NEURODEGENERATIVE DISORDERS: ROLE OF MEDICINAL PLANTS IN TREATMENT

NEURODEGENERATIVE DISORDERS: ROLE OF MEDICINAL PLANTS IN TREATMENT

Ahmad Sarfaraz *, Sudhir Kumar Mishra, Kumar Krishna and Khan Zoya

K. R. Mangalam University, Sohna Road, Gurugram, Haryana, India.

ABSTRACT: Neurons are the nervous system's basic components that involve the spinal cord and brain. Neurons do not usually replicate or substitute them because the body cannot replace them as they get impaired or die. Neurological conditions are untreatable and disabling diseases that result in irreversible deterioration/death of the human brain's nerve cells or neurons. Treating these conditions with extended synthetic drug administration can lead to serious side effects. So, herbal therapy is preferable over traditional therapies. Using herbal remedies can provide significant potential benefits in preventing and treating Neurological disorders. Herbal medicines have been gaining much attention for their therapeutic value over many years. Herbal plants have been used to treat and manage various ailments from ancient times due to their economic availability and lesser side effects than conventional anti-parkinsonian drugs. The current review incorporates research on medicinal plants, which has demonstrated the ability to transcend the development of neurological disorders and highlights the significance of traditional plant species in the role and mechanisms involved in neuroprotection. Ayurveda is regarded as an ancient-age traditional medicine with substantial use of herbs and herbal supplements proven to diagnose different conditions.

Keywords: Alzheimer’s, Dementia, Neuro-Protection, Parkinson’s, Herbal plants

INTRODUCTION: Neurons are the nervous system's basic components that involve the spinal cord and brain. Neurons do not usually replicate or substitute them because the body cannot replace them as they get impaired or die. Neurodegenerative disorders are untreatable and chronic illnesses that lead to the gradual deterioration/extinction of nerve cells in the brain. This triggers movement problems (called ataxias) or mental control ("Dementias") ¹.

The degenerate neurons aren't replaced, resulting in cognitive impairment and neuro-degenerative problems, which lead to depression, schizophrenia, Alzheimer's disease, dementia, epilepsy, cerebral ischemia, and Parkinsonism ². Such disorders include different pathological or structural characteristics affecting neurons in different brain regions.

Neurodegenerative disorders are ramped up by how we live our everyday lives. According to a new survey by the Indian Council of Medical Research (ICMR), the percentage of reported deaths owing to lifestyle-associated had risen from 37.09 percent in 1990 to 61.8 percent in 2016. Therefore, there's still an enormous need to establish methods for its elimination as there are growing numbers of people who suffer from related diseases every day. Ayurveda is regarded as an ancient-age traditional medicine with substantial use of herbs and herbal supplements proven to diagnose different conditions. Much beyond established variations in pathogenic processes of human disorders, neurodegenerative disorders, recognized as the process that leads to the progressive degradation of functional characteristics of neurons before apoptosis, reflect the central point in this category of disorders and promote scientific interests in attempting to explain specific pathological processes and attain relevant interventions ³. The precise reason for multiple neurological disorders is a healthcare mystery. The widely researched factors of neurological conditions involve environmental causes, oxidative stress, inflammation, anomalous neuronal protein accumulation, mitochondrial deficiencies, protein degradation, and medical history ⁴. Different classical preparations for neurological disorders are mentioned in the Ayurvedic Formulary of India (AFI), which also offers a database of records on a single crop, animal, and mineral products, including their original names with Common counterparts for simple identification ⁵. The present analysis draws together literature on plant origin that has shown potential in overcoming the progression of neurological disorders and emphasizes the importance of traditional medicinal plants on neuroprotective roles and mechanisms involved.

Neurological Disorders: There are several neurological system disorders; some are listed in Fig. 1.

FIG. 1: NEUROLOGICAL DISORDERS

Alzheimer's disease (AD): Alzheimer's disease (AD) was initially known as presenile dementia, which denotes an inherited psychiatric disorder with a lack of critical ability to interact with social functioning. This is correlated with regional brain shrinkage and neuron loss, particularly in the hippocampus and the basal forebrain. The beta-amyloid peptide (BAP) plays an important role in AD growth. While synthetic drugs cannot cure AD, but can be handled with them to some level. Numerous researches have shown that antioxidant compounds, like beta-carotene, vitamin C, and vitamin E, are effective in the free radical scavenging produced during this disease progression. Memory failure is believed to stem from a lack of a nerve transmitter, acetylcholine. The level of such a transmitter in the brain could be improved by hindering the enzyme activity, acetylcholinesterase, which fragments or disintegrates the transmitter material. Synthetic, medicinal products which restrict the collapse of transmitter acetylcholine could postpone disease progression ⁶.

Parkinson's disease: Parkinson's disease is a developmental infection affecting slow motion and body stiffness. The psychiatric diagnosis involves bradykinesia (experiencing problems triggering movement), rest tremors, hypokinesia, and rigidity, with non-motor symptoms including autonomic psychosis disorder, and depression. Other signs include rigid posture of the face, gait, psychological changes, repetitive motions, loss of blinking, autonomic dysfunction, micrography, seborrhoea and neurological, sensory effects, and atrophy of the muscles.

It is defined by neuronal failure in substantia nigra and other brain areas, often connected to intracellular protein inclusions such as Lewy bodies. Depleting dopaminergic neurons, contributes to dopamine being released into the striatum getting limited.

The main suspect is mitochondrial dysfunction and oxidative attack. The latest treatment available for PD focuses mainly on Levodopa, which can delay the progression of the disease to a certain degree but has several adverse effects ^7-9.

Huntington’s disease: The infection is characterized via an autosomal dominantly inherited CAG trinucleotide repeat amplification on chromosome 4 in the huntingtin (HTT) gene. Consequently, mutated huntingtin (mHTT) proteins via an unusually large polyglutamine loop can be produced. Someone with more than 39 CAG repeats seemed to acquire the illness, whereas those with 36 to 39 repetitions have decreased susceptibility. Whenever the genome is transmitted through the paternal way, it's also possible that even a husband with a CAG repeat sequence throughout the average range will produce a kid with an enlarged pathogenic repeated length.

It's because male sperm has more repetition variation and more repetition lengths than somatic tissue. A verified genetic makeup of HD, a confirmed genetic test, and the beginning of motor dysfunction are used to make the diagnosis. The score goes between 0 (without motor irregularities indicative of HD) - 4, with either a score of 4 indicating motor start ^10-12.

Ataxia: Ataxia, described as poor control of voluntary muscular action, seems to be a clinical finding rather than an illness, as well as the root because it must be researched. It might be the patient's primary concern or one of several clinical presentations. Cerebellar impairment or reduced vestibular or proprioceptive afferent stimulation to the cerebellum are generally the causes.

The position of the lesion within the cerebellum is frequently associated with signs and indications. Ipsilateral signs and symptoms are caused by lateralized cerebellar lesions, while diffuse cerebellar abnormalities generate more widespread symmetrical signs. Injuries in the cerebellar lobe cause limb ataxia. Truncal and gait ataxia is caused by vermis injuries, with limbs remaining largely unaffected. Inquiries about work, possibly hazardous exposures to substances, sexual exploits, drug addiction, and excessive drinking can all be part of the social and historical record. A background of substance abuse might point to chemicals or intoxication. Poisoning can occur due to workplace heavy metal exposure or chemicals ¹³.

Multiple System Atrophy (MSA): MSA is now an uncommon and deadly neurological condition characterized by a varied mix of parkinson's disease, cerebellum abnormalities, and cognitive impairment. The pathological characteristic has been the formation of accumulated α-synuclein in oligodendrocytes, resulting in glial cytoplasmic inclusion, defining MSA as a synucleinopathy alongside dementia.

Before clinical trials, pre-clinical modeling was utilized for several years to explore the mechanisms that underlie MSA development, discover new therapeutic targets, and verify the most effective drugs. Such systems were first created to mimic coupled nigral and striatal degradation with toxic substances used to simulate Parkinson's and Huntington's disease. Autonomic abnormalities occur as the initial sign in a substantial proportion of MSA cases, in either conjunction with it or independently of motor symptoms ¹⁴.

Progressive Supranuclear Palsy (PSP): The pathological substances of the latest entity of progressive supranuclear palsy (PSP), also recognized as Steele-Richardson-Olszewski syndrome, were identified as immense degeneration of subcortical neurofibrillary primarily found throughout the subthalamic nucleus, globus pallidus, cerebellar dentate nucleus, and substantia nigra. The clinical manifestations of such PSP subgroups are particularly distinct during the first 2 years after onset.

It has still been regarded as the typical and most common clinical manifestation of PSP-tau disease, accounting for 50% more than PSP patients with post-mortem diagnoses. PSP-P has been the second most prevalent form, accounting for up to one-third of all PSP occurrences. PSP-PAGF, cortical PSP variations (PSP-CBS, PSP-PNFA, PSP-bvFTD), and recently discovered PSP-C are all uncommon, accounting for fewer than 5% of all PSP instances. Anecdotal data from published studies suggests that zolpidem, a GABA agonist, can enhance motor skills, dysarthria, and visual problems. Selective serotonin reuptake inhibitors (SSRIs) are excellent treatments for depression, obsessive-compulsive disorder, and mood changes, but they may exacerbate apathy. In people with PNFA, memantine can give symptomatic relief ¹⁵.

Ayurvedic Treatment Favoured Over Prescription Medications: Ethnopharmacology, a knowledge-driven method of drug development, plays a part in drug development centered on natural or conventional awareness of the pharmaceutical or toxicological effects in the human population from animals, plants, and fungi ¹⁶. Over 119 commercially accepted medicines are actually extracted from medicinal herbs. Of these, 74 percent have been identified through chemical detection of the components necessary for patient therapeutic use. Such 119 herbal medicines are made commercially from more than 90 plant species. With more than 25,000 organisms on the planet, their comprehensive study will produce more effective medicines against common viruses ¹⁷.

Ethno-pharmacological method for drug research is found to be highly effective for developing new drugs ranging from digitalis to vincristine. The most critical step in identifying medicines from plant sources is choosing the most appropriate materials based on ethnomedicinal and ethnobotanical applications. Table 1 shows some medicinal herbs widely used for their neuroprotective impact. Also, various plants which show neuroprotective activity are listed in Fig. 2.

FIG. 2: MEDICINAL PLANTS UTILIZED IN THE TREATMENT OF NEUROLOGICAL DISORDERS

TABLE 1: MEDICINAL HERB WITH NEUROPROTECTIVE MECHANISM OF ACTION

Aloe vera: Aloe vera is a perennial, evergreen, and succulent herb grown worldwide, particularly in medicinal and agricultural applications. It consists of aloenin, aloe resin, aloe emodin, aloin A, aloin B and chrysophanol ^{23, 24}. Aloe-emodin is stated to boost memory deficits in mice caused by scopolamine ²⁵. The utilization of aloin as an alternative treatment for vascular complications has proven to lower reactive species and minimize calcium ions + output, which really is liable for neurons depolarization and mortality ²⁶. Aloe vera gel displayed anti-inflammatory and antioxidant effects once administered to rats with an injury to the sciatic nerve ²⁷.

Terminalia chebula: In ayurvedic medicines, Terminalia chebula (Combretaceae, widely known as Haritaki) is being utilized to show neuroprotective behaviour. It constitutes of chebuloside (glycosides), gallic acid, ellagic acid, chebulinic acid and chebulagic acid ^{28, 29}. The fruit pericarp constitutes Triphala, commonly utilized in the formulations of ayurveda. Fructus chebulae, fruit extract (methanolic -70 percent), has indeed been illustrated by protecting from neuronal degeneration to rescue brain ischemia. Promising findings were demonstrated in-vivo and in-vitro studies ³⁰. After treatment with the extract, microglial death, lower concentrations of cellular nitric oxide, and MDA (malondialdehyde) are reported. An interruption of oxidative and inflammatory pathways may be the fundamental theory. Its constituents have already shown their impacts on specific sites by providing neuroprotective action in several cells ^{31, 32}.

Bacopa monnieri: Bacopa monnieri is a unique herbal herb belonging to family Scrophulariaceae. It is a neuronal tonic that enhances intelligence and intellect and has a cognitive function effect ^{33, 34}. Its formulation consisting of 43 percent dry leaf extract, with 20 percent bacoside, reduced the generation of reactive oxygen species and 8-iso-PFG2α and thus reducing the stress of oxidation incited by amyloid peptide, H₂O₂ and basal in the studies on rat ³⁵.

In a different study, the dosage-related increases in activities of peroxidase of glutathione, catalase, and superoxide dismutase in the hippocampus, striatum and cerebral cortex were observed as with Bacopa monnieri extract (82 ± 0.5 percent) once orally administered in the concentrations of 5 and 10 mg per kg ³⁶. Bacopa monnieri increases memory and cognitive decline in rats once taken orally. Immunohistology of superoxide dismutase and histological changes were reported in the hippocampus (CA1 area) ³⁷. The 5 percent (w/w) saponins extract comprises bacopaside I, bacopaside II, bacopasaponin C, bacopasaponin X and bacoside demonstrates enhanced cognitive capacity in model of disorder of Alzheimer's and neuroprotective effects ^{38, 39}. Bacoside-treated rats showed significant improvements in the grades of antioxidants (enzymatic and nonenzymatic), suggesting that the Bacopa monnieri antioxidants state of the mouse brain is strengthened by the plant ⁴⁰. Bacopa monnieri extracts inhibited the development of oxygen radicals concentrations and suggested crucial security in dopaminergic cytotoxicity (N27 cell lines) mediated by 3-nitropropionic acid. Extract of plants with 55 percent of bacosides showed a protective effect on the memory obstruction caused by ischemia and decreased the size of the ischemic brain infarct (ISB) ⁴¹. In addition, it enhanced the effect of catalase activity and reduced peroxidation of lipid and activity of nitrate. Cultures of neurons on treatment with Bacopa monnieri, defended neurons against cell toxicity caused by β-amyloid ⁴².

The extract shielded cultured cells from glutamate-induced excitotoxicity because glutamate-medium toxicity could not be suppressed. The plant extract showed a decline in the action of lipoxygenase and peroxidation of lipid induced by hydrogen peroxide in Alzheimer's animal illness model (Bl6 mice) ⁴³. Bacopa monnieri induces neuroprotective functions and decreases β-amyloid residues in the same model. The extract has also demonstrated a beneficial impact on Parkinson's disorder caused by rotenone in cell lines of PC-12 ⁴⁴.

Asparagus racemosus: Asparagus racemosus methanol extracts reduced cytokine degrees, malondialdehyde (as the indicator for peroxidation production), and nitrous oxides with essential increases in glutathione, superoxide dismutase, and catalase. Its root extract (100 mg per kg) has healed neurodegeneration (specific to region) and showed a dosage-dependent increase in memory following histopathological studies in albino rats ⁴⁵. There has been a marked reduction in the duration of the transfer period and a major increase in AchE (acetylcholinesterase) in histopathological recognition indicating neuroprotective, cholinergic and antioxidant characteristics of Asparagus racemosu ⁴⁶. EuMil (pharmaceutical formulation) has also been used to rebuild a difference in the amount of dopamine, 5-hydroxytryptamines, and nor-adrenaline (100 mg per kg per oral for fourteen days) containing standard extracted Asparagus racemosus for stress-related issues, has been found ⁴⁷.

The results in levels of growth factor of pro-brain, NCF (nerve growth factor), glutathiones, glutathione disulfide, malondialdehyde, lactic dehydrogenase, and cell viability studies were significant together for Asparagus racemosus and Withania somnifera ⁴⁸. Ovariectomized female Wistar rats demonstrated a substantial increase in the levels of sex hormones (ERα and ERβ), as well as an improvement of neurotrophic input variables (brain-derived), in the region of the frontal cortex and hippocampus. A high expression of sex hormones and an increase in brain-related neurotrophic control factors can be supplied as evidence for the protective effect of an Asparagus racemosus ethanol extract ^{49, 50}. A substantial benefit is observed just after Mentat supplementation (BR-16A), which includes an Asparagus racemosus leading to pentylene-tetrazole threshold reduction in rats and mice caused by the withdrawal of ethanol. For the neuroprotective effect in Alzheimer’s, sarsasapogenin, saponin (steroidal) of Asparagus racemosus, was researched ⁵¹. The notable impairment on acetylcholinesterase, beta-secretase 1, monoamine oxidase-B and butyrylcholinesterase, main enzymes relevant to Alzheimer's pathophysiology, has been demonstrated by sarsasapogenin. Sarsasapogenin had an immense protective effect on cells of PC12 at the time of cytotoxic effects interceded by H₂O₂ and Aβ42 in the study. These findings indicated that sarsasapogenin might be used to treat various pathogenic components of Alzheimer’s as a multiple target-driven ligand and as a rational leading agent ⁵².

Foeniculum vulgare: Foeniculum extract decreased amnesia and memory losses in aging-induced mice. Foeniculum vulgare extract has shown acetylcholine inhibition and has substantially increased the duration in the rodents in the model of exteroceptive behavioural ⁵³. Fennel volatile oils exposure reduces anxiety and depression caused by beta-amyloid (1-42) and suggests that additional clinical usage can occur ⁵⁴. In the experimental model of Foeniculum vulgare, there have been enhancements to Parkinson’s ⁵⁵. Therapeutically, intake of fennel in overweight females lowered body mass, reduced serum Aβ proteins, and improved brain abilities ⁵⁶. The expression patterns of oxidant markers of stress (Peroxiredoxin-6 and dismutase of superoxide), an isoform of APP (695 and 770), and the anatomical degradation of neural cells caused by Pb were also enhanced ⁵⁷.

Azadirachta indica: Azadirachta indica has been shown to minimize neurotoxicity induced by cisplatin in rats, frequently referred to as Neem in northern India, and has a protective role on hypoperfusion and reperfusion of ischemia in cerebral cortex ^{58, 59}. In Parkinson-induced functionally impaired individuals, extracts were proven to be neuroprotective, anti-apoptotic, and anti-oxidative ^{60, 61}. A standard indica leaf (complete bitterness 4.3 percent), as demonstrated in anti-apoptotic, antioxidant, and anti-inflammatory research, was neuroprotective in the significant injury of nerves in rats ⁶².

Picrorhiza kurroa: Ayurvedic plant, Picrorhiza kurroa, seems to have a potential for vitiligo photochemotherapy. Picrorhiza kurroa, apocynin is seen to be in-vivo neuroprotective. In an animal model of colitis induced chemically, this also demonstrates a preventive role ^63-64. It facilitates long-term memory rehabilitation, aids in hippocampal neuroprotective effects, and decreases the activation by the glial cells after transient globalized brain ischemia in rats. Numbers of significance in plasma (C_max) are 502, 104, 244 ng/ml with a half-life of six, eight, and fourteen hours, respectively, of apocynin, picrosides II and I ^{65, 66}. Picrorhiza kurroa often avoids memory impairment by hindering the activation of NLRP3 inflammatory and the expression of BACE1 in 5xFAD mouse ⁶⁷. Plant iridoid medicinal attributes in diseases such as alzheimer's disorders have lately been assessed separately ^{68, 69}.

Berberis aristata: Berberine has already been demonstrated to provide neuroprotection by Nrf2 increased expression and antioxidant activity and stimulate Akt /PI3K signalling in SH-SY5Y cells to relieve the rotenone-mediated cell toxicity. In mouse models of Alzheimer’s, neuroprotective activities of berberine were also reported ^{70, 71}. The beneficial role of Berberine nanostructures towards neurodegenerative changes triggered by LPS was demonstrated ⁷². Berberine gives neuroprotective effects by blocking inflammatory cytokines in the treatments of cerebral ischemia ^{73, 74}. The underlying proprieties of the mediated CA1 neurons of the Aß neuroinflammation were changed, berberine also showed a preventive role. Several forms berberine neurons are covered and recently updated. Authors considered it to be a possible contender to fight neurological disorders ^{75, 76}.

Withania somnifera: Withania somnifera, also recognized as Ashwagandha, is also an herbal medication. It improves memory capacity, is an immune booster, is neuroprotective, and shows anti-stress, antioxidant, and anti-inflammatory action. Raut et al. researched the dosage tolerance, protection, and behaviour of Withania somnifera and proposed a mean dose tolerance of 750–1250 mg per day ^{77, 78}. Withania somnifera acts on NADPH-d by hindering corticosterone secretion and stimulating choline acetyltransferases which enhance serotonin in the hippocampus. Withania somnifera active ingredients like withanolide VI, withanolide IV and withanolide A, can repair the post- and pre-synapses and include neural axons and dendrites regeneration ⁷⁹. Many species of plants have been used to cure various diseases, and their medicinal effect is demonstrated through extracts as a raw and semi-purified types. The anti-stress behaviour of W. somnifera derivatives treatment in Wistar rats and psychological distress caused by distortions were shown in study ⁸⁰.

Acorus calamus: Acorus calamus Linn. (Acoraceae), commonly called Vacha in Sanskrit, seems to be an aromatic mid-term perennial herb used in the Ayurveda medical systems. The rhizomes of the vegetation are brown, circular, bent, and have a small nod. The leaves have a sword-like shape that is considerably thicker and has curved borders ⁸¹.

The calamus oil extracted from the rhizome were tested for MES, minimal clonic seizure (MCS), and pentylenetetrazol (PTZ), models at various dosages.  At 300 mg/kg, oil was found to be neurotoxic, despite its effectiveness in the MCS testing at 6 Hz. The oil has been shown to have a protection index of 4.65 ⁸². The open field test (OFT) was used to assess the anxiolytic effect of A. calamus tensarin medication in mice. At each of the three dosing levels (50, 100, and 200 mg/kg). An increase in rearing, passage number, and duration employed by mice provided an anxiolytic effect in a dose-dependent manner ⁸³.

The ethanolic extract was tested for memory and learning activities (doses of 25, 50, and 100 mg/kg,). Male levels were employed as participants using the shuttle box and Y maze test. The results revealed an increase in evidence of spatial recognition ⁸⁴. It also can potentially increase dopaminergic neuron activity by boosting external dopamine levels and tyrosine hydroxylase expression in substanianigra, and hence may contribute to Parkinson's disease. This also boosts DJ-1 expression of genes throughout the striatum, making it neuroprotective against Parkinson's disease ⁸⁵.

Effects of Medicinal Plant on Learning and Memory: Memory is a person's ability to remember perceptual stimulation, activities, details, and so on., sustain these across a short and long period , and retrieve the same as needed at a subsequent time. Learning is just the act of gaining information more about the environment, and memory may be described as storing the knowledge gained that could be recalled if or when needed ⁸⁶. Memory disruptions may vary from moderate to extreme and gradual or instant. Most studies have shown that learning and memory play a key role in the cholinergic system. Reduced cholinergic neurons and decreased development of choline acetyltransferase in the hippocampus and cerebral cortex are associated with reports of Alzheimer's disease (AD) ⁸⁷. Plants involved in learning and memory are shown below in Table 2.

TABLE 2: PLANT USED FOR LEARNING AND MEMORY

Other Plants: Several species used in conventional neurological condition treatments have to be investigated phytochemically and compared with current studies. The listing of species with identified neuroprotective activity is given in Table 3.

TABLE 3: HERBAL PLANTS HAVING POTENTIAL FOR NEUROPROTECTIVE ACTION

CONCLUSION: The use of herbal medicines has been gaining much attention over many years for their therapeutic value. Herbal plants have been used to treat and manage various ailments from ancient times due to their economic availability and lesser side effects than conventional anti-parkinsonian drugs. Recent findings have reported that various plants like Acorus calamus, Aloe vera, Azadirachta indica, Asparagus racemosus, Bacopa monnieri, Terminalia chebula, and Withania somnifera are beneficial in preventing the neurodegeneration in PD and in AD. The active constituent’s present in the plant, like Alkaloids, Polysaccharides, Vitamins, Tannins, Phenolic acid, and Flavonoids, are well-known antioxidants and can prevent oxidative damage to the neurons in the substantial nigra and other parts of the brain cortex. Apart from preventing neuronal damage, some plant constituents can enhance the synthesis and secretion of dopamine and acetylcholine, as required in PD and AD. In the current review, plants used for neurodegenerative diseases have been discussed along with their active constituents. Various phytoconstituents and derivatives of plant species showed the beneficial role of neurodegenerative diseases. Although several studies have reported the utility and value of herbal plants in the therapy of neurodegenerative disorders, there are still several unanswered questions regarding their efficacy in neurodegenerative disorders. Since the presence of bioactive compounds is the major concern for the therapy of neurological disorders to establish the exact mechanism of medicinal plants in neuronal damage and protection, further In-vivo pre-clinical studies should be designed to understand their actual mechanism in the prevention of neurodegeneration.

Disclosure Statement: The authors report no conflict of interest.

Funding: This research did not receive any specific grant from the public, commercial, or not-for-profit funding agencies.

ACKNOWLEDGMENT: The authors are thankful for (Dr.) Sudhir Kumar Mishra, Assistant Professor of SGT University, Gurugram, for his guidance and support.

REFERENCES:

1. Brown RC, Lockwood AH and Sonawane BR: Neurodegenerative diseases: an overview of environmental risk factors. Environ Health Perspectives 2005; 1250-6.
2. Mattson MP: Metal‐catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders. Annals of the New York Academy of Sciences 2004; 37-50.
3. Mosconi L, Mistur R, Switalski R, Brys M, Glodzik L, Rich K, Pirraglia E, Tsui W, De Santi S and De Leon MJ: Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease. Neurology 2009; 513-20.
4. Joshi VK, Joshi A and Dhiman KS: The Ayurvedic Pharmacopoeia of India, development and perspectives. Journal of Ethnopharmacology 2017; 32-8.
5. Hassan MA, Balasubramanian R, Masoud AD, Burkan ZE, Sughir A and Kumar RS: Role of medicinal plants in neurodegenerative diseases with special emphasis to Alzheimer’s. Phytomedicine 2014; 454-62.
6. Saroya AS and Singh J: Pharmacotherapeutic potential of natural products in neurological disorders. Springer Singapore 2018; 19.
7. Benedetti F, Bernasconi A and Pontiggia A: Depression and neurological disorders. Current Opinion in Psychiatry 2006; 14-8.
8. Shulman JM and De Jager PL: Evidence for a common pathway linking neurodegenerative diseases. Nature Genetics 2009; 1261-2.
9. DeLisi LE, Szulc KU, Bertisch HC, Majcher M and Brown K: Understanding structural brain changes in schizophrenia. Dialogues in Clinical Neuroscie 2022; 1.
10. Curatolo P, D'Agati E and Moavero R: The neurobiological basis of ADHD. Italian Journal of Pediatrics 2010; 1-7.
11. McColgan P and Tabrizi SJ: Huntington's disease: a clinical review. European J of Neurology 2018; 24-34.
12. Ashizawa T and Xia G: Ataxia. Continuum: Lifelong Learning in Neurology 2016; 22 (4): 1208.
13. Meissner WG, Fernagut PO, Dehay B, Péran P, Traon AP, Foubert‐Samier A, Lopez Cuina M, Bezard E, Tison F and Rascol O: Multiple system atrophy: recent developments and future perspectives. Move Disorders 2019; 1629-42.
14. Ling H: Clinical approach to progressive supranuclear palsy. Journal of Movement Disorders 201; 3.
15. Cordell GA and Colvard MD: Some thoughts on the future of ethnopharmacology. J of Ethnopharma 2005; 5-14.
16. Dutta T, Nandy S and Dey A; Urban ethnobotany of Kolkata, India: a case study of sustainability, conservation and pluricultural use of medicinal plants in traditional herbal shops. Environment Development and Sustainability 2022; 1207-40.
17. Wang D, Yuan X, Liu T, Liu L, Hu Y, Wang Z and Zheng Q: Neuroprotective activity of lavender oil on transient focal cerebral ischemia in mice. Molecules 2012; 9803-17.
18. Sancheti S, Um BH and Seo SY: 1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucose: A cholinesterase inhibitor from Terminalia chebula. South African J of Botan 2010; 285-8.
19. Chatterji N, Rastogi RP and Dhar ML: Chemical examination of Bacopa monniera Wettst: part II—the constitution of bacoside A. Indian J of Chem 1965; 24-9.
20. Joshi H and Parle M: Cholinergic basis of memory-strengthening effect of Foeniculum vulgare Journal of Medicinal Food 2006; 413-7.
21. Jayaprakasam B, Padmanabhan K and Nair MG: Withanamides in Withania somnifera fruit protect PC‐12 cells from β‐amyloid responsible for Alzheimer's disease. Phytotherapy Research 2010; 859-63.
22. Saleem R, Faizi S, Deeba F, Siddiqui BS and Qazi MH: Anthrones from Aloe barbadensis. Phytochemistry 1997; 1279-82.
23. Speranza G, Gramatica P, Dadá G, Manitto P. Aloeresin C, a bitter C, O-diglucoside from Cape Aloe. Phytochemistry 1985; 1571-3.
24. Tao L, Xie J, Wang Y, Wang S, Wu S, Wang Q and Ding H: Protective effects of aloe-emodin on scopolamine-induced memory impairment in mice and H₂O₂-induced cytotoxicity in PC12 cells. Bioorganic & Medicinal Chemistry Letters 2014; 5385-9.
25. Chang R, Zhou R, Qi X, Wang J, Wu F, Yang W, Zhang W, Sun T, Li Y and Yu J: Protective effects of aloin on oxygen and glucose deprivation-induced injury in PC12 cells. Brain Research Bulletin 2016; 75-83.
26. Guven M, Gölge UH, Aslan E, Sehitoglu MH, Aras AB, Akman T and Cosar M: The effect of Aloe vera on ischemia Reperfusion injury of sciatic nerve in rats. Biomedicine & Pharmacotherapy 2016; 201-7.
27. Kundu AP and Mahato SB: Triterpenoids and their glycosides from Terminalia chebula. Phytochemistry 1993; 999-1002.
28. Lee DY, Kim HW, Yang H and Sung SH: Hydrolyzable tannins from the fruits of Terminalia chebula Retz and their α-glucosidase inhibitory activities. Phytochemistry 2017; 109-16.
29. Gaire BP and Kim H: Neuroprotective effects of Fructus Chebulae extracts on experimental models of cerebral ischemia. Journal of Traditional Chinese Medicine 2014; 69-75.
30. Kim HJ, Kim J, Kang KS, Lee KT and Yang HO: Neuroprotective effect of chebulagic acid via autophagy induction in SH-SY5Y cells. Biomol Ther 2014; 275-281.
31. Shen YC, Juan CW, Lin CS, Chen CC and Chang CL: Neuroprotective effect of Terminalia chebula extracts and ellagic acid in Pc12 cells. Afr J Tradit Complement Altern Med 2017; 22-30.
32. Song JH, Shin MS, Hwang GS, Oh ST, Hwang JJ and Kang KS: Chebulinic acid attenuates glutamate-induced HT22 cell death by inhibiting oxidative stress, calcium influx and MAPKs phosphorylation. Bioorganic & Medicinal Chemistry Letters 2018; 249-53.
33. Sukumaran NP, Amalraj A and Gopi S: Neuropharmacological and cognitive effects of Bacopa monnieri (L.) Wettst–A review on its mechanistic aspects. Complementary Therapies in Medicine 2019; 68-82.
34. Menghini L, Ferrante C, Leporini L, Pintore G, Chiavaroli A, Shohreh R, Recinella L, Orlando G, Vacca M and Brunetti L: A natural formulation increases brain resistance to oxidative stress. European Journal of Medicinal Plants 2014; 171-82.
35. Bhattacharya SK, Bhattacharya A, Kumar A and Ghosal S: Antioxidant activity of Bacopamonniera in rat frontal cortex, striatum and hippocampus. Phytotherapy Research 2000; 174-9.
36. Khan MB, Ahmad M, Ahmad S, Ishrat T, Vaibhav K, Khuwaja G and Islam F: Bacopa monniera ameliorates cognitive impairment and neurodegeneration induced by intracerebroventricular-streptozotocin in rat: behavioral, biochemical, immunohistochemical and histopathological evidences. Metabolic Brain disease 2015; 115-27.
37. Shinomol GK, Mythri RB and Srinivas Bharath MM: Bacopa monnieri extract offsets rotenone-induced cytotoxicity in dopaminergic cells and oxidative impairments in mice brain. Cellular and Molecular Neurobiology 2012; 455-65.
38. Uabundit N, Wattanathorn J, Mucimapura S and Ingkaninan K: Cognitive enhancement and neuroprotective effects of Bacopa monnieri in Alzheimer's disease model. Journal of Ethnopharmacology 2010; 26-31.
39. Anbarasi K, Vani G, Balakrishna K and Devi CS: Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats. Life Sciences 2006; 1378-84.
40. Saraf MK, Prabhakar S and Anand A: Neuroprotective effect of Bacopa monniera on ischemia induced brain injury. Pharmacology Biochem and Behavior 2010; 192-7.
41. Limpeanchob N, Jaipan S, Rattanakaruna S, Phrompittayarat W and Ingkaninan K: Neuroprotective effect of Bacopa monnieri on beta-amyloid-induced cell death in primary cortical culture. Journal of Ethnopharmacology 2008; 112-7.
42. Swathi G and Rajendra W: Protective role of Bacopa monnieri on induced Parkinson’s disease with particular reference to Catecholamine system. Int J Pharm Pharm Sci 2014; 379-382.
43. Ramaiah CV and Rajendra W: Protective role of Bacopa monnieri against Rotenone-induced Parkinson’s disease in PC 12 cell lines. Int J of Phytomedicine 2017; 219-22.
44. Ahmad MP, Hussain A, Siddiqui HH, Wahab S and Adak M: Effect of methanolic extract of Asparagus racemosus Willd. on lipopolysaccharide induced-oxidative stress in rats. Pak J Pharm Sci 2015; 509-13.
45. Saxena G, Singh M, Meena P, Barber S, Sharma D, Shukla S and Bhatnagar M: Neuroprotective effects of Asparagus racemosus Linn root extract: an experimental and clinical evidence. Annals of Neurosciences 2010; 57-63.
46. Parihar MS and Hemnani T: Experimental excitotoxicity provokes oxidative damage in mice brain and attenuation by extract of Asparagus racemosus. Journal of Neural Transmission 2004; 1-2.
47. Ven Murthy MR, K Ranjekar P, Ramassamy C and Deshpande M: Scientific basis for the use of Indian ayurvedic medicinal plants in the treatment of neurodegenerative disorders: 1. Ashwagandha. Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Central Nervous System Agents) 2010; 238-46.
48. Sarbishegi M, Heidari Z, Mahmoudzadeh-Sagheb H, Valizadeh M and Doostkami M: Neuroprotective effects of Withaniac oagulans root extract on CA1 hippocampus following cerebral ischemia in rats. Avicenna Journal of Phytomedicine 2016; 399.
49. Sarbishegi M, Heidari Z, Mahmoudzadeh-Sagheb H, Valizadeh M and Doostkami M: Neuroprotective effects of Withaniacoagulans root extract on CA1 hippocampus following cerebral ischemia in rats. Avicenna Journal of Phytomedicine 2016; 399.
50. Pahwa P and Goel RK: Ameliorative effect of Asparagus racemosus root extract against pentylenetetrazol-induced kindling and associated depression and memory deficit. Epilepsy & Behavior 2016; 196-201.
51. Kulkarni SK and Verma A: Protective effect of BR-16A (Mentat), a herbal preparation on alcohol abstinence-induced anxiety and convulsions. Indian Journal of Experimental Biology 1993; 435-9.
52. Kashyap P, Muthusamy K, Niranjan M, Trikha S and Kumar S: Sarsasapogenin: A steroidal saponin from Asparagus racemosus as multi target directed ligand in Alzheimer’s disease. Steroids 2020; 1085-29.
53. Cioanca O, Hancianu M, Mircea C, Trifan A and Hritcu L: Essential oils from Apiaceae as valuable resources in neurological disorders: Foeniculi vulgare Industrial Crops and Products 2016; 51-7.
54. Lal UR and Lal S: Bioactive molecules from Indian medicinal plants as possible candidates for the management of neurodegenerative disorders. Bioactive Compounds in Nutraceutical and Functional Food for Good Human Health 2020; 7.
55. Nemati M, Hemmati AA, Najafzadeh H, Mansouri MT and Khodayar MJ: Evaluation of the effects of Foeniculum vulgare essence on behavioral-motor disorders of Parkinson’s disease induced by reserpine in ovariectomized and non ovariectomized rats. Jundishapur Journal of Natural Pharmaceutical Products 2018; 13.
56. Bhatti S, Ali Shah SA, Ahmed T and Zahid S: Neuroprotective effects of Foeniculum vulgare seeds extract on lead-induced neurotoxicity in mice brain. Drug and Chemical Toxicology 2018; 399-407.
57. Xiang X, Wu L, Mao L and Liu Y: Anti oxidative and anti apoptotic neuroprotective effects of Azadirachta indica in Parkinson induced functional damage. Molecular Medicine Reports 2018; 7959-65.
58. Yanpallewar S, Rai S, Kumar M, Chauhan S and Acharya SB: Neuroprotective effect of Azadirachta indica on cerebral post-ischemic reperfusion and hypoperfusion in rats. Life Sciences 2005; 1325-38.
59. Kandhare AD, Mukherjee AA and Bodhankar SL: Neuroprotective effect of Azadirachta indica standardized extract in partial sciatic nerve injury in rats: Evidence from anti-inflammatory, antioxidant and anti-apoptotic studies. EXCLI Journal 2017; 546.
60. Moneim AE: Azadirachta indica attenuates cisplatin-induced neurotoxicity in rats. Indian Journal of Pharmacology 2014; 316.
61. Bedi KL, Zutshi U, Chopra CL and Amla V: Picrorhizakurroa, an ayurvedic herb, may potentiate photochemotherapy in vitiligo. J of Ethnoph 1989; 347-52.
62. Simonyi A, Serfozo P, Lehmidi TM, Cui J, Gu Z, Lubahn DB, Sun AY and Sun GY: The neuroprotective effects of apocynin. Frontiers in Bioscie (Elite Edition) 2012; 2183.
63. Marín M, Giner RM, Ríos JL and Recio MC: Protective effect of apocynin in a mouse model of chemically-induced colitis. Planta Medica 2013; 392-1400.
64. Romanini CV, Ferreira ED, Soares LM, Santiago AN, Milani H and de Oliveira RM: 4 ‐ hydroxyl ‐ 3 ‐ methoxy ‐ acetophenone ‐ mediated long‐lasting memory recovery, hippocampal neuroprotection, and reduction of glial cell activation after transient global cerebral ischemia in rats. Journal of Neuroscience Research 2015; 1240-9.
65. Zahiruddin S, Khan W, Nehra R, Alam MJ, Mallick MN, Parveen R and Ahmad S: Pharmacokinetics and comparative metabolic profiling of iridoid enriched fraction of Picrorhizakurroa an Ayurvedic Herb. Journal of Ethnopharmacology 2017; 157-64.
66. Kim N, Do J, Ju IG, Jeon SH, Lee JK and Oh MS: Picrorhizakurroa prevents memory deficits by inhibiting NLRP3 inflammasome activation and BACE1 expression in 5xFAD mice. Neurotherapeutics 2020; 189-99.
67. Morikawa T, Nakanishi Y, Inoue N, Manse Y, Matsuura H, Hamasaki S, Yoshikawa M, Muraoka O and Ninomiya K: Acylated iridoid glycosides with hyaluronidase inhibitory activity from the rhizomes of Picrorhizakurroa Royle ex Benth. Phytochemistry 2020; 1121-85.
68. Dinda B, Dinda M, Kulsi G, Chakraborty A and Dinda S: Therapeutic potentials of plant iridoids in Alzheimer's and Parkinson's diseases: A review. European Journal of Medicinal Chemistry 2019; 185-99.
69. Tavakkoli A, Iranshahi M, Hasheminezhad SH, Hayes AW and Karimi G: The neuroprotective activities of natural products through the Nrf2 upregulation. Phytotherapy Research 2019; 2256-73.
70. Wu X, Liu X, Yang L and Wang Y: Berberine Protects against Neurological Impairments and Blood-Brain Barrier Injury in Mouse Model of Intracerebral Hemorrhage Neuroimmunomodulation 2021; 1-0.
71. Soudi SA, Nounou MI, Sheweita SA, Ghareeb DA, Younis LK and El-Khordagui LK: Protective effect of surface-modified berberine nanoparticles against LPS-induced neurodegenerative changes: a pre-clinical study. Drug Delivery and Translational Research 2019; 906-19.
72. Maleki SN, Aboutaleb N and Souri F: Berberine confers neuroprotection in coping with focal cerebral ischemia by targeting inflammatory cytokines. Journal of Chemical Neuroanatomy 2018; 54-9.
73. Haghani M, Shabani M and Tondar M: The therapeutic potential of berberine against the altered intrinsic properties of the CA1 neurons induced by Aβ neurotoxicity. European J of Pharmacology 2015; 82-8.
74. Fan D, Liu L, Wu Z and Cao M: Combating neurodegenerative diseases with the plant alkaloid berberine: molecular mechanisms and therapeutic potential. Current Neuropharmacology 2019; 563-79.
75. Lin X and Zhang N: Berberine: Pathways to protect neurons. Phytotherapy Research 2018; 1501-10.
76. Khan S, Malik F, Suri KA and Singh J: Molecular insight into the immune up-regulatory properties of the leaf extract of Ashwagandha and identification of Th1 immunostimulatory chemical entity. Vaccin 2009; 6080-7.
77. Raut AA, Rege NN, Tadvi FM, Solanki PV, Kene KR, Shirolkar SG, Pandey SN, Vaidya RA, Vaidya AB. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers. J of Ayurveda and Integrative Med 2012; 111.
78. Jayaprakasam B, Zhang Y, Seeram NP and Nair MG: Growth inhibition of human tumor cell lines by withanolides from Withania somnifera Leaves Life Sciences 2003; 125-32.
79. Bhatnagar M, Sharma D, Salvi M. Neuroprotective effects of Withania somnifera a possible mechanism. Neurochemical Research 2009; 34 (11): 1975-83.
80. Bhattacharya SK and Muruganandam AV: Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress. Pharmacology Biochemistry and Behavior 2003; 75(3): 547-55.
81. Quraishi A, Mehar S, Sahu D and Jadhav SK: In-vitro mid-term conservation of Acorus calamus via cold storage of encapsulated microrhizome. BABT 2017; 60.
82. Kaushik R, Jain J, Yadav R, Singh L, Gupta D and Gupta A: Isolation of beta-Asarone from Acorus calamus and Evaluation of its Anticonvulsant Activity using MES and PTZ Models in Mice. Pharmacology Toxicology and Biomedical Reports 2017; 3(2).
83. Rauniar GP, Deo S and Bhattacharya SK: Evaluation of anxiolytic activity of tensarin in mice. Kathmandu University Medical Journal (KUMJ) 2007; 188-94.
84. Sharma V, Sharma R, Gautam DS, Kuca K, Nepovimova E and Martins N: Role of Vacha (Acorus calamus) in neurological and metabolic disorders: evidence from ethnopharmacology, phytochemistry, pharmacology and clinical study. Journal of Clinical Medicine 2020; 1176.
85. Paterna JC, Leng A, Weber E, Feldon J and Büeler H: DJ-1 and Parkin modulate dopamine-dependent behavior and inhibit MPTP-induced nigral dopamine neuron loss in mice. Molecular Therapy 2007; 698-704.
86. Joshi H, Megeri K, Bidchol MA and Kulkarni VH: Clerodendron phlomidis Linn improves short term memory of chemically and naturally induced amnesia in mice. Natural Product 2007; 166-70.
87. Kim DH, Yoon BH, Kim YW, Lee S, Shin BY, Jung JW, Kim HJ, Lee YS, Choi JS, Kim SY and Lee KT: The seed extract of Cassia obtusifolia ameliorates learning and memory impairments induced by scopolamine or transient cerebral hypoperfusion in mice. JPS 2007; 82-93.
88. Khalifa AE: Hypericum perforatum as a nootropic drug: enhancement of retrieval memory of a passive avoidance conditioning paradigm in mice. J of Ethnopha 2001; 49-57.
89. Das A, Shanker G, Nath C, Pal R, Singh S and Singh HK: A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba: anticholinesterase and cognitive enhancing activities. Pharmacology Biochemistry and Behavior 2002; 893-900.
90. Ikeya Y, Takeda S, Tunakawa M, Karakida H, Toda K, Yamaguchi T Clerodendronphlomidis Aburada M: Cognitive improving and cerebral protective effects of acylated oligosaccharides in Polygala tenuifolia. Biological and Pharmaceutical Bulletin 2004; 1081-5.
91. Wake G. Court J, Pickering A, Lewis R, Wilkins R and Perry E: CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory. J Ethnopharmacol 2000; 105-14.
92. Lekha G, Kumar BP, Rao SN and Arockiasamy I: Clerodendron phlomidis Mohan K: Cognitive enhancement and Neuroprotective effect of Celastrus paniculatus seed oil (Jyothismati oil) on male Wistar rats. J of Pharmaceutical Science and Techn 2010; 130-8.
93. Bhattacharya S and Haldar PK: Neuropharmacological properties of T, dioica CJNM 2013; 158-63.
94. Singh H, Kaur T, Manchanda S and Kaur G: Intermittent fasting combined with supplementation with Ayurvedic herbs reduces anxiety in middle aged female rats by anti-inflammatory pathways. Biogerontology 2017; 601-14.
95. Sharma A and Kaur G: Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in-vitro BMC Complementary and Alternative Medicine 2018; 1-7.
96. Birla H, Rai SN, Singh SS, Zahra W, Rawat A, Tiwari N, Singh RK, Pathak A and Singh SP: Tinospora cordifolia suppresses neuroinflammation in parkinsonian mouse model. Neuromolecular Medicine 2019; 42-53.
97. SJ RD and Kumar BP: In-silico Screening for Anti-inflammatory Bioactive Molecules from Ayurvedic Decoction, Balaguluchyadikashayam. Current Computer-Aided Drug Design 2020; 435-50.
98. Shukla, Sunil Dutt, Sushma Jain, Kanika Sharma and Maheep Bhatnagar: Stress induced neuron degeneration and protective effects of Semecarpus anacardium and Withania somnifera Dunn. in hippocampus of albino rats. An Ultrastructural Study 2000.
99. Patel NG, Patel KG, Patel KV and Gandhi TR: Validated HPTLC method for quantification of luteolin and apigenin in Premnamucronata Roxb., Verbenaceae. Advances in Pharmacological Sciences 2015; 20-25.
100. Srivastava P, Mohanti S, Bawankule DU, Khan F and Shanker K: Effect of Pluchea lanceolata bioactives in LPS-induced neuroinflammation in C6 rat glial cells. Naunyn-Schmiedeberg's Archiv of Pharma 2014; 119-27.
101. Mundugaru R, Sivanesan S, Udaykumar P, Rao N and Chandra N: Protective effect of Pluchea lanceolata against aluminum chloride-induced neurotoxicity in Swiss albino mice. Pharmacognosy Magazine 2017; 567.
102. Ghosal S, Srivastava RS, Bhattacharya SK and Debnath PK: The active principles of Alhagi pseudalhagi: β–phenethylamine and tetrahydroisoquinoline bases. Planta Medica 1974; 318-26.
103. Singh VP, Yadav B and Pandey VB: Flavanone glycosides from Alhagi pseudalhagi. Phytochemistry 1999; 587-90.
104. Muhammad G, Hussain MA, Anwar F, Ashraf M and Gilani AH: Alhagi: a plant genus rich in bioactives for pharmaceuticals. Phytotherapy Research 2015; 1-3.
105. Asghari MH, Fallah M, Moloudizargari M, Mehdikhani F, Sepehrnia P and Moradi B: A systematic and mechanistic review on the phytopharmacological properties of Alhagi species. Ancient Science of Life 2016; 65.
106. Singh GK, Chauhan SK, Rai G, Chatterjee SS and Kumar V: Potential antianxiety activity of Fumaria indica: A pre-clinical study. Pharmacognosy Magazine 2013; 14.
     

     ---

     How to cite this article:

     Sarfaraz A, Mishra SK, Krishna K and Zoya K: Neurodegenerative disorders: role of medicinal plants in treatment. Int J Pharm Sci & Res 2023; 14(6): 2705-16. doi: 10.13040/IJPSR.0975-8232.14(6).2705-16.

     ---

     All © 2023 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.