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

Authors: Abdul Waheed Khan; Arif-ullah Khan; Syed Muhammad Mukarram Shah; Aziz Ullah; Muhammad Faheem; Muhammad Saleem
Journal: Evidence-Based Complementary and Alternative Medicine
 (2019)

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## 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.


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## Body

## 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, PhenelzineTranylcypromine, 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 includingBacopa monnieri, Cannabis sativa,Solanum nigrum, Withania somnifera, Papaver somniferum, Zizyphus jujube,Tribulus terrestris, andVerbena 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 (Table3). 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 given1/2 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 (Table3). 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 (Figure2).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 (Figure3). 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) (Figure4). 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 (Table4) 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. Antidepressant2. Anticonvulsant3. Anti-Alzheimer 1. Dried bulbs2. Oil3. 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. Antidepressant2. Anxiolytic3. Anticonvulsant4. Anti-Parkinson 1. Leaves2. Stems and leaves3. Leaves4. 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 anxiolytic2. Anticonvulsant3. Anti-Alzheimer and antidementia4. Sedative 1. Leaves2. Leaves3. Flowers4. 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. Antidepressant2. Anti-seizure3. Anti-Parkinson 1. Leaves2. Seeds3. 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-seizure2. Sedative 1. Leaves2. 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-Parkinson2. Anxiolytic and antidepressant3. Anticonvulsant 1. Whole plant2. Roots3. 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 hypnotic2. Anxiolytic3. Anti-seizure 1. Seeds2. Leaves3. 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. Anxiolytic2. Antidepressant3. Sedative 1. Leaves2. Whole plant3. 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. Antidepressant2.Anticonvulsant, anxiolytic and sedative 1. Leaves2. 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. Anticonvulsant2. Nootropic and anxiolytic 1. Leaves2. Leaves Alkaloids, flavonoids, phenols, saponins; steroids and terpenoids Albizia saponins A, B and C, albizinin, melacacidin, catechin lebbecacidin, friedelin, andβ-sitosterol [165–168]  12 Avena sativa 1. Antidepressant2. Anxiolytic 1. Seeds2. 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. Anticonvulsant2. Sedative, anxiolytic and antidepressant 1. Essential oil of leaves2. 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. Anticonvulsant2. Antidepressant 1. Fruits2. 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. Antiepileptic2. Sedative and hypnotics 1. Leaves2. 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. Antidepressant2. Anti-Parkinson3. Neuroprotective4. Anticonvulsant5. Anti-Alzheimer6. Anxiolytic and sedative 1. Flowers2. Flowers and leaves3. Whole plant4. Flowers and leaves5. Flowers6. 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. Antidepressant2. Anticonvulsant 1. Essential oil of plant2. 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. Antidepressant2. Anticonvulsant3. Memory enhancement4. Anti-Parkinson 1. Fruits2. Dried fruit extract3. Dried fruit extract4. 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. Antidepressant2. Anticonvulsant3. Anxiolytic and sedative4. Enhance memory retention 1. Essential oil2. Leaves3. Aerial parts4. 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. Antidepressant2. Anxiolytic and anticonvulsant3. Anti-Alzheimer4. Memory enhancement 1. Fruits2. Leaves3. Fruits4. 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 monnieriplant 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 officinalisLinn. 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 (Table5).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.



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