TREATMENT STRATEGIES FOR NEURODEGENERATIVE DISEASES THROUGH IMPORTANT MEDICINAL PLANTS USED IN UNANI MEDICINE

TREATMENT STRATEGIES FOR NEURODEGENERATIVE DISEASES THROUGH IMPORTANT MEDICINAL PLANTS USED IN UNANI MEDICINE

Tarana Umar, Rampratap Meena *, Mustehasa, Ghazala Javed and Asim Ali Khan

Central Council for Research in Unani Medicine, 61-65, Institutional Area. Opp. D Block. Janakpuri, Delhi, India.

ABSTRACT: Neurodegenerative diseases (NDs) that are characterized by progressive loss of functioning and structure of neurons are of great burden to the individuals and the society. With several hypotheses, the existent cause still remains a mystery for various NDs in healthcare. Protein degradation, inflammation, oxidative stress, environmental factor, mitochondrial defects, abnormal protein accumulation in neuron and familial history are amongst the commonly studied environmental causative factors for NDs. These disorders are a significant cause of disability and mortality, and consequently increasing life spans is one of the key challenges for medical research. The excessive treatment cost has led the world to move to alternative therapy with lower cost and minimal side effects compared to conventional treatments. Medicinal plants have been used for treating various diseases since ancient times in India. Medicinal plants used in Unani System of Medicine cover most of the NDs. It has defined a huge number of plants with multiple therapeutic benefits. In this review, the role of important medicinal plants, viz., Prunella vulgaris L., Melissa officinalis L., Morinda citrifolia L., Hypericum perforatum Linn., Lycopodium serratum, Polygala tenuifolia Willd., Celastrus paniculatus Willd., Cyperus rotundus L., Ziziphus jujube Mill., Juglans regia L., Withania somnifera (L.) Dunal, Acorus calmus L., Centella asiatica (L.) Urban, Boswellia serrata Roxb. ex Colebr., Ferula asafoetida L., and Zingiber officinale Rosc., on NDs has been discussed. This review highlights the studies carried out on medicinal plants having biological activity to treat several diseases with special reference to ND.

Keywords: Neurodegenerative diseases, Alzheimer’s disease, Medicinal plants, β-amyloid, Acetyl cholinesterase

INTRODUCTION:

Neurodegenerative Diseases: Neurodegenerative disorders are a diversified group of diseases marked by escalating structural and functional degeneration of the central or peripheral nervous system.

Neurodegenerative diseases (NDs) comprising of Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), vascular dementia (VD), frontotemporal dementia, Prion disease, Pick’s disease, brain trauma, progressive supranuclear palsy and spinocerebellar ataxias are illnesses related with significant mortality and morbidity rates ^{1, 2}.

In the course of past decade, substantial improvement has been achieved in understanding the phenomenon of cell death ³ which is a significant characteristic for most of the NDs ⁴. Depending upon the pathways of cell death in these diseases their symptoms and the exacerbations varies and specific mechanisms of cell death requires novel therapeutic strategies. The underlying mechanisms associated with neurodegeneration are not fully understood and the effectiveness of current treatments for NDs is still narrow. Hence, attempts are being made to explore novel biological mechanism of ND models and develop their respective/suitable novel therapeutic strategies.

Fig. 1. Major Neurodegenerative diseases (NDs) comprising of Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), vascular dementia (VD), frontotemporal dementia, Prion disease. Use of natural plant products are being prescribed for treating various ailments. Large-scale researches are being carried out worldwide on different plants. Studies provide promising results of medicinal plants regarding its efficacy for treatment of several diseases such as cognitive problems, ^5-7 gastrointestinal problems ⁸ stroke ⁹ and many others disease. Medicinal plants are rather more economical, have lesser side effects and more therapeutic benefits than allopathic medicine. Medicinal plants play an important role in the Unani system of medicine and have provided numerous Unani Single and Compound drugs. Plants with medicinal benefits are being used for neuroprotection, longevity promotion and cognitive improvement in traditional folklore since a long period of time.

Alzheimer’s disease: NDs primarily includes Alzheimer’s disease (AD), Huntington’s disease (HD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), vascular dementia (VD), etc. AD is amongst the most common source of mental deterioration in healthy population and is a major ND ¹⁰. Pathological signs of AD covers aggregation of beta-amyloid plaques in between the nerve cells and formation of neurofibrillary tangles inside nerve cells by Tau proteins, as the major events of AD ^11-13. Both acetyl cholinesterase enzymes (AChE) and butyrylcholinesterase (BChE) are accountable for the breakdown of neurotransmitter acetylcholine in synaptic region. Reduced levels of acetylcholine in brain have been related to age-related diseases leading to reduction of cognitive power. It is a genetic and sporadic ND that results in non-amnestic cognitive impairment in its less frequent variants and an amnestic cognitive impairment in prototypical presentation.

Medicinal plants used for the treatment of AD include Hypericum perforatum, Prunella vulgaris, Lepidium meyenii, Cyperus rotundus, Lavandula officinalis, Zizyphus jujube, Salvia officinalis, Ginkgo biloba, Melissa officinalis, Panax ginseng C.A. Mey., Morinda citrifolia, Polygala tenuifolia, Lycopodium serratum, Celastrus paniculatus. Prunella vulgaris L. is widely distributed over Europe, China, Japan and Korea. This traditional Korean and Chinese medicine has been employed for treating inflammation, dizziness, headache and eye pain ¹⁴. According to research studies P. Vulgaris has been found to possess various active compounds like ursolic acid, oleic acid, butyric acid, rosmarinic acid and flavonoids. Besides, it also has anti-inflammatory, anti-allergy, antioxidant, antiviral activity and antimicrobial ^{15, 16}.

Melissa officinalis L. also called lemon balm is a lemon scented herb. M. officinalis (Lamiaceae) has been used for over 2000 years as traditional medicine. It has been acclaimed regarding the promotion of long life and memory restoration ¹⁷. The plant leaves consist of phenol carboxylic acids (e.g. rosmarinic acid), showing antiamyloidogenic, antioxidative and antiapoptotic effects and monoterpenes (e.g. citral) having weak anti-AChE activity.

Morinda citrifolia L. is a popular herb. Juice of M. citrifolia is employed as substitute medicine for several diseases like cancer, heart disease, ulcers, arthritis, high blood pressure, diabetes, menstrual problems, atherosclerosis and depression ¹⁸. The fruit and extract have antioxidant, anti-inflammatory and analgesic properties ¹⁹. Ethyl acetate extract of this herb has been shown to prevent oxidative stress and memory deficit induced by amyloid β in mice ²⁰. Further, the treatment with its ethyl acetate, chloroform and butanol extracts reduced AChE activity in brain of scopolamine-treated mice models ¹⁹.

Hypericum perforatum Linn. (St. John’s Wort) shows clinical effects via amelioration of neurological diseases, as antidepressant, wound healing, anti-inflammatory, anti-anxiety and analgesic effects ²¹. Lycopodium serratum commonly called Club moss is a pteridophyte (Lycopodiaceae). This medicinal plant is an active participant of homeopathic preparations for raising memory and learning potential, for treatment of cancer ²², Alzheimer’s disease ²³ and oitis media in children ²⁴. The aforesaid medicinal plant has applications in the treatment of inflammation, fever, schizophrenia, and blood disorders ²⁵. Further, it is reversible, selective and effective inhibitor of AChE. Efficacy of AChE inhibition is comparable or higher than that of standard compounds Donepezil, Tacrine, Galanthamine and physostigmine ²⁶. Genus Lycopodium (Lycopodiaceae), produces a potent therapeutic agent known as huperzine A ²⁷. Huperzine A is a significant candidate for AD treatment. Additional protective effects related to AD involve decrease in glutamate-induced toxicity, mitochondrial dysfunction, protection against Amyloid β-induced oxidative damage and neuronal apoptosis, the regulation of nerve growth factor as well as anti-inflammation ^{28, 29}. Research data reveals Huperzine A significantly increases level of ACh in the rat brain ²⁸.

Polygala tenuifolia Willd. is another plant of medicinal importance, the roots of which are used as a tonic, an expectorant, and a tranquilizer for the treatment and prevention of dementia ^{30, 31}. Its roots are the typical participant in formulae for cognition. This plant have multiplex neuroprotective potential with regard to Alzheimer’s, such as anti-Tau protein,³² anti-Amyloid β aggregation,³³ anti-inflammation,³⁴ antioxidant, anti-neuronal, apoptosis,³⁵ promote neuronal proliferation and improving central cholinergic system ^{36, 37}.

Celastrus paniculatus Willd. (Black Oil Plant): is useful a stimulant nervine tonic, sedative, rejuvenant, diuretic and tranquilizer ³⁸. According to a study report the oral administration of seed oil in rat brain reduced levels of dopamine, noradrenaline and 5-hydroxytryptamine leading to improvement in memory and learning processes. Furthermore, the seed oil was not neurotoxic ³⁹.

Cyperus rotundus L. (Nut Grass) belonging to Cyperaceae –family is also called purple nutgrass or nutsedge. It is a common perennial weed that is widely used as a traditional herbal medicine for analgesic, sedative, antimalarial, antispasmodic, stomach disorders and to alleviate diarrhoea ⁴⁰. Cyperus rotundus L. includes alkaloids, quercetin, flavonoids, kaempferol, tannins, glycosides, starch, chalcones, p-coumaric acid and gallic acid ^{41, 42}.

According to scientific research Cyperus rotundus L. demonstrates acetylcholinesterase inhibitory (AChEI), antioxidant, memory-enhancing and neuroprotective activities ^43-47. Ziziphus jujube Mill. (Chinese Date) fruit is edible and sweet in taste tasting having medicinal properties like soothing effect and anti-grouch properties.

It has been employed for reduction in anxiety and strengthening of spleen, stomach and gastrointestinal system ⁴⁸ in traditional Chinese and Korean medicine.

Inhibition of Cholinesterase Activity: Inducing release of neurotransmitter acetylcholine in brain is one of the treatment ways used for NDs such as AD that may control further decline in higher cognitive function and dementia. ¹⁰ Cholinesterase inhibition is the most accepted treatment strategy for AD that can inactivate the enzyme acetylcholinesterase (AChE) to raise levels of acetylcholine in the brain. Despite production of several synthetic drugs for the treatment of learning and memory disorders, the therapeutic effectiveness is low and is accompanied by undesirable side effects. This has led to an increase in the inclination of people toward traditional medicines. ⁴⁹ Herbs like Juglans regia L., Withania Somnifera (L.) Dunal., Acorus calmus L., Centella asiatica (L.) Urban, Boswellia serrata Roxb. ex Colebr., are used in Unani medicine to enhance memory by clearing the Acetylcholinesterase and β-amyloid plaques, antioxidation and anti-inflammatory activity.

Juglans regia L. (Walnuts) posses a high amount (3.68 mmol/oz) of antioxidants, such as flavonoids, melatonin, phenolic acid (ellagic acid), gamma tocopherol (vitamin E), folate, juglone, selenium, and proanthocyanidins ^50-51. It has various constituents possessing anti-inflammatory and antioxidant effects. A diet with walnuts has been reported to show beneficial effects on memory, anxiety, coordination, learning, motor and locomotor activity gas ⁵¹. Studies demonstrated reduction in oxidative stress both by decreasing free radical levels and by boosting antioxidant defence, thus reducing oxidative damage to lipids and proteins.

Withania somnifera (L.) Dunal. (Winter Cherry) is an evergreen shrub. The apparent properties of this medicinal plant include the potential to ameliorate concentration, mood, and memory, as well as furnish resilience against disease and pathogens ⁵². Traditionally, formulations involving Withania somnifera (L.) Dunal. are used for asthma, ulcers, goiter, and arthritis, insomnia, anxiety and neurological disorders. Acorus calamus L. (Sweet Flag) is a wild plant referred to as a potent medication for enhancing memory in the popular sources of the Iranian traditional medicine 53 and has been suggested for treating AD ^{54, 55}. Centella asiatica (L.) Urban, (Indian pennywort) from the Apiaceae family is used in Ayurvedic medicine and traditional Chinese to enhance memory function ⁵⁶. Extracts of this medicinal plant have been widely known to show mitoprotective and neuronal antioxidant results in-vitro and in-vivo ^{57, 58}.

Oleo-gum resin of Boswellia serrata Roxb. ex Colebr. also called Kundur is popularly used in the Unani system of medicine for various ailments especially skin diseases, rheumatism, dyspepsia, dysentery, haemorrhoids, lung diseases, corneal ulcer and urinary disorders ⁵⁹. Also it is considered as a promising substitute to nonsteroidal anti-inflammatory drug ⁶⁰. Kundur has been used for treating inflammatory diseases in traditional medicine ⁶⁰.

Anti-Inflammatory and Antioxidative Activities: Many medicinal plants are available that exhibit anti-inflammatory activity inhibiting cyclooxygenase-1 (COX-1) that is present around amyloids plaque in microglia. The collection of this enzyme in AD patients in microglia cells may be the cause of local growth in oxidative stress and synthesis of prostaglandin ⁶¹. Plants Ferula assafoetida L., Zingiber officinale Rosc. and Syzygium aromaticum Merr. & L.M. Perry have been shown to possess anti-COX-1 activity. ⁶¹ Ferula assafoetida L. (Asafoetida) has previously been used in traditional medicines for treating diseases like asthma, bronchitis, epilepsy, ulcer, intestinal parasites, antihelminthic influenza, whooping cough, and as a memory enhancer ^62-65.

Further, it possesses neuroprotective, ⁶⁶ antioxidant, ⁶⁷  cancer chemopreventive, ⁶⁸ anticarcinogenesis, ^{68, 69} anti-diabetic, ⁷⁰ relaxant effect, ⁷¹ antimicrobial, ⁷² antifungal, ⁷³ antiviral, ⁷⁴ antispasmodic and hypotensive ⁷⁵ activities. Outcomes of F. asafoetida extract were investigated on learning and memory in rat models by Vijayalakshmi et al. ⁷⁶ Marked improvements of memory score and transfer latency in elevated plus maze model was shown by the extract. Also, increased antioxidant levels and inhibition of cholinesterase levels in the brain were observed.

Hence, the ability of F. asafoetida as memory enhancer may be accredited to acetylcholinesterase inhibition and antioxidation characteristics. Zingiber officinale Rosc. (Dry Ginger) contains gingerol, shogaol, and paradols ⁷⁷. Data from scientific research have shown Z. officinale to possess antioxidant, neuroprotective, acetylcholinesterase inhibitory (AChEI), and memory-improving effects. It displayed anti-COX-1 and free radical scavenging activities that may be due to the presence of prominent phytochemicals: shogaols and gingerols ⁷⁸.

Syzygium aromaticum Merr. & L.M. Perry (Clove) has been used in the traditional medicinal systems owing to its various pharmacological activities. Its antioxidant and antimicrobial properties have led to its use as preservative in many foods ⁷⁹. There are various formulations containing this plant that imparts cognitive improvement. A study was conducted by Hossein M. et al that indicates that clove extract improves mice's learning and memory recall ability in an inverse dose-dependent manner ⁸⁰.

CONCLUSION: Neuronal death and degeneration is the underlying process accountable for clinical manifestations of plenty of different neurological disorders of aging. AD is a chronic ND, considered amongst the most intractable medical problems with large economic and social costs. AD has no proper treatment to cure the disease till date. Medicinal plants depict promise in ND treatment due to active phyto-constituents and their biological activities with cognitive benefits and mechanisms of action. The application of medicinal plants has gained much interest for their therapeutic efficacy for numerous decades. Clinical evidence shows medicinal plants can ameliorate memory and learn in patients with mild-to-moderate AD. Biological and pharmacological studies have been seen for several medicinal plants, such as Prunella vulgaris L., Melissa officinalis L., Morinda citrifolia L., Hypericum perforatum Linn., Lycopodium serratum, Polygala tenuifolia Willd., Celastrus paniculatus Willd., Cyperus rotundus L., Ziziphus jujube Mill., Juglans regia L., Withania somnifera (L.) Dunal, Acorus calmus L., Centella asiatica (L.) Urban, Boswellia serrata Roxb. ex Colebr., Ferula asafoetida L., and Zingiber officinale Rosc. The active components of these plants exhibit one or more properties amongst inhibition of AChE, alteration of Aβ processing, oxidative stress, protection against apoptosis, anti-inflammatory effects, cognitive improvement and neuroprotection. Ultimately the application of medicinal plants for treating ND, specifically AD, and the pharmacological treatment currently used need to be compared for further advancement.

ACKNOWLEDGEMENT: The Authors are thankful to the whole CCRUM team.

CONFLICTS OF INTEREST: Authors declare no conflict of interest.

REFERENCES:

1. Erkkinen MG: Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases. Cold Spring Harb Perspect Biol 2018; 10(4): 033118.
2. Hage-Melim LIS: The Impact of Natural Compounds on the Treatment of Neurodegenerative Diseases. Current Organic Chemistry 2019; 23(3): 335-360.
3. Hengartner MO: The biochemistry of apoptosis. Nature 2000; 407: 770–776.
4. Yuan J and Yankner BA: Apoptosis in the nervous system. Nature 2000; 407: 802–809.
5. Rabiei ZS: Effects of Zizyphus jujube extract on memory and learning impairment induced by bilateral electric lesions of the nucleus basalis of Meynert in rat. Neurochem Res 2014; 39(2): 353-360.
6. Rabiei Z: The effect of pretreatment with different doses of Lavandula officinalis ethanolic extract on memory, learning and nociception. Biomed Aging Pathol 2014; 4(1): 71-76.
7. Rabiei Z: Effect of Cyperus rotundus tubers ethanolic extract on learning and memory in animal model of Alzheimer. Biomed Aging Pathol 2013; 3(4): 185-191.
8. Moradi M: Antispasmodic effects of yarrow (Achillea millefolium) extract in the isolated ileum of rat. Afr J Tradit Complement Altern Med 2013; 10(6): 499-503.
9. Rabiei Z: Effect of dietary olive leaf extract on brain cholesterol, cholesterol ester and triglyceride levels and of brain edema in rat stroke model. Razi J Med Sci 2013; 19(103): 18-25.
10. Umar T and Hoda N: Alzheimer's disease: A Systemic Review of Substantial Therapeutic Targets and the Leading Multi-functional Molecules. Curr Top Med Chem 2017; 17(31): 3370-3389.
11. Karran E and Strooper BD: The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics. Nature Reviews Drug Discovery 2022; 21: 306–318.
12. Umar T: Recent updates in the development of small molecules as potential clinical candidates for Alzheimer's disease: A review. Chemical Biology & Drug Design 2022; 00: 1–8.
13. Kametani F and Hasegawa M: Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's disease. Frontiers in Neuroscience 2018; 12. 10.3389/fnins.2018.00025.
14. Park SJ: The ameliorating effect of the extract of the flower of Prunella vulgaris lilacina on drug-induced memory impairments in mice. Food Chem Toxicol 2010; 48(6): 1671-1676.
15. Ru M: A tyrosine aminotransferase involvedin rosmarinic acid biosynthesis in Prunella vulgaris Sci Rep 2017; 7(1): 4892.
16. Wang SJ: Prunella vulgaris: A Comprehensive Review of Chemical Constituents, Pharmacological Effects and Clinical Applications. Current Pharmaceutical Design 2019; 25: 359-369.
17. Miraj S: A Review Study With an Antioxidant Prospective. J Evid Based Complementary Altern Med 2017; 22(3): 385-394.
18. Assi RA: Morinda citrifolia (Noni): A comprehensive review on its industrial uses, pharmacological activities, and clinical trials. Arabian Journal of Chemistry 2017; 10(5): 691-707.
19. Dewi RT: Quality control standardization of Indonesian noni fruit (Morinda citrifolia) extract and evaluation of their angiotensin-converting enzyme inhibitory activity. Pharmacia 2022; 69(3): 709-717.
20. Muralidharan P: Protective effect of Morinda citrifolia fruits on β-amyloid (25-35) induced cognitive dysfunction in mice: an experimental and biochemical study. Phytother Res 2010; 24(2): 252-258.
21. Alahmad A: Identification of Major Constituents of Hypericum perforatum Extracts in Syria by Development of a Rapid, Simple, and Reproducible HPLC-ESI-Q-TOF MS Analysis and Their Antioxidant Activities. ACS Omega 2022; 7(16): 13475–13493.
22. Paramita P: Evaluation of potential anti-cancer activity of cationic liposomal nanoformulated Lycopodium clavatum in colon cancer cells. IET Nanobiotechnol 2018; 12: 727–732.
23. Xiao XQ: Huperzine A attenuates amyloid beta-peptide fragment 25-35-induced apoptosis in rat cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation. J Neurosci Res 2002; 67(1): 30-6. doi: 10.1002/jnr.10075.
24. Friese KH: The homoeopathic treatment of otitis media in children--comparisons with conventional therapy. Int. J. Clin Pharmacol Ther 1997; 35(7): 296-301.
25. Salim MA: Lycopodium Mitigates Oxidative Stress and Inflammation in the Colonic Mucosa of Acetic Acid-Induced Colitis in Rats. Molecules 2022; 27(9): 2774.
26. Wang H and Tang XC: Anticholinesterase effects of huperzine A, E2020, and tacrine in rats. Zhongguo Yao Li Xue Bao 1998; 19(1): 27-30.
27. Takayama H: Seven new lycopodium alkaloids, lycoposerramines-C,-D,-E,-P,-Q,-S, and-U, from Lycopodium serratum Thunb. Tetrahedron Lett 2002; 43(46): 8307-8311.
28. Zangara A: The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer’s disease. Pharmacol Biochem Behav 2003; 75(3): 675-686.
29. Zhang HY: Potential therapeutic targets of huperzine A for Alzheimer’s disease and vascular dementia. Chem Biol Interact 2008; 175(1-3): 396-402.
30. Jiang N: Protective Effects and Mechanism of Radix Polygalae against Neurological Diseases as Well as Effective Substance. Front. Psychiatry 2021; 12: 688703.
31. Deng X: Polygala tenuifolia: a source for anti-Alzheimer’s disease drugs. Pharm Biol 2020; 58(1): 410-416.
32. Xu KL: Effect of tenuigenin on tau protein phosphorylation at Ser396 site in neurons of AD rats induced by Ab1-40. Chinese J Pathophysiol 2012; 34: 3–1609.
33. Park H: The protective effects of PSM-04 against beta amyloid-induced neurotoxicity in primary cortical neurons and an animal model of Alzheimer’s disease. Front Pharmacol 2019; 10: 1–13.
34. Wang X: Tenuigenin inhibits LPS-induced inflammatory responses in microglia via activating the Nrf2-mediated HO-1 signaling pathway. Eur J Pharmacol 2017; 809: 196–202.
35. Li X: Senegenin inhibits hypoxia/reoxygenation-induced neuronal apoptosis by upregulating RhoGDIalpha Mol Neurobiol 2015; 52: 1561–1571.
36. Zhu XQ: Effects of senegenin against hypoxia/ reoxygenation-induced injury in PC12 cells. Chin J Integr Med 2016; 22: 353–361.
37. Denga X: Polygala tenuifolia: a source for anti-Alzheimer’s disease drugs. Pharmaceutical Biology 2020; 58(1): 410–416.
38. Biswal B: Bioactivity studies of an endangered medicinal plant Celastrus paniculatus: an overview. International Journal of Biotechnology 2020; 1(1): 1.
39. Gattu M: Reversal of scopolamine-induced deficits in navigational memory performance by the seed oil of Celastrus paniculatus. Pharmacol Biochem Behav 1997; 57(4): 793-799.
40. Kamala A: Plants in traditional medicine with special reference to Cyperus rotundus: a review. 3 Biotech 2018; 8(7): 309.
41. Kilani JS: Evaluation of in-vitro antioxidant and apoptotic activities of Cyperus rotundus. Asian Pac J Trop Dis 2014; 7(2): 105–12.
42. Sivapalan SR and Jeyadevan P: Physico-chemical and phyto-chemical study of rhizome of Cyperus rotundus Int J Pharmacol Pharm Technol 2012; 1(2): 42–46.
43. Bashir A: Investigation on the antioxidant activity of Dheela grass (Cyperus rotundus). Afr J Basic Appl Sci 2012; 4(1): 1–6.
44. Sharma R and Gupta R: Cyperus rotundus extract inhibits acetylcholinesterase activity from animal and plants as well as inhibits germination and seedling growth in wheat and tomato. Life Sci 2007; 80: 2389–92.
45. Rabiei Z: Effect of Cyperus rotundus tubers ethanolic extract on learning and memory in animal model of Alzheimer. Biomed Aging Pathol 2013; 3(4): 185–91.
46. Hemanth K: Neuroprotective effects of Cyperus rotundus on SIN-1 induced nitric oxide generation and protein nitration: ameliorative effect against apoptosis mediated neuronal cell damage. Neurotox 2013; 34: 150–9.
47. Saenghong N: Zingiber officinale improves cognitive function of the middle-aged healthy women. Evid Based Complement Alternat Med 2012; Article ID 383062, doi:10.1155/2012/383062.
48. Koetter U: Interactions of Magnolia and Ziziphus extracts with selected central nervous system receptors. J Ethnopharmacol 2009; 124(3): 421-425.
49. Kim HG and Oh MS: Herbal medicines for the prevention and treatment of Alzheimer’s disease. Curr Pharm Des 2012; 18(1): 57-75.
50. Delaviz H: A Review Study on Phytochemistry and Pharmacology Applications of Juglans Regia Plant. Pharmacogn Rev 2017; 11(22): 145–152.
51. Chauhan A and Chauhan V: Beneficial Effects of Walnuts on Cognition and Brain Health. Nutrients 2020; 12(2): 550.
52. Doshi GM: Rasayans and non-rasayans herbs: Future immunodrug - Targets. Pharmacogn Rev 2013; 7(14): 92–96.
53. Ahmadian-Attari MM: Treatment of Alzheimer's disease in Iranian traditional medicine. Iran Red Crescent Med J 2015; 17(1): 18052.
54. Dastmalchi K: Plants as potential sources for drug development against Alzheimer's disease. Int J Biomed Pharm Sci 2007; 1: 83–104.
55. Nandakumar S: A rapid HPLC-ESI-MS/MS method for determination of β-asarone, a potential anti-epileptic agent, in plasma after oral administration of Acorus calamus extract to rats. Biomed Chromatogr 2013; 27: 318–26.
56. Shinomol G: Exploring the role of “Brahmi” (Bocopa monnieri and Centella asiatica) in brain function and therapy. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery 2011; 5(1): 33–49.
57. Gray N: Centella asiatica attenuates Aβ-induced neurodegenerative spine loss and dendritic simplification. Neuroscience Letters 2017; 646: 24–29.
58. Gray N: Centella asiatica attenuates mitochondrial dysfunction and oxidative stress in Aβ-exposed hippocampal neurons. Oxidative Medicine and Cellular Longevity 2017; 7023091.
59. Alam M: A review on Phytochemical and Pharmacological studies of Kundur (Boswellia serrata Roxb ex Colebr.) -A Unani drug. J Appl Pharm Sci 2012; 2(3): 148-156.
60. Bertocchi M: Anti-inflammatory activity of Boswellia serrata extracts: an in-vitro study on porcine aortic endothelial cells. Oxid Med Cell Longev 2018; 2504305. doi: 10.1155/2018/2504305.
61. Ali SK: In-vitro evaluation of selected Egyptian traditional herbal medicines for treatment of Alzheimer disease. BMC Complement Altern Med 2013; 13: 121
62. Takeoka G: Volatile constituents of Asafoetida. In: Takeoka GR, Guntert M, Engel KH: editors. Aroma Active Compounds in Foods. American Chemical Society; Washington DC 2001; 33–44.
63. Mahendra P and Bisht S: Ferula asafoetida: traditional uses and pharmacological activity. Pharmacogn Rev 2012; 6: 141–146.
64. Lee CL: Influenza A (H1N1) antiviral and cytotoxic agents from Ferula asafoetida. J Nat Prod 2009; 72: 1568–1572.
65. Al-Jafari AH: Antifungal compounds from the rhizome and roots of F. hermonis. Phytothe Res 2013; 27(6): 911-5.
66. Moghaddama M and Farhadi N: Influence of environmental and genetic factors on resin yield, essential oil content and chemical composition of Ferula asafoetida L. populations. J App Res Med Aromat Plants 2015; 2: 69–76.
67. Kavoosi G and Rowshan V: Chemical composition, antioxidant and antimicrobial activities of essential oil obtained from Ferula asafoetida oleo-gum-resin: effect of collection time. Food Chem 2013; 138: 2180–2187.
68. Saleem M: Asafoetida inhibits early events of carcinogenesis: a chemopreventive study. Life Sci 2001; 68: 1913–1921.
69. Mallikarjuna GU: Chemomodulatory influence of Ferula asafoetida on mammary epithelial differentiation, hepatic drug metabolizing enzymes, antioxidant profiles and N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats. Breast Cancer Res Treat 2003; 81: 1–10.
70. Abu-Zaiton AS: Anti-diabetic activity of Ferula asafoetida extract in normal and alloxan-induced diabetic rats. Pak J Biol Sci. 2010; 13: 97–100.
71. Khazdair MR and Boskabady MH: The relaxant effect of Ferula asafoetida on smooth muscles and the possible mechanisms. J HerbMed Pharmacol 2015; 4: 40–44.
72. Patil SD: Evaluation of antimicrobial activity of asafoetida. Int J Pharm Sci Res 2015; 6: 722–727.
73. Mostafa Z: Antifangal effects of asafoetida seed essential oil on in-vitro growth of five species of plant pathogenic fungi. Int Res J Appl Basic Sci 2013; 4: 1159–1162.
74. Srinivasan K: Dietary spices as beneficial modulators of lipid profile in conditions of metabolic disorders and diseases. Food Funct 2013; 4: 503–521.
75. Fatehi M: Antispasmodic and hypotensive effects of Ferula asafoetida gum extract. J Ethnop 2004; 91: 321–24.
76. Vijayalakshmi: Evaluation of the effect of Ferula asafoetida Linn. gum extract on learning and memory in Wistar rats. Indian J Pharmacol 2012; 44: 82–87.
77. Prasad S and Amit KT: Ginger and Its Constituents: Role in Prevention and Treatment of Gastrointestinal Cancer. Gastroenterol Res Pract 2015; Article ID 142979.
78. Ali SK: In-vitro evaluation of selected Egyptian traditional herbal medicines for treatment of Alzheimer disease. BMC Complement Altern Med 2013; 13: 121.
79. Cortes-Rojas DF: Clove (Syzygium aromaticum): A precious spice. Asian Pac J Trop Med 2014; 4:90–96. doi: 10.1016/S2221-1691(14)60215-X.
80. Hossein M and Morshedi A: The effects of Syzygium aromaticum (clove) on learning and memory in mice. Asian J Tradit Med 2009; 4(4): 128-133.
    

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    Umar T, Meena R, Mustehasa, Javed G and Khan AA: Treatment strategies for neurodegenerative diseases through important medicinal plants used in Unani medicine. Int J Pharm Sci & Res 2023; 14(4): 1604-10. doi: 10.13040/IJPSR.0975-8232.14(4).1604-10.

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