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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5609_Библиотеки_им_академика_М_И_Перельмана
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x Contents
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Chapter 9 Role of Phytopharmaceuticals as Adjuncts in Treatment
of Glioblastoma Multiforme ............................................................. 161
Ameya Kothekar, Rajesh Pradhan, and Rajeev Taliyan
9.1 Introduction ........................................................................... 161
9.2 Pathogenesis of Glioblastoma Multiforme ............................ 162
9.2.1 Unique Histopathology of Glioblastoma
Multiforme
9.2.2 Oncogenic Pathways ................................................. 163
9.3 Therapeutic Approaches to GBM .......................................... 165
9.3.1 Surgery ..................................................................... 165
9.3.2 Radiation Therapy .................................................... 165
9.3.3 Chemotherapy .......................................................... 166
9.3.4 Shortcomings of Chemotherapy ............................... 168
9.4 Bioactive Phytopharmaceutical as Adjuncts to
Chemotherapy ........................................................................ 169
9.4.1 Resveratrol ................................................................ 170
9.4.2 Quercetin .................................................................. 172
9.4.3 Curcumin .................................................................. 173
9.4.4 Boswellic Acids ........................................................ 175
9.4.5 Epigallocatechin Gallate .......................................... 176
9.5 Emerging Nanotechnology Delivery Approach
for Bioactive Phytopharmaceutical: A Potential
Therapeutic Strategy to GBM ............................................... 179
9.6 Regulatory Aspect of Phytopharmaceuticals ........................ 180
9.7 Conclusion and Future Prospectives ...................................... 180
Conict of Interest ............................................................................ 181
References ........................................................................................ 181
............................................................... 163
Chapter 10 Eugenol as Neuro-Phytomedicine: Recent Trends
Pertaining to the Treatment of Neurological Disorders ................... 187
Bhagawati Saxena
10.1 Introduction ........................................................................... 187
10.2 Eugenol and its Properties ..................................................... 188
10.3 Neuroprotective Effects and Mechanisms of
Eugenol in Various Neurological Disorders .......................... 189
10.3.1 Depression ................................................................ 189
10.3.2 Alzheimer’s Disease ................................................. 190
10.3.3 Parkinson’s Disease .................................................. 193
10.3.4 Stress and Stress-Related Disorders ......................... 194
10.3.5 Eugenol for the Treatment of Stroke ........................ 195
10.3.6 Traumatic Brain Injury ............................................. 196
10.4 Conclusion ............................................................................. 196
References ........................................................................................ 196
Chapter 11 Deciphering the Deep Learning and Machine
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Learning Tactics in Advancement of Neuroprotection
by Phytochemicals ............................................................................205
Gadde Shareena and Dileep Kumar
11.1 Introduction ...........................................................................205
11.2 Phytochemical Constituents of Natural Plant Products ........206
11.3 Alzheimer’s Disease – A Critical Prospect of
Neurotoxicity .........................................................................207
11.4 Cognition ............................................................................... 209
11.5 Bioactivities of Naturally Derived Phytoconstituents ........... 210
11.5.1 Polyphenols .............................................................. 210
11.5.2 Saponin ..................................................................... 210
11.5.3 Carotenoids (CT) ...................................................... 211
11.5.4 Flavonoids ................................................................ 212
11.6 Machine Learning and Deep Learning Tactics in
Natural Product Drug Discovery and Development ..............213
11.6.1 Machine Learning Approaches ................................ 213
11.6.2 Deep Learning Approaches ..................................... 214
11.7 Conclusion ............................................................................. 215
Acknowledgment .............................................................................. 216
Conict of Interest ............................................................................ 216
Abbreviations ................................................................................... 217
References ........................................................................................ 217
xiContents
Chapter 12 Future Trends and Directives for Research on
Phytochemicals in Neurological Diseases ....................................... 221
Srishti Raja, Chandini Sengupta, Kamarajan Rajagopalan,
Inbathamizh L, Sudha S, and Jackson Durairaj Selvan Christyraj
12.1 Introduction ........................................................................... 221
12.2 Molecular Mechanisms Associated with Benecial
Effects of Phytochemicals .................................................222
12.3 Phytochemicals in the Regulation of Biochemical
Activities ................................................................................ 223
12.3.1 Modulation of Enzyme Activities ............................223
12.3.2 Stimulation of Adaptive Responses ..........................223
12.3.3 DNA Methylation ..................................................... 224
12.3.4 Antioxidant and Anti-Inammatory Effects ............ 224
12.3.5 Induction of Tumour Suppressor Genes ................... 225
12.3.6 Stimulation of the Immune System ..........................225
12.3.7 Antibacterial and Antiviral Effect ...........................225
12.4 Phytochemicals and Neurohormetics .................................... 226
12.4.1 Phytochemicals Protecting Neuroinammation
in Neurodegenerative Diseases ................................226
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12.4.2 Neuroprotective Mechanisms ................................... 227
12.4.3 Neurohormetic Phytochemicals Regulating
Immune Function ..................................................... 227
12.4.4 Hormesis-induced Memory Performance ................ 228
12.4.5 Hormetic Studies ...................................................... 229
12.4.6 Drug Reaction to Neurological Medications ............ 233
12.5 Issues Concerning the Use of Phytochemicals in
Human Health........................................................................ 233
12.5.1 Phytochemicals and Biphasic Dose Responses ........ 234
12.6 Conclusion .............................................................................234
12.7 Future Discussions ................................................................. 235
References ........................................................................................ 235
Index ...................................................................................................................... 2 41
List of Figures and Tables
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Figure 1.1 Mechanism involved in the development of neurodegenerative
diseases and neuroprotectors. ............................................................... 4
Figure 1.2 Medical properties of medicinal herbs with different
mechanisms. ...................................................................................... 13
Figure 2.1 Factors leading to conformational changes of protein in the
progression of neurodegenerative disorders. ......................................22
Figure 3.1 List of conventional and advanced methods of extraction. ................ 40
Figure 3.2 List of techniques used for the purication of phytochemicals. ........ 45
Figure 3.3 List of techniques used for the identication of phytochemicals. ...... 51
Figure 4.1 Structure of neuroprotective alkaloids. .............................................. 58
Figure 4.2 Neuroprotective mechanism of various alkaloids. ............................. 59
Figure 5.1 Diagrammatic representation of various phytoconstituents
and their role in major neuropsychiatric disorders (stress,
anxiety, depression and psychosis). ...................................................84
Figure 5.2 Diagrammatic representation of stress pathway, representing
HPA axis dysregulation. ..................................................................... 85
Figure 7.1 Nanoparticles mediated drug delivery of phytochemicals for
neurodegenerative disorders. ............................................................ 127
Figure 7.2 Neurodegenerative diseases and the types of neurons affected
(Bhattacharya et al, 2022). ...............................................................127
Figure 7.3 Schematic representation of nanotechnology-based therapy
for CNS disorders. ............................................................................ 131
Figure 7.4 Nanoformulations used to improve the effectiveness of
natural compounds. .......................................................................... 134
Figure 8.1 A line graph plotting the amount of the trade of herbal
medicine in India in different years. Signicant increase in
the trade is observed from 2020 to 2022. ......................................... 146
Figure 8.2 Phytomedicine and health care system. ........................................... 149
Figure 8.3 Phytochemicals and treatment of neurological diseases. ................. 151
Figure 8.4 Neurophytomedicine and nanotechnology. ...................................... 154
Figure 8.5 Neurophytomedicine and biotechnology. ......................................... 156
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xiv List of Figures and Tables
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Figure 8.6 Future prospective of neurophytomedicine. ..................................... 157
Figure 9.1 Schematic drawing depicting characteristics of glioblastoma
multiforme (GBM). .......................................................................... 162
Figure 9.2 Oncogenic signalling pathways involved in GBM. .......................... 164
Figure 9.3 Mechanism action of TMZ against GBM. ....................................... 167
Figure 9.4 Different bioactive small molecule compounds targeting
peripheral molecular targets. ............................................................ 168
Figure 9.5 Structure of resveratrol. .................................................................... 170
Figure 9.6 Mechanism of resveratrol in controlling oncogenic signalling. ....... 171
Figure 9.7 Structure of quercetin. ...................................................................... 172
Figure 9.8 Anti-cancer activity of quercetin in GBM. ...................................... 173
Figure 9.9 Structure of curcumin. ..................................................................... 174
Figure 9.10 Role of curcumin in inhibiting oncogenic signalling in GBM. ........ 174
Figure 9.11 Structures of boswellic acid derivatives. .......................................... 176
Figure 9.12 Mechanism of boswellic acids in inducing apoptosis in
tumour cells. ..................................................................................... 177
Figure 9.13 Structure of epigallocatechin gallate. ............................................... 177
Figure 9.14 Effects of epigallocatechin gallate (EGCG) on GBM
metastasis. ........................................................................................ 178
Figure 10.1 Neuroprotective mechanisms of eugenol in Alzheimer’s
disease. ............................................................................................ 192
Figure 11.1 The schematic diagram displays the therapeutic effect
of natural plant products, such as curcumin, resveratrol,
and osmotin, on the pathogenic AD species ....................................208
Figure 11.2 The above illustration depicts a contrasting feature between
ML approaches and deep learning techniques, utilized in
drug discovery and development, virtual screening, and
SAR study of phytochemicals and natural products. ....................... 215
Figure 12.1 Neurohormetic responses linked to signal transduction
pathways mediated by phytochemicals. ........................................... 222
Table 4.1 Neuroprotective Plant Extract Rich in Alkaloids and Their
Biological Activities. ............................................................................ 56
Table 4.2 Alkaloids along with Their Neuroprotective Mechanism. ................... 68
Table 4.3 Synthetic and Semi-Synthetic Derivatives of Neuroprotective
Alkaloids. .............................................................................................71
xvList of Figures and Tables
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Table 5.1 Summary of Phytoconstituents Reported for Various
Neuropsychiatric Disorders and Their Mechanism of Action. ............89
Table 7.1 Gait Characteristics in the Most Common Neurodegenerative
Diseases (Cicirelli et al, 2021). ........................................................... 129
Table 7.2 Phyto-nanoformulations in Neurodegenerative Disorders
(Moradi et al, 2020). ........................................................................... 135
Table 8.1 List of Some Phytochemicals and Their Neurological Effects. ......... 150
Table 10.1 Eugenol Occurrence and Concentration in Various Plants
(Charan Raja, 2015; Khalil et al, 2017). ............................................. 188
Table 12.1 Neurohormetic Phytochemicals Inducing
Memory-Performance.........................................................................228
Table 12.2 Some Neurohormetic Phytochemicals Reducing Symptoms of
Parkinson’s Disease. ........................................................................... 229
Table 12.3 Some Neurohormetic Phytochemicals Reducing Symptoms of
Schizophrenia. .................................................................................... 230
Table 12.4 Some Neurohormetic Phytochemicals Reducing Symptoms of
Huntington’s Disease. ......................................................................... 231
Table 12.5 Some Neurohormetic Phytochemicals Reducing Symptoms of
Alzheimer’s Disease. .......................................................................... 232
Table 12.6 Some Neurohormetic Phytochemicals Reducing Symptoms of
Autism Spectrum Disorder (ASD). ..................................................... 233
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Preface
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Neurological disorders categorized as neurodegenerative, neuropsychiatric, and neurotraumatic impose a substantial health burden and cause a frail impact on the life
attributes. Neuronal cell damage occurring from oxidative stress, inammation, and
other molecular etiologies contributes to various chronic and acute neurological ailments. The tactics involved in neurotherapeutics are complex and challenging and
bear a shortcoming of side effects of synthetic chemicals. Research on neuroprotection aiming utilization of safer natural compounds, phytochemicals specically,
is a cutting-edge approach. Phytochemicals are known to exhibit various biological activities in humans and are naturally found in plants, herbs, vegetables, and
edible fruits. Alkaloids, avonoids, isoavonoids, phytosterols, saponins, terpenes,
polyphenols, etc., are the phytochemicals known to have neuroprotective efcacy.
The molecular mechanisms behind the curative effects of phytoconstituents rely
largely on subsiding oxidative stress, neuro-inammation, and signal transduction
related with protein folding. However, the particular molecular mechanisms connected with advantageous effects of phytochemicals still continue as a matter of
quest.“NeuroPhytomedicine” intends to present readers with a wide-ranging and
state-of-the-art appearance at the benecial properties of phytochemicals on the
neurodegenerative (Parkinson’s disease, Alzheimer’s disease, Huntington’s disease,
amyotrophic lateral sclerosis, etc.), neuropsychiatric (anxiety, seizures, cognitive
decit, palsies, addictions, depression, etc.), and neurotraumatic (traumatic brain
injury, cerebral ischemia, etc.) ailments. A recent advancement in the discovery of
phytochemicals as neuro-protectives, their mechanism of action, study on semisynthetic derivatives, and their conventional and nanotechnology-based formulations
has been presented. This comprehension will be helpful to neuroscientists, physicians, ethnopharmacologists, and researchers in understanding the neuroprotection
by natural plant-derived compounds.
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Editor Biography
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Dr. Mithun Singh Rajput is working with the Institute of
Pharmacy, Nirma University, Ahmedabad, Gujarat, India
as a capacity of Assistant Professor. He has expertise in
neuropharmacology and received a doctoral degree from
the Faculty of Medicine, M.G.M. Medical College, Indore,
India. He is a recipient of two years’ National Postdoctoral
Fellowship from SERB, Department of Science and
Technology, India and associated with the research project
as principal investigator. He has an overall research experi-
ence of 12 years. His area of interest includes diagnosis and
mitigating strategies for various neurodegenerative disorders like Alzheimer’s
disease and cerebral ischemia, diabetes-associated cognitive impairment, etc.
Mithun has one patent and three book chapters published and edited four books.
Mithun has been credited with 30 publications in peer-reviewed indexed journals and is currently bagged with an h-index of eighteen. He has been serving
many government funding agencies and journals and as a reviewer and editorial
board member.
Dr. Tewarit Sarachana is the Head of Chulalongkorn
SYstems Neuroscience of Autism and PSychiatric disorders
(SYNAPS) Research Unit. He is teaching at the Department
of Clinical Chemistry, Medical Technology Program, Faculty
of Allied Health Sciences, Chulalongkorn University. He pur-
sued a doctoral degree in Neuroscience at School of Medicine
and Health Sciences, The George Washington University,
Washington, DC, USA and received postdoctoral research
training at The Ofce of Blood Research and Review, Center
for Biologics Evaluation and Research, U.S. Food and Drug
Administration (FDA), Bethesda, Maryland, USA. He also serves as a technical
assessor for the medical laboratory standards ISO 15189:2012 and ISO 15190:2003,
Bureau of Laboratory Quality Standards, Department of Medical Sciences,
Ministry of Public Health, Thailand. He has handled more than 20 governmentfunded research grants and supervised ample postdoctoral, doctoral, and master’s
candidates for their research. He has published more than 30 research articles,
review articles, and book chapters and is a reviewer for more than 15 international
journals, including Molecular Autism, Current Medicinal Chemistry, and Frontiers
in Neuroscience.
Prof. Purnima Dey Sarkar is serving as Head of the Department of Biochemistry,
M.G.M. Medical College, Indore, India and has vast experience of teaching and
research of 40 years in various medical colleges of Madhya Pradesh, India. She
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