Table of Contents
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FOREWORD
PREFACE
ABBREVIATIONS
List of Contributors
Globalizing Traditional Knowledge of Indian Medicine: Evidence-based Therapeutics
Abstract
INTRODUCTION
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Naturally-occurring Bioactive Molecules with Anti-Parkinson Disease Potential
Abstract
INTRODUCTION
NEUROPROTECTIVE POTENTIAL OF BOTANICALS
In-vitro Studies
In-vivo Studies
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Indopathy for Neuroprotection in Parkinson’s Disease
Abstract
INTRODUCTION
CLASSIFICATION OF NEUROPROTECTIVE PHYTOCHEMICALS USED IN AYURVEDIC HERBAL FORMULATIONS
Polyphenols
Flavonoids
Non-flavonoids
Terpenes
Alkaloids
Other Nitrogen-Containing Phytochemicals
MECHANISTIC ACTION OF PHYTOCHEMICALS IN NEUROPROTECTION
Reactive Oxygen Species (ROS) Regulation
Mitochondrial Dysfunction
Anti-Neuroinflammatory Pathways
Modulating Cell Signaling Pathways
Apoptosis
Autophagy
Hypoxia Inducible Factor 1 Alpha (HIF-1 α) Pathway
α- Synuclein Aggregation
NEUROPROTECTIVE PLANTS IN AYURVEDA FOR PARKINSON’S DISEASE MANAGEMENT (Table 2)
Bacopa monnieri (Brahmi)
Mucuna pruriens (Velvet Beans)
Withania somnifera (Ashwagandha or Indian Ginseng)
Curcuma longa (Turmeric)
Centella asiatica (Gotu Kola)
Camellia sinensis (Tea Plant)
Vitis vinifera (Common Grapevine)
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Neuroprotective Sri Lankan Plants: Back to the Future with Phytomedicine
Abstract
INTRODUCTION
Nrf2 AS A POTENTIAL THERAPEUTIC TARGET
Nrf2 IN AGING/ NEURODEGENERATIVE DISORDERS
Alzheimer’s Disease (AD)
Parkinson’s Disease (PD)
Huntington’s Disease (HD)
Spinocerebellar Ataxias
Muscular Dystrophy
Migraine
Stroke
TARGETING Nrf2 BY NATURAL PRODUCTS FOR NEUROLOGICAL DISORDERS
Targeting Ca2+ Through Nrf2
Targeting Inflammation by Nrf2
Targeting Mitochondria by Nrf2
Targeting Proteostasis by Nrf2
Targeting Muscle Regeneration by Nrf2
NATURAL PRODUCTS BASED CLINICAL TRIALS FOR NEUROLOGICAL DISORDERS (Tables 1, 2 and 3)
BIOFUNCTIONS OF SRI LANKAN PHYTOCHEMICALS IN MODULATING THE Nrf2/Keap1 SYSTEM
Cinnamon
Emblica officinalis (Nelli)
Bacopa monnieri (Brahmi)
Annona muricata (Katu Anoda)
Centella asiatica (Gotu Kola)
Green Tea
Allium sativum (Garlic)
Zingiber officinale (Ginger)
Piper nigrum (Black Pepper)
THE DARK SIDE OF Nrf2 ACTIVATION
PLANT-BASED INHIBITORS OF Nrf2
CONCLUSION AND FUTURE DIRECTION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGMENTS
REFERENCES
Phytochemicals from Indian Medicinal Herbs in the Treatment of Neurodegenerative Disorders
Abstract
INTRODUCTION
B. Monnieri
Phytoconstituents of B. monnieri
Neuroprotective Activity of B. monnieri
C. Asiatica
Phytoconstituents of C. asiatica
Neuroprotective Activity of C. asiatica
C. longa
Phytoconstituents of C. longa
Neuroprotective Activity of C. longa
A. Sativum
Phytoconstituents of A. sativum
Neuroprotective Activity of A. sativum
T. chebula
Phytoconstituents of T. chebula
Neuroprotective Activity of T. chebula
C. paniculatus
Phytoconstituents of C. paniculatus
Neuroprotective Activity of C. paniculatus
G. glabra
Phytoconstituents of G. glabra
Neuroprotective Activity of G. glabra
A. calamus
Phytoconstituents of A. calamus
Neuroprotective Activity of A. calamus
OTHER IMPORTANT INDIAN MEDICINAL HERBS FOR THE TREATMENT OF NEURODEGENERATIVE DISORDERS
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGMENTS
REFERENCES
Neuroprotective Alkaloids: Neuromodulatory Action on Neurotransmitter Pathway
Abstract
INTRODUCTION
SOURCE STRUCTURE AND CLASSIFICATION OF ALKALOIDS
NEUROTRANSMITTERS
Cholinergic Signaling and Alkaloids
Alkaloids Acetylcholinesterase Inhibitor
Glutamatergic Signaling and Alkaloid
Gabaergic Signaling and Alkaloid
Alkaloids as Monoamine Inhibitors
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
South Indian Medicinal Herb: An Extensive Comparison of the Neuroprotective Activity
Abstract
INTRODUCTION
NEURODEGENERATIVE DISEASE
MEDICINAL PLANTS
Avicennia marina forssk. Vierh
Azadirachta indica A. Juss
Aloe vera (L.) Burm. f.
Asparagus racemosa Willd
Baccopa monnieri (L.) Pennell
Centella asiatica (L.) Urban
Curcuma longa L.
Desmodium gangedicum (L.) DC
Evolvulus alsinoides Linn.
Foeniculum vulgare Mill
Ficus religiosa Linn.
Garcinia indica Choisy
Hippophae rhamnoides L.
Moringa oligofera Lam.
Morinda pubescens Sm
Pedalium murex Linn
Punica granatum L.
Phyllanthus amarus Schumah & Thonn
Portulaca oleracea L
Sesbania grandiflora L.
Terminalia chebula Retz.
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGMENTS
REFERENCES
Therapeutic Anti-Parkinson's Role of Bacopa monnieri and Reconsideration of Underlying Mechanisms
Abstract
INTRODUCTION
THE LINK BETWEEN NEURODEGENERATION AND AYURVEDIC HERB
PD
PREVALENCE OF PD
SYMPTOMS OF PD
Motor Symptoms
Non-Motor Symptoms
RISK FACTORS: ENVIRONMENTAL AND GENETIC FACTORS
HALLMARK OF PD: α -syn
PATHOPHYSIOLOGY OF PD
B. monnieri AND ITS HISTORICAL PERSPECTIVE
Geographical Distribution, Plant Description, and Classification
B. monnieri and its Biologically Active Components
Role of B. monneiri as Nootropic Drug
MECHANISTIC UNDERSTANDING OF B. monneiri IN THE LIGHT OF PD: PHARMACOLOGICAL EFFECTS
Anti-Inflammatory and Analgesic Effects
Antioxidative Effect
B. monnieri Reduced α-Syn Protein Aggregation
B. monnieri Enhances Cognition
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Diabetic Neuropathy and Neuroprotection by Natural Products
Abstract
INTRODUCTION
DIABETES MELLITUS AND NEUROLOGICAL COMPLICATIONS
Causes of Diabetes
Signs and Symptoms
Diabetic Complications of the Nervous system
DIABETIC NEUROPATHY
Pathophysiology of Diabetic Neuropathy
Therapeutics and Management of Diabetic Neuropathy
Glycemic Control
Type 1 Diabetes Mellitus
Diabetes Control and Complications Trial
Continuous Glucose Monitoring
Type 2 Diabetes Mellitus
Symptomatic Treatment of Peripheral Neuropathy
DIABETIC POLYNEUROPATHY (DPN)
Antidepressants
Tricyclic and Tetracyclic Reagents
Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors
Anticonvulsants
Calcium channel α2-δ ligands.
Topical agents.
NATURAL PRODUCTS AND NEUROPROTECTION IN DIABETES
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Autism Spectrum Disorder: An Update on the Pathophysiology and Management Strategies
Abstract
INTRODUCTION
HISTORY
EPIDEMIOLOGY
AUTISM SYMPTOMATOLOGY
Impaired Social Behavior
Repetitive Stereotypical Behavior
Irritability
Inattention and Hyperactivity
Cognitive Impairments
PATHOPHYSIOLOGY
Excitatory-Inhibitory Neural Activity
N-methyl D-aspartate (NMDA)
GABA
α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) Receptor
Mitochondrial Dysfunction
Synaptic Plasticity
Oxidative Stress
Neuroinflammation
Neural Connectivity
Calcium (Ca2+ )Signaling
Neural Migration
Neuro-immune Disturbances
Dendritic Morphology
Other Theories
ROLE OF DIFFERENT NEUROTRANSMITTERS IN PATHOPHYSIOLOGY OF AUTISM
Monoamines
Glu and GABA
Neuropeptides
Endo-cannabinoid
Secretin System and Autism
CURRENT APPROACHES FOR THE MANAGEMENT OF ASD
PHARMACOTHERAPY
USFDA-APPROVED DRUGS
Risperidone
Aripiprazole
OTHER TREATMENT OPTIONS (REPURPOSING)
Antipsychotics
Antidepressants
Diuretic
Hormones
Vitamins
Tetrahydrobiopterin
Omega-3 Fatty Acid
TRADITIONAL MEDICINES
NEWER TARGETS
CONCLUSION AND CHALLENGES
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Neuroprotective Effect of Ginkgo Biloba and its Role in Alzheimer’s Disease
Abstract:
INTRODUCTION
LEAF EXTRACT OF G. biloba
PHARMACOLOGICAL IMPORTANCE
NEUROPROTECTIVE IMPORTANCE
PHYTOCHEMICAL PROPERTIES OF G. biloba
BENEFITS OF G. biloba
ECONOMICAL IMPORTANCE OF G. biloba
MARKETING ANALYSIS OF G. biloba
WARNING AND ADVERSE EFFECT OF G. biloba
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGMENTS
REFERENCES
Role of Withania somnifera (Ashwagandha) in Neuronal Health
Abstract
INTRODUCTION
CHEMICAL COMPOSITION OF ASHWAGANDHA
CEREBRAL ISCHEMIA
TRAUMATIC BRAIN INJURY
EPILEPSY
HUNTINGTON’S DISEASE (HD)
AMYOTROPHIC LATERAL SCLEROSIS (ALS)
ALZHEIMER’S DISEASE (AD)
PARKINSON’S DISEASE (PD)
Spinal Cord Injury (SCI)
OTHER NEUROLOGICAL CONDITIONS
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Modulation of Proinflammatory Cytokines by Flavonoids in the Main Age-related Neurodegenerative Diseases
Abstract
INTRODUCTION
FLAVONOIDS
AGING
NEUROINFLAMMATION
NEURODEGENERATIVE AGE-RELATED DISEASES
Alzheimer's Disease (AD)
Parkinson's Disease (PD)
Huntington's Disease (HD)
EFFECTS OF FLAVONOIDS IN AD, PD, AND HD
In-vitro Studies
MODULATORY EFFECTS OF FLAVONOID IN AD.
In-vitro Studies
Animal Models
Clinical
MODULATORY EFFECTS OF FLAVONOIDS IN PD
In-vitro Studies
Animal Models Studies
MODULATORY EFFECTS OF FLAVONOID IN HD
In-vitro Studies
In-vivo Studies
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Utilization of Nutraceuticals and Ayurvedic Drugs in the Management of Parkinson’s Disease
Abstract
INTRODUCTION
NUTRACEUTICALS USED IN PD THERAPEUTICS
AYURVEDIC PREPARATIONS IN PD THERAPEUTICS
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Systems Analysis Based Approach for Therapeutic Intervention in Mixed Vascular-Alzheimer Dementia (MVAD) Using Secondary Metabolites
Abstract
INTRODUCTION
METHODS
PATHOGENESIS OF MIXED DEMENTIA
POTENTIAL SECONDARY METABOLITES AS THERAPEUTIC AGENTS
SYSTEMS BIOLOGY BASIS OF INTEGRATED MECHANISM BEHIND MIXED-DEMENTIA
AMELIORATION OF MIXED DEMENTIA BY SECONDARY METABOLITES
Withania somnifera
Phytoconstituents of W. somnifera
W. somnifera in Alzheimer’s Dementia
Galanthus nivalis
Phytoconstituents of G. nivalis
G. nivalis in Mixed Dementia
Genista tinctoria
Phytoconstituents of G. tinctoria
G. tinctoria in Alzheimer's Dementia
Silybum marianum
Phytoconstituents of S. marianum
S. marianum in Alzheimer’s Dementia
Curcuma longa
Phytoconstituents of C. longa
C. longa in mixed Dementia
Ginkgo biloba
6.6.1. Phytoconstituents of G. biloba
G. biloba in Mixed Dementia
Centella asiatica
Phytoconstituents of C. asiatica
C. asiatica in Mixed Dementia
Bacopa monnieri
6.8.1. Phytoconstituents of B. monnieri
B. monnieri in mixed Dementia
Crocus sativus
Phytoconstituents of C. sativus
C. sativus in mixed Dementia
VALIDATION ANALYSIS OF PRECLINICAL/CLINICAL EFFICACY
8. DISCUSSION
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Indopathy for Neuroprotection: Recent Advances
Edited by
Surya Pratap Singh
Department of Biochemistry
Institute of Science, Banaras Hindu University
Varanasi-221005, India
Hagera Dilnashin
Department of Biochemistry
Institute of Science, Banaras Hindu University
Varanasi-221005, India
Hareram Birla
Department of Biochemistry
Institute of Science, Banaras Hindu University
Varanasi-221005, India
&
Chetan Keswani
Department of Biochemistry
Institute of Science, Banaras Hindu University
Varanasi-221005, India
BENTHAM SCIENCE PUBLISHERS LTD.
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FOREWORD
Exposure to plant-based phytochemicals can promote health and prevent chronic neurodegenerative diseases. Most traditional treatment prescriptions consist of a combination of several drugs. The combination of multiple drugs is thought to maximize therapeutic effectiveness by promoting synergies and improving or preventing potential side effects while targeting multiple goals.
Indopathy is a valuable source of information for discovering new remedies for a variety of human illnesses. The complex etiology of neurodegenerative diseases and the multifactorial effects of Indopathy and its active ingredients may give a broad perspective on traditional indian medicine in neuroprotection. Some indian medicinal plants and their active ingredients have shown promising results for oxidative stress, inflammation, apoptosis, and neurodegeneration in laboratory studies. Indopathy has excellent prospects for the treatment of neurodegenerative diseases and is considered to be effective in neuroprotection.
Combining modern molecular medicine principles with some ideas of traditional indian empirical medicine may be beneficial to translation medicine.
The proposed book focuses on indopathy for the treatment of neurodegenerative diseases. This book reviews a subset of traditional indian medicines and highlights their neuroprotective active ingredients for their antioxidant, anti-inflammatory, and cognitive-enhancing effects. This volume provides a comprehensive introduction to therapeutic options for some popular plant-derived neuroprotective agents. I congratulate the editor for synchronizing with global authorities on the subject to underline the upcoming challenges and present the most viable options for translating commercially viable ideas into easily affordable products and technologies.
I wish all the editors great success with the launch of this book and thank them for their dedication to plant-based neuroprotection around the world.
Dr. Amulya K. Panda
Former Director
National Institute of Immunology
New Delhi
India
PREFACE
With the rapid increase in life expectancy and the proportion of the elderly population, the global prevalence of various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease, is rising dramatically. The demographic trend of the aged population has attracted people's attention to the discovery and treatment of new drugs for age-related diseases. Currently, there are various drugs and treatments available for the treatment of neurodegenerative diseases, but side effects or insufficient drug efficacy have been reported. With a long history of herbs or natural compounds used in the treatment of age-related diseases, new evidence has been reported to support the pharmacological effects of Indopathy in ameliorating symptoms or interfering with the pathogenesis of neurodegenerative diseases.
Many indian medicinal plants have been used for thousands of years in indopathy. Amongst these are plants used for the management of neurodegenerative diseases, such as Parkinson's, Alzheimer's, loss of memory, degeneration of nerves, and other neuronal disorders by Ayurvedic practitioners. Though the etiology of neurodegenerative diseases remains enigmatic, there is evidence indicating that defective energy metabolism, excitotoxicity, and oxidative damage may be crucial factors.
This book summarizes the new therapeutic leads from herbal sources for various types of neurodegenerative diseases. Based on recent research, this book makes an effort to utilize existing knowledge of some popular medicinal plants, and their biologically active components have been discussed, especially those used in indopathy. Several promising plants such as Withania somnifera, Bacopa monnieri, Centella asiatica, and Mucuna pruriens are worth exploring for the development of neuroprotective drugs.
Surya Pratap Singh
Department of Biochemistry
Institute of Science, Banaras Hindu University
Varanasi-221005, IndiaHagera Dilnashin
Department of Biochemistry
Institute of Science, Banaras Hindu University
Varanasi-221005
IndiaHareram Birla
Department of Biochemistry
Institute of Science, Banaras Hindu University
Varanasi-221005
India
&Chetan Keswani
ABBREVIATIONS
Glossary6-OHDA6-HydroxydopamineABCATP-Binding-CassetteAP-1Activator Protein 1ADPAdenosine Dinucleotide Phosphateα-SynAlpha-SynucleinADAlzheimer DiseaseAβAmyloid-BetaAPPAmyloid-Beta Precursor ProteinApoEApolipoprotein EASCApoptosis-associated Speck-like Protein comprising a Caspase Recruitment DomainAIFApoptosis-Inducing FactorAIArtificial IntelligenceBcl-2B-Cell Lymphoma 2BaxBcl-2 Associated XBACE1Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1HEXABeta Hexosaminidase AHEXBBeta Hexosaminidase BBBBBlood-Brain BarrierBDNFBrain-derived Neurotrophic FactorJNKc-Jun N-Terminal KinaseCLRC-Type Lectin ReceptorIba1Calcium-Binding Adaptor Molecule 1CATCatalaseCNSCentral Nervous SystemCSFCerebrospinal FluidCVDCerebrovascular DiseaseCOPDChronic Obstructive Pulmonary DiseaseCELA3AChymotrypsin-Like Elastase Family Member 3ACOX-2Cyclooxygenase-2CBGCytosolic Βeta GlucosidaseDATDA TransporterDAMPDamage-Associated Molecular PatternDMCDemethoxycurcuminDADopamineDaergicDopaminergicERADEndoplasmic Reticulum Associated DegradationEDSExcessive Daytime SomnolenceEXOticExosomal Transfer into CellsERKExtracellular Signal-Regulated KinasesFADFamilial ADFDG-PETFluorodeoxyglucose Positron Emission TomographyfMRIFunctional Magnetic Resonance ImagingNG2Glial Antigen-2GDNFGlial-derived Neurotrophic FactorGFAPGlial Fibrillary Acidic ProteinGBAGlucocerebrosidaseGSHGlutathioneHO1Hemeoxygenase 1HDHuntington's DiseaseiPDIdiopathic PDIGLV1-33Immunoglobulin Lambda Variable 1-33iNOSInduced Nitric Oxide SynthaseIRF3Interferon Regulatory Factor 3IL-1βInterleukin-1 BetaIL-2Interleukin2KMOKynurenine 3-MonooxygenaseLPHLactase Phlorizin HydrolaseLTFLactoferrinLRRK-2Leucine Rich Repeat Kinase 2LRRLeucin Rich RepeatsL-DopaLevodopaLBsLewy BodiesLRP-1Low-Density Lipoprotein Receptor-Related Peptide 1LSDLysergic Acid DiethylamideMRIMagnetic Resonance ImagingmTORMammalian Target of RapamycinMPTP1-Methyl-4-Phenyl-1, 2, 3, 6-TetrahydroxypyridiineMPP+1-Methyl-4-phenylpyridiniumMCAOMiddle Cerebral Artery OcclusionMCIMild Cognitive ImpairmentMAPKMitogen-Activated Protein KinaseMAO-BMonoamine Oxidase BMSAMultiple System AtrophyNLRNOD-LRR-Containing ReceptorNEPNeprilysin ProteaseNCAMNeural Cell Adhesion MoleculeNFTsNeurofibrillary TanglesNADHNicotinamide Adenine DinucleotideNONitric OxideNOSNitric Oxide SynthaseNrf2Nuclear Factor Erythroid 2–Related Factor 2NF-κBNuclear Factor Kappa BNODNucleotide-Binding Oligomerization DomainOPCOligodendrocyte Precursor CellPRKNParkinPDParkinson’s DiseasePAMPPathogen-Associated Molecular PatternPRRPattern Recognition ReceptorPNSPeripheral Nervous SystempMCAOPermanent Distal Middle Cerebral Artery OcclusionPPARγPeroxisome Proliferator-Activated Receptor GammaPI3KPhosphoinositide 3-KinasePARP1Poly (ADP-Ribose) Polymerase-1PETPositron Emission TomographyPSENPresenilinPSPProgressive Supranuclear PalsyPKBProtein Kinase BPINKPTEN-induced Putative Kinase 1REMRapid Eye MovementROSReactive Oxygen SpeciesRAGEReceptor For Advanced Glycation End ProductsREM8Receptor-Mediated Endocytosis 8RBDREM Sleep Behaviour DisorderRIG1Retinoic Acid-Inducible Gene 1RXRRetinoid X ReceptorRLHRIG1-Like HelicaseRLRRIG1-Like ReceptorHTRA2Serine ProteaseSema3ASemaphorin-3ASA-β-GALSenescence-Associated Βeta GalactosidaseSASPSenescence-Associated Secretory PhenotypeSNPsSingle Nucleotide PolymorphismsSPECTSingle-photon Emission TomographySNSubstantia NigraSNpcSubstantia Nigra Pars CompactaSODSuperoxide DismutaseSOCSSuppressor of Cytokine Signaling ProteinsTLRsToll-Like ReceptorsTCMTraditional Chinese MedicineTBITraumatic Brain InjuryTCSTranscranial SonographyTGF-βTransforming Growth Factor BetaTUBB4BTubulin Beta 4B Class IVbTNF-αTumor Necrosis Factor AlphaTNFR1Tumor Necrosis Factor Receptor 1THTyrosine HydroxylaseUCHL-1Ubiquitin Carboxy-Terminal Hydrolase 1UPRUnfolded Protein ResponseVPS35Vacuolar Protein Sorting 35VCIVascular Cognitive ImpairmentVaDVascular DementiaVHMVenous Hypertensive MicroangiopathyWHOWorld Health Organization
List of Contributors
Abhishek MishraDepartment of Pharmacology, Post Graduate Institute of Medical Education & Research, Chandigarh-160012 (Punjab), IndiaAmbarish Kumar SinhaDepartment of Clinical Research, School of Biosciences and Biomedical Engineering, Galgotias University, Greater Noida, Uttar Pradesh, IndiaAnil Kumar SinghDepartment of Dravyguna, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaAnindita BhattacharjeeNeuroimaging Laboratory, School of Bio-Medical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaAparna MishraDepartment of Bioscience and Biotechnology, Banasthali Vidyapith University, Banasthali-304022 (Rajasthan), IndiaArchana DwivediDepartment of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaAshutosh KumarDepartment of Pharmacology, Faculty of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaAtul KabraSchool of Pharmacy, Raffles University, Neemrana, Alwar-301020 (Rajasthan), IndiaBikash MedhiDepartment of Pharmacology, Post Graduate Institute of Medical Education & Research, Chandigarh-160012 (Punjab), IndiaBipin MauryaLaboratory of Morphogenesis, Centre of Advance Study in Botany, Institute of Science, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaCaridad Ivette Fernandez VerdeciaInternational Center of Neurological Restoration (CIREN), Basic Division, La Habana, CubaChetan KeswaniDepartment of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaChristophe HanoLaboratoire de Biologie des Ligneux et des Grandes Cultures, INRAUSC1328, Universitéd’Orléans, 45100 Orléans, FranceDarshi AttanayakeInterdisciplinary Centre for Innovation in Biotechnology and Neurosciences, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Jayewardenepura Kotte, Sri LankaDeepika JoshiDepartment of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaDivya Raj PrasadDepartment of Genetics and Plant Breeding, Institute of Agricultural Sciences, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaGaurav KumarDepartment of Clinical Research, School of Biosciences and Biomedical Engineering, Galgotias University, Greater Noida, Uttar Pradesh, IndiaHagera DilnashinDepartment of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaHardik KoriaDepartment of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Charusat Campus, Changa-388421, (Gujarat), IndiaHareram BirlaDepartment of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaHéctor Eduardo López-ValdésDepartamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, MéxicoHilda Martínez-CoriaDepartamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, MéxicoHimanshu VermaDepartment of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaKamal UddinAligarh College of Pharmacy, Aligarh-202002 (U.P), IndiaK. Ranil D. de SilvaInterdisciplinary Centre for Innovation in Biotechnology and Neurosciences, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Jayewardenepura Kotte, Sri Lanka
Institute for Combinatorial Advanced Research & Education (KDU-CARE), General Sir John Kotelawala Defence University, Colombo, Sri Lanka
European Graduate School of Neuroscience, Maastricht University, Maastricht, The NetherlandsLakmal GonawalaInterdisciplinary Centre for Innovation in Biotechnology and Neurosciences, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Jayewardenepura Kotte, Sri Lanka
European Graduate School of Neuroscience, Maastricht University, Maastricht, The Netherlands,Nalaka WijekoonInterdisciplinary Centre for Innovation in Biotechnology and Neurosciences, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Jayewardenepura Kotte, Sri Lanka
European Graduate School of Neuroscience, Maastricht University, Maastricht, The NetherlandsNatália Cruz-MartinsFaculty of Medicine, University of Porto, Porto, Portugal
Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal,
Institute of Research and Advanced Training in Health Sciences and Technologies (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra PRD, PortugalNaveen ShivavediShri Ram Group of Institutions, Faculty of Pharmacy, Jabalpur-482002 (M.P.), IndiaNilay SolankiDepartment of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Charusat Campus, Changa-388421 (Gujarat), IndiaPhulen SarmaDepartment of Pharmacology, Post Graduate Institute of Medical Education & Research, Chandigarh-160012 (Punjab), IndiaPrasanta Kumar NayakDepartment of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaPrasun Kumar RoyNeuroimaging Laboratory, School of Bio-Medical Engineering, Indian Institute of Technology Banaras Hindu University, Varanasi-221005 (U.P.), India
Centre for Tissue Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaPratibha ThakurDepartment of Bioscience, Endocrinology Unit, Barkatullah University, Bhopal- 462026 (M.P.), IndiaPratistha SinghDepartment of Dravyguna, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaRaffaele CapassoUniversita Degli Studi di Napoli Federico II, Naples, ItalyRohit SharmaDepartment of Rasa Shastra and Bhaishjya Kalpana, Faculty of Ayurveda, IMS, Banaras Hindu University, Varanasi-221005 (U.P), IndiaRubal SinglaDepartment of Pharmacology, Post Graduate Institute of Medical Education & Research, Chandigarh-160012 (Punjab), IndiaRuchika KabraSchool of Pharmacy, Raffles University, Neemrana, Alwar-301020 (Rajasthan), IndiaRupa JoshiDepartment of Pharmacology, Post Graduate Institute of Medical Education & Research, Chandigarh-160012 (Punjab), IndiaSarika SinghDepartment of Neuroscience and Ageing Biology and Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow-226031, (U.P.), IndiaShilpa NegiDepartment of Neuroscience and Ageing Biology and Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow-226031, (U.P.), IndiaSukala PrasadBiochemistry & Molecular Biology Laboratory, Department of Zoology, Brain Research Centre, Banaras Hindu University, Varanasi-221001 (U.P.), IndiaSurya Pratap SinghDepartment of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaUttam Singh BaghelDepartment of Pharmacy, University of Kota, Kota-324005 (Rajasthan), IndiaVartika GuptaBiochemistry & Molecular Biology Laboratory, Department of Zoology, Brain Research Centre, Banaras Hindu University, Varanasi-221005 (U.P.), IndiaYoonus ImranInterdisciplinary Centre for Innovation in Biotechnology and Neurosciences, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Jayewardenepura Kotte, Sri Lanka
Globalizing Traditional Knowledge of Indian Medicine: Evidence-based Therapeutics
Hagera Dilnashin1,*,Hareram Birla1,Chetan Keswani1,Surya Pratap Singh1,*
1 Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi-221005 (U.P.), India
Abstract
With the advent of modern medicine, the use of medicinal plants is an ancient therapeutic strategy used by traditional healers and is very useful in traditional medicine. Medicinal plants are compatible with human physiology, which has been adapted for centuries.
Keywords: Indopathy, Medicinal plants, Therapeutic strategy, Therapeutics, Traditional medicine.
*Corresponding authors Hagera Dilnashin and Surya Pratap Singh: Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi-221005 (U.P.), India; E-mails:
[email protected] and
[email protected]INTRODUCTION
In today's scenario, scientists need to focus on finding the compounds of herbs involved in the cure, alleviation, and cure of the disease. Traditional medicine includes long-term treatments that people inherit and practice to prevent and treat illness. Plants have formed the basis of traditional medicinal systems. It consists of several medicinal systems from different parts of the world, which include Chinese herbal medicine (China), Indian herbal medicine (India), Kampo medicine (Japan), Native American medicine (US), Tibetan medicine (Tibetan), Jamu Genndong (Indonesia), traditional African medicine (Africa), and traditional Hawaiian medicine (Hawaii) [1, 2].
India has an ancient heritage of traditional medicine. Materia medica of India provides a wealth of information on the folklore practices and traditional aspects of therapeutically important natural products. Each of these traditional systems has unique aspects, but there is a common thread among their fundamental principles and practices in the use of natural products, mostly herbs [3-5].
Indopathy is a traditional Indian medicinal system that includes Ayurveda, Yoga, and Naturopathy, Unani, Siddha, and Homeopathy (AYUSH). It is a well-known medication system because of its various pharmacological effects that are beneficial to human health [6]. In addition to its strong neuroprotective potential, many studies have also described the significant therapeutic effects of herbal medicine against several central nervous system diseases [4, 7-9]. The biological effects of herbal plants have been generally attributed to ancient science's major protective effect. The results of studies with different mechanisms indicate the neuroprotective effects of plants, most of which mention positive effects on oxidative stress and other assessment parameters [5, 10-13]. The modulatory role of the alternative medicinal system will not only bring new drug discoveries [14] but also treat central nervous system diseases and help understand the complex pathophysiology of neurodegenerative diseases [3, 15-18].
CONCLUSION
Over time, Indopathy has been tested, and people have used it for their medical care for a long time. Before British rule, these were the main treatments in India but later changed under the influence of western culture. So Indopathy are well-rooted with a profound clinical basis, where scientific validation is sometimes the major constraint for their development. Despite these setbacks, Indopathy remains in India and continues to grow in the global market [19]. As the Western world pays more and more attention to herbal drugs, especially Indopathy, it is necessary to examine these systems and take appropriate measures to restore the concept of traditional medicine as the main therapeutic medicinal system [20, 21].
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The author declares no conflict of interest, financial or otherwise.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1]Mukherjee PK, Maiti K, Mukherjee K, Houghton PJ. Leads from Indian medicinal plants with hypoglycemic potentials. J Ethnopharmacol 2006; 106(1): 1-28.[http://dx.doi.org/10.1016/j.jep.2006.03.021] [PMID: 16678368][2]Law BYK, Wu AG, Wang MJ, Zhu YZ. Chinese medicine: a hope for neurodegenerative diseases? J Alzheimers Dis 2017; 60(s1): S151-60.[http://dx.doi.org/10.3233/JAD-170374] [PMID: 28671133][3]Singh SS, Rai SN, Birla H, et al. Neuroprotective effect of chlorogenic acid on mitochondrial dysfunction-mediated apoptotic death of DA neurons in a Parkinsonian mouse model. Oxid Med Cell Longev 2020; 2020: 1-14.[http://dx.doi.org/10.1155/2020/6571484] [PMID: 32566093][4]Birla H, Keswani C, Singh SS, et al. Unraveling the neuroprotective effect of tinospora cordifolia in parkinsonian mouse model through proteomics approach. ACS Chem Neurosci 2021; 12(22): 4319-35.[5]Birla H, Keswani C, Rai SN, et al. Neuroprotective effects of Withania somnifera in BPA induced-cognitive dysfunction and oxidative stress in mice. Behav Brain Funct 2019; 15(1): 9.[http://dx.doi.org/10.1186/s12993-019-0160-4] [PMID: 31064381][6]Gitler AD, Dhillon P, Shorter J. Neurodegenerative disease: models, mechanisms, and new hope. The Company of Biologists Ltd Dis Model Mech 2017; 10(5): 499-502.[7]Zahra W, Rai SN, Birla H, et al. The global economic impact of neurodegenerative diseases: Opportunities and challenges. 2020333-45.[8]Rai SN, Birla H, Singh SS, et al. Pathophysiology of the Disease Causing Physical Disability. Biomedical Engineering and its Applications in Healthcare. 2019573-95.[9]Rai SN, Singh BK, Rathore AS, et al. Quality control in huntington’s disease: a therapeutic target. Neurotox Res 2019; 36(3): 612-26.[http://dx.doi.org/10.1007/s12640-019-00087-x] [PMID: 31297710][10]Rathore AS, Birla H, Singh SS, et al. Epigenetic modulation in parkinson’s disease and potential treatment therapies. neurochem res 2021; 46(7): 1618-26.[http://dx.doi.org/10.1007/s11064-021-03334-w] [PMID: 33900517][11]Singh S, Rai S, Birla H, et al. Chlorogenic acid protects against MPTP induced neurotoxicity in parkinsonian mice model via its anti-apoptotic activity. Journal of Neurochemistry 2019.[12]Rai SN, Dilnashin H, Birla H, et al. The role of PI3K/Akt and ERK in neurodegenerative disorders. Neurotox Res 2019; 35(3): 775-95.[http://dx.doi.org/10.1007/s12640-019-0003-y] [PMID: 30707354][13]Beal MF. Aging, energy, and oxidative stress in neurodegenerative diseases. Ann Neurol 1995; 38(3): 357-66.[http://dx.doi.org/10.1002/ana.410380304] [PMID: 7668820][14]Bhatnagar M. Novel leads from herbal drugs for neurodegenerative diseases. Herbal drugs: Ethnomedicine to modern medicine 2009221-38.[http://dx.doi.org/10.1007/978-3-540-79116-4_14][15]Hassan MAG, Balasubramanian R, Masoud AD, Burkan ZE, Sughir A, Kumar RS. Role of medicinal plants in neurodegenerative diseases with special emphasis to alzheimer’s. International Journal of Phytopharmacology 2014; 5(6): 454-62.[16]Zahra W, Rai SN, Birla H, et al. Neuroprotection of rotenone-induced Parkinsonism by ursolic acid in PD mouse model. CNS & Neurological Disorders-Drug Targets. 2020; 19(7): 527-40.[17]Rai SN, Zahra W, Singh SS, et al. Anti-inflammatory activity of ursolic acid in MPTP-induced parkinsonian mouse model. Neurotox Res 2019; 36(3): 452-62.[http://dx.doi.org/10.1007/s12640-019-00038-6] [PMID: 31016688][18]Zahra W, Rai SN, Birla H, et al. Economic Importance of Medicinal Plants in Asian Countries. Bioeconomy for Sustainable Development 2020359-77.[http://dx.doi.org/10.1007/978-981-13-9431-7_19][19]Mukherjee PK, Bahadur S, Harwansh RK, Nema NK, Bhadra S. Development of traditional medicines: globalizing local knowledge or localizing global technologies. Pharma Times 2013; 45(9): 39-42.[20]Mukherjee P, Wahile A. Perspectives of safety for natural health products. Herbal Drugs-A Twenty first Century Perspectives 200650-9.[21]Orhan IE. Urban: from traditional medicine to modern medicine with neuroprotective potential. Evidence-based complementary and alternative medicine 2012.
Naturally-occurring Bioactive Molecules with Anti-Parkinson Disease Potential
Atul Kabra1,*,Kamal Uddin2,Rohit Sharma3,Ruchika Kabra1,Raffaele Capasso4,Caridad Ivette Fernandez Verdecia5,Christophe Hano6,*,Natália Cruz-Martins7,8,9,*,Uttam Singh Baghel10,*
1 School of Pharmacy, Raffles University, Neemrana, Alwar-301020 (Rajasthan), India
2 Aligarh College of Pharmacy, Aligarh-202002 (U.P), India
3 Department of Rasa Shastra and Bhaishjya Kalpana, Faculty of Ayurveda, IMS, Banaras Hindu University, Varanasi, 221005 (U.P), India
4 Universita Degli Studi di Napoli Federico II, Naples, Italy
5 International Center of Neurological Restoration (CIREN), Basic Division, La Habana, Cuba
6 Laboratoire de Biologie des Ligneux et des Grandes Cultures, INRAUSC 1328, Université d’ Orléans, 45100 Orléans, France
7 Faculty of Medicine, University of Porto, Porto, Portugal
8 Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
9 Institute of Research and Advanced Training in Health Sciences and Technologies (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal
10 Department of Pharmacy, University of Kota, Kota-324005 (Rajasthan), India
Abstract
Parkinson's disease (PD) is a complex limiting neurodegenerative disorder, with a rising incidence. Current therapeutic options for PD have multiple limitations, and naturally occurring biomolecules, often known as phytochemicals, with potent neuroprotective activities, have been searched to meet the need. Thus, this chapter encompasses in-depth information on reported anti-PD activities of medicinal plants in light of available pre-clinical and clinical studies and shares the mechanisms of action proposed in fighting PD. Published information from PubMed, Scopus, Science Direct, Springer, Google Scholar, and other allied databases was analyzed. There is rising interest among researchers in investigating medicinal plants and their isolated compounds for their anti-PD efficacy. Scattered information about the anti-PD potential of plants and bioactive compounds is reported in the scientific domain. A total of 92 medicinal plants belonging to 63 families, exhibiting anti-PD activity were
discussed. Botanical species have revealed an extreme potential, encouraging future examination. Data discussed here can be used for further research and clinical purposes.
Keywords: Bioactive molecules, Dopamine, Lewy bodies, Medicinal plant extracts, Parkinson's disease, Substantia nigra.
*Corresponding authors Atul Kabra, Christophe Hano, Natália Cruz-Martins & Uttam Singh Baghel: School of Pharmacy, Raffles University, Neemrana, Alwar-301020 (Rajasthan), India, Laboratoire de Biologie des Ligneux et des Grandes Cultures, INRAUSC1328, Universitéd’Orléans, 45100 Orléans, France, Faculty of Medicine, University of Porto, Porto, Portugal & Department of Pharmacy, University of Kota, Kota-324005 (Rajasthan), India; E-mails:
[email protected],
[email protected],
[email protected] &
[email protected]INTRODUCTION
Despite presenting a pathological mark of slowness, the manifestation and progression of Parkinson’s Disease (PD) are insinuated [1], featured by the progressive loss of dopaminergic neurons in the pars compacta of substantia nigra and by the decline in dopamine levels in the basal ganglia striatum [2, 3]. Consequently, the cholinergic neurons’ activity becomes comparatively dominant, while the nigrostriatal dopaminergic neuronal activity is decreased, which results in the advancement of movement disorder [4-6]. In the human system, PD is categorized by symptoms of motor neurons, viz. bradykinesia, resting tremors, rigidity, and postural instability [7], besides non-motor manifestations, such as neuropsychiatric abnormalities, disturbed sleep, dysautonomia, gastrointestinal disturbances, and sensory problems [8-12].
At the molecular level, although the pathophysiology of the disease still remains unclear, several pathways have been proposed to be involved in dopaminergic neuronal death, such as oxidative stress, mitochondrial injury, excitatory amino acid toxicity, ubiquitin-proteasome system damage, proteolytic stress, immune disorders, inflammatory reactions, dopamine transporter (DAT) inactivation, abnormal deposition of α-synuclein, and cell apoptosis through c-Abl activation [1, 13-15]. In this context, environmental factors, like permethrin pesticide exposure during brain development, have been associated with genetic and epigenetic changes leading to PD in rats, as well as in their untreated offspring (Fig. 1) [16-19].
For several decades, the therapeutic gold standard for PD has been based on the use of levodopa, in combination with a peripheral decarboxylase inhibitor. However, the long-term use of these drugs often leads to multiple secondary effects, including gastrointestinal, respiratory, and neurological symptoms [20-22]. More recently, several drugs were approved by FDA for treating PD, but they also have various side effects, as summarized in Table 1 [23-27]. Hence, the search for natural products with anti-PD activity has largely increased in these years owing to their safer approach and cost-effectiveness. Though plentiful research has been carried out during the past decades on the anti-PD potential of several botanical preparations, extracts, and isolated phytocompounds, only scattered information exploring their activity is accessible. Besides, earlier reports did not provide complete information apropos plant extract doses, animals used, and their possible anti-PD mechanism.
Considering this, the present chapter attempts to provide a comprehensive report on the anti-PD potential of several botanicals in light of available experimental and clinical studies.
Fig. (1))
Genetic, environmental, and lifestyle factors leading to PD.
Table 1Recently FDA-approved anti-PD drugs.S. No.DrugBrand NameMechanism of ActionUseSide EffectsApproval YearCompany Name1.SafinamideXadagoMAO-B inhibitorAdjunctive treatment to levodopa/carbidopa in patients with PDDyskinesia, fall, Nausea, Insomnia2017Newron Pharmaceuticals2.AmantadineGocovriAn uncompetitive antagonist of the NMDA receptorPD dyskinesiaHallucination, Dizziness, Dry Mouth, Peripheral Edema, Orthostatic, Hypotension2017Adamas Pharmaceuticals3.PimavanserinNuplazidInverse agonist and antagonist activity at serotonin 5-HT2A receptorsHallucinations and delusions associated with PDPeripheral edema, confusional state2016Acadia Pharmaceuticals4.Carbidopa and levodopaDuopaInhibits the peripheral levodopa decarboxylationMotor fluctuations in patients with advanced PDHypertension, Peripheral Edema, Erythema, Upper Respiratory Tract Infection, Oropharyngeal Pain2015Abbvie Pharmaceuticals5.Carbidopa and levodopaRytary--Hypotension, Insomnia, Abnormal Dreams, Dry Mouth, Dyskinesia, Anxiety2015Impax Labs
NEUROPROTECTIVE POTENTIAL OF BOTANICALS
Available reports reveal that functional foods, such as green legumes, condiments, cereals, different medicinal plant parts, phytoconstituents obtained from leaves, bark, fruits, flowers and seeds, crude extractives and active phytocompounds are being investigated in experimental studies, while meagre attempts are found at clinical levels. These botanicals were found to exhibit significant neuroprotective activities and have been used as potent remedies for PD. Macroscopic features of common anti-PD plants and their bioactive compounds are mentioned in Fig. (2).
Fig. (2))
Macroscopic features and bioactive compounds of medicinal plants with anti-PD potential.
In-vitro Studies
The majority of available in-vitro studies were carried out on neuronal PC-12 and SH-SY5Y cell lines, while some studies were carried out on SK-N-SH, MN9D, BV-2 microglial, D8, HT22 murine hippocampal, N9 and EOC20 microglial cell lines (Table 2). Sesamine isolated from Acanthopanax senticosus was able to decrease CAT activity, increase SOD as well as protein expression at a dose of 1 pM on PC-12 cells [28]. Protocatechuic acid isolated from kernels of Alpinia oxyphylla at a dose of 0.06-2.4 mM on PC-12 cells increases SOD, CAT, and GSH-Px levels [28], besides its ethanolic extract from ripe seeds also inhibits NO and iNOS production [29]. Aqueous and ethanol extracts from Bacopa monnieri at 50 and 10 µg/ml decreased ROS and mitochondrial superoxide levels and increased GSH levels [30, 31]. Polyphenolic catechins obtained from Camellia sinensis leaves were shown to decrease the accumulation of ROS and intracellular free Ca2+ ions, nNOS, and iNOS at a dose of 50, 100, and 200 µM [32]. EGCG, ECG isolated from Camellia sinensis exhibited anti-PD potential on PC-12 cells by activating MAPK and potentiating the ability of the cellular antioxidant defense system at a dose of 50-200 µM [33]. In PC-12 cells, EGCG also modulated DAT internalization by exerting an inhibitory effect on DAT at a dose of 1-100 µM [34]. Dried GT and BT extracts of Camellia sinensis attenuated NF-κB activation on SH-SY5Y cell and PC-12 cell at a dose of 0.6-3 µM [35].
Table 2In vitro anti-PD activity of medicinal plants.Plant NameFamilyPart UsedExtract/Fraction/CompoundDoseIn-vitroExperimental ModelsResultReferencesAcantho panaxsenticosus (Rupr. et Maxim.) Harms.AraliaceaeSeedsSesamine1 pMPC12 cellsMPP+ induced↑SOD, ↑protein expression, ↓CAT[51, 52]Eleutheroside B---↑ ERK ½ phosphorylation and ↓ c-fos and c-jun expressions-Ajuga ciliate BungeciliateLabiataeWhole plantClerodane diterpenes3-30 μMSH-SY5Y cellsMPP+-induced↑ Cell viability[53]Alpinia oxyphylla Miq.ZingiberaceaeRipe seedsEthanol extract---Neuronal PC12 cells6-OHDA induced↓IL-1β and TNF-α gene expression and inhibit NO production and iNOS expression[29, 54]KernelsProtocatechuic acid0.06-2.4 mMPC12 cellsH2O2 induced cell death↑SOD, CAT, GSH-Px-Anemo paegmamirandum (Catuaba)Bignoniaceae---Commercial Extract0.312, 0.625 and 1.250 mg/mlSH-SY5Y cellsRotenone induced↑ Cell viability[28]Apium graveolens L.ApiaceaeSeedDL-3-n-butylphthalide (NBP)0.1-100 µMSH-SY5Y cellsRotenone induced↑Mitochondrial membrane potential, ↓ROS, ↑Cell viability[55]Astragalus membranaceus (Fisch.) Bge.LeguminosaeRootsAstragaloside IV---SH-SY5Y cellsMPP+ inducedInhibit ROS production and ↑ Bax/Bcl-2 ratio and activity of caspase-3[56]Bacopa monnieri (L.) Wettst.PlantaginaceaeWhole plantAqueous extract50 μg/mlSH-SY5Y cellsMPTP and Paraquat induced↑GSH, ↓ROS, mitochondrial superoxide level[30, 31]Ethanol extract10 μg/mlPC-12
CellsRotenone induced↑GSH, ↓ROS-Buddleja officinalis MaximScrophulariaceae---Verbascoside0.1, 1 or 10 µg/mlPC-12
CellsMPTP induced↓Caspase-3 activation and collapse of mitochondrial membrane[57]Camellia sinensis (L.) KuntzeTheaceaeLeavesPolyphenolic catechins50, 100, 200 µMSH-SY5Y cells6-OHDA induced↓ ROS and intracellular free Ca+2, nNOS and iNOS[32-34, 36, 58]EGCG, ECG, EC, C, EGC50-200 µMPC12 cellsIn-vitroActivation of MAPK, ↑antioxidant enzymes-EGCG(1–100 μM)PC12 cellsMPP+ induced neurotoxicityModulation of DAT internalization-Dried GT and BT extracts0.6–3 μMSH-SY5Y cells and PC-12 cell6-OHDA induced↓ NF-κB activation-1, 3, and 10 μMSH-SY5Y cellsDDT-inducedPAINS-Carthamus tinctorius L.Compositae---kaempferol 3-O-β-rutinoside and 6-hydroxykaempferol
3,6-di-O-β-D-glucoside1 μMPC-12 cellsH2O2 inducedBind DJ-1 (protein associated with PD); ↓Levels of H2O2 induced ROS and restore TH activity[36]Cassia obtusifolia L.LeguminosaeRipe seedEthanol extract0.1–10 mg/mlPC-12 cells6-OHDA inducedInhibit ROS overproduction, glutathione depletion, mitochondrial membrane depolarization, and caspase-3 activation[37]Chrysanthemum morifolium RamatCompositae---Aqueous extract-SH-SY5Y cellsMPP+ inducedInhibit mitochondrial apoptotic pathway and ↓ROS accumulation and ↑ cell viability.[59, 60]Chrysanthemum indicum Linn.SeedMethanolic extract1, 10, and 100 μgSH-SY5Y cellsMPP+ induced↓ROS production, inhibit PARP proteolysisBV-2 cellsLPS induced↓Production of PGE2, COX-2, blocked IκB-α degradation and ↓activation of NF-κBCistanche deserticola Y. C. MaOrobanchaceae---Acteoside10, 20 or 40 mg/lSH-SY5Y cellsRotenone inducedInhibit the aggregation of α-Syn[38, 39]Tubuloside B-PC12 cellsMPP+ induced↓ROS, DNA fragmentation-Citrus aurantium L., Citrus sinensis (L.) Osbeck and Citrus unshiu (Yu. Tanaka ex Swingle) Marcow.RutaceaeCitrus Fruit flavanolHesperidin2.5, 5, 10, 20, and 40 𝜇gSK-N-SH cellsRotenone induced↓ROS formation by ↓levels of TBARS and restored antioxidant enzyme activity and GSH[61, 62]--Hesperetin--PC12 cellsOxidative stress-inducedTriggers ER- and TrkA-mediated parallel pathways-Clausena lansium (Lour.) SkeelsRutaceaeLeavesBu-70.1 and 10 μmol/LPC12 cellsRotenone inducedInhibit the phosphorylation of both JNK and p38 and ↓p53 levels.[63]Coptis chinensis Franch.RanunculaceaeRhizomeAqueous extract---SH-SY5Y cellsMPP+ induced↑cell viability, ↑intracellular ATP concentration, and ↑TH[64]Curcuma longa L.ZingiberaceaeRhizomeAqueous extract0.001, 0.01, 0.05, 0.1, 0.2 and 0.4 mg/mlSH-SY5Y cellsSalsolinol induced toxicityInhibition of apoptosis and ↓Gene expression levels of apoptosis markers (p53, Bax, and caspase 3)[65]Cuscuta australis R. Br. or Cuscuta chinensis Lam.ConvolvulaceaeRipe seedsAqueous extract0.001, 0.01, 5, and 10 μgPC12 cellsMPP+ induced↓GPx, ↓ROS[66, 67]Flavonoid0.001, 0.01, 5, and 10 μgPC12 cellsH2O2 induced apoptosis↓ROS, ↑Antioxidant enzymes-Eucommia ulmoides Oliv.EucommiaceaeBarkBetulinic acid, betulin, wogonin, oroxylin A, genipin, geniposidic, and aucubin10 μMSH-SY5Y cellsMPP+ induced↑ Proteasome activity, ↑Cell viability[68]Fraxinus sieboldiana BlumeOleaceae-----Esculin, 6,7-Di-O-glucopyranosyl-esculetin and liriodendrin10−7, 10−6, and 10−5 MSH-SY5Y cells-↓ROS level, ↑Mitochondrion membrane potential, ↑SOD activity, and ↓glutathione GSH and regulate P53, Bax, and Bcl-2 expression; inhibit the release of cytochrome-c, apoptosis-inducing factor, and caspase 3 activation[69]Gardenia jasminoides J. EllisRubiaceaeFruitGeniposide5 and 50 µg/mlSH-SY5Y cellsCorticosterone inducedInhibit cell apoptosis, ↓P21, and P53 protein expression[70]Gastrodiaelata BlumeOrchidaceaeRhizomeEthanolic extract10, 100, 200 g/mLSH-SY5Y cellsMPP+ induced↓ROS, ↓Caspase-3 activity, ↓Bax/Bcl-2 ratio[71, 72]RhizomeVanillyl alcohol---MN9D cellsMPP+ inducedInhibiting ROS levels, ↓Bax/Bcl-2 ratio, ↓caspase-3, and PARP proteolysis-Ginkgo biloba LGinkgoaceaeLeavesEGb 76110, 20, and 40 μg/mLPC12 cellsParaquat (PQ) induced↓caspase-3 activation through a mitochondria-dependent pathway[73]Hypericum perforatum L.HypericaceaeAerial partMethanolic extract10-100 μg/mlPC12 cellsH2O2 inducedInhibiting ROS[40, 41]Ethyl acetate fractionHyperoside10-180 µg/mlPC12 cellsH2O2 induced↓LDH level, ↑Cell viability-Lonicera japonica Thunb.CaprifoliaceaeFlower budsAqueous extract0.5, 5, 2.5, 5, and 10 μg/mLBV-2 microglial cellsLipopolysaccharide (LPS) inducedInhibit proinflammatory cytokines and chemokines, TNF-α IL-1β, monocyte chemoattractant protein-1, ↓ROS production[42]Lycium chinense Mill.Solanaceae-Extract-PC12 cellsRotenone induced↑Cell viability, ATP level, ↓caspase activation, ↓mitochondrial membrane depolarization, ↓mitochondrial superoxide production.[74]Magnolia officinalis Rehder & E. H. WilsonMagnoliaceaeStem barkMagnolol30 mg/kgSH-SY5Y cellsMPP+ induced↓ROS production[75]Morus alba L.MoraceaeFruit70% ethanol extract1, 10 and 100 µg/mlSH-SY5Y cells6-OHDAAntioxidant and antiapoptotic effects[43]Murraya koenigii (L.) Spreng.RutaceaeLeavesAqueous extract----PC12 cells6-OHDA↓antioxidant enzymes[45]Paeonia lactiflora Pall.PaeoniaceaeRootPaeoniflorin20-200 μg/mlPC12 cellsMPP+ induced↑expression of HATs, ↑H3K9ac and H3K27ac of Histone H3[76]Panax ginseng C. A. Mey.AraliaceaeRhizomeAqueous extract0.001, 0.01, 0.1 or 0.2 mg/mLSH-SY5Y cellsMPP+ induced↓ROS production, ↓Bax/Bcl-2 ratio, ↓activation of caspase-3[45-47]RootGinsenoside Rg10.1-10 µMPC12 cellsH2O2 induced↓DA-induced apoptosis by suppressing oxidative stress and NF-κB activation-Ginsenoside Rb1---SH-SY5Y cells6-OHDA inducedInduction of NrF2 nuclear translocation and PI3K activation-Panax notoginseng (Burkill) F.H.ChenAraliaceaeRootEthanolic extract25, 50 and 100 µg/mlN9 and EOC20 microglial cell linesIn-vitro↓Production of inflammatory mediators (IL-6 and TNF-α)
↓NO[75, 77]Panaxatriol saponins0.5 mg/mlPC12 cellsMPP+ induceInduce thioredoxin-I-Polygala tenuifoliaWilld.PolygalaceaeRootAqueous extract0.5-1 µg/mlPC12 cells6-OHDA induced↓ROS, ↓NO, ↓Caspase-3 activity[78, 79]Tenuigenin1.0-10 µMSH-SY5Y cells6-OHDA induced↓Caspase-3 activity, ↑TH, ↑SOD,-Polygonum cuspidatum Willd. ex Spreng.PolygonaceaeRhizomeResveratrol12.5, 25, and 50 µMSH-SY5Y cellsRotenone induced↑degradation of α-synucleins[48, 49, 80, 81]Resveratrol and Quercetin----PC12 cellsMPP+ induced↑mRNA level-Naphthoquinone, 2-methoxy-6acetyl-7-methyljuglone2.5 µMPC12 cellsTert-butyl hydroperoxide inducedInduce the phosphorylation of ERK 1/2, JNK, and p38 MAPK,-Pinostilbene1-10 µMSH-SY5Y cells6-OHDA induced↓Phosphorylation of JNK and c-jun-Psoralea corylifolia L.LeguminosaeSeedPetroleum ether extract0.1, 1 and 10 µg/mlSK-N-SH cell lineMPP+ inducedThe extract has inhibitive effects on the DA transporter and NA transporter.[82]1, 10 and 100 µg/mlD8 cell linePueraria lobata (Willd.) OhwiFabaceaeRootPuerarin50 µMSH-SY5Y cellsMPP+ inducedActivate PI3K/Akt pathway[83]50 µMPC12 cellsMPP+ inducedInhibit the activation of caspase-9 and caspase-3Pueraria thomsonii Benth.FabaceaeRootDaidzein and genistein100 μMPC12 cells6-OHDA inducedInhibit caspase-8 and partially inhibit caspase-3 activation[84]Rehmannia glutinosa (Gaertn.) DC.PlantaginaceaeRootCatalpol----PC12 cellsLPS induced↓ROS, ↓ LPS-induced the expression of iNOS[85]Rhodiola crenulata (Hook. f. & Thomson) H.Ohba and Rhodiola rosea L.CrassulaceaeRootSalidroside1, 10 and 30 μMPC12 cellsMPP+ inducedinhibiting the NO pathway and activating PI3K/Akt pathway[86]Salviamiltiorrhiza BungeLamiaceaeRootSalvianic acid B0.1–10 µMSH-SY5Y cells6-OHDA induced↓Caspase-3 activity, ↓ cytochrome C translocation into the cytosol from mitochondria[87-89]10-100 µMSH-SY5Y cellsMPP+-induced↓Caspase-3 activity, ↓ Ros ↓Bax/Bcl-2 ratio-0.1-10 µMPC12 cellsH2O2 induced↓ intracellular Ca2+ elevation and ↓caspase-3-Schisandra chinensis (Turcz.) Baill.SchisandraceaeFruitSchisantherin A---SH-SY5Y cellsMPP+ induced↑CREB-mediated Bcl-2 expression and activating PI3K/Akt survival signalling[90]Scutellaria baicalensis GeorgiLamiaceaeRootBaicalein0.05, 0.5 and 5 µg/mLPC12 cells6-OHDA↓ROS, ↑ mitochondrial membrane potential, ↓ caspase-3/7 activation[91, 92]10-50 µMHT22 murine hippocampal neuronal cellsTG and BFA induced cell death↓ROS and C/EBP homologous protein induction-Thuja orientalis L.CupressaceaeLeafEthanolic extract10 µg/mLSH-SY5Y cells6-OHDA induced↓ROS[93]Toxicodendron vernicifluum (Stokes) F.A.BarkleyAnacardiaceaeLeafExtract---SH-SY5Y cellsRotenone induced↑TH level[94]Uncaria rhynchophylla (Miq.) Miq. ex Havil.RubiaceaeHookAqueous extract0.1, 0.5 and 1.0 µgPC12 cells6-OHDA induced↑GSH, ↓ROS, and inhibited caspase-3 activity[95]Valeriana jatamansi JonesCaprifoliaceaeRootsBakkenolidesvalerilactones A (1), and B (2), and two known analogues, bakkenolide-H (3)-SH-SY5Y cellsMPP+-induced neuronal cell death↓NO production[50]Valeriana offcinalis subsp. collina (Wallr.) NymanCaprifoliaceae-Aqueous extract0.049, 0.098 and 0.195 mg/mLSH-SY5Y cellsRotenone induced↓NO production, ↑Cell viability[96]
PD: Parkinson's disease; CAT: Catalase; DA: Dopamine, H2O2: Hydrogen peroxide; LPS: Lipopolysaccharide; NO: Nitrogen Monoxide; iNOS: inducible Nitric Oxide Synthase; ROS: Reactive Oxygen Species; MPTP: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NA: Noradrenaline; NF-κB: Nuclear factor-κB; 6- OHDA: 6-Hydroxydopamine; MPP+: 1-methyl-4-phenyl-pyridinium iodide; PI3K: Phosphoinositide 3-kinase; TH: Tyrosine hydroxylase; DAT: Dopamine transporter; MAO-B: Monoamine oxidase B; MDA: Malondialdehyde; SNpc: Substantia nigra pars compacta; SOD: Superoxide dismutase; GSH-Px: Glutathione Peroxidase; BFA: Brefeldin A; COX: Cyclooxygenase; CHOP: C/EBP Homologous Protein; PRAP: Poly (ADP-ribose) Polymerase; PI: Propidium Iodide; TG: Thapsigargin; MAPK: Mitogen Activated Protein Kinase; LDH: Lactate Dehydrogenase; LPO: Lipid Peroxidation ; CTG: Cistanche Total Glycosides; T-AOC: Total Antioxidant Capacity; GFAP: Glial Fibrillary Acidic Protein; P53: Tumor protein p53; EGCG: Epigallocatechin gallate; ECG: (−)-epicatechin-3-gallate; EGC: (−)-epigallocatechin; EC: (−)-epicatechin; GT: Green Tea; BT: Black Tea; EGb 761: Extract of Ginkgo biloba 761; PC12: Pheochromocytoma 12.
K3R and AYB, two bioactive compounds obtained from Carthamus tinctorius belonging to the Asteraceae family, at 1 μM increased cell viability on PC12 cells by Bind DJ-1 and decreased the H2O2-induced ROS levels [36]. Ripe seed ethanol extract of Cassia obtusifolia inhibited ROS overproduction, glutathione depletion, mitochondrial membrane depolarization, and caspase-3 activation in PC-12 cells at 0.1-10 µg/ml [37]. Acetosoide isolated from Cistanche deserticola at a dose of 10, 20 and 40 mg/l inhibited α-Synuclein protein aggregation in the brain [38]; tubuloside-B also obtained from its stem decreased ROS production and attenuated DNA fragmentation in PC12 cell against MPP+ induced Parkinson [39]. EGb 761, a standardized extract from Ginkgo biloba, at a dose of 10, 20, and 40 µg/ml, decreased caspase-3 activation in PC-12 cells against paraquat-induced PD [40]. Hypericum perforatum aerial part methanolic extract at 10-100 µg/ml decreased ROS level in PC-12 cells [41], as well as hyperoside isolated from the ethylacetate fraction, and at 10-180 µg/ml raised cell viability against hydrogen peroxide-induced PD [42].
Magnolol isolated from Magnolia officinalis stem bark at 30 mg/kg inhibited ROS production in SH-SY5Y cells [43]. Morus alba fruits ethanolic extract at 70% exerted antioxidant and antiapoptotic effects in SH-SY5Y cells against MPP+ induced PD at a dose of 1, 10, and 100 µg/ml [44]. Paeoniflorin, a bioactive compound isolated from Paeonia lactiflora roots, increased Hats, H3K9ac, and H3K27ac expression of Histone H3 [45]. Panax ginseng aqueous extract from rhizomes at 0.001, 0.01, 0.1 or 0.2 mg/ml decreased ROS production, Bax/Bcl-2 ratio and caspase-3 expression [46]. Ginsenoside Rg1, a bioactive compound isolated from Panax ginseng roots at a dose of 0.1-10 µM, increased cell viability by inhibiting apoptosis and oxidative stress and inhibiting NF-κB activation [47]. Resveratrol isolated from Polygonum cuspidatum rhizomes increased α-synucleins degradation in SH-SY5Y cells and PC-12 cells at a dose of 12.5, 25, and 50 µM [48]. Napthaquinone, 2-methoxy-6-acetyl-7methyljuglone is another compound isolated from P. cuspidatum that increases PC12 cell viability by inhibiting apoptotic pathways and increasing the level of antioxidant enzymes at 2.5 µM [49]. Uncaria rhynchophylla aqueous extract at 0.1, 0.5 and 1.0 µg also decreased ROS and caspase-3 activity in PC-12 cells [50].
Most aforesaid studies examined the effect of extracts, fractions, and their active compounds on SOD, GSH, CAT, DA, LDH, TH, and ROS levels; Bax/Bcl-2 ratio; caspase-3 activity; α-synuclein protein aggregation, mitochondrial activity, and NF-κB activity.
In-vivo Studies
Based on the outcomes from in-vitro reports, a few potent anti-PD botanicals were further subjected to in-vivo studies by using various neurotoxin and drug-induced anti-PD models, like 6-OHDA, rotenone, MPP+, MPTP, haloperidol, and reserpine (Table 3). Acanthopanax senticosus root and rhizome ethanolic extract at 80%, at doses of 182 and 45.5 mg/kg increased DA level in C57BL/6 mice, while 100% and 50% ethanol extract and hot water extract at 250 mg/kg also raised the DA level in Male rat of Lewis strain. Sesamin isolated from A. senticosus stem bark increased DA levels at 3 and 30 mg/kg in male rats [97]. Alpinia oxyphylla ripe seed ethanol extract at 80% decreased IL-1β, TNF-α, and NO levels and activated the PI3K-AKT pathway in zebrafish [97]. Standard extract of Bacopa monnieri at 200 mg/kg decreased NOS, MDA and HP levels in the paraquat-induced mice model; its acetone extract at 0.25, 0.50 and 1.0 µl/ml and standardized extract at 0.01, 0.025, 0.05, and 0.1% decreased NOS, MDA, HP, and oxidative stress levels and apoptosis in Drosophila melanogaster. Concentrated mother tincture of B. monnieri decreased α-synuclein aggregation and prevented dopaminergic neurodegeneration in the NL5901 strain of Caenorhabditis elegans of nematodes [98].
EGCG, a bioactive compound obtained from Camellia sinensis leaves, reduced NOS levels at 25 mg/kg and increased TH, DA, HVA, and 3,4-dihydroxyphenylacetic acid [98]. Flavonoid-rich dried flower petals extract of Carthamus tinctorius at 70 mg/kg in SD rats reduced α-synuclein aggregation and suppressed reactive astrogliosis [99-101]. Ripe seeds ethanol extract of Cassia obtusifolia at 50 mg/kg increased DA, GSH levels and decreased ROS levels in C57BL/6 mice [97]. CTG (100, 200, 400 mg/kg) and acetoside (30 mg/kg) isolated from Cistanche deserticola stem increased TH and DA levels in SD rat and C57BL/6 mice [95]. Eucommia almoidea bark at 100, 300, and 600 mg/kg increased DA, DOPAC, and HVA levels in mice [68]. Geniposide isolated from fruits of Gardenia jasminoides at 100 mg/kg in mice increased TH and decreased Bcl-2 and caspase-3 [71]. EGb 761, a bioactive compound from Ginkgo biloba leaves at 50, 100, and 150 mg/kg in rats, augmented the level of antioxidants enzymes and reduced the level of thiobarbituric acid reactive substances (TBARS) [97]. The methanol extract from Hypericum perforatum aerial part at 300 mg/kg inhibited MAO-B activity and reduced astrocytes activation in the striatal area in swiss albino mice; the standardized extract at 4 mg/kg increased antioxidant enzymes levels and decreased MDA level [97]. Fucoidan, a sulfated polysaccharide from Laminaria japonica seaweeds, augmented the level of antioxidant enzymes and decreased the level of LPO at 12.5 and 25 mg/kg in C57BL/6 mice [102]. Magnolol isolated from Magnolia officinalis bark at 30 mg/kg inhibited MAO-B and decreased the level of ROS and TBARS while increasing the AKT phosphorylation in C57BL/6 mice [43]. Morus alba fruits ethanol extract at 70%, at 500 mg/kg decreased NO, ROS and Bcl-2, and caspase-3 levels [97]. Paeoniflorin isolated from Paeonia lactiflora roots inhibited neuroinflammation by activating A1AR (adenosine A1 receptor) in mice and SD rats [97]. Ginseng extract G115 in SD rats at 100 mg/kg suppressed oxidative stress and blocked JNK signalling activation and protected dopaminergic neurons [97]. Ginsenoside Re isolated from Panax ginseng, at 6.5, 13, and 26 mg/kg in mice decreased Bax, Bax mRNA and iNOS expression and caspase-3 activation. Aqueous extract from P. ginseng at 37.5, 75 and 150 mg/kg in C57BL/6 mice led to inhibition of MAPKs and NF-κB pathways [103].
Table 3Medicinal plants tested in-vivo for anti-PD activity.Plant NameFamilyPart UsedExtract/Fraction/CompoundDosein-vivoExperimental ModelsMechanism of ActionReferenceAcanthopanax senticosus (Rupr. et Maxim) HarmsAraliaceaeRoots and rhizomes80% ethanolic extract182, 45.5 mg/kgC57BL/6 miceMPTP induced↑ DA[112]Stem bark100% ethanol, 50% ethanol, and hot water250 mg/kgMale rats of the Lewis strainMPTP induced↑DAStem barkSesamin3, 30 mg/kgMale rats of the Lewis strainRotenone-induced↑DAAlbizia adianthifolia (Schum.) W. WightLeguminosaeLeavesAqueous extract150, 300 mg/kgMale Wistar rats6-OHDA induced↑SOD, GPX, and GSH
↓MDA and protein carbonyl[97]Allium sativum L.AmaryllidaceaeClovesEthanol extract200, 400 mg/kgFemale Swiss Albino MiceHaloperidol induced↑ SOD, GPX, and GSH[113-115]---S-allylcysteine120 mg/kgMiceMPTP induced↓TNF-α, iNOS, GFAP, ↑DA-125 mg/kgC57BL/6J miceMPP+ induced↑DA, LPO-Aloe arborescens Mill.XanthorrhoeaceaeFresh LeavesGel200 mg/kgRatCopper inducedDA[116]Alpinia oxyphylla Miq.ZingiberaceaeRipe seeds80% ethanolic extract--Zebrafish6-OHDA induced↓IL-1β, TNF-α, NO
activation of PI3K/AKT pathway[112]--Protocatechuic acid--C58BL/6J miceMPTP inducedDAAlternanthera sesilis (L.) R.Br. ex DC.AmaranthaceaeWhole plantEthanolic extract200 mg/kgMale Wistar albino ratRotenone induced↑GSH, ↓ LPO[117]Bacopa monnieri (L.) Wettst.Plantaginaceae--Concentrated mother tincture50 µMNL5901 strain of Caenorhabditis elegans6-OHDA induced↓α-synuclein aggregation prevents dopaminergic neurodegeneration restores the lipid content in nematodes[118]---Standard extract200 mg/kgMiceParaquat-induced↓NOS, MDA, HP----Standard extract---MiceRotenone induced↓NOS, MDA, HP-LeafAcetone extract0.25, 0.50 and 1.0 μl/mlDrosophila melanogasterRotenone model↓Oxidative stress and apoptosis---standardized extract0.01, 0.025, 0.05 and 0.1%Drosophila melanogasterRotenone model↓NOS, MDA, HP-Whole plant--40 mg/kgSwiss albino miceMPTP model↑TH, caspase-3 and expression of neurogenic gene in the SN-Whole plantEthanolic extract180 mg/kgRatRotenone Induced Model↓ Glutamine content, GDH and GS ↑Glutaminase-Berberis aristata DC.BerberidaceaeRootsMethanolic extract100, 300 and 500 mg/kgSprague dawley rats Rat6-OHDA↑SOD, CAT, GSH, and total thiol
↓LPO[98]Beta vulgaris L.AmaranthaceaeLeavesMethanolic extract100, 200 and 300 mg/kgWistar RatsReserpine, Haloperidol and tacrine induced↑SOD, CAT
↓LPO[119]Bougainvillea spectabilis Willd.NyctaginaceaeFlowerMethanolic extract25 and 50 mg/kgSD RatRotenone induced↓LPO, inhibit (butyrylcholinesterase) BChE, (paraoxonase-1) PON-1 activity and increased brain Il-1β[120]Brassica oleracea L.BrassicaceaePowderHydroalcoholic extract250 and 500 mg/kgWistar albino ratsHaloperidol induced↑GSH and ↓LPO[121]Camellia sinensis (L.) KuntzeTheaceaeLeavesGTP-Rat6-OHDA inducedInhibition of ROS-NO pathway[118]LeavesEGCG25 mg/kgC57B6 miceMPTP induced↓NOS expression
↑TH, DA, HVA, 3,4-dihydroxyphenylacetic acid-Carthamus tinctorius L.CompositaeDried flower petalsFlavonoid extract70 mg/kgSD RatMPTP and 6-OHDA induced↓α-synuclein aggregation, suppression of reactive astrogliosis[122]Cassia obtusifolia L.LeguminosaeRipe seedEthanolic extract50 mg/kgC57BL/6MiceMPTP and 6-OHDA induced↑ DA, GSH, ↓ROS[112]Chaenomeles speciosa (Sweet) NakaiRosaceaeDried fruitAqueous extract0.5 gm/kgSD Rat6-OHDA inducedInhibit DAT, ↑DA[99]C57BL/6 MiceMPTP inducedCistanche deserticola Y.C.MaOrobanchaceaeStemCTG100, 200 and 400 mg/kgC57BL/6 MiceMPTP induced↑TH and nigral dopaminergic neurons[112]Acetoside30 mg/kgCistanche salsa (C.A.Mey.) BeckStemEchinacoside30 mg/kgC57Bl/6 MiceMPTP induced↑expression of GDNF and BDNF mRNA and protein inducer of NTFs and inhibitor of apoptosis-3.5 and 7.0 mg/kgWistar rat6-OHDA induced↑DA, DOPAC, and HVA-CitrusRutaceaePeel, seedTangerine peel, grape seeds, cocoa, and red clover35, 100, 100 and 200 mg/kgRat6-OHDA induced↑DA, DOPAC, and HVA[123]Combretum leprosum Mart.CombretaceaeFlowerEthanolic extract100 mg/kgC57Bl/6MPTP induced↑DA[124]Crocus sativus L.IridaceaeFruit and flower----0.01% w/vBALB/c miceMPTP modelProtect dopaminergic cells of SN and retina[125]Crocetin25, 50 and 75 µg/kgWistar rats6-OHDA Model↑GSH, DA
↓TBARSCynodon dactylon (L.) Pers.PoaceaeWhole plantAqueous extract150 and 300 mg/kgRatRotenone induced↑GSH, SOD, and CAT
↓TBARS, MDA, and NO[112]Swiss albino miceReserpine inducedDecalepis hamiltonii
