireesh Kumar Singh, Hans Raj Bhat, Surajit Kumar Ghosh and Anshul Shakya*
DOI: 10.2174/9789815040197123010004
PDF Price: $30
Abstract
Parkinson's disease (PD) is a complex multi-factorial, neurodegenerative
disease characterized by neurodegeneration of dopaminergic neurons in the substantia
nigra (SN) of the ventral midbrain area. Loss of dopamine (DA) supply induces an
imbalance of multiple neurotransmitter networks in different parts of the brain. This
contributes to many motor and non-motor symptoms in PD. The main goal of modern
allopathic medicine is to restore DA function with synthetic levodopa (L-DOPA) and
DA agonist, which has been partially effective; however, there are still several
inadequacies and adverse effects that patients often cannot cope with. In the field of
herbal medicine, extensive studies on bioactive phytocompounds have shown that it
has immense potential as a neuroprotective therapy for neurodegenerative disorders,
such as PD. Bioactive phytocompounds are very promising because they have minimal
side effects and very high anti-inflammatory, anti-oxidant, and anticholinesterase
activity. Recent preclinical studies suggest that several bioactive phytocompounds can
be developed into pharmaceutical formulations for the treatment of PD. Ayurvedic
medicines have been used in many countries and particularly in India since ancient
times to prevent or cure PD. This article focuses on the recent evidence-based
neuroprotective activity of medicinal plants like Mucuna pruriens, Curcuma longa,
Zingiber officinale, Bacopa monnieri, Nardostachys jatamansi, Withania somnifera,
and Silybum marianum in in vivo and in vitro PD research models.
Delineating the Neuroinflammatory Crosstalk in Neurodegeneration and Probing the Near Future Therapeutics
Page: 24-46 (23)
Author: Vinod Tiwari*, Ankit Uniyal, Vineeta Tiwari, Vaibhav Thakur, Mousmi Rani and Akhilesh
DOI: 10.2174/9789815040197123010005
PDF Price: $30
Abstract
Neurodegenerative disorders are threatening mankind with significant health
and economic burden. Neurodegeneration involves the deterioration of neurons in the
central nervous system (CNS), resulting in decreased neuronal survival. Therefore, it is
of utmost requirement to develop a promising pharmacological strategy to minimize or
prevent the progression of the underlying disease pathogenesis. In neurodegenerative
disease conditions, neurons and glial cells present in the specific brain regions are
damaged and depraved, resulting in specified disease symptoms in the patients.
Neuroinflammation plays a major role in the degeneration of neuronal cells by
regulating the expression of interleukin-1 beta (IL-1β), IL-6, IL-8, IL-33, tumor
necrosis factor-alpha (TNF-α), chemokines Cxcl3 (C-C motif) ligand 2 (CCL2),
CXCL5, granulocyte-macrophage colony-stimulating factor (GM-CSF), glia
maturation factor (GMF), substance P, reactive oxygen species (ROS), reactive
nitrogen species (RNS), impaired tuning of immune cells and nuclear factor kappa-B
(NF-κB). Considering this, it is very important to understand the in-depth role of
neuroinflammation in the initiation and progression of various neurodegenerative
diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's
Disease (HD), as well as Multiple Sclerosis (MS). Recent shreds of evidence have
suggested that using exogenous ligands to approach various biological molecules or
cellular functioning that modulates the neuroinflammation, such as microglia response,
P2X7 receptors, TLR receptors, oxidative stress, PPARγ, NF-κB signaling pathway,
NLRP3 inflammasome, caspase-1 signaling pathway, and mitochondrial dysfunction,
helps to combat neurodegeneration in a variety of diseases. Thus, targeting the
neuroinflammatory drive could provide a beacon for the management of
neurodegenerative diseases. Here, we have attempted to provide comprehensive
literature suggesting the role of neuroinflammation in neurodegeneration and its
implication in the development of near-future neurotherapeutics.
Modulations of SIRTUINs and Management of Brain Disorders
Page: 47-81 (35)
Author: Sudhir Kumar Shekhar*, Sarfraj Ahmad Siddiqui* and Girish Rai
DOI: 10.2174/9789815040197123010006
PDF Price: $30
Abstract
Neurodegenerative disorders are the conditions in which neurons of the
central and peripheral nervous systems degenerate. Various cellular and molecular
processes are associated with the progression of such degeneration, including
inflammation, apoptosis, and axonal degeneration. Recently, SIRTUINs have emerged
as one of the key factors associated with neurodegenerative disorders. SIRTUINs are
involved in the regulation of several cellular and molecular processes in neurons of the
nervous system through the deacetylation of target proteins. The chapter focuses on the
modulatory role of SIRTUINs in neurodegenerative disorders and their potential
therapeutic application.
Beyond the Synthetic Drugs: Fungal Endophytes Derived Bioactive Compounds in the Management of Neurodegenerative Disorders
Page: 82-102 (21)
Author: Ashish Verma, Nilesh Rai, Swapnil C. Kamble, Pradeep Mishra, Suvakanta Barik, Rajiv Kumar, Santosh Kumar Singh, Prafull Salvi and Vibhav Gautam*
DOI: 10.2174/9789815040197123010007
PDF Price: $30
Abstract
Fungal endophytes are a group of fungi that reside in plant tissues and show
a symbiotic relationship with the host plants. They protect against pathogens and
increase food availability without causing any harmful effects on the host plant. Fungal
endophytes are known to produce a wide range of bioactive compounds with several
biological activities, including neuroprotective effects. Neurodegenerative disorders
lead to miscommunication between nerve cells, damage or loss in structure and
function of the central nervous system (CNS) or peripheral nervous system (PNS).
Reactive oxygen species, neuroinflammation, protein degradation or aggregation,
familial history, mutation in mitochondrial genes, and aging contribute to
neurodegenerative disorders. Plant-associated fungal endophytes produce bioactive
compounds, which show anti-neuroinflammatory, antioxidant, and anti-cholinesterase
activities. Several pro-inflammatory (TNF-α and NF-κB) and depressant (serotonin,
dopamine, and noradrenaline) molecules or neuronal signaling pathways leading to
neurodegenerative disorders are known to be inhibited or down-regulated by fungal
endophyte-derived bioactive compounds. Therefore, bioactive compounds produced
from fungal endophytes could be a promising approach to treating various health ailments. The present chapter discusses selected fungal endophyte-derived potential
bioactive compounds with neuroprotective effects for managing neurodegenerative
disorders.
Neuroprotective Role of Medicinal Plants from North Eastern Region of India
Page: 103-128 (26)
Author: Bedanta Bhattacharjee, Bhargab Deka, Naveen Shivavedi, Hans Raj Bhat, Saurabh Kumar Sinha, Surajit Kumar Ghosh and Anshul Shakya*
DOI: 10.2174/9789815040197123010008
PDF Price: $30
Abstract
The term neurodegenerative disease means the loss of neuronal cells in the
brain, including Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and
Huntington's disease. It is one of the most common types of disease associated with
elevated rates of mortality and morbidity worldwide. At the same time, modern
allopathic medicines have a large number of synthetic chemicals for the symptomatic
treatment and control of these diseases. These drugs have failed miserably due to
clinical insufficiency and debilitating adverse effects. In the past decade, natural
ingredients have gained notable interest in the prevention and treatment of
neurodegeneration due to their powerful anti-inflammatory and anti-oxidant properties
with minimal side effects. However, there is also an issue of safety and effectiveness
due to the absence of an ample amount of research findings. The most common cellular
mechanism for every neurodegenerative disorder is neuroinflammation and oxidative
stress. Several preclinical and clinical studies conducted across the world have
demonstrated that different bioactive compounds of herbal origin can potentially arrest
these processes to prevent or treat neurodegeneration and can be developed into
promising pharmaceutical formulations. This article discusses and analyses the various
herbal compounds, such as Allium sativum, Camella sinensis, Centella asiatica,
Coriandrum sativum, Crocus sativus, Glycyrrhiza glabra, and Morus alba used for
phytotherapy of neurodegenerative diseases by combining recent in vitro and in vivo
models.
Tinospora cordifolia in Neurodegeneration: A Strong Antioxidant and Anti-inflammatory Phytotherapeutic Drug Candidate
Page: 129-143 (15)
Author: Anuradha Sharma and Gurcharan Kaur*
DOI: 10.2174/9789815040197123010009
PDF Price: $30
Abstract
Tinospora cordifolia is a Rasayana herb of Ayurveda, commonly known as
“Heavenly Elixir” or “Amrita”, and one of the most exploited herbs in herbal
medicines. T. cordifolia is well reported for its various pharmacological properties,
such as anti-diabetic, anti-inflammatory, antipyretic, immunomodulatory, anti-cancer,
cardioprotective, neuroprotective, and hepatoprotective activities. The prevalence of
neurodegenerative diseases and other neurologic disorders is increasing worldwide.
Oxidative stress and neuroinflammation are among the major pathologic mechanisms
underlying neurodegenerative diseases. This chapter discusses the pieces of scientific
evidence of the beneficial effects of T. cordifolia in various brain-related ailments.
Various research groups have demonstrated the ability of T. cordifolia and its extracts
to normalize oxidative stress and suppress the inflammatory response against various
causative agents, and thus suggested that T. cordifolia has the potential to be a
neurotherapeutic drug candidate in the future.
Mucuna pruriens and Parkinson’s Disease: A Natural Approach to Treat PD
Page: 144-159 (16)
Author: Mamta Tiwari* and Anurag Pandey
DOI: 10.2174/9789815040197123010010
PDF Price: $30
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative
disease after Alzheimer’s disease affecting the aged population. The variable loss of
dopaminergic neurons within substantia nigra pars compacta (SNpc) of the brain,
which controls movement, and the presence of intracellular protein aggregates called
Lewy bodies are major pathological findings. The recent years’ research in PD is
directed to herbal drug discovery for PD as a large number of patients, particularly in
western countries, prefer to use “natural therapies” and drugs instead of
pharmaceuticals. Kapikachhu (Mucuna pruriens Linn.) is one of the popular drugs in
Ayurveda, the classical system of medicine in India. The seeds of M. pruriens contain
5% L-3, 4-dihydroxyphenylalanine (L-DOPA), and it has emerged as a promising
single drug treatment of PD. The present manuscript is an attempt at obtaining
complete knowledge regarding Parkinson’s disease as mentioned in Ayurveda for
achieving a natural and holistic approach to better management and prevention of
disease with herbal drugs, such as M. pruriens.
Bacopa monnieri and Neural Health: An Indian Herb
Page: 160-176 (17)
Author: Prachi Pattnaik, Chetan Panda, Tarun Minocha, Sanjeev Kumar Yadav, Namrata Dwivedi and Sandeep Kumar Singh*
DOI: 10.2174/9789815040197123010011
PDF Price: $30
Abstract
The disorders of the central nervous system are increasingly recognized as
one of the most prevalent disorders in the present world. It has been envisaged that
neurological disorders will be of great concern in the present and future populations
worldwide. The different neurological disorders may be associated with signs, such as
loss of memory, impaired brain function, cognitive deficits, etc. The occurrence of such
degenerative diseases of the nervous system certainly imposes medical and public
health burdens on populations worldwide. The multifactorial nature of such neural
disorders entails the use of modern medicine in combination with conventional
medicines for treatment. There has been undeniably a revolution in the foundation of
existing medical facilities, which have been strengthened by the amalgamation of
phytomedicine. In recent times, the use of medicinal herbs to improve mental function
has come into the limelight in both developed and developing countries. Increased
research is being carried out to discover Ayurvedic medications owing to their
biosafety profile and utility in cognitive impairment. The current chapter deals with the
depiction of one such plant, that is Bacopa monnieri, which possesses neuroprotective
properties, and is considered to be Medhya Rasayana (a nootropic drug). This Indian
herb, being a dietary anti-oxidant, has several modes of action to protect the brain
against oxidative damage and age-related issues. A majority of the plant compounds,
such as polyphenols, alkaloids, and terpenes, present in medicinal plants, have been
known to have therapeutic properties against neurodegeneration mainly by virtue of
their antioxidant, anti-inflammatory, and anti-amyloidogenic effects.
Role of Curcumin in the Treatment of Neurological Disorders
Page: 177-190 (14)
Author: Bhuwan Chandra Joshi and Yogita Dobhal*
DOI: 10.2174/9789815040197123010012
PDF Price: $30
Abstract
The global burden of neurological diseases is increasing at a much faster rate
causing a social and economic impact on the people. Neurological diseases, including
Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis, and
many more, are the current hot topics. The current treatment strategy in combating
neurological diseases only focuses on symptomatic relief and thus causes severe side
effects. Therefore, the therapeutic approach to combating neurological diseases has
shifted towards herbal plants. One such plant of great importance is Curcuma longa L.
and its associated active constituent curcumin. In this book chapter, we have focused
on the important role of curcumin in neurological diseases, in which we have
summarized data from 10 years (2010-2020) to get a comprehensive idea for further
research in this field. We have also described the role of curcumin in the treatment of
neurological diseases, including its cellular and common molecular mechanisms.
Pharmacology of Rosmarinic Acid against Psychological Disorders
Page: 191-212 (22)
Author: Himanshu Verma, Naveen Shivavedi, Mukesh Kumar and Prasanta Kumar Nayak*
DOI: 10.2174/9789815040197123010013
PDF Price: $30
Abstract
Anxiety and depression are the major psychological disorders globally,
increasing the risk of morbidity and mortality and considerably leading to a
socioeconomic burden by 2030. Both disorders impact day-to-day life via several
symptoms (fear, insomnia, anorexia, irritability, loss of concentration, and inability to
think). The available treatment strategy for psychological disorders has shown major
adverse effects, which limits its use and paves the way for the development of the
herbal drug-based novel drug. Natural compounds are offered as the most contented
option because they possess very least side effects, are easily available, and are of low
cost with high therapeutic activity. In the present chapter, we focus on the
pharmacology of a plant polyphenol, Rosmarinic acid (RA), against psychological
disorders. Specific plant constituents of Rosmarinus officinalis (rosmarinic acid) help
treat anxiety and depression by reducing oxidative stress and inflammatory mediators.
Other important targets, such as neurotransmitters (noradrenaline, 5-HT, and
dopamine), neuroendocrine (Hypothalamus-pituitary-adrenal-axis), brain-derived
neurotrophic factor, T-type calcium channels, mitogen kinase protein-1, and
phosphorylated extracellular regulated kinase 1 and 2 protein, are also involved in the
pathophysiology of psychological disorders (anxiety and depression). Thus, in this
chapter, we have illustrated the pharmacology of RA in major psychological disorders,
including anxiety and depression.
Neuroprotective Effects of Berberine in Neurodegenerative and Neuropsychiatric Disorders
Page: 213-229 (17)
Author: Rupinder Kaur Sodhi and Anurag Kuhad*
DOI: 10.2174/9789815040197123010014
PDF Price: $30
Abstract
Berberine is an isoquinoline alkaloid obtained naturally from the roots,
rhizomes, and bark of various plant species, such as Berberis, Phellodendron, etc. It is
an integral part of various medical systems, such as Ayurveda, Chinese traditional
medicine, and Yunani medicine. It possesses various properties, such as anti-diabetic
and anti-obesity properties, controls lipid profile, and is a strong antioxidant that helps
in protecting against oxidative stress. It acts on multiple pathways throughout the brain
and periphery to exert a wide variety of effects that can be beneficial for human use.
Berberine is effective in protecting against neurodegenerative diseases, such as
Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and ischemia, and it
also protects against neuropsychiatric disorders, such as schizophrenia, mania, anxiety,
and depression. It is a potent PI3K/Akt pathway activator, decreases proinflammatory
cytokine production, reduces glutamate excitotoxicity, triggers the synthesis of
neurotrophic factors, increases levels of biogenic monoamines, such as serotonin,
dopamine, and norepinephrine, and shows anxiolytic effects by modulating GABA
levels. In this chapter, we discuss how berberine mediates these effects, modulates
which pathways in the brain and body, and how does it provide a wide array of
responses.
Resveratrol: A Novel Drug for the Management of Neurodegenerative Disorders
Page: 230-251 (22)
Author: Sapna Bala, Anamika Misra, Upinder Kaur and Sankha Shubhra Chakrabarti*
DOI: 10.2174/9789815040197123010015
PDF Price: $30
Abstract
Resveratrol is a naturally occurring polyphenol (stilbenoid) that works as a phytoalexin, a part of plants’ defense system against infection, ultraviolet radiation, stress and injury. Common dietary sources of resveratrol include grapes, berries, peanuts, red wine, and some herbal preparations. In animal models, resveratrol exhibits a wide spectrum of potential therapeutic activities, including antioxidant, antiinflammatory, neuroprotective, and longevity-promoting properties. Resveratrol mimics the antioxidant, anti-aging, and neuroprotective effects of caloric restriction, mainly mediated through the increased expression of genes encoding antioxidants and the anti-aging factors (AMPK and Sirtuin 1). Therapeutic strategies for the treatment of neurodegenerative diseases currently have several shortcomings. Naturally occurring compounds may play a significant role in augmenting these therapeutic options. Resveratrol has been shown to maintain homeostasis, protect the brain against oxidative stress, preserve neuronal function, and ultimately minimize age-related neurological decline. It has shown positive effects in animal models and cell culturebased experiments in treating Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis, Huntington’s disease, and other neurodegenerative diseases. Resveratrol enhances learning memory and neurogenesis and alleviates neural apoptosis in the hippocampus of AD mice. Beneficial effects of resveratrol in PD result from the inhibition of α-synuclein aggregation and cytotoxicity, lowering of total and oligomeric α-synuclein levels, reduction of neuroinflammation, and oxidative stress. Clinical trials are also evaluating the role of the drug in the major neurodegenerative disorders.
Protective Effect of Potent Protein-like Drug Isolated from Indian Medicinal Plants over Diabetic Neuropathy
Page: 252-264 (13)
Author: Harsha Kashyap*, Hagera Dilnashin and Mukesh Kumar
DOI: 10.2174/9789815040197123010016
PDF Price: $30
Abstract
Diabetes is a hyperglycemic metabolic condition. Diabetes may lead to obesity and neuropathic changes in a patient. Damage to any neurological part or organ during diabetes causes diabetic neuropathy. Neuropathy occurs due to hypersensitivity in nerves because of abnormal epinephrine-mediated transmission of the impulse from axon to axon. In 1864, Marchal de Calvi explained that diabetes causes neurologic lesions by observing the pain in sciatic distribution and peripheral areas of anesthesia. Anti-hyperglycemic components, polypeptide-p and osmotin, can not only reduce the blood glucose level of mice but have also proven to be without any side effect or negative impact as they reduce oxidative stress level, improve the activities of endogenous antioxidants, and positively alter the activities of neurotransmitters, like cholinesterase, serotonin, and γ- aminobutyric acid (GABA).
Natural Herbs Polishing Memory: Neuroprotection against Alzheimer's Disease
Page: 265-283 (19)
Author: Manisha Thakkur*, Hagera Dilnashin and Priyanka Kumari Keshri
DOI: 10.2174/9789815040197123010017
PDF Price: $30
Abstract
Alzheimer's Disease (AD) is an irreversible and progressive neurodegenerative disorder that directly deteriorates the memory and cognitive function of the human brain in such a way that a person finds difficulties in dealing with daily life tasks. It is characterized by irregular neurofibrillary tangles (NFTs), intraneuronal accumulation, and the development of senile plaque (SP) consisting of abnormal polypeptide accumulation called βA4 amyloid. The pathophysiology can be collectively explained by five major hypotheses that are amyloid β (A β) hypothesis, the hyperphosporelated tau hypothesis, chronic inflammation, the cholinergic hypothesis, and the metal ion hypothesis. WHO estimated that a total of 40 million people worldwide are tested for the ill effects of dementia, and this is predicted to be twice as high as 114 million by around 2050. Currently, FDA-approved treatments for Alzheimer’s involve Donepezil, Rivastigmine, Galantamine, and Memantine that do not act specifically against Alzheimer's pathology and are also associated with loss of appetite, increased frequency of bowel movements, mental confusion, and dizziness as their side effects promote the approach to disease-modifying drugs. Nowadays, treatment with herbal medicines is a powerful alternative worldwide due to their high safety of margin against the side effects of allopathic drugs. Herbs are not restricted to a specific activity; they are generally enclosed with lignans, flavonoids, tannins, triterpenes, sterols, and alkaloids with wide pharmacological activities, such as antiinflammatory, anti-amyloidogenic, anti-cholinesterase, and anti-oxidant effects. Many herbal plants of India, such as Glycyrrhiza glabra, Acorus calamus, Convolvulus pluricaulis, Centella asiatica, Sesbania grandiflora, etc., have already proved their efficacies in treating dementia in various scientific studies.
Neuroprotective Effect of Natural Products in Attenuation of Aging-associated Neurodegeneration
Page: 284-300 (17)
Author: Abhai Kumar and Rameshwar Nath Chaurasia*
DOI: 10.2174/9789815040197123010018
PDF Price: $30
Abstract
Age-associated neurodegenerative disorders are a growing cause of mortality and morbidity in the elderly population globally. The patients suffering from neurodegenerative disorders pose medical, economic, and social issues. The agingassociated neurodegenerative disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), have different clinical and neuropathological signatures, but they share a pattern of neurodegeneration in anatomical and functionally related regions. Natural products offer great potential in the prevention and therapy of neurodegenerative diseases. Plant-derived products protect neurons by targeting oxidative stress, mitochondrial dysfunction, neurotrophic factor deficit, and abnormal protein accumulation. The current chapter discusses the neuroprotective effect of natural products in the prevention of aging-associated neurodegenerative disorders.
Subject Index
Page: 301-307 (7)
Author: Surya Pratap Singh, Hareram Birla and Chetan Keswani
DOI: 10.2174/9789815040197123010019
Introduction
Advances in the treatment of neurodegenerative diseases (NDs) are nominal. Currently available therapies are merely symptomatic treatments that cannot prevent the development of the disease. Several herbs have been found very useful for managing neurological diseases. There are immense possibilities to discover a more successful line of ND treatment. Phytochemicals from medicinal plants may play a vital role in maintaining the chemical balance of the brain by affecting the capacity of receptors for the major inhibitory neurotransmitters. A few plants have already gained popularity for the potential treatment of NDs. This volume highlights the therapeutic role of medicinal plants and their scientific validation for improving neuronal health. It presents 15 chapters that cover the herbal treatment of NDs, including Parkinson’s disease and Alzheimer’s disease. The contents cover a range of pharmaceutical agents like sirtuins, berberine, rosmarinic acid and resveratrol. The book serves as a reference for pharmacology and herbal medicine scholars as well as healthcare workers interested in information about alternative and complementary therapies for neurological disorders.