Evidence-Based Complementary and Alternative Medicine
Volume 2019 (2019), Article ID 6191505, 27 pages
https://doi.org/10.1155/2019/6191505

Review Article

An Updated List of Neuromedicinal Plants of Pakistan, Their Uses, and Phytochemistry

Abdul Waheed Khan,¹ Arif-ullah Khan,² Syed Muhammad Mukarram Shah,³ Aziz Ullah,⁴ Muhammad Faheem,² and Muhammad Saleem²

¹Department of Pharmacy, University of Lahore, Islamabad, Pakistan
²Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
³Department of Pharmacy, University of Swabi, Khyber Pakhtunkhwa, Pakistan
⁴Department of Pharmacy, Forman Christian College, Lahore, Pakistan

Correspondence should be addressed to Arif-ullah Khan; arif.ullah@riphah.edu.pk

Received 12 November 2018; Revised 14 January 2019; Accepted 5 February 2019; Published 3 March 2019

Guest Editor: José C. T. Carvalho

Copyright © 2019 Abdul Waheed Khan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Background. Almost every region of Pakistan is stacked with a large number of medicinal plants. Due to high cost and unavailability of allopathic medicines for the neurological diseases, especially in rural areas, traditional healers prescribe phytotherapy for various neurological diseases like epilepsy, depression, anxiety, insomnia, Alzheimer, and migraine. Such treatments are considered to be most effective by the native people. Methods. The data was collected from articles published on medicinal plants of various districts of Pakistan, using article search engines like Medline, Pubmed, Web of Science, Science Direct, and Google Scholar. Also, information regarding various neurological uses and mode of applications of medicinal plants was obtained from traditional healers, folk medicine users, and local elderly people having knowledge of medicinal plants. Results. A total of 54 families were found to be used in various neurological diseases, of which the highest use was of Solanaceae (22.22%), Asteraceae (12.96%), Lamiaceae, Papaveraceae, and Poaceae, 9% each, and Caprifoliaceae, Cucurbitaceae, Rhamnaceae, and Rosaceae, 5.5% each. According to districts, 15% of plants that were effective in neurological affections were found in Bahawalpur, 11% in Swat, 8% in Muzaffarabad, 7% in Malakand, and 6% in Bahawalnagar, Dir, Gilgat, and Sarghoda each, with 5% in Dera ghazi khan and Jhelum each. According to the plant’s habit, out of total of 103 plants, 61.15% were found to be herbs, 22.33% trees, 11.65% shrubs, and 4.85% climbers. According to the part used of plant, whole plant, leaves, fruits, roots, seeds, and flowers were found to be used 32.03%, 24.27%, 20.38%, 16.50%, 13.59%, and 11.65%, respectively. According to disease’s types, 45.63% were found to be effective in insomnia, 31.06% in epilepsy 12.62% in depression, 6.80% in anxiety, 7.77% in hysteria, and 5.88% in migraine. Conclusion. Taking into consideration this useful knowledge on medicinal properties of the plants for curing neurologic diseases, it is believed that research in areas of ethnomedicine and ethnopharmacology can bring auspicious results that have potential of adding value to the very rich natural resources of Pakistan. This study will help all the researchers from diverse backgrounds working on plants based medicine for neurological diseases.

1. Introduction

Globally, neurological diseases are among the major contributors to mortality and morbidity, particularly in developing nations. The well-known manifestations of neurological diseases include mood swing, restlessness, hopelessness, poor coordination, seizures, impaired cognition, paralysis, distress of sensation, muscle weakness, pain, and confusion [1]. There are more than six hundred neurological diseases, some of which are relatively common and well known while others are rare or poorly recognized [2]. Demographic, socioeconomic, and geographic conditions are the major factors affecting epidemiology of neurological diseases. Globally, the overall burden of neurological diseases is about 6.5%. In lower income countries, neurological diseases range from 4 to 5%, as compared to high income countries where such diseases range from 10 to 11%. This high ratio of neurological diseases in advanced countries may be due to their more advanced public health system and health-related facilities that provide and maintain complete data of their patients [1].

About 45 million people of the world, above 18 years of age, suffer from schizophrenia at some stage of their lives, 340 million are affected by depression, and both these diseases are accountable for 60 % of all suicides, while Alzheimer and epilepsy affect about 11 and 45 million people, respectively, around the world accounting for 1% of the total disease burden in the world [3].

In Pakistan, about 10 % people suffer from mental diseases, representing a foggy picture with 2% prevalence of’ epilepsy, 5% depression, 1% Alzheimer, and 1.5% schizophrenia [4] as shown in (Table 1). These mental morbidities are responsible for high suicidal rate. Major factors contributing to this alarming increase in mental diseases are unemployment, poverty, political unreliability, violence, and other social horrors and evils beyond the genetic and biological susceptibility [5].

Table 1: Global epidemiology of neurological diseases and theircomparative prevalence in Pakistan and neighboring countries.

Migraine
Stroke
Epilepsy
Depression
Anxiety
Parkinson
Alzheimer

Worldwide
14.9% [49]
5% [50]
0.5-1% [51]
4.4% [52]
3.6% [52]
1% [53]
11.2% [54]

Asia
9.1% [55]
0.94%[56]
0.49% [57]
4.4% [52]
2.8% [58]
0.63% [59]
1.9% [54]

Africa
5.61% [60]
0.4% [61]
1.13% [62]
5.2% [52]
4.4% [52]
0.44% [63]
1.6% [54]

North America
14.4% [64]
2.7% [65]
0.8% [66]
10.6% [67]
7.7% [58]
1.3% [59]
6.4% [54]

South America
11.6% [64]
0.7% [68]
0.98% [57]
13.8% [67]
10.4% [69]
2.3% [59]
4.6% [54]

Europe
15% [70]
6.25%[71]
0.82% [62]
4.2% [52]
3.9% [52]
1.6% [72]
4.4% [54]

Australia
6% [73]
1.8% [74]
0.44% [75]
5.9% [52]
7% [52]
0.46% [76]
6.4% [77]

Pakistan
26.1% [78]
0.25% [79]
2% [4]
4.2% [52]
3.5% [52]
0.23% [51]
1% [4]

India
25.2% [51]
3.69%[71]
0.39% [80]
4.5% [52]
3.0% [52]
0.07% [81]
1.91% [82]

Iran
14% [51]
0.36% [51]
1.8% [80]
4.9% [52]
4.6% [52]
0.29% [83]
2.3% [84]

China
9.3% [78]
4.3% [71]
0.3% [80]
4.2% [52]
3.1% [52]
1.7 % [85]
3.21% [85]

Afghanistan
0.9% [86]
5.2% [87]
8.9% [88]
51.8% [89]
38.5% [89]
35.4% [90]
15.3% [91]

Medicinal plants have been used from the very beginning in health care systems. Studies have been carried out globally to verify their efficacy and some of the findings have led to the production of plant-based medicines. Due to limited access to modern medicine, the local population uses medicinal plants to treat most diseases [6, 7]. Recent focus on plant research has increased worldwide and most evidence has been collected to determine the immense potential of medicinal plants [8]. Medical plants have therapeutic benefits and fewer side effects in comparison with synthetic drugs [9]. Drugs used for neurological diseases along with their side effects are given in (Table 2).

Table 2: Side effects of currently using drugs in treatment of various neurological diseases.

Drug Class
Subclasses
Drugs
Side effects
References

Antidepressants
TCA
Imipramine, Amitriptyline, Desipramine, Nortriptyline, Doxepin
weight gain, sedation, dry mouth, nausea, blurred vision, constipation, tachycardia, dry mouth, constipation, hypotension, increased heart rate
[92]

MAOI
Isocarboxazid, Phenelzine
Tranylcypromine, Selegiline
weight gain, fatigue, sexual dysfunction, nausea, hypotension, dry mouth, diarrhea or constipation, headache, drowsiness, insomnia

SSRI
Fluoxetine, Paroxetine, Fluvoxamine, Sertraline, Citalopram
headache, sedation, dizziness, nervousness, somnolence, extrapyramidal effects, nausea, dry mouth, diarrhea, agitation, insomnia, sexual dysfunction, weight gain,
[93]

SNRI
Venlafaxine, Duloxetine, Desvenlafaxine, Levomilnacipran
nausea, insomnia, dry mouth, headache, increased blood pressure, sexual dysfunction, weight gain, urinary retention, hyponatremia, tremors, vertigo, tachycardia, shock-like sensations, paresthesia, myalgia, tinnitus, neuralgia, ataxia
[92, 94]

Atypical
Bupropion, Mirtazapine, Trazodone, Vilazodone
headache, agitation, insomnia, sweating, sedation, increased appetite, weight gain, nausea, dizziness
[92]

Anxiolytics
BZDs
Alprazolam, Clonazepam, Lorazepam, Midazolam, Diazepam
sedation, memory disturbances, tolerance, fatigue, dependence, drowsiness, lethargy, At higher dosages, impaired motor coordination, dizziness, vertigo, slurred speech, blurry vision, mood swings, euphoria
[95]

Azapirones
Buspirone, Binospirone, Gepirone, Tandospirone
dizziness, drowsiness, headaches, restlessness, nausea, diarrhea
[96]

BAR
Phenobarbital, Amobarbital, Secobarbita, Butabarbital, Pentobarbital
sedation, dizziness, headache, nausea, withdrawal include, tremors, agitation, abnormal breathing, coma, confusion, fainting, hallucinations
[97]

Anti-Alzheimer
AChEIs
Donepezil, Rivastigmine, Galantamine
vomiting, diarrhea, weight loss, bradycardia, insomnia, nausea, agitation, syncope
[98]

Anti-Aβ
Bapineuzumab, Solanezumab, Gantenerumab
microhemorrhage, vasogenic edema, arrhythmia, skin and subcutaneous tissue disorders

NMDAR Antagonists
Memantine
psychosis, nausea, vomiting, memory impairment, and neuronal cell death, drowsiness
[99]

Anti-Parkinson
DA
Bromocriptine, Pergolide, Cabergoline, Pramipexole
nausea, hypotension, confusion, delirium, pulmonary fibrosis, vasospasm, erythromelalgia, sleep attacks
[100]

COMT Inhibitors
Entacapone, Tolcapone
dyskinesia, nausea, confusion, urine discoloration, diarrhea, abdominal pain

MAO-B
Selegiline
confusion, delirium, hallucinations, unusual thoughts or behavior, dizziness, nausea, insomnia, trouble breathing

Antiepileptic
Sodium Channel Blockers
Phenytoin, Carbamazepine, Lamotrigine, Lacosamide, Oxcarbazepine,
dizziness, drowsiness, diplopia, nausea, vomiting, fatigue, ataxia, neurotoxicity, cardiac arrhythmias, hirsutism, hepatotoxicity, steven-johnson syndrome
[101]

Calcium Channel Blockers
Ethosuximide, Zonisamide, Trimethadione
nausea, vomiting, headache, mental status changes, neuropathy, change in weight
[102]

GABA transaminase Inhibitors
Vigabatrin, L-Cycloserine, Ethanolamine-O-Sulfate, Valproate
drowsiness, nystagmus, hyperexcitability, insomnia, fever, memory impairment, depression, confusion, agitation, asthenia, laryngitis, weight gain, vomiting
[103]

TCA: tricyclic antidepressant; MAOI: monoamine oxidase inhibitor; SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin norepinephrine reuptake inhibitor; BZDs: benzodiazepines; BAR: barbiturates; AChEIs: acetylcholinesterase inhibitors; Aβ: amyloid beta; NMDAR: N-methyl-D-aspartate receptor; DA: dopamine agonists; COMT: catechol-O-methyltransferase; MAO-B: monoamine oxidase B; GABA: gamma-aminobutyric acid.

Herbs may provide a source of new compounds including many drugs that are derived from plant sources. For several neurological diseases, modern medicine offers symptomatic treatment that is often expensive and associated with side effects. Indian system of medicine has traditionally been used in several neurological conditions. The accessibility, cost effectiveness, and lower incidence of side effects of plant products offer considerable advantages [10].

Various plant extracts have been screened and investigated for their potential neuropharmacological activities in different experimental models of animals comprising mice and rats. Herbal extracts and natural products including Bacopa monnieri, Cannabis sativa, Solanum nigrum, Withania somnifera, Papaver somniferum, Zizyphus jujube, Tribulus terrestris, and Verbena officinalis showed different neuropharmacological activities. These agents can be used alone or as adjuncts to standard drugs, used for various neurological diseases like depression, epilepsy, schizophrenia, Alzheimer, Parkinson, hysteria, melancholia, and dementia, for increasing their efficacy and decreasing side effects.

In developing countries, plant-based medicines are being used by 75-80% of population [11]. The knowledge of indigenous medicinal plants is a part of Pakistani culture and traditionally, majority of Pakistani people use herbal medicines for various diseases [12].

In Pakistan, folk medicines have more use in rural and less developed areas for the treatment of various diseases because of easy access, cost effectiveness, less side effects, and unavailability of allopathic therapeutic agents [13]. This type of treatment, using traditional medicinal flora, is practiced regularly in homes and transferred from generation to generation as a cultural virtue. However, this tradition and associated knowledge are diminishing rapidly due to negligence and less interest of new generation to receive this gift of ethnomedicinal prosperity from their ancestors. Various parameters like industrialization, migration from rural to urban areas for education and jobs, passion towards advanced lifestyles, deforestation, and allopathic medicine might have brought this change in behavior. Therefore, before it is lost forever, this valuable traditional knowledges need to be urgently collected and systematically documented for the interest of humanity [14].

2. Materials and Methods

First the articles published on the medicinal plants of various districts of Pakistan were searched in online research database, i.e., Medline, PubMed, Web of Science, Science Direct, and Google Scholar, by using special key words “medicinal plants”, herbal plants, neurological diseases, specific districts names, antialzheimer, antiparkinson, antidepression, sedative, anxiolytic, antiepileptics, epidemiology, and prevalence, from January to March 2018, and downloaded. These entire articles were then viewed and the data of medicinal plants, which have neurological effects, were collected and tabulated in (Table 3). We have personally visited districts Bahawalpur, Bannu, Buner, Dir, Gilgat, Islamabad, Jhelum, Malakand, Mianwali, Rawalpindi, Sargodha, and Swat in April-June 2018 and collected information regarding plants local names, local use, mode of applications, and administration of these plants in neurological diseases from local traditional healers, folk medicine users, and local elderly people of those districts having knowledge of medicinal plants. Information was also collected from distant districts with the help of friends living there via social media (phone calls, text messages, WhatsApp calls and messages, and emails).

Table 3: Traditionally used medicinal plants for the treatment of various neurological diseases.

S #
Botanical Name
Local Name
Family
Habitat
Part Used
Used for
Mode of Applications
Location
Reference

1
Achyranthes aspera
Ayokanda
Amaranthaceae
Herb
Leaves and Shoot
Nerve tonic
Paste of dried leaves and shoots is applied on head
Sargodha
[104]

2
Ailanthus altissima
Backyanra
Simarubacea
Tree
Bark
Hysteria
Decoction of bark to make tea
Malakand
[105]

3
Albizia lebbeck
Sirin
Mimosaceae
Tree
Roots
Depression, Migraine and Anxiety
Decoction of root to make tea
Mianwali
[106]

4
Allium sativum
Ooga
Amaryllidaceae
Herb
Bulbs and Leaves
Hysteria and Epilepsy
Decoction of bulbs and leaves
Swat
[107]

5
Alnus nitida
Geiray
Betulaceae
Tree
Flowers
Insomnia
Powder of dried flowers mixed with water and used orally
Dir
[108]

6
Alternanthera sessilis
Waglon
Amaranthaceae
Herb
Leaves
Neuralgia and Sedative
Sniffing of leaves sap
Bahawalpur
[109]

7
Anagallis arvensis
Billy booti
Primulaceae
Herb
Whole plant
Nervine, mania and Epilepsy
Extract of whole plant
Bahawalpur
[109]

8
Artemisia scoparia
Jaukay
Asteraceae
Herb
Roots
Epilepsy
Powder of roots taken with water
Dir
[108]

9
Asparagus officinalis
Phala-moosa
Asparagaceae
Herb
Leaves
Insomnia
Tea of leaves are used on empty stomach
Lahore
[110]

10
Atropa accuminata
Bargak
Solanaceae
Herb
Leaves
Insomnia and narcotic
Powder of leaves are taken with water
Dir
[108]

11
Avena fatua
Jodal
Poaceae
Herb
Seeds
Depression and nervous exhaustion
Either the seeds fluid extract or oatmeal obtained by crushing and grinding seeds
Dera Ghazi Khan
[111]

12
Avena sativa
Jai
Poaceae
Herb
Seeds
Nerve tonic and Insomnia
A tincture of juice of immature seeds
Islamabad
[112]

13
Bacopa monnieri
Brahmi sak
Scrophulariaceae
Herb
Whole plant
Epilepsy
Extract of whole plant is taken orally
Mianwali
[106]

14
Buglossoides arvensis
Kalu
Boraginaceae
Herb
Leaves
Insomnia
Infusion of leaves is used orally
Kotli
[113]

15
Caltha alba
Makanpat
Ranunculaceae
Herb
Whole plant
Insomnia
Extract of whole plant
Dir
[108]

16
Campanula pallida
Beli Flower
Campanulaceae
Herb
Flowers
Insomnia
An infusion of flowers is used orally
Kotli
[113]

17
Cannabis Sativa
Bhang
Cannabaceae
Herb
Flowers
Insomnia
The ground flowers are used by mixing with other fruits
Bannu
[114]

18
Capparis decidua
kdler
Capparidaceae
Shrub
Flowers, fruits and shoots
Insomnia
The powder of flowers and shoots while fruits are eaten as such
Gawadar
[115]

19
Capparis spinosa
Kawir
Capparidaceae
Shrub
Whole plant
Mental disorders
Fresh extract of whole plant is used
Gilgat
[116]

20
Carthamus tinctorius
Tukhmiga-rtum
Asteraceae
Herb
Roots, oil and flowers
Insomnia
Decoction of roots to make tea while oil is applied externally
Rawalpindi
[117]

21
Celtis australis
Karr
Cannabaceae
Tree
Bark
Epilepsy
Decoction of bark is used orally
Sargodha
[118]

22
Cenchrus pennisetiformis
Cheetah- gha
Poaceae
Herb
Leaves and fruits
Epilepsy
Extracts and juice of leaves and fruits
Hafizabad
[119]

23
Citrullus colocynthis
Tumma
Cucurbitaceae
Climber
Roots and fruits
Epilepsy
The extract of roots is taken with water while fruit’s powder is mixed with sugar
Jhelum
[120]

24
Citrus limon
Nimboo
Rutaceae
Tree
Whole plant
Anxiety and Depression
whole plant extract
Bahawalpur
[109]

25
Citrus medica
Khatti
Rutaceae
Tree
Leaves, seeds, latex
Insomnia
Powder of leaves, seeds and dry latex are taken orally with water
Bahawalpur
[109]

26
Colebrookia oppositifolia
Lansa
Lamiaceae
Shrub
Leaves and roots
Epilepsy
Fresh leaves extract and roots decoction tea is taken orally
Malakand
[121]

27
Commiphora wightii
Guggul, Mukul
Burseraceae
Herb
Gum
Nervous diseases
The aqueous extract of gum is used
Muzaffarabad
[122]

28
Convolvulus arvensis
Baily
Convolvulaceae
Herb
Whole plant
Epilepsy
whole plant extract
Malakand
[121]

29
Cucurbita maxima
Walayti kadoo
Cucurbitaceae
Climber
Fruits
Nervous disorders
Juice of both unripe and ripe fruits is used
Azad Jammu & Kashmir
[123]

30
Cuscuta reflexa
Bepari, Kasus
Cuscutaceae
Tree
Seeds
Insomnia
An infusion of seed is used
Muzaffarabad
[122]

31
Cymbopogon citratus
Lemon- grass
Poaceae
Herb
Oil of whole plant
Nervous system tonic
Oil is externally applied on head
Bahawalpur
[109]

32
Cynodon dactylon
Lawn grass
Poaceae
Herb
Whole plant
Epilepsy and Hysteria
Extracted juice of plant is used
Dera Ghazi Khan
[111]

33
Cyperus rotundus
Deela
Cyperaceae
Herb
Tubers
Epilepsy
Oil obtained from tubers are used
Bahawalnagar
[124]

34
Datura alba
Datura
Solanaceae
Shrub
Leaves and seeds
Neuralgia, Epilepsy, Hysteria and Insomnia
Lotion of seed’s powder is applied locally for neuralgia while tea of leaves is used for Epilepsy
Bahawalpur
[109]

35
Datura innoxia
Datura
Solanaceae
Herb
Leaves
Epilepsy and Insomnia
Extract of leaves in water
Dir
[108]

36
Datura metel
Dhaturo
Solanaceae
Herb
Leaves and seeds
Epilepsy and Insomnia
Leaves extract and seed’s decoction are used
Muzaffarabad
[122]

37
Datura stramonium
Datura
Solanaceae
Herb
Whole plant
Insomnia and Parkinson
Extraction of whole plant is used
Dera Ghazi Khan
[111]

38
Daucus carota
Gajar
Apiaceae
Herb
Whole plant
Nerve tonic
Eaten as a whole or its juice is used
Sargodha
[104]

39
Eclipta alba
Bhringaraj
Asteraceae
Herb
Roots, oil and leaves
Insomnia
Oil is externally applied while roots and leaves extract is used orally
Bahawalpur
[109]

40
Eruca sativa
Tara meera
Cruciferaceae
Herb
Whole plant
Epilepsy
Fluid extraction of plant is used
Islamabad
[112]

41
Evolvulus alsinoides
Sankha-holi
Convolvulaceae
Herb
Whole plant
Epilepsy
Decoction of whole plant is used
Islamabad
[112]

42
Ficus lyrata
Beeri patta
Moraceae
Tree
Leaves
Migraine
Extraction of leaves is used orally
Bahawalpur
[109]

43
Flueggea leucopyrus
Shina
Phyllanthaceae
Shrub
Roots
Epilepsy
Decoction and extraction of roots are used
Dir
[125]

44
Fumaria indica
Pitpapra
Fumariaceae
Herb
Leaves and stem
Insomnia
Fresh juice of leaves and stem is used
Rawalpindi
[117]

45
Gmelina arborea
Kumbar
Lamiaceae
Tree
Roots
Epilepsy
Extraction and decoction of roots tea is used
Sargodha
[118]

46
Hyoscyamus niger
Ajwain-i- Khurasani
Solanaceae
Herb
Leaves and seeds
Insomnia and Nervous afflection
Extraction of fresh leaves and powder of seeds are used orally
Gilgat
[126]

47
Hypericum perforatum
Bulhsana
Hypericaceae
Herb
Whole plant
Depression and Insomnia
Fresh extract of whole plant is used orally
Gujrat
[127]

48
Hyssopus officinalis
Zufa, Zupa
Lamiaceae
Herb
Whole plant
Nervous affection
Extraction of fresh whole plant
Ziarat
[128]

49
Indigofera heterantha
Kainthi
Papilionaceae
Shrub
Whole plant
Epilepsy and neuropathy
Extract of whole plant is used
Gilgat
[116]

50
Jasminum grandiflorum
Chanbeli
Oleaceae
Climber
Whole plant
Anxiety, tension and Depression
Oil or tea of leaves and flowers extract are used
Bahawalpur
[109]

51
Jasminum officinale
Chanbeli
Oleaceae
Climber
Whole plant
Insomnia
Oil is rubbed on heart as nerve sedative
Swat
[107]

52
Juglans regia
Ghuz
Juglandaceae
Tree
Fruits
Depression
Fruits are taken as whole orally
Malakand
[105]

53
Lactuca serriola
Berham dandi
Asteraceae
Herb
Whole plant
Memory Enhancing
Fresh plant is ground in water along with black pepper
Jhelum
[120]

54
Linum usitatissimum
Alsi
Linaceae
Herb
Stem
Depression, Schizophrenia and Anxiety
Extraction of fresh stem is used
Kotli
[113]

55
Lycopersicon esculentum
Tamator
Solanaceae
Herb
Fruits
Nervous weakness
Eaten as a whole or its juice is used
Sargodha
[104]

56
Martricaria chamomilla
Babuna
Asteraceae
Herb
Whole plant
Insomnia
Extraction of whole plant is used orally and oil massage or aromatherapy into skin of head is performed
Rawalpindi
[117]

57
Martynia annua.
Bichhu-butti
Martyniaceae
Herb
Leaves and fruits
Epilepsy
Juice of leaves or leaves are cooked to make curry and fruits are taken as dry powder with water
Kotli
[113]

58
Melia azedarach
Bakyana
Meliaceae
Tree
Leaves
Hysteria
Decoction of leaves to makes tea
Malakand
[105]

59
Mimordica dioca
Jungli karela
Cucurbitaceae
Climber
Fruits and seeds
Insomnia
Fruit’s extract and seed oil are used
Mianwali
[129]

60
Moringa oleifera
Sohan-jana
Moringaceae
Tree
Seeds and bark
Migraine
Seeds oil used externally while powder of leaves
Gujrat
[127]

61
Ocimum basilicum
Niazbo
Lamiaceae
Herb
Leaves, flowers, seeds and roots
Migraine, Insomnia and Depression
Juice of fresh leaves and flowers while oil of seeds is applied externally on head
Bahawalnagar
[124]

62
Paeonia emodi
Mamaikh
Paeoniaceae
Herb
Rhizome
Epilepsy
Rhizome powder is given teaspoon twice a day
Malakand
[105]

63
Papaver dubium
Koko-kanga
Papaveraceae
Herb
Flowers
Insomnia
Fluid extract of flowers is used
Kotli
[113]

64
Papaver hybridum
Post
Papaveraceae
Herb
Fruits
Insomnia
Fruit and its decoction are used
Jhelum
[120]

65
Papaver nudicaule
Zangali kashkash
Papaveraceae
Herb
Flowers
Insomnia
Fluid extract of flowers is used
Buner
[130]

66
Papaver rhoeas
Alak jinai
Papaveraceae
Herb
Flowers
Insomnia
Fluid extract of flowers is used
Buner
[130]

67
Papaver somniferum
Qash-Qash
Papaveraceae
Herb
Fruit’s latex
Insomnia
Latex of unripe fruit is dissolved in water and used orally
Swat
[107]

68
Parthenium hysterophorus
Ragweed
Asteraceae
Herb
Leaves
Insomnia
Leaves extraction is used
Buner
[130]

69
Peganum harmala
Harmal
Zygophyllaceae
Herb
Seeds
Hysteria
A small amount of seeds added to sufficient grapes juice, boiled to make thick solution and used orally
Dera Ghazi Khan
[111]

70
Populus caspica
Nakhtar
Pinaceae
Tree
Fruits
Insomnia
Whole raw fruits are consumed
Malakand
[105]

71
Primula veris
Cowslips
Primulaceae
Herb
Flowers
Insomnia
A tasty wine of flowers is made which is used orally
Gilgat
[126]

72
Prunus persica
Ardou
Rosaceae
Tree
Leaves, flowers and fruits
Insomnia
Extract of leaves & flowers and fruits are taken as such
Gilgat
[126]

73
Punica granatum
Darrona
Punicaceae
Shrub
Fruits
Memory enhancing
Fruit’s juice or fresh seeds are eaten as such
Azad Jammu & Kashmir
[123]

74
Pyrus communis
Nashpatai
Rosaceae
Tree
Fruits
Insomnia
Fruits are eaten as such
Dir
[131]

75
Pyrus pashia
Tangai
Rosaceae
Herb
Fruits
Insomnia
Fruits are eaten as such
Swat
[107]

76
Ranunculus muricatus
Ziar Gulay
Ranunculaceae
Herb
Whole plant
Sciatic and nerve pain
Extraction of dried whole plant is used
Swat
[132]

77
Raphanus sativus
Mooli
Brassicaceae
Herb
Seeds
Nervous weakness
Decoction of seeds is used
Sargodha
[104]

78
Ricinus communis
Arand
Euphorbiaceae
Shrub
Roots, seeds, leaves
Insomnia and as narcotic
Extract of leaves and roots while oil of seeds are used
Rawalpindi
[117]

79
Salvadora oleoides
Peelu
Salvadoraceae
Tree
Whole plant
Epilepsy
Fruit is eaten as raw while tea of leaves and roots are also used
Bahawalpur
[109]

80
Schinus molle
False pepper
Anacardiaceae
Tree
Bark and leaves
Depression
Decoction of bark and leaves to make tea
Sargodha
[118]

81
Scutellaria chamaedrifolia
Skullcap
Lamiaceae
Herb
Shoots
Insomnia and Depression
Decoction of shoots to make its tea
Swat
[133]

82
Solanum miniatum
Peelak
Solanaceae
Herb
Whole plant
Insomnia
whole plant decoction is mixed with sugar
Jhelum
[120]

83
Solanum nigrum
Mako
Solanaceae
Herb
Whole plant
Insomnia
Juice of whole plant
Bahawalpur
[109]

84
Solanum Surratense
Wara-mara ghinrhye
Solanaceae
Herb
Fruits
Melancholia and Depression
The paste of fruits crushed powders is applied on head externally
Bannu
[114]

85
Taxus baccata
Banhya
Taxaceae
Tree
Leaves and fruits
Epilepsy
Extraction of dried leaves and fruits are consumed as such
Swat
[134]

86
Taxus wallichiana
Barmi
Taxaceae
Tree
Bark, leaves and fruits
Epilepsy and Insomnia
Extract of dried bark and leaves while flesh of fruits are consumed
Battagram
[135]

87
Terminalia arjuna
Arjun
Combretaceae
Tree
Fruits, bark and leaves
Anxiety
Bark infusion left whole night, then its decoction taken early in the morning and used orally
Bahawalpur
[109]

88
Tribulus terrestris
Bakhra
Zygophyllaceae
Herb
Whole plant
Epilepsy and Depression
Powder of dried whole plant
Bahawalnagar
[124]

89
Valeriana jatamansi
Mushk-bala
Vahliaceae
Herb
Whole plant
Epilepsy and neurosis
Fresh extract of whole plant
Muzaffarabad
[122]

90
Verbascum thapsus
Jungle tambako
Scrophulariceae
Herb
Roots
Migraine
Decoction of root to make tea to use as drink
Mianwali
[106]

91
Verbena officinalis
Shamkay
Verbenaceae
Herb
Whole plant
Depression, Migraine and Epilepsy
Extract of dried whole plant is used
Battagram
[135]

92
Viburnum cotinifolium
Guch
Caprifoliaceae
Shrub
Stem’s bark
Insomnia
Extract of stem’s bark
Muzaffarabad
[122]

93
Viburnum opulus
Sunaira Phul
Caprifoliaceae
Shrub
Bark
Insomnia and Hysteria
Decoction of bark is used
Muzaffarabad
[122]

94
Viburnum prunifolium
Blackhaw
Caprifoliaceae
Tree
Root’s bark
Hysteria, Anxiety and Epilepsy
Decoction of root’s bark is used
Muzaffarabad
[122]

95
Vicia sativa
Muttri
Papilionaceae
Herb
Flowers
Epilepsy and nervous disorders
The juice of flowers petals is used
Kotli
[113]

96
Viola betonicifolia
Banafsh
Violaceae
Herb
Whole plant
Epilepsy and nervous disorders
Fresh extract of whole plant orally
Malakand
[105]

97
Viola canescens
Banafsha
Violaceae
Herb
Whole plant
Insomnia and Epilepsy
Extract and decoction tea of whole plant
Swat
[133]

98
Withania coagulans
Paneer doda
Solanaceae
Herb
Fruits, roots and leaves
Nervous Exhaustion, memory loss and tension
Extract of leaves, roots and fruits are used
Bahawalnagar
[124]

99
Withania somnifera
Asgandh
Solanaceae
Shrub
Roots
Insomnia
Powder of roots is taken with water
Bahawalpur
[109]

100
Xanthium strumarium
Chota dhatura
Asteraceae
Herbs
Fruits, seeds and roots
Insomnia
Decoction of fruits, roots and seeds to make tea
Attock
[136]

101
Ziziphus jujuba
Beri
Rhamnaceae
Tree
Leaves, roots and fruits
Anxiety and Insomnia
Extract of leaves, decoction of roots and dried fruits are consumed
Bahawalnagar
[124]

102
Ziziphus mauritiana
Ber
Rhamnaceae
Tree
Roots
Nerve tonic
Decoction of roots is used as tea
Sargodha
[104]

103
Ziziphus nummularia
Jangli beri
Rhamnaceae
Shrub
Leaves and fruits
Insomnia
Extract of leaves while fruits are taken as such
Attock
[136]

3. Results and Discussion

A total of 54 families were found to be useful in various neurological diseases, of which the highest use was of Solanaceae (22.22 %), Asteraceae (12.96 %), Lamiaceae, Papaveraceae, and Poaceae, 9 % each, and Caprifoliaceae, Cucurbitaceae, Rhamnaceae, and Rosaceae, 5.5 % each (Table 3). As per district point of view, 15% plants, effective in neurological affections, were found in Bahawalpur, 11% in Swat, 8 % in Muzaffraabad, 7% in Malakand, and 6% in Bahawalnagar, Dir, Gilgat, and Sarghoda each, with 5% in Dera ghazi khan and Jhelum each (Figure 1).

Figure 1: District-wise percentage of plants used for neurological diseases.

This district-wise plant distribution will help the researchers, who are willing to research in neuropharmacological area, to easily collect the target plants from the regions to which the plants belong. According to the plant’s habit, out of total of 103 plants, 61.15% were found to be herbs, 22.33 % trees, 11.65% shrubs, and 4.85% climbers (Figure 2).

Figure 2: Habit-wise percentage of plants used for neurological diseases.

The habit of plants shows that herbs are most important according to neuropharmacological point of view which is another benefit for researchers working in neuropharmacological area to concentrate on herbs more while selecting neurological active plants. According to the part used of plant, whole plant, leaves, fruits, roots, seeds, flowers, and other parts (bulbs, latex, gum, tubers, and rhizome) were found to be used 32.03 %, 24.27 %, 20.38 %, 16.50 %, 13.59 %, 11.65 %, and 15.53 %, respectively (Figure 3). As some plants have more than one part to be used for various neurological diseases, so such plants were counted into percentage of all respective parts. This division of neuropharmacological plants ensures the researchers to select the most appropriate parts of plants having specific neuropharmacological activities, for their research, as used by traditional healers and folk medicine users.

Figure 3: Parts-wise percentage of plants used for neurological diseases.

According to disease’s types, 45.63 % were found to be of therapeutic value in insomnia, epilepsy (31.06%), depression (12.62%), anxiety (6.80%), hysteria (7.77%), and migraine (5.88%) and 20.38 % in other neurological diseases (neuralgia, mania, Parkinson, schizophrenia, and nerve pain) (Figure 4). As some plants are used for multiple neurological ailments, so such plants were counted into percentage of all respective diseases. This disease-wise plant division will help the local researchers to select their interest areas in the field of neuropharmacology, by selecting the neurological disease, for which most of the plant’s percentage was found to be used by traditional healers and folk medicine users in various districts of Pakistan.

Figure 4: Disease-wise percentage of plants used for neurological diseases.

The pharmacological activities of plants are due to the presence of various phytochemicals mainly alkaloids, flavonoids, tannins, saponins, resins, glycosides, terpenoids, phenols, sterols, essential oils, vitamins, and nutrients. Some of these are effective in the treatment of neurological diseases; some are useful for cardiovascular, respiratory, and gastrointestinal diseases while others have chemotherapeutic and antibacterial effects. Some of the important phytochemicals of the plants (Table 4) including alkaloids (like nicotine and scopolamine) are reported to have anxiolytic, antidepressant, and anti-Parkinson activities [15–18], saponins (like bacosides) have been reported for anxiolytic, antiepileptic, antiamnesia, and neuroprotective and memory enhancement activities [19–22], terpenoids (like cannabigerol, tetrahydrocannabinol, and cannabidiol) are reported for their neuroprotective effects [23], flavonoids (like kaempferol, luteolin, quercetin, rutin, and hesperidin) have been reported for their anxiolytic, antidepressant, antiepileptic, anti-Alzheimer, and neuroprotective and memory enhancement activities [24–30], glycosides (like hastatoside and verbenalin) are reported for sleep promoting activity [31], steroids (like sitoindosides VII–X and withaferin-A) have been reported for anxiolytic activity [32].

Table 4: Phytochemical constituents and pharmacological properties of some well-known medicinal plants.

S.#
Medicinal Plants
Pharmacological Properties
Part used
Phytochemical Constituents
Chemical Compounds Identified
References

1
Allium sativum
1. Antidepressant
2. Anticonvulsant
3. Anti-Alzheimer
1. Dried bulbs
2. Oil
3. Whole garlic
Thiosulfinates, sapogenins phenols, saponins, volatile compounds, antioxidants, flavonoids, vitamins, minerals and proteins
Alliin, allixin, 1,2-vinyldithiin, ajoenes, S-allyl-cysteine sulfoxide, calcium, Potassium, vitamin B and vitamin C
[137–140]

2
Bacopa monnieri
1. Antidepressant
2. Anxiolytic
3. Anticonvulsant
4. Anti-Parkinson
1. Leaves
2. Stems and leaves
3. Leaves
4. Conc. tincture of plant
Alkaloid,tannin, saponin, phlobatannin, glycoside, terpenoid, flavonoid, sterols, phenol, steroid, anthraquinone and carbohydrate
Brahmin, nicotine, herpestine, bacosides A & B, hersaponin, betulic acid, monnierin, apigenin, b-sitosterol, stigma-sterol and luteolin
[33–36, 141]

3
Cannabis sativa
1. Antidepressant and anxiolytic
2. Anticonvulsant
3. Anti-Alzheimer and antidementia
4. Sedative
1. Leaves
2. Leaves
3. Flowers
4. Whole plant
Alkaloid, flavonoids, tannins, phenols, resins, cardiac glucosides, terpenes, steroids, volatile oils and balsam
Cannabinoids, cannabidiol, dronabinol, cannabigerol, tetrahydrocannabinolic acid, cannabichromenic acid, cannabidiolic acid, anandamide, cannabigerolic acid and cannabichromene
[37–40, 142, 143]

4
Hyoscyamus niger
1. Antidepressant
2. Anti-seizure
3. Anti-Parkinson
1. Leaves
2. Seeds
3. Seeds
Alkaloids, withanolide steroids, lignanamides, tyramine derivative, steroidal saponins, glycosides, lignans, coumarinolignan, and flavonoids
Apoatropine, L-DOPA, Cuscohygrine, choline Daturamine, Hyoscine, tropine, hyoscypicrin, phytin, aphoyoscine, alpha and beeta belladonine and Skimmianine
[144–148]

5
Solanum nigrum
1. Anti-seizure
2. Sedative
1. Leaves
2. Fruits
Alkaloids, flavonoids, tannins, saponins, glycosides, proteins, carbohydrates, coumarins and phytosterols
Pinoresinol, syringaresinol, medioresinol, scopoletin, tetracosanoic acid and beta-sitosterol
[149–152]

6
Withania somnifera
1. Anti-Parkinson
2. Anxiolytic and antidepressant
3. Anticonvulsant
1. Whole plant
2. Roots
3. Stems and roots
Alkaloids, steroidal lactones, saponins and iron
Withanolides, withaferins, Withanine, isopellertierine, anferine, Anahygrine, Cuscohygrine, Beta-Sisterol, Chlorogenic acid, Scopoletin, choline, Somniferiene, Somniferinine and Tropanol
[45–47, 153]

7
Papaver somniferum
1. Anticonvulsant
1. Seeds
Alkaloids, glycosides, tannins, Phytosterols, Terpenoids, Flavanoids and Carbohydrates
Morphine, Codeine, thebaine, noscapine, papaverine, Salutarifine, meconidine, codmine, neoprene, lanthothine, rophyroxine, narcotisline and papaveramine
[154–159]

8
Ziziphus jujube
1. Sedative and hypnotic
2. Anxiolytic
3. Anti-seizure
1. Seeds
2. Leaves
3. Fruits
Triterpenic acids, flavonoids, saponins, cerebrosides, amino acids, phenolic acids, vitamins, total sugars and nucleosides
Zizybeoside I and II, Chryseoriol, Swertisin, Quercetin, Jujubasaponin IV, Lotoside I and II, Zizyphus saponin I and II
[160]

9
Tribulus terrestris
1. Anxiolytic
2. Antidepressant
3. Sedative
1. Leaves
2. Whole plant
3. Whole plant
Saponins, flavonoids, glycosides, alkaloids and tannins
Tigogenin, neotigogenin, rutin, chlorogenin, caffeoyl, ruscogenin, kaempferol, tribulosid, terrestribisamide, quercetin, β-sitosterol, stigmasterols, harmane, norharmane and tribulusterine
[161–164]

10
Verbena officinalis
1. Antidepressant
2.Anticonvulsant, anxiolytic and sedative
1. Leaves
2. Whole plant
Alkaloids, flavonoids, diterpenes, proteins, amino acids, tannins, saponins, phytosterols and phenolic compounds
Verbenin, oleanolic acid, verbenalin, hastatoside, alpha-sitosterol, ursolic acid, kaempferol, aucubin, luteolin, verbascoside, apigenin, scutellarein, limonene and spathulenol
[42, 43]

11
Albizia lebbeck
1. Anticonvulsant
2. Nootropic and anxiolytic
1. Leaves
2. Leaves
Alkaloids, flavonoids, phenols, saponins; steroids and terpenoids
Albizia saponins A, B and C, albizinin, melacacidin, catechin lebbecacidin, friedelin, and β-sitosterol
[165–168]

12
Avena sativa
1. Antidepressant
2. Anxiolytic
1. Seeds
2. Whole plant
Carbohydrates, alkaloids, flavanoids, steroids, glycosides, saponins, amino acids, gums and mucilage
Gramine, flavone, apigenin and luteolin, flavonolignans, saponins and ferulic acid
[169–171]

13
Capparis decidua
1. Sedative and anticonvulsant
1. Flowers and fruits
Alkaloids, glycosides, terpenoids, sterols, flavanoids, phenols and fatty acids
Capparine, cappariline, capparinine, β-sitosterol, capparidisine, capparisine, codonocarpine, Capric acid, cadabacine, quercetin and rutin l-stachydrine
[172, 173]

14
Citrus limon
1. Anticonvulsant
2. Sedative, anxiolytic and antidepressant
1. Essential oil of leaves
2. Essential oil of leaves
Phenols, flavonoids, terpenoids, essential oils, carotenoids, citric acid and ascorbic acid
Limonene, α-pinene, β-pinene, linalool, α-terpineol, linalyl acetate, acetate geranyl, nerolidol, acetate neryl, farnesol, sabinene, myrcene, cineol and geranial
[174–176]

15
Citrullus colocynthis
1. Anticonvulsant
2. Antidepressant
1. Fruits
2. Fruits
Alkaloids, flavonoids, glycosides, saponosides, Phenolic compounds and ascorbic acid
Colocynthin, colocynthein, colocynthetin, Cucurbitane type triterpen glycoside, quercetin and Flavone
[15, 16, 177]

16
Datura metel
1. Antiepileptic
2. Sedative and hypnotics
1. Leaves
2. Seeds
Alkaloids, resins, flavonoids, reducing sugars, tannins, terpenoids and steroid glycosides
Hyoscyamine, scopolamine, atropine, daturabietatriene, daturasterol,, b-sitosterol and Melatonin and serotonin
[17–21]

17
Hypericum perforatum
1. Antidepressant
2. Anti-Parkinson
3. Neuroprotective
4. Anticonvulsant
5. Anti-Alzheimer
6. Anxiolytic and sedative
1. Flowers
2. Flowers and leaves
3. Whole plant
4. Flowers and leaves
5. Flowers
6. Flowers
Phenylpropanes, flavonoids, biflavones, phloroglucinols proanthocyanidins, amino acids, essential oil and naphthodianthrones
Hyperoside, adhyperforin Quercitrin, Rutin, Hypericin, Kaempferol, Biapigenin and Hyperforin
[22–28]

18
Jasminum grandiflorum
1. Antidepressant
2. Anticonvulsant
1. Essential oil of plant
2. Leaves
Coumarins, steroids, cardiac glycosides, essential oils, flavonoids, phenolics and saponins
Rutin, kaempferol, quercetin, β-primeveroside, kaempferol, hesperidin Methyl jasmonate, methyl anthranilate, linalool β-rutinoside, oleuropein and daucosterol
[29–31]

19
Lycopersicon esculentum
1. Antidepressant
2. Anticonvulsant
3. Memory enhancement
4. Anti-Parkinson
1. Fruits
2. Dried fruit extract
3. Dried fruit extract
4. Seeds
flavonoids, tannins, saponin, glycosides, Steroids, fatty acids, carbohydrates and proteins
Chlorogenic acid, rutin, naringenin, noradrenaline lycopene, dopamine, tomatin, tomatoside-A, ascorbic acid, bergapten, serotonin and adrenaline
[32, 178–180]

20
Ocimum basilicum
1. Antidepressant
2. Anticonvulsant
3. Anxiolytic and sedative
4. Enhance memory retention
1. Essential oil
2. Leaves
3. Aerial parts
4. Leaves
Terpenoids, essential oil, polyphenols, tannins and flavonoids
Cineole, geraniol, linalool, cadinol and sabinene, methyl chavicol, β-caryophyllene and neral, quercetin, myricetin, kaempferol, catechin and eugenol
[181–184]

21
Punica granatum
1. Antidepressant
2. Anxiolytic and anticonvulsant
3. Anti-Alzheimer
4. Memory enhancement
1. Fruits
2. Leaves
3. Fruits
4. Fruit’s peel
Flavonoids, glycosides, amino acids, pectin, indoleamines, tannins, sterols, polyphenols, carbohydrates, ellagitannins, anthocyanins and triterpenoid
Catechin, rutin, quercetin epicatechin, estriol, luteolin kaempferol, anthocyanins, gallagyldilacton, stigmasterol, β-sitosterol, testosterone, tocopherols and isoflavones
[185–188]

Bacopa monnieri plant is reported for anxiety, depressant, epilepsy, and Parkinsonism and contains alkaloids (Brahmin, nicotine, herpestine, and bacosides A & B), saponins (hersaponin and monnierin), flavonoids (luteolin and apigenin), and sterols like b-sitosterol and stigma-sterol. These constituents are already reported for such neuropharmacological properties and so might be responsible for said activities of this plant [33–36].

Cannabis sativa L. has been reported for the treatment of depression, anxiety, convulsion, Alzheimer, dementia, and insomnia and its constituents responsible for these properties are cannabigerol, tetrahydrocannabinol, and cannabidiol [37–41].

Verbena officinalis Linn. has been reported as anxiolytic, antidepressant, anticonvulsant, and sedative and its constituents responsible for these activities are verbenin, verbenalin, hastatoside, kaempferol, luteolin, verbascoside, aucubin, and apigenin [42–44].

Withania somnifera has been shown to have anxiolytic, antidepressant, anticonvulsant, and anti-Parkinson effects, mainly due to the presence of withanolides, sitoindosides VII–X, and withaferin-A [45–48].

These chemical constituents of plants act on the central nervous system through various mechanisms including regulation of neurotransmitters like adrenergic, cholinergic and serotonergic activity, acting through receptor like GABA and N-methyl-D-aspartate, and ion channels like sodium, potassium, and calcium ion channels. Some of the plant-based drugs and phytochemicals which either are approved or are under clinical trials for the treatment of neurological diseases, mechanism of actions, and their current status in clinical trials are given in (Table 5).

Table 5: The different phytochemicals effective in various neurological diseases and their current clinical phase status.

Sr #
Phytochemicals
Source
Family
Disease
Mechanism
Development stage
Trade Name
Reference

1
Cannabidiol
Cannabis sativa
Cannabaceae
Epilepsy
Modulation of intracellular calcium and neuronal inhibition
FDA approved, 2018
Epidiolex as 5- 10 mg/kg/day
[189]

2
Cannabidol
Cannabis sativa L.
Cannabaceae
Chronic Neuropathic pain
CB1 and CB2 receptor activation
FDA approved, 2005
Sativex Spray (CBD 25mg/ml + THC27mg/ml)
[190]

3
Capsaicin
Capsicum annum L.
Solanaceae
Postherpetic neuralgia
TRPV1 activator
FDA approved, 2010
Qutenza as Patch (179mg capsacin)
[190]

4
Curcumin
Curcuma longa
Zingiberaceae
Dementia
Anti-amyloid, AChEI
phase II

[191]

5
Galantamine
Galanthus nivalis
Amaryllidaceae
Alzheimer
AChEI, allosteric modulation of nicotinic ACh receptor
FDA approved, 2004
Razadyne as 8-12 mg BD
[192]

6
Huperzine A
Huperzia serrata
Huperziaceae
Alzheimer
AChEI, inhibits NMDA and glutamate toxicity
approved in China

[193]

7
Ibogaine
Tabernanthe iboga
Apocynaceae
Parkinson
Dopaminergic agonist, NMDA antagonism
preclinical

[193]

8
Psychollatine
Psychotria umbellate
Rubiaceae
Parkinson
MAO inhibitor
preclinical

[193]

9
Resveratrol
Vitis vinifera L.
Vitaceae
Alzheimer
Reduces Aβ formation and promote Aβ decomposition
phase II

[194]

10
Scyllo-Inositol
Cornus florida L.
Cornaceae
Alzheimer
Breakdown of neurotoxic fibrils, allowing amyloid peptides to clear the body rather than form amyloid plaques
phase II

[195]

FDA: food and drug administration; TRPV1: transient receptor potential vanilloid 1; CB1 and CB2: cannabinoid receptor type 1 & type 2; Ach: acetylcholine; AChEI: acetylcholinesterase inhibitor; CBD: cannabidiol; THC: tetrahydrocannabinol; BD: bis in die; NMDA: N-methyl-D-aspartate; MAO: monoamine oxidase; Aβ: amyloid beta.

Taking into consideration this useful knowledge on the medicinal properties of plants for curing neurologic diseases, it is believed that the research in the areas of ethnomedicine and ethnopharmacology can bring auspicious results that have potential of adding importance to the very rich natural resources of Pakistan. Various phytochemicals from the above medicinal plants can be further researched under clinical trials and better drugs for treatment of neurological diseases can be obtained with outstanding results and lesser side effects. This study will help all the researchers, especially from Asian countries including Pakistan, China, Iran, India, Sri Lanka, and Bangladesh, working on plants based medicine for neurological diseases.

4. Conclusion

The mental illnesses are one of the major problems of the world mainly in communities presenting with poor socioeconomic conditions. In Pakistan and other countries of this region, there is no accurate and up to date record of the neurological ailments. In order to find any treatment for these diseases, first realistic survey would be required to find out the exact percentage of various neurological diseases. Being an alarming psychiatric problem, Alzheimer opens a new area of research, affecting an enormous part of world population, but it is still untreatable. A lot of attempts have been conducted but still there is no such drug that can either slow or stop the process of Alzheimer disease. Allopathic medicines are available for psychological diseases including anxiety, depression, epilepsy, Parkison, and Alzheimer, but these are either not so effective or costly or have serious associated adverse effects. The world is full of natural medicinal resources, of which the main source is plant. We should invest money and go for systemic scientific investigations to perceive such drug candidates’ form these plants, which are most efficacious, have minor side effects, and are cost friendly. For this purpose, this study is a gift for researchers who have interest to design and perform research based activities in the field of neuropharmacology by evaluating the unexplored medicinal plants mentioned here for their folkloric uses, determining its mechanistic pathways and identifying chemical constituents responsible for therapeutic effects.

Data Availability

No personal data was collected from the interviewees and therefore no such data is kept or shared in any form.

Consent

Prior informed consent was obtained from all participants before conducting interviews. This manuscript does not contain any individual person’s data and further consent for publication is not required.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

Abdul Waheed Khan, Arif-ullah Khan, and Syed Muhammad Mukarram Shah designed the study, performed field work, and researched various medicinal plants articles on scientific search engines. Aziz Ullah, Muhammad Faheem, and Muhammad Saleem analyzed the data and drafted the manuscript. All authors read and approved the final manuscript.

Acknowledgments

The authors heartily thank all the contributors for taking part and sharing their valuable knowledge with us. They humbly acknowledge Mr. Muhammad Adnan, Mr. Mubashir Shahid, Mr. Rooh Ullah, Mr. Imran ul Haq, Mr. Najeeb Shah, Mr Rizwan Ullah, Ms Qurat ul Ain, Ms. Fizza Bukhari, and Ms Rubia Anwar for their continuous support in the dissemination and collection of the questionnaires in various districts of Pakistan.

References

G. Hussain, H. Anwar, A. Shahzad et al., “Neurological disorder burden in faisalabad, punjab-pakistan: data from the major tertiary carecenters of the city,” Pakistan Journal of Neurological Sciences (PJNS), vol. 12, no. 3, pp. 3–10, 2017.

S. Guo, “Using zebrafish to assess the impact of drugs on neural development and function,” Expert Opinion on Drug Discovery, vol. 4, no. 7, pp. 715–726, 2009.

A. A. Gadit, “State of mental health in Pakistan.,” Journal of the Pakistan Medical Association, vol. 51, no. 7, pp. 238-239, 2001.

S. Awan, S. Shafqat, A. K. Kamal et al., “Pattern of neurological diseases in adult outpatient neurology clinics in tertiary care hospital,” BMC Research Notes, vol. 10, no. 1, p. 545, 2017.

W. H. Organization, Neurological Disorders: Public Health Challenges, World Health Organization, 2006.

A. Sofowora, E. Ogunbodede, and A. Onayade, “The role and place of medicinal plants in the strategies for disease prevention,” The African Journal of Traditional, Complementary, and Alternative Medicines, vol. 10, no. 5, pp. 210–229, 2013.

N. H. Rakotoarivelo, F. Rakotoarivony, A. V. Ramarosandratana et al., “Medicinal plants used to treat the most frequent diseases encountered in Ambalabe rural community, Eastern Madagascar,” Journal of Ethnobiology and Ethnomedicine, vol. 11, no. 1, p. 68, 2015.

J. S. C. Júnior, A. B. Ferraz, T. O. Sousa et al., “Investigation of biological activities of dichloromethane and ethyl acetate fractions of platonia insignis mart. seed,” Basic & Clinical Pharmacology & Toxicology, vol. 112, no. 1, pp. 34–41, 2013.

M. Govindappa, “A review on role of plant (s) extracts and its phytochemicals for the management of diabetes,” Journal of Diabetes & Metabolism, vol. 6, no. 7, Article ID 1000565, 2015.

Y. Gupta, “Indian traditional medicine in neurological disorders,” Planta Medica, vol. 78, no. 05, p. OP19, 2012.

H. Kanwal and B. A. Sherazi, “Herbal medicine: trend of practice, perspective, and limitations in pakistan,” Asian Pacific Journal of Health Sciences, vol. 4, no. 4, pp. 6–8, 2017.

R. A. Qureshi, M. A. Ghufran, S. Gilani, Z. Yousaf, G. A. Miana, and A. Batool, “Indigenous medicinal plants used by local women in southern himalayan regions of pakistan,” Pakistan Journal of Botany, vol. 41, no. 1, pp. 19–25, 2009.

A. Mahmood, A. Mahmood, H. Shaheen, R. A. Qureshi, Y. Sangi, and S. A. Gilani, “Ethno medicinal survey of plants from district bhimber azad jammu and kashmir, pakistan,” Journal of Medicinal Plants Research, vol. 5, no. 11, pp. 2348–2360, 2011.

H. Bhatia, Y. P. Sharma, R. K. Manhas, and K. Kumar, “Ethnomedicinal plants used by the villagers of district Udhampur, J&K, India,” Journal of Ethnopharmacology, vol. 151, no. 2, pp. 1005–1018, 2014.

B. Pravin, D. Tushar, P. Vijay, and K. Kishanchnad, “Review on citrullus colocynthis,” International Journal of Research in Pharmaceutical Sciences, vol. 3, no. 1, pp. 46–53, 2013.

S. Mehrzadi, A. Shojaii, S. A. Pur, and M. Motevalian, “Anticonvulsant activity of hydroalcoholic extract of citrullus colocynthis fruit: involvement of benzodiazepine and opioid receptors,” Evidence-Based Complementary and Alternative Medicine, vol. 21, no. 4, pp. NP31–NP35, 2016.

M. Ali and M. Shuaib, “Characterization of the chemical constituents of datura mete/linn,” Indian Journal of Pharmaceutical Sciences, vol. 58, no. 6, pp. 243–245, 1996.

S. J. Murch, A. R. Alan, J. Cao, and P. K. Saxena, “Melatonin and serotonin in flowers and fruits of datura metel L,” Journal of Pineal Research, vol. 47, no. 3, pp. 277–283, 2009.

S. Babalola, M. Suleiman, A. Hassan, and D. Adawa, “Evaluation of datura metel L seed extract as a sedative/hypnotic: a priliminary study,” Journal of Veterinary Advances, vol. 5, no. 4, p. 857, 2015.

A. Tijani, U. Eyineyi, J. Ibrahim, and S. Okhale, “Neuro-toxicological impacts of datura metel linn. (family: solanaceae) leaves extract in mice,” The Journal of Neurobehavioral Sciences, vol. 2, no. 3, pp. 97–101, 2015.

C. Bhawana, S. Sushil, and S. Amit, “Evaluation of antiepileptic activity of datura metel leaf extract in experimental animal,” International Journal of Research in Pharmacy and Chemistry, vol. 6, no. 3, 2016.

A. Nahrstedt and V. Butterweck, “Biologically active and other chemical constituents of the herb of hypericum perforation L,” Pharmacopsychiatry, vol. 30, no. 2, pp. 129–134, 1997.

H. Hosseinzadeh, G.-R. Karimi, and M. Rakhshanizadeh, “Anticonvulsant effect of hypericum perforatum: role of nitric oxide,” Journal of Ethnopharmacology, vol. 98, no. 1-2, pp. 207-208, 2005.

A. Rezaie, K. R. Dorostkar, M. Pashazadeh, and S. M. Nejad, “Study of sedative and anxiolytic effects of herbal extract hypericum perforatum in comparison with diazepam in rats,” International Journal of Infectious Diseases, vol. 12, p. e171, 2008.

J. Tian, F. Zhang, J. Cheng, S. Guo, P. Liu, and H. Wang, “Antidepressant-like activity of adhyperforin, a novel constituent of hypericum perforatum L,” Scientific Reports, vol. 4, p. 5632, 2014.

D. D. Vecchia, M. G. Schamne, M. M. Ferro et al., “Effects of hypericum perforatum on turning behavior in an animal model of parkinson's disease,” Brazilian Journal of Pharmaceutical Sciences, vol. 51, no. 1, pp. 111–115, 2015.

A. I. Oliveira, C. Pinho, B. Sarmento, and A. C. P. Dias, “Neuroprotective activity of hypericum perforatum and its major components,” Frontiers in Plant Science, vol. 7, p. 1004, 2016.

K. Zerrouki, N. Djebli, E. E. Ozkan, N. Ozsoy, O. Gul, and A. Mat, “Hypericum perforatum improve memory and learning in alzheimer’s model: (experimental study in mice),” International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 8, pp. 49–57, 2016.

P. Kunhachan, C. Banchonglikitkul, T. Kajsongkram, A. Khayungarnnawee, and W. Leelamanit, “Chemical composition, toxicity and vasodilatation effect of the flowers extract of jasminum sambac (L.) ait. “g. duke of tuscany”,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 471312, 7 pages, 2012.

R. K. Gupta and P. S. Reddy, “Antinociceptive and anticonvulsant activities of hydroalcoholic extract of Jasminum grandiflorum (jasmine) leaves in experimental animals,” Pharmacognosy Research, vol. 5, no. 4, pp. 286–290, 2013.

S. Umukoro, A. Adebesin, G. Agu, O. Omorogbe, and S. B. Asehinde, “Antidepressant-like activity of methyl jasmonate involves modulation of monoaminergic pathways in mice,” Advances in Medical Sciences, vol. 63, no. 1, pp. 36–42, 2018.

P. Milind and M. Suman, “Eat tomato a day to keep depression at bay,” Asian Journal of Biological Sciences, vol. 4, no. 2, pp. 258–262, 2009.

S. K. Bhattacharya and S. Ghosal, “Anxiolytic activity of a standardized extract of Bacopa monniera: an experimental study,” Phytomedicine, vol. 5, no. 2, pp. 77–82, 1998.

D. Kaushik, A. Tripathi, R. Tripathi, M. Ganachari, and S. A. Khan, “Anticonvulsant activity of bacopa monniera in rodents,” Brazilian Journal of Pharmaceutical Sciences, vol. 45, no. 4, pp. 643–649, 2009.

P. Jadiya, A. Khan, S. R. Sammi, S. Kaur, S. S. Mir, and A. Nazir, “Anti-parkinsonian effects of bacopa monnieri: insights from transgenic and pharmacological caenorhabditis elegans models of parkinson's disease,” Biochemical and Biophysical Research Communications, vol. 413, no. 4, pp. 605–610, 2011.

M. A. Mannan, A. B. Abir, and M. R. Rahman, “Antidepressant-like effects of methanolic extract of bacopa monniera in mice,” BMC Complementary and Alternative Medicine, vol. 15, no. 1, p. 337, 2015.

E. A. Carlini and J. M. Cunha, “Hypnotic and antiepileptic effects of cannabidiol,” The Journal of Clinical Pharmacology, vol. 21, 1, no. 8-9, pp. 417S–427S, 1981.

J. T. Pickens, “Sedative activity of cannabis in relation to its Δ‘‐trans‐tetrahydrocannabinol and cannabidiol content,” British Journal of Pharmacology, vol. 72, no. 4, pp. 649–656, 1981.

L. Volicer, M. Stelly, J. Morris, J. McLaughlin, and B. J. Volicer, “Effects of dronabinol on anorexia and disturbed behavior in patients with alzheimer's disease,” International Journal of Geriatric Psychiatry, vol. 12, no. 9, pp. 913–919, 1997.

A. R. M. de Schier, N. P. O. de Ribeiro, D. S. Coutinho et al., “Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa,” CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), vol. 13, no. 6, pp. 953–960, 2014.

S. Valdeolivas, C. Navarrete, I. Cantarero, M. L. Bellido, E. Muñoz, and O. Sagredo, “Neuroprotective properties of cannabigerol in huntington’s disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice,” Neurotherapeutics, vol. 12, no. 1, pp. 185–199, 2015.

T. Jawaid, S. A. Imam, and M. Kamal, “Antidepressant activity of methanolic extract of Verbena Officinalis Linn. plant in mice,” Asian Journal of Pharmaceutical and Clinical Research, vol. 8, no. 4, pp. 308–310, 2015.

A. W. Khan, A.-U. Khan, and T. Ahmed, “Anticonvulsant, anxiolytic, and sedative activities of Verbena officinalis,” Frontiers in Pharmacology, vol. 7, 2016.

Y. Makino, S. Kondo, Y. Nishimura, Y. Tsukamoto, Z.-L. Huang, and Y. Urade, “Hastatoside and verbenalin are sleep‐promoting components in verbena officinalis,” Sleep and Biological Rhythms, vol. 7, no. 3, pp. 211–217, 2009.

S. K. Bhattacharya, A. Bhattacharya, K. Sairam, and S. Ghosal, “Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study,” Phytomedicine, vol. 7, no. 6, pp. 463–469, 2000.

M. Ahmad, S. Saleem, A. S. Ahmad et al., “Neuroprotective effects of Withania somnifera on 6-hydroxydopamine induced Parkinsonism in rats,” Human & Experimental Toxicology, vol. 24, no. 3, pp. 137–147, 2005.

S. K. Raju, P. L. Basavanna, H. N. Nagesh, and A. D. Shanbhag, “A study on the anticonvulsant activity of Withania somnifera (Dunal) in albino rats,” National Journal of Physiology, Pharmacy and Pharmacology, vol. 7, no. 1, pp. 17–21, 2017.

S. K. Bhattacharya, R. K. Goel, R. Kaur, and S. Ghosal, “Anti‐stress activity of sitoindosides VII and VIII, new acylsterylglucosides from withania somnifera,” Phytotherapy Research, vol. 1, no. 1, pp. 32–37, 1987.

R. C. Burch, S. Loder, E. Loder, and T. A. Smitherman, “The prevalence and burden of migraine and severe headache in the united states: updated statistics from government health surveillance studies,” Headache: The Journal of Head and Face Pain, vol. 55, no. 1, pp. 21–34, 2015.

D. Kadojić, M. Dikanović, M. Bitunjac, V. Vuletić, L. Čengić, and B. Bijelić, “Epidemiology of Stroke,” Periodicum Biologorum, vol. 114, no. 3, pp. 253–257, 2012.

G. Hussain, A. Rasul, H. Anwar et al., “Epidemiological data of neurological disorders in pakistan and neighboring countries: a review,” Pakistan Journal of Neurological Sciences (PJNS), vol. 12, no. 4, pp. 52–70, 2017.

W. H. Organization, Depression and Other Common Mental Disorders: Global Health Estimates, 2017.

D. M. Radhakrishnan and V. Goyal, “Parkinson's disease: a review,” Neurology India, vol. 66, no. 7, p. 26, 2018.

C. P. Ferri, M. Prince, C. Brayne et al., “Global prevalence of dementia: a Delphi consensus study,” The Lancet, vol. 366, no. 9503, pp. 2112–2117, 2005.

K. P. Peng and S. J. Wang, “Epidemiology of headache disorders in the a sia‐p acific region,” Headache: The Journal of Head and Face Pain, vol. 54, no. 4, pp. 610–618, 2014.

N. Venketasubramanian, B. W. Yoon, J. Pandian, and J. C. Navarro, “Stroke epidemiology in south, east, and south-east asia: A review,” Journal of Stroke, vol. 19, no. 3, pp. 286–294, 2017.

S. Churl, “The worldwide prevalence of epilepsy: a systematic review and meta-analysis,” Epilepsy Currents, vol. 13, p. 322, 2013.

O. Remes, C. Brayne, R. van der Linde, and L. Lafortune, “A systematic review of reviews on the prevalence of anxiety disorders in adult populations,” Brain and Behavior, vol. 6, no. 7, p. e00497, 2016.

T. Pringsheim, N. Jette, A. Frolkis, and T. D. L. Steeves, “The prevalence of parkinson's disease: a systematic review and meta-analysis,” Movement Disorders, vol. 29, no. 13, pp. 1583–1590, 2014.

Y. W. Woldeamanuel, A. P. Andreou, and R. P. Cowan, “Prevalence of migraine headache and its weight on neurological burden in Africa: A 43-year systematic review and meta-analysis of community-based studies,” Journal of the Neurological Sciences, vol. 342, no. 1-2, pp. 1–15, 2014.

D. Adeloye, “An estimate of the incidence and prevalence of stroke in Africa: A systematic review and meta-analysis,” PLoS ONE, vol. 9, no. 6, p. e100724, 2014.

Diseases, O.M.d.l.S.P.f.N et al., Atlas: Epilepsy Care in The World, World Health Organization, 2005.

D. G. Massi, “Epidemiology of Parkinsons disease in Africa: Challenges and opportunities. Parkinsonism Related Disorders,” in Epidemiology of Parkinson’s disease in Africa: Challenges and opportunities. Parkinsonism Related Disorders, pp. 46–e10, p. e10, 46, 2018.

R. B. Lipton and M. E. Bigal, “Migraine: epidemiology, impact, and risk factors for progression,” Headache: The Journal of Head and Face Pain, vol. 45, pp. S3–S13, 2005.

D. Mozaffarian, E. J. Benjamin, A. S. Go et al., “Heart disease and stroke statistics—2016 update: a report from the american heart association,” Circulation, p. CIR. 0000000000000350, 2015.

W. H. Theodore, S. S. Spencer, S. Wiebe et al., “Epilepsy in north america: a report prepared under the auspices of the global campaign against epilepsy, the international bureau for epilepsy, the international league against epilepsy, and the world health organization,” Epilepsia, vol. 47, no. 10, pp. 1700–1722, 2006.

G. Y. Lim, W. W. Tam, Y. Lu, C. S. Ho, M. W. Zhang, and R. C. Ho, “Prevalence of depression in the community from 30 countries between 1994 and 2014,” Scientific Reports, vol. 8, no. 1, p. 2861, 2018.

G. Saposnik and O. H. D. Brutto, “Stroke in South America: a systematic review of incidence, prevalence, and stroke subtypes,” Stroke, vol. 34, no. 9, pp. 2103–2107, 2003.

A. J. Baxter, K. M. Scott, T. Vos, and H. A. Whiteford, “Global prevalence of anxiety disorders: a systematic review and meta-regression,” Psychological Medicine, vol. 43, no. 5, pp. 897–910, 2013.

L. J. Stovner and C. Andree, “Prevalence of headache in europe: a review for the eurolight project,” The Journal of Headache and Pain, vol. 11, no. 4, pp. 289–299, 2010.

N. P. Şensöz, Ü. T. Börü, C. Bölük et al., “Stroke epidemiology in Karabük city Turkey: Community based study,” eNeurologicalSci, vol. 10, pp. 12–15, 2018.

M. d. de Rijk, C. Tzourio, M. M. Breteler et al., “Prevalence of parkinsonism and parkinson's disease in europe: the europarkinson collaborative study. european community concerted action on the epidemiology of parkinson's disease,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 62, no. 1, pp. 10–15, 1997.

E. Shao, J. Hughes, and R. Eley, “The presenting and prescribing patterns of migraine in an australian emergency department: a descriptive exploratory study,” World Journal of Emergency Medicine, vol. 8, no. 3, p. 170, 2017.

W. A. D. o. Health, Epidemiology Profile of Neurological Conditions in Western Australia, Health Strategy and Networks Branch, Australia, 2015.

M. Bellon, R. J. Panelli, and F. Rillotta, “Epilepsy-related deaths: An Australian survey of the experiences and needs of people bereaved by epilepsy,” Seizure, vol. 29, pp. 162–168, 2015.

P. Mehta, A. Kifley, J. J. Wang, E. Rochtchina, P. Mitchell, and C. M. Sue, “Population prevalence and incidence of Parkinson’s disease in an Australian community,” Internal Medicine Journal, vol. 37, no. 12, pp. 812–814, 2007.

M. Prince, R. Bryce, E. Albanese, A. Wimo, W. Ribeiro, and C. P. Ferri, “The global prevalence of dementia: a systematic review and metaanalysis,” Alzheimer’s & Dementia, vol. 9, no. 1, Article ID e2, pp. 63–75, 2013.

B. Ray, N. Paul, A. Hazra et al., “Prevalence, burden, and risk factors of migraine: a community-based study from eastern india,” Neurology India, vol. 65, no. 6, pp. 1280–1288, 2017.

M. I. khan, J. I. Khan, S. I. Ahmed, and U. U. Haq, “The epidemiology of stroke in a developing country (Pakistan),” Journal of Neurology & Stroke, vol. 8, no. 1, 2018.

H. Ebrahimi, M. Shafa, and S. H. Asl, “Prevalence of active epilepsy in kerman, iran: a house based survey,” Acta Neurologica Taiwanica, vol. 21, no. 3, pp. 115–124, 2012.

A. K. Verma, J. Raj, V. Sharma, T. B. Singh, S. Srivastava, and R. Srivastava, “Epidemiology and associated risk factors of parkinson's disease among the north indian population,” Clinical Epidemiology and Global Health, vol. 5, no. 1, pp. 8–13, 2017.

P. S. Mathuranath, A. George, N. Ranjith et al., “Incidence of alzheimer’s disease in india: a 10 yearsfollow-up study,” Neurology India, vol. 60, no. 6, p. 625, 2012.

S.-M. Fereshtehnejad, M. Shafieesabet, A. Rahmani, A. Delbari, and J. Lökk, “Medium-to-high prevalence of screening-detected parkinsonism in the urban area of Tehran, Iran: Data from a community-based door-to-door study,” Neuropsychiatric Disease and Treatment, vol. 11, pp. 321–332, 2015.

S. Gholamzadeh, B. Heshmati, A. Manni, P. Petramfar, and Z. Baghery, “The prevalence of Alzheimer’s disease; its risk and protective factors among the elderly population in Iran,” Shiraz E Medical Journal, vol. 18, no. 9, 2017.

J. Ni, F. Han, J. Yuan et al., “The discrepancy of neurological diseases between china and western countries in recent two decades,” Chinese Medical Journal, vol. 131, no. 8, pp. 886–891, 2018.

L. J. Stovner, E. Nichols, T. J. Steiner et al., “Global, regional, and national burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the global burden of disease study 2016,” The Lancet Neurology, vol. 17, no. 11, pp. 954–976, 2018.

V. L. Feigin, M. H. Forouzanfar, R. Krishnamurthi et al., “Global and regional burden of stroke during 1990–2010: findings from the global burden of disease study 2010,” The Lancet, vol. 383, no. 9913, pp. 245–255, 2014.

P. Ventevogel, W. van de Put, H. Faiz, B. van Mierlo, M. Siddiqi, and I. H. Komproe, “Improving access to mental health care and psychosocial support within a fragile context: a case study from afghanistan,” PLoS Medicine, vol. 9, no. 5, p. e1001225, 2012.

S.-M. Shin, H. J. Kim, L. Liw, and S. Kim, “Depression and PTSD in pashtun women in kandahar, afghanistan,” Asian Nursing Research, vol. 3, no. 2, pp. 90–98, 2009.

E. R. Dorsey, A. Elbaz, E. Nichols et al., “Global, regional, and national burden of parkinson's disease, 1990–2016: a systematic analysis for the global burden of disease study 2016,” The Lancet Neurology, vol. 17, no. 11, pp. 939–953, 2018.

G. Miller, “A battle no soldier wants to fight,” American Association for the Advancement of Science, vol. 333, no. 6042, pp. 517-518, 2011.

D. Santarsieri and T. L. Schwartz, “Antidepressant efficacy and side-effect burden: a quick guide for clinicians,” Drugs in Context, vol. 4, 2015.

J. M. Ferguson, “SSRI antidepressant medications: adverse effects and tolerability,” Primary Care Companion to the Journal of Clinical Psychiatry, vol. 3, no. 1, pp. 22–27, 2001.

A. F. Carvalho, M. S. Sharma, A. R. Brunoni, E. Vieta, and G. A. Fava, “The safety, tolerability and risks associated with the use of newer generation antidepressant drugs: a critical review of the literature,” Psychotherapy and Psychosomatics, vol. 85, no. 5, pp. 270–288, 2016.

C. E. Griffin III, A. M. Kaye, F. R. Bueno, and A. D. Kaye, “Benzodiazepine pharmacology and central nervous system-mediated effects,” Ochsner Journal, vol. 13, no. 2, pp. 214–223, 2013.

F. Batool, “Buspirone and anxiety disorders: a review with pharmacological and clinical perspectives,” The Internet Journal of Pharmacology, vol. 5, no. 2, 2007.

H. M. Kwon, J. W. Baek, S. P. Lee, and J. I. Cho, “A fatal adverse effect of barbiturate coma therapy: dyskalemia,” Korean Journal of Neurotrauma, vol. 12, no. 2, pp. 156–158, 2016.

F. Stella, M. Radanovic, P. R. Canineu, V. J. R. de Paula, and O. V. Forlenza, “Anti-dementia medications: current prescriptions in clinical practice and new agents in progress,” Therapeutic Advances in Drug Safety, vol. 6, no. 4, pp. 151–165, 2015.

Y.-J. Huang, C.-H. Lin, H.-Y. Lane, and G. E. Tsai, “NMDA neurotransmission dysfunction in behavioral and psychological symptoms of Alzheimer's disease,” Current Neuropharmacology, vol. 10, no. 3, pp. 272–285, 2012.

V. S. C. Fung, M. A. Hely, G. De Moore, and J. G. L. Morris, “Drugs for parkinson's disease,” Australian Prescriber, vol. 24, no. 4, pp. 92–95, 2001.

M. J. Brodie, “Sodium channel blockers in the treatment of epilepsy,” CNS Drugs, vol. 31, no. 7, pp. 527–534, 2017.

B. J. Kopecky, R. Liang, and J. Bao, “T-type calcium channel blockers as neuroprotective agents,” Pflügers Archiv - European Journal of Physiology, vol. 466, no. 4, pp. 757–765, 2014.

J. T. Lerner, N. Salamon, and R. Sankar, “Clinical profile of vigabatrin as monotherapy for treatment of infantile spasms,” Neuropsychiatric Disease and Treatment, vol. 6, p. 731, 2010.

R. Qureshi, M. Ilyas, G. Rahim, W. Ahmad, H. Shaheen, and K. Ullah, “Ethnobotanical study of bhera, district sargodha, pakistan,” Archives Des Sciences, vol. 65, no. 11, pp. 690–707, 2012.

T. A. Alamgeer, M. Rashid, M. N. H. Malik, and M. N. Mushtaq, “Ethnomedicinal survey of plants of valley alladand dehri, tehsil batkhela, district malakand, pakistan,” International Journal of Basic Medical Sciences and Pharmacy (IJBMSP), vol. 3, no. 1, 2013.

A. Shah, S. K. Marwat, and F. Gohar, “Ethnobotanical study of medicinal plants of semi-tribal area of Makerwal &amp; Gulla Khel (lying between Khyber Pakhtunkhwa and Punjab Provinces), Pakistan,” American Journal of Plant Sciences, vol. 4, no. 01, p. 98, 2013.

I. Iqbal and M. Hamayun, “Studies on the traditional uses of plants of malam jabba valley, district swat, pakistan,” Ethnobotanical Leaflets, vol. 2004, no. 1, p. 15, 2004.

A. Hazrat, M. Nisar, J. Shah, and S. Ahmad, “Ethnobotanical study of some elite plants belonging to dir, kohistan valley, khyber pukhtunkhwa, pakistan,” Pakistan Journal of Botany, vol. 43, no. 2, pp. 787–795, 2011.

M. Haider and L. Zhong, “Ethno-medicinal uses of plants from district bahawalpur, pakistan,” Current Research Journal of Biological Sciences, vol. 6, pp. 183–190, 2014.

A. A. Shah, M. Ramzan, and R. Saba, “Ethnoecological studies of herbs and shrubs of miani sahib graveyard, lahore city, punjab, pakistan,” Journal of Bioresource Management, vol. 3, no. 2, p. 5, 2016.

A. B. Gulshan, A. A. Dasti, S. Hussain, M. I. Atta, and M. Amin-ud-Din, “Indigenous uses of medicinal plants in rural areas of dera ghazi khan, punjab, pakistan,” Journal of Agricultural & Biological Science, vol. 7, no. 9, pp. 750–762, 2012.

S. S. Ahmad, “Medicinal wild plants from lahore-islamabad motorway (M-2),” Pakistan Journal of Botany, vol. 39, no. 2, pp. 355–375, 2007.

M. Ajaib, Z. Khan, and A. Zikrea, “Ethnobotanical survey of some important herbaceous plants of district kotli, azad jammu & kashmir,” Biologia (Pakistan), vol. 60, no. 1, pp. 11–22, 2014.

S. U. Khan, R. U. Khan, I. Ullah, S. Mehmood, A. Muhammad, and M. Ullah, “Morpho-anatomical study of selected plants of district bannu, khyber pakhtunkhwa, pakistan,” Pakistan Journal of Weed Science Research, vol. 19, no. 4, pp. 447–464, 2013.

A. Noman, I. Hussain, Q. Ali, M. A. Ashraf, and M. Z. Haider, “Ethnobotanical studies of potential wild medicinal plants of ormara, gawadar, pakistan,” Emirates Journal of Food and Agriculture, vol. 25, no. 10, pp. 751–759, 2013.

M. R. Awan, Z. Jamal, and A. Khan, “Ethno-botanical studies of economically important plants from mountainous region of Gilgit-Baltistan,” Science, Technology and Development, vol. 32, pp. 308–318, 2013.

S. Z. Husain, R. N. Malik, M. Javaid, and S. Bibi, “Ethonobotanical properties and uses of medicinal plants of morgah biodiversity park, rawalpindi,” Pakistan Journal of Botany, vol. 40, no. 5, pp. 1897–1911, 2008.

A. Shah, S. Rahim, K. H. Bhatti et al., “Ethnobotanical study and conservation status of trees in the district sargodha, punjab, pakistan,” Phyton, International Journal of Experimental Botany, vol. 84, no. 1, pp. 34–44, 2016.

M. Umair, M. Altaf, and A. M. Abbasi, “An ethnobotanical survey of indigenous medicinal plants in hafizabad district, Punjab-Pakistan,” PLoS ONE, vol. 12, no. 6, Article ID e0177912, 2017.

H. Iqbal, Z. Sher, and Z. U. Khan, “Medicinal plants from salt range pind dadan khan, district jhelum, punjab, pakistan,” Journal of Medicinal Plants Research, vol. 5, no. 11, pp. 2157–2168, 2011.

W. Murad, A. Ahmad, G. Ishaq, M. S. Khan, M. A. H. Khan, and I. Ullah, “Ethnobotanical studies on plant resources of hazar nao forest, district malakand, pakistan,” Pakistan Journal of Weed Science Research, vol. 18, no. 4, 2012.

Z. I. Awan, H. Rehman, A. A. Awan, F. A. Minhas, and M. N. Khan, “Ethnobotanical importance of some highly medicinal plants of district muzaffarabad, pakistan with special reference to the species of the genus viburnum,” IOSR Journal of Pharmacy and Biological Sciences, vol. 6, no. 2, pp. 53–66, 2013.

A. M. Hussain, M. S. A. Abbasi, N. Hussain, and S. A. Majid, “A survey of important indigenous medicinal plants of district bhimber azad jammu & kashmir, pakistan,” International Journal of Advanced Research, vol. 1, pp. 635–644, 2013.

M. F. Nisar, F. Jaleel, and S. M. Haider, “Exploration of ethno-medicinal plants and their ritual uses in bahawalnagar, pakistan,” Middle-East Journal of Scientific Research, vol. 21, no. 9, pp. 1466–1471, 2014.

A. T. Khalil, Z. K. Shinwari, M. Qaiser, and K. B. Marwat, “Phyto-therapeutic claims about euphorbeaceous plants belonging to pakistan; an ethnomedicinal review,” Pakistan Journal of Botany, vol. 46, no. 3, pp. 1137–1144, 2014.

S. M. Wazir, A. A. Dasti, and J. Shah, “Common medicinal plants of chapursan valley, gojal ii, gilgit-pakistan,” Journal of Research (Science) Bahauddin Zakariya University, Multan, Pakistan, vol. 15, pp. 41–43, 2004.

A. M. M. Kanwal, S. Shaukat, R. Javed, and R. Ilyas, “Exploration of ethnomedicinal values of imperative plants of district gujrat, pakistan,” Middle-East Journal of Scientific Research, vol. 7, pp. 397–400, 2011.

A. M. Sarangzai, A. Ahmed, and S. K. Laghari, “Traditional uses of some useful medicinal plants of ziarat district balochistan, pakistan,” FUUAST Journal of Biology, vol. 3, no. 1, p. 101, 2013.

A. Ghani, Z. Ali, and S. Perveen, “Folk recipes and ethno botanical survey of medicinal plants mianwali district (pakistan),” International Journal of Current Pharmaceutical Research, vol. 4, no. 2, pp. 61–63, 2012.

Z. Sher, Z. U. D. Khan, and F. Hussain, “Ethnobotanical studies of some plants of chagharzai valley, district buner, pakistan,” Pakistan Journal of Botany, vol. 43, no. 3, pp. 1445–1452, 2011.

M. Shuaib and I. Khan, “Study of Medicinal Plants of Lower Dir, Timergara, Tehsil Balambat, Khyber Paktunkhaw-Pakistan,” American-Eurasian Journal of Agricultural & Environmental Sciences, vol. 2015., 15, p. 2088, 2088.

I. Ahmad, M. Ibrar, Barkatullah, and N. Ali, “Ethnobotanical study of tehsil kabal, swat district, KPK, pakistan,” Journal of Botany, vol. 2011, Article ID 368572, 9 pages, 2011.

M. Ilyas, R. Qureshi, Z. K. Shinwari, M. Arshad, S. N. Mirza, and Zia-Ul-Haq, “Some ethnoecological aspects of the plants of qalagai hills, kabal valley, swat, pakistan,” International Journal of Agriculture and Biology, vol. 15, no. 5, pp. 801–810, 2013.

N. Ahmad, S. Anwar, H. Fazal, and B. H. Abbasi, “Medicinal plants used in indigenous herapy by people of madyan valley in district swat, pakistan,” International Journal of Medicinal and Aromatic Plants, vol. 3, no. 1, pp. 47–54, 2013.

F. Haq, H. Ahmad, and M. Alam, “Traditional uses of medicinal plants of nandiar khuwarr catchment (district battagram), pakistan,” Journal of Medicinal Plants Research, vol. 5, no. 1, pp. 39–48, 2011.

R. A. Qureshi and M. A. Ghufran, “Indigenous knowledge of selected medicinal wild plants of district attock, punjab, pakistan,” Pakistan Journal of Botany, vol. 39, pp. 2291–2299., 2007.

N. B. Chauhan and J. Sandoval, “Amelioration of early cognitive deficits by aged garlic extract in alzheimer's transgenic mice,” Phytotherapy Research, vol. 21, no. 7, pp. 629–640, 2007.

D. Dhingra and V. Kumar, “Evidences for the involvement of monoaminergic and GABAergic systems in antidepressant-like activity of garlic extract in mice,” Indian Journal of Pharmacology, vol. 40, no. 4, pp. 175–179, 2008.

U. Advani, A. Ansari, and E. Menghani, “Anticonvulsant potentials of sesamum indicum and allium sativum oil alone and in combination in animal models,” International Journal of Pharmacy and Pharmaceutical Sciences, vol. 3, 4, pp. 154–158, 2011.

N. Martins, S. Petropoulos, and I. C. F. R. Ferreira, “Chemical composition and bioactive compounds of garlic (Allium sativum L.) as affected by pre- and post-harvest conditions: A review,” Food Chemistry, vol. 211, pp. 41–50, 2016.

P. Jain, H. P. Sharma, F. Basri, K. Priya, and P. Singh, “Phytochemical analysis of bacopa monnieri (L.) wettst. and their anti-fungal activities,” Indian Journal of Traditional Knowledge, vol. 16, no. 2, pp. 310–318, 2017.

E. B. Russo, “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects,” British Journal of Pharmacology, vol. 163, no. 7, pp. 1344–1364, 2011.

B. S. Audu, P. C. Ofojekwu, A. Ujah, and M. N. O. Ajima, “Phytochemical, proximate composition, amino acid profile and characterization of marijuana (cannabis sativa L.),” The Journal of Phytopharmacology, vol. 3, no. 1, pp. 35–43, 2014.

H. M. Reza, H. Mohammad, E. Golnaz, and S. Gholamreza, “Effect of methanolic extract of hyoscymus niger L. on the seizure induced by picritoxin in mice,” Pakistan Journal of Pharmaceutical Sciences, vol. 22, no. 3, pp. 308–312, 2009.

J. Li, J. Shi, X.-W. Yu et al., “Chemical and pharmacological researches on Hyoscyamus niger,” Chinese Herbal Medicine, vol. 3, pp. 117–126, 2011.

T. Sengupta, J. Vinayagam, N. Nagashayana, B. Gowda, P. Jaisankar, and K. P. Mohanakumar, “Antiparkinsonian effects of aqueous methanolic extract of Hyoscyamus niger seeds result from its monoamine oxidase inhibitory and hydroxyl radical scavenging potency,” Neurochemical Research, vol. 36, no. 1, pp. 177–186, 2011.

J. Talairach and P. Thournoux, Co-Planar Stereotaxic Atlas of the Human Brain, Thieme Medical Publishers, Stuttgart, Germany, 1988.

K. Aparna, A. Joshi, and M. Vyas, “Adverse reaction of Parasika Yavani (Hyoscyamus niger Linn): Two case study reports,” AYU (An International Quarterly Journal of Research in Ayurveda), vol. 36, no. 2, p. 174, 2015.

R. M. Perez G., J. A. Perez L., L. M. Garcia D., and H. Sossa M., “Neuropharmacological activity of Solanum nigrum fruit,” Journal of Ethnopharmacology, vol. 62, no. 1, pp. 43–48, 1998.

N. N. Wannang, J. A. Anuka, H. O. Kwanashie, S. S. Gyang, and A. Auta, “Anti-seizure activity of the aqueous leaf extract of Solanum nigrum Linn. (solanaceae) in experimental animals,” African Health Sciences, vol. 8, no. 2, pp. 74–79, 2008.

Y. Zhao, F. Liu, and H.-X. Lou, “[Studies on the chemical constituents of Solanum nigrum].,” Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials, vol. 33, no. 4, pp. 555-556, 2010.

M. A. B. Nyeem, “Solanum nigrum (Maku): A review of pharmacological activities and clinical effects,” IJAR, vol. 3, no. 1, pp. 12–17, 2017.

S. C. Kaul and R. Wadhwa, Science of Ashwagandha: Preventive and Therapeutic Potentials, Springer International Publishing, Cham, 2017.

W.-H. Peng, M.-T. Hsieh, Y.-S. Lee, Y.-C. Lin, and J. Liao, “Anxiolytic effect of seed of Ziziphus jujuba in mouse models of anxiety,” Journal of Ethnopharmacology, vol. 72, no. 3, pp. 435–441, 2000.

J.-G. Jiang, X.-J. Huang, and J. Chen, “Comparison of the sedative and hypnotic effects of flavonoids, saponins, and polysaccharides extracted from Semen Ziziphus Jujube,” Natural Product Research (Formerly Natural Product Letters), vol. 21, no. 4, pp. 310–320, 2007.

M. Pahuja, J. Mehla, K. H. Reeta, S. Joshi, and Y. K. Gupta, “Hydroalcoholic extract of Zizyphus jujuba ameliorates seizures, oxidative stress, and cognitive impairment in experimental models of epilepsy in rats,” Epilepsy & Behavior, vol. 21, no. 4, pp. 356–363, 2011.

S. Kumaravel and K. Alagusundaram, “Antimicrobial activity and Phytochemical analysis of selected Indian spices,” Journal of Pure and Applied Microbiology, vol. 8, no. 5, pp. 4131–4136, 2014.

R. Sabbaghzadeh and M. Asadbegi, “Effects of Methanolic extracts of Papaver Somniferum on Picrotoxin induced seizure in mice,” Advances in Environmental Biology, vol. 8, no. 10, pp. 740–743, 2014.

I. Rayment, H. M. Holden, M. Whittaker et al., “Structure of the actin-myosin complex and its implications for muscle contraction,” Science, vol. 261, no. 5117, pp. 58–65, 1993.

S. Wang, J. Zhang, Z. Zhang et al., “Identification of chemical constituents in the extract and rat serum from Ziziphus Jujuba mill. By HPLC-PDA-ESI-MSn,” Iranian Journal of Pharmaceutical Research, vol. 13, no. 3, pp. 1055–1064, 2014.

Z. Wang, D. Zhang, S. Hui, Y. Zhang, and S. Hu, “Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stress depression rats,” Journal of Traditional Chinese Medicine, vol. 33, no. 2, pp. 228–232, 2013.

S. Ahmed, S. Lutfullah, I. Ahmed, R. Farooq, and J. Iqbal, “Anxiolytic activity of Tribulus terrestris on elevated plus maze,” Journal of Applied Pharmaceutical Science, vol. 4, no. 2, pp. 126–128, 2014.

S. Chhatre, T. Nesari, G. Somani, D. Kanchan, and S. Sathaye, “Phytopharmacological overview of Tribulus terrestris,” Pharmacognosy Reviews, vol. 8, no. 15, pp. 45–51, 2014.

O. A. Phillips, K. T. Mathew, and M. A. Oriowo, “Antihypertensive and vasodilator effects of methanolic and aqueous extracts of Tribulus terrestris in rats,” Journal of Ethnopharmacology, vol. 104, no. 3, pp. 351–355, 2006.

V. S. Kasture, C. T. Chopde, and V. K. Deshmukh, “Anticonvulsive activity of Albizzia lebbeck, Hibiscus rosa sinesis and Butea monosperma in experimental animals,” Journal of Ethnopharmacology, vol. 71, no. 1-2, pp. 65–75, 2000.

H. D. Une, V. P. Sarveiya, S. C. Pal, V. S. Kasture, and S. B. Kasture, “Nootropic and anxiolytic activity of saponins of Albizzia lebbeck leaves,” Pharmacology Biochemistry & Behavior, vol. 69, no. 3-4, pp. 439–444, 2001.

V. Padamanabhan, M. Ganapathy, and V. K. Evanjelene, “Preliminary phytochemical and anti-bacterial studies on flowers and pods of Albizia lebbeck (Benth),” International Journal of Emerging Technology and Advanced Engineering, vol. 3, no. 9, pp. 541–544, 2013.

S. Desai, P. Tatke, and S. Gabhe, “Isolation of catechin from stem bark of Albizia lebbeck,” International Journal of Analytical, Pharmaceutical and Biomedical Sciences, vol. 3, no. 2, pp. 31–35, 2014.

R. Singh, S. De, and A. Belkheir, “Avena sativa (oat), a potential neutraceutical and therapeutic agent: an overview,” Critical Reviews in Food Science and Nutrition, vol. 53, no. 2, pp. 126–144, 2013.

K. Usha Rani, M. Ramaiah, K. Nagaphani, V. Preethi, and M. Srinadh, “Screening for antidepressant-like effect of methanolic seed extract of Avena sativa using animal models,” Pharmacognosy Journal, vol. 6, no. 3, pp. 86–92, 2014.

D. Kaur, A. Kamboj, and R. Shri, “Comparative evaluation of anxiolytic effects of various extracts of oats (Avena sativa), rice bran (Oryza sativa) and spinach (Spinacia oleracea) in experimental animals,” International Journal of Pharmaceutical Sciences and Research, vol. 7, no. 10, p. 4110, 2016.

M. Goyal, B. P. Nagori, and D. Sasmal, “Sedative and anticonvulsant effects of an alcoholic extract of Capparis decidua,” Journal of Natural Medicines, vol. 63, no. 4, pp. 375–379, 2009.

P. D. Verma, R. D. Dangar, K. N. Shah, D. M. Gandhi, and B. N. Suhagia, “Pharmacognostical potential of Capparis decidua Edgew,” Journal of Applied Pharmaceutical Science, vol. 1, no. 10, pp. 6–11, 2011.

L. M. Campêlo, S. G. Lima, C. M. Feitosa, and R. M. Freitas, “Evaluation of central nervous system effects of Citrus limon essential oil in mice,” Revista Brasileira de Farmacognosia, vol. 21, no. 4, pp. 668–673, 2011.

L. M. Lopes Campêlo, C. Gonçalves e Sá, A. A. C. de Almeida et al., “Sedative, anxiolytic and antidepressant activities of Citrus limon (Burn) essential oil in mice,” Die Pharmazie-An International Journal of Pharmaceutical Sciences, vol. 66, no. 8, pp. 623–627, 2011.

A. Ben Hsouna, N. Ben Halima, S. Smaoui, and N. Hamdi, “Citrus lemon essential oil: Chemical composition, antioxidant and antimicrobial activities with its preservative effect against Listeria monocytogenes inoculated in minced beef meat,” Lipids in Health and Disease, vol. 16, no. 1, 2017.

S. Najafi, N. Sanadgol, B. S. Nejad, M. A. Beiragi, and E. Sanadgol, “Phytochemical screening and antibacterial activity of Citrullus colocynthis (Linn.) schrad against Staphylococcus aureus,” Journal of Medicinal Plants Research, vol. 4, no. 22, pp. 2321–2325, 2010.

V. Kumar, S. K. Sharma, K. Nagarajan, and P. K. Dixit, “Effects of lycopene and sodium valproate on pentylenetetrazol-induced kindling in mice,” Iranian Journal of Medical Sciences, vol. 41, no. 5, pp. 430–436, 2016.

K. Gokul, “Oral supplements of aqueous extract of tomato seeds alleviate motor abnormality, oxidative impairments and neurotoxicity induced by rotenone in mice: relevance to Parkinson's disease,” Neurochemical Research, vol. 39, no. 7, pp. 1382–1394, 2014.

J. Bae, M. Han, H. Shin et al., “Lycopersicon esculentum extract enhances cognitive function and hippocampal neurogenesis in aged mice,” Nutrients, vol. 8, no. 11, p. 679, 2016.

J. S. Oliveira, L. A. Porto, and C. S. Estevam, “Phytochemical screening and anticonvulsant property of Ocimum basilicum leaf essential oil,” Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas, vol. 8, no. 3, 2009.

S. Sarahroodi, S. Esmaeili, Z. Hemmati, P. Mikaili, and Y. Saberi, “The effects of green Ocimum basilicum hydroalcoholic extract on retention and retrieval of memory in mice,” Ancient Science of Life, vol. 31, no. 4, p. 185, 2012.

M. Rabbani, S. E. Sajjadi, and A. Vaezi, “Evaluation of anxiolytic and sedative effect of essential oil and hydroalcoholic extract of Ocimum basilicum L. and chemical composition of its essential oil,” Research in Pharmaceutical Sciences, vol. 10, no. 6, pp. 535–543, 2015.

S. S. Ali, M. G. Abd El Wahab, N. N. Ayuob, and M. Suliaman, “The antidepressant-like effect of Ocimum basilicum in an animal model of depression,” Biotechnic & Histochemistry, vol. 92, no. 6, pp. 390–401, 2017.

S. Adiga, P. Trivedi, V. Ravichandra, D. Deb, and F. Mehta, “Effect of Punica granatum peel extract on learning and memory in rats,” Asian Pacific Journal of Tropical Medicine, vol. 3, no. 9, pp. 687–690, 2010.

S. Das and P. Sarma, “A study on the anticonvulsant and antianxiety activity of ethanolic extract of punica granatum linn,” International Journal of Pharmacy and Pharmaceutical Sciences, vol. 6, no. 2, pp. 389–392, 2014.

T. Yuan, H. Ma, W. Liu et al., “Pomegranate’s neuroprotective effects against alzheimer’s disease are mediated by urolithins, its ellagitannin-gut microbial derived metabolites,” ACS Chemical Neuroscience, vol. 7, no. 1, pp. 26–33, 2015.

R. Shastry, A. Sharma, V. Sayeli, and U. S. Dinkar, “Screening of antidepressant activity of punica granatum in mice,” Pharmacognosy Journal, vol. 9, no. 1, pp. 27–29, 2017.

J. Wise, “FDA approves its first cannabis based medicine,” British Medical Journal Publishing Group, 2018.

A. G. Atanasov, B. Waltenberger, E. M. Pferschy-Wenzig et al., “Discovery and resupply of pharmacologically active plant-derived natural products: a review,” Biotechnology Advances, vol. 33, no. 8, pp. 1582–1614, 2015.

N. Brondino, S. Re, and A. Boldrini, “Curcumin as a therapeutic agent in dementia: a mini systematic review of human studies,” The Scientific World Journal, vol. 2014, Article ID 174282, 6 pages, 2014.

N. Gurnani, D. Mehta, M. Gupta, and B. k. Mehta, “Natural Products: source of potential drugs,” African Journal of Basic & Applied Sciences, vol. 6, pp. 171–186, 2014.

S. Girdhar, A. Girdhar, S. K. Verma, V. Lather, and D. Pandita, “Plant derived alkaloids in major neurodegenerative diseases: from animal models to clinical trials,” Journal of Ayurvedic and Herbal Medicine, vol. 1, no. 3, pp. 91–100, 2015.

C. Sawda, C. Moussa, and R. S. Turner, “Resveratrol for alzheimer’s disease,” Annals of the New York Academy of Sciences, vol. 1403, no. 1, pp. 142–149, 2017.

M. S. Rafii, B. G. Skotko, M. E. McDonough et al., “A randomized, double-blind, placebo-controlled, phase II study of oral ELND005 (scyllo -inositol) in young adults with down syndrome without dementia,” Journal of Alzheimer's Disease, vol. 58, no. 2, pp. 401–411, 2017.