Evidence-Based Complementary and Alternative Medicine

Evidence-Based Complementary and Alternative Medicine / 2019 / Article
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Ethnopharmacological Studies for the Development of New Drugs 2019

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Volume 2019 |Article ID 6191505 | https://doi.org/10.1155/2019/6191505

Abdul Waheed Khan, Arif-ullah Khan, Syed Muhammad Mukarram Shah, Aziz Ullah, Muhammad Faheem, Muhammad Saleem, "An Updated List of Neuromedicinal Plants of Pakistan, Their Uses, and Phytochemistry", Evidence-Based Complementary and Alternative Medicine, vol. 2019, Article ID 6191505, 27 pages, 2019. https://doi.org/10.1155/2019/6191505

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

Academic Editor: José C. T. Carvalho
Received12 Nov 2018
Revised14 Jan 2019
Accepted05 Feb 2019
Published03 Mar 2019

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].


MigraineStrokeEpilepsyDepressionAnxietyParkinsonAlzheimer

Worldwide14.9% [49]5% [50]0.5-1% [51]4.4% [52]3.6% [52]1% [53]11.2% [54]
Asia9.1% [55]0.94%[56]0.49% [57]4.4% [52]2.8% [58]0.63% [59]1.9% [54]
Africa5.61% [60]0.4% [61]1.13% [62]5.2% [52]4.4% [52]0.44% [63]1.6% [54]
North America14.4% [64]2.7% [65]0.8% [66]10.6% [67]7.7% [58]1.3% [59]6.4% [54]
South America11.6% [64]0.7% [68]0.98% [57]13.8% [67]10.4% [69]2.3% [59]4.6% [54]
Europe15% [70]6.25%[71]0.82% [62]4.2% [52]3.9% [52]1.6% [72]4.4% [54]
Australia6% [73]1.8% [74]0.44% [75]5.9% [52]7% [52]0.46% [76]6.4% [77]
Pakistan26.1% [78]0.25% [79]2% [4]4.2% [52]3.5% [52]0.23% [51]1% [4]
India25.2% [51]3.69%[71]0.39% [80]4.5% [52]3.0% [52]0.07% [81]1.91% [82]
Iran14% [51]0.36% [51]1.8% [80]4.9% [52]4.6% [52]0.29% [83]2.3% [84]
China9.3% [78]4.3% [71]0.3% [80]4.2% [52]3.1% [52]1.7 % [85]3.21% [85]
Afghanistan0.9% [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).


Drug ClassSubclasses Drugs Side effects References

AntidepressantsTCAImipramine, Amitriptyline, Desipramine, Nortriptyline, Doxepinweight gain, sedation, dry mouth, nausea, blurred vision, constipation, tachycardia, dry mouth, constipation, hypotension, increased heart rate[92]
MAOIIsocarboxazid, Phenelzine
Tranylcypromine, Selegiline
weight gain, fatigue, sexual dysfunction, nausea, hypotension, dry mouth, diarrhea or constipation, headache, drowsiness, insomnia
SSRIFluoxetine, Paroxetine, Fluvoxamine, Sertraline, Citalopramheadache, sedation, dizziness, nervousness, somnolence, extrapyramidal effects, nausea, dry mouth, diarrhea, agitation, insomnia, sexual dysfunction, weight gain,[93]
SNRIVenlafaxine, Duloxetine, Desvenlafaxine, Levomilnaciprannausea, 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]
AtypicalBupropion, Mirtazapine, Trazodone, Vilazodoneheadache, agitation, insomnia, sweating, sedation, increased appetite, weight gain, nausea, dizziness[92]

AnxiolyticsBZDsAlprazolam, Clonazepam, Lorazepam, Midazolam, Diazepamsedation, memory disturbances, tolerance, fatigue, dependence, drowsiness, lethargy, At higher dosages, impaired motor coordination, dizziness, vertigo, slurred speech, blurry vision, mood swings, euphoria[95]
AzapironesBuspirone, Binospirone, Gepirone, Tandospironedizziness, drowsiness, headaches, restlessness, nausea, diarrhea[96]
BARPhenobarbital, Amobarbital, Secobarbita, Butabarbital, Pentobarbitalsedation, dizziness, headache, nausea, withdrawal include, tremors, agitation, abnormal breathing, coma, confusion, fainting, hallucinations[97]

Anti-AlzheimerAChEIsDonepezil, Rivastigmine, Galantaminevomiting, diarrhea, weight loss, bradycardia, insomnia, nausea, agitation, syncope[98]
Anti-AβBapineuzumab, Solanezumab, Gantenerumabmicrohemorrhage, vasogenic edema, arrhythmia, skin and subcutaneous tissue disorders
NMDAR AntagonistsMemantinepsychosis, nausea, vomiting, memory impairment, and neuronal cell death, drowsiness[99]

Anti-ParkinsonDABromocriptine, Pergolide, Cabergoline, Pramipexolenausea, hypotension, confusion, delirium, pulmonary fibrosis, vasospasm, erythromelalgia, sleep attacks[100]
COMT InhibitorsEntacapone, Tolcaponedyskinesia, nausea, confusion, urine discoloration, diarrhea, abdominal pain
MAO-BSelegilineconfusion, delirium, hallucinations, unusual thoughts or behavior, dizziness, nausea, insomnia, trouble breathing

AntiepilepticSodium Channel BlockersPhenytoin, Carbamazepine, Lamotrigine, Lacosamide, Oxcarbazepine,dizziness, drowsiness, diplopia, nausea, vomiting, fatigue, ataxia, neurotoxicity, cardiac arrhythmias, hirsutism, hepatotoxicity, steven-johnson syndrome[101]
Calcium Channel BlockersEthosuximide, Zonisamide, Trimethadionenausea, vomiting, headache, mental status changes, neuropathy, change in weight[102]
GABA transaminase InhibitorsVigabatrin, L-Cycloserine, Ethanolamine-O-Sulfate, Valproatedrowsiness, 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).


S #Botanical NameLocal NameFamilyHabitatPart UsedUsed forMode of ApplicationsLocationReference

1Achyranthes asperaAyokandaAmaranthaceaeHerbLeaves and ShootNerve tonicPaste of dried leaves and shoots is applied on headSargodha[104]

2Ailanthus altissimaBackyanraSimarubaceaTreeBarkHysteriaDecoction of bark to make teaMalakand[105]

3Albizia lebbeckSirinMimosaceaeTreeRootsDepression, Migraine and AnxietyDecoction of root to make teaMianwali[106]

4Allium sativum OogaAmaryllidaceaeHerbBulbs and LeavesHysteria and EpilepsyDecoction of bulbs and leavesSwat[107]

5Alnus nitida GeirayBetulaceaeTreeFlowersInsomniaPowder of dried flowers mixed with water and used orallyDir[108]

6Alternanthera sessilisWaglonAmaranthaceaeHerbLeavesNeuralgia and SedativeSniffing of leaves sapBahawalpur[109]

7Anagallis arvensisBilly bootiPrimulaceaeHerbWhole plantNervine, mania and EpilepsyExtract of whole plantBahawalpur[109]

8Artemisia scoparia JaukayAsteraceaeHerbRootsEpilepsyPowder of roots taken with waterDir[108]

9Asparagus officinalisPhala-moosaAsparagaceaeHerbLeavesInsomniaTea of leaves are used on empty stomachLahore[110]

10Atropa accuminataBargakSolanaceaeHerbLeavesInsomnia and narcoticPowder of leaves are taken with waterDir[108]

11Avena fatuaJodalPoaceaeHerbSeedsDepression and nervous exhaustionEither the seeds fluid extract or oatmeal obtained by crushing and grinding seedsDera Ghazi Khan[111]

12Avena sativaJaiPoaceaeHerbSeedsNerve tonic and InsomniaA tincture of juice of immature seedsIslamabad[112]

13Bacopa monnieri Brahmi sakScrophulariaceaeHerbWhole plantEpilepsyExtract of whole plant is taken orallyMianwali[106]

14Buglossoides arvensisKaluBoraginaceaeHerbLeavesInsomniaInfusion of leaves is used orallyKotli[113]

15Caltha albaMakanpatRanunculaceaeHerbWhole plantInsomniaExtract of whole plantDir[108]

16Campanula pallidaBeli FlowerCampanulaceaeHerbFlowersInsomniaAn infusion of flowers is used orallyKotli[113]

17Cannabis SativaBhangCannabaceaeHerbFlowersInsomniaThe ground flowers are used by mixing with other fruitsBannu[114]

18Capparis deciduakdlerCapparidaceaeShrubFlowers, fruits and shootsInsomniaThe powder of flowers and shoots while fruits are eaten as suchGawadar[115]

19Capparis spinosa KawirCapparidaceaeShrubWhole plantMental disordersFresh extract of whole plant is usedGilgat[116]

20Carthamus tinctorius Tukhmiga-rtumAsteraceaeHerbRoots, oil and flowersInsomniaDecoction of roots to make tea while oil is applied externallyRawalpindi[117]

21Celtis australis KarrCannabaceaeTreeBarkEpilepsyDecoction of bark is used orallySargodha[118]

22Cenchrus pennisetiformisCheetah- ghaPoaceaeHerbLeaves and fruitsEpilepsyExtracts and juice of leaves and fruitsHafizabad[119]

23Citrullus colocynthisTummaCucurbitaceaeClimberRoots and fruitsEpilepsyThe extract of roots is taken with water while fruit’s powder is mixed with sugarJhelum[120]

24Citrus limonNimbooRutaceaeTreeWhole plantAnxiety and Depressionwhole plant extractBahawalpur[109]

25Citrus medicaKhattiRutaceaeTreeLeaves, seeds, latexInsomniaPowder of leaves, seeds and dry latex are taken orally with waterBahawalpur[109]

26Colebrookia oppositifoliaLansaLamiaceaeShrubLeaves and rootsEpilepsyFresh leaves extract and roots decoction tea is taken orallyMalakand[121]

27Commiphora wightii Guggul, MukulBurseraceaeHerbGumNervous diseasesThe aqueous extract of gum is usedMuzaffarabad[122]

28Convolvulus arvensisBailyConvolvulaceaeHerbWhole plantEpilepsywhole plant extractMalakand[121]

29Cucurbita maxima Walayti kadooCucurbitaceaeClimberFruitsNervous disordersJuice of both unripe and ripe fruits is usedAzad Jammu & Kashmir[123]

30Cuscuta reflexa Bepari, KasusCuscutaceaeTreeSeedsInsomniaAn infusion of seed is usedMuzaffarabad[122]

31Cymbopogon citratusLemon- grassPoaceaeHerbOil of whole plantNervous system tonicOil is externally applied on headBahawalpur[109]

32Cynodon dactylonLawn grassPoaceaeHerbWhole plantEpilepsy and HysteriaExtracted juice of plant is usedDera Ghazi Khan[111]

33Cyperus rotundusDeelaCyperaceaeHerbTubersEpilepsyOil obtained from tubers are usedBahawalnagar[124]

34Datura albaDaturaSolanaceaeShrubLeaves and seedsNeuralgia, Epilepsy, Hysteria and InsomniaLotion of seed’s powder is applied locally for neuralgia while tea of leaves is used for EpilepsyBahawalpur[109]

35Datura innoxia DaturaSolanaceaeHerbLeavesEpilepsy and InsomniaExtract of leaves in waterDir[108]

36Datura metelDhaturoSolanaceaeHerbLeaves and seedsEpilepsy and InsomniaLeaves extract and seed’s decoction are usedMuzaffarabad[122]

37Datura stramonium DaturaSolanaceaeHerbWhole plantInsomnia and ParkinsonExtraction of whole plant is usedDera Ghazi Khan[111]

38Daucus carota GajarApiaceaeHerbWhole plantNerve tonicEaten as a whole or its juice is usedSargodha[104]

39Eclipta albaBhringarajAsteraceaeHerbRoots, oil and leavesInsomniaOil is externally applied while roots and leaves extract is used orallyBahawalpur[109]

40Eruca sativa Tara meeraCruciferaceaeHerbWhole plantEpilepsyFluid extraction of plant is usedIslamabad[112]

41Evolvulus alsinoides Sankha-holiConvolvulaceaeHerbWhole plantEpilepsyDecoction of whole plant is usedIslamabad[112]

42Ficus lyrataBeeri pattaMoraceaeTreeLeavesMigraineExtraction of leaves is used orallyBahawalpur[109]

43Flueggea leucopyrusShinaPhyllanthaceaeShrubRootsEpilepsyDecoction and extraction of roots are usedDir[125]

44Fumaria indicaPitpapraFumariaceaeHerbLeaves and stemInsomniaFresh juice of leaves and stem is usedRawalpindi[117]

45Gmelina arboreaKumbarLamiaceaeTreeRootsEpilepsyExtraction and decoction of roots tea is usedSargodha[118]

46Hyoscyamus niger Ajwain-i- KhurasaniSolanaceaeHerbLeaves and seedsInsomnia and Nervous afflectionExtraction of fresh leaves and powder of seeds are used orallyGilgat[126]

47Hypericum perforatumBulhsanaHypericaceaeHerbWhole plantDepression and InsomniaFresh extract of whole plant is used orallyGujrat[127]

48Hyssopus officinalis Zufa, ZupaLamiaceaeHerbWhole plantNervous affectionExtraction of fresh whole plantZiarat[128]

49Indigofera heteranthaKainthiPapilionaceaeShrubWhole plantEpilepsy and neuropathyExtract of whole plant is usedGilgat[116]

50Jasminum grandiflorumChanbeliOleaceaeClimberWhole plantAnxiety, tension and DepressionOil or tea of leaves and flowers extract are usedBahawalpur[109]

51Jasminum officinale ChanbeliOleaceaeClimberWhole plantInsomniaOil is rubbed on heart as nerve sedativeSwat[107]

52Juglans regiaGhuzJuglandaceaeTreeFruitsDepressionFruits are taken as whole orallyMalakand[105]

53Lactuca serriolaBerham dandiAsteraceaeHerbWhole plantMemory EnhancingFresh plant is ground in water along with black pepperJhelum[120]

54Linum usitatissimumAlsiLinaceaeHerbStemDepression, Schizophrenia and AnxietyExtraction of fresh stem is usedKotli[113]

55Lycopersicon esculentum TamatorSolanaceaeHerbFruitsNervous weaknessEaten as a whole or its juice is usedSargodha[104]

56Martricaria chamomillaBabunaAsteraceaeHerbWhole plantInsomniaExtraction of whole plant is used orally and oil massage or aromatherapy into skin of head is performedRawalpindi[117]

57Martynia annua.Bichhu-buttiMartyniaceaeHerbLeaves and fruitsEpilepsyJuice of leaves or leaves are cooked to make curry and fruits are taken as dry powder with waterKotli[113]

58Melia azedarachBakyanaMeliaceaeTreeLeavesHysteriaDecoction of leaves to makes teaMalakand[105]

59Mimordica diocaJungli karelaCucurbitaceaeClimberFruits and seedsInsomniaFruit’s extract and seed oil are usedMianwali[129]

60Moringa oleiferaSohan-janaMoringaceaeTreeSeeds and barkMigraineSeeds oil used externally while powder of leavesGujrat[127]

61Ocimum basilicumNiazboLamiaceaeHerbLeaves, flowers, seeds and rootsMigraine, Insomnia and DepressionJuice of fresh leaves and flowers while oil of seeds is applied externally on headBahawalnagar[124]

62Paeonia emodiMamaikhPaeoniaceaeHerbRhizomeEpilepsyRhizome powder is given teaspoon twice a dayMalakand[105]

63Papaver dubiumKoko-kangaPapaveraceaeHerbFlowersInsomniaFluid extract of flowers is usedKotli[113]

64Papaver hybridum PostPapaveraceaeHerbFruitsInsomniaFruit and its decoction are usedJhelum[120]

65Papaver nudicauleZangali kashkashPapaveraceaeHerbFlowersInsomniaFluid extract of flowers is usedBuner[130]

66Papaver rhoeas Alak jinaiPapaveraceaeHerbFlowersInsomniaFluid extract of flowers is usedBuner[130]

67Papaver somniferum Qash-QashPapaveraceaeHerbFruit’s latexInsomniaLatex of unripe fruit is dissolved in water and used orallySwat[107]

68Parthenium hysterophorusRagweedAsteraceaeHerbLeavesInsomniaLeaves extraction is usedBuner[130]

69Peganum harmalaHarmalZygophyllaceaeHerbSeedsHysteriaA small amount of seeds added to sufficient grapes juice, boiled to make thick solution and used orallyDera Ghazi Khan[111]

70Populus caspicaNakhtarPinaceaeTreeFruitsInsomniaWhole raw fruits are consumedMalakand[105]

71Primula verisCowslipsPrimulaceaeHerbFlowersInsomniaA tasty wine of flowers is made which is used orallyGilgat[126]

72Prunus persicaArdouRosaceaeTreeLeaves, flowers and fruitsInsomniaExtract of leaves & flowers and fruits are taken as suchGilgat[126]

73Punica granatumDarronaPunicaceaeShrubFruitsMemory enhancingFruit’s juice or fresh seeds are eaten as suchAzad Jammu & Kashmir[123]

74Pyrus communisNashpataiRosaceaeTreeFruitsInsomniaFruits are eaten as suchDir[131]

75Pyrus pashiaTangaiRosaceaeHerbFruitsInsomniaFruits are eaten as suchSwat[107]

76Ranunculus muricatusZiar GulayRanunculaceaeHerbWhole plantSciatic and nerve painExtraction of dried whole plant is usedSwat[132]

77Raphanus sativusMooliBrassicaceaeHerbSeedsNervous weaknessDecoction of seeds is usedSargodha[104]

78Ricinus communisArandEuphorbiaceaeShrubRoots, seeds, leavesInsomnia and as narcoticExtract of leaves and roots while oil of seeds are usedRawalpindi[117]

79Salvadora oleoidesPeeluSalvadoraceaeTreeWhole plantEpilepsyFruit is eaten as raw while tea of leaves and roots are also usedBahawalpur[109]

80Schinus molle False pepperAnacardiaceaeTreeBark and leavesDepressionDecoction of bark and leaves to make teaSargodha[118]

81Scutellaria chamaedrifoliaSkullcapLamiaceaeHerbShootsInsomnia and DepressionDecoction of shoots to make its teaSwat[133]

82Solanum miniatumPeelakSolanaceaeHerbWhole plantInsomniawhole plant decoction is mixed with sugarJhelum[120]

83Solanum nigrumMakoSolanaceaeHerbWhole plantInsomniaJuice of whole plantBahawalpur[109]

84Solanum SurratenseWara-mara ghinrhyeSolanaceaeHerbFruitsMelancholia and DepressionThe paste of fruits crushed powders is applied on head externallyBannu[114]

85Taxus baccata BanhyaTaxaceaeTreeLeaves and fruitsEpilepsyExtraction of dried leaves and fruits are consumed as suchSwat[134]

86Taxus wallichianaBarmiTaxaceaeTreeBark, leaves and fruitsEpilepsy and InsomniaExtract of dried bark and leaves while flesh of fruits are consumedBattagram[135]

87Terminalia arjunaArjunCombretaceaeTreeFruits, bark and leavesAnxietyBark infusion left whole night, then its decoction taken early in the morning and used orallyBahawalpur[109]

88Tribulus terrestrisBakhraZygophyllaceaeHerbWhole plantEpilepsy and DepressionPowder of dried whole plantBahawalnagar[124]

89Valeriana jatamansiMushk-balaVahliaceaeHerbWhole plantEpilepsy and neurosisFresh extract of whole plantMuzaffarabad[122]

90Verbascum thapsus Jungle tambakoScrophulariceaeHerbRootsMigraineDecoction of root to make tea to use as drinkMianwali[106]

91Verbena officinalis ShamkayVerbenaceaeHerbWhole plantDepression, Migraine and EpilepsyExtract of dried whole plant is usedBattagram[135]

92Viburnum cotinifoliumGuchCaprifoliaceaeShrubStem’s barkInsomniaExtract of stem’s barkMuzaffarabad[122]

93Viburnum opulusSunaira PhulCaprifoliaceaeShrubBarkInsomnia and HysteriaDecoction of bark is usedMuzaffarabad[122]

94Viburnum prunifoliumBlackhawCaprifoliaceaeTreeRoot’s barkHysteria, Anxiety and EpilepsyDecoction of root’s bark is usedMuzaffarabad[122]

95Vicia sativaMuttriPapilionaceaeHerbFlowersEpilepsy and nervous disordersThe juice of flowers petals is usedKotli[113]

96Viola betonicifoliaBanafshViolaceaeHerbWhole plantEpilepsy and nervous disordersFresh extract of whole plant orallyMalakand[105]

97Viola canescens BanafshaViolaceaeHerbWhole plantInsomnia and EpilepsyExtract and decoction tea of whole plantSwat[133]

98Withania coagulansPaneer dodaSolanaceaeHerbFruits, roots and leavesNervous Exhaustion, memory loss and tensionExtract of leaves, roots and fruits are usedBahawalnagar[124]

99Withania somniferaAsgandhSolanaceaeShrubRootsInsomniaPowder of roots is taken with waterBahawalpur[109]

100Xanthium strumarium Chota dhaturaAsteraceaeHerbsFruits, seeds and rootsInsomniaDecoction of fruits, roots and seeds to make teaAttock[136]

101Ziziphus jujubaBeriRhamnaceaeTreeLeaves, roots and fruitsAnxiety and InsomniaExtract of leaves, decoction of roots and dried fruits are consumedBahawalnagar[124]

102Ziziphus mauritianaBerRhamnaceaeTreeRootsNerve tonicDecoction of roots is used as teaSargodha[104]

103Ziziphus nummulariaJangli beriRhamnaceaeShrubLeaves and fruitsInsomniaExtract of leaves while fruits are taken as suchAttock[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).

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).

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.

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.

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 [1518], saponins (like bacosides) have been reported for anxiolytic, antiepileptic, antiamnesia, and neuroprotective and memory enhancement activities [1922], 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 [2430], 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].


S.#Medicinal PlantsPharmacological PropertiesPart usedPhytochemical ConstituentsChemical Compounds IdentifiedReferences

1Allium sativum1. 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 proteinsAlliin, allixin, 1,2-vinyldithiin, ajoenes, S-allyl-cysteine sulfoxide, calcium, Potassium, vitamin B and vitamin C[137140]

2Bacopa monnieri1. 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 carbohydrateBrahmin, nicotine, herpestine, bacosides A & B, hersaponin, betulic acid, monnierin, apigenin, b-sitosterol, stigma-sterol and luteolin[3336, 141]

3Cannabis sativa1. 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 balsamCannabinoids, cannabidiol, dronabinol, cannabigerol, tetrahydrocannabinolic acid, cannabichromenic acid, cannabidiolic acid, anandamide, cannabigerolic acid and cannabichromene[3740, 142, 143]

4Hyoscyamus niger1. 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 flavonoidsApoatropine, L-DOPA, Cuscohygrine, choline Daturamine, Hyoscine, tropine, hyoscypicrin, phytin, aphoyoscine, alpha and beeta belladonine and Skimmianine[144148]

5Solanum nigrum1. Anti-seizure
2. Sedative
1. Leaves
2. Fruits
Alkaloids, flavonoids, tannins, saponins, glycosides, proteins, carbohydrates, coumarins and phytosterolsPinoresinol, syringaresinol, medioresinol, scopoletin, tetracosanoic acid and beta-sitosterol[149152]

6Withania somnifera1. Anti-Parkinson
2. Anxiolytic and antidepressant
3. Anticonvulsant
1. Whole plant
2. Roots
3. Stems and roots
Alkaloids, steroidal lactones, saponins and ironWithanolides, withaferins, Withanine, isopellertierine, anferine, Anahygrine, Cuscohygrine, Beta-Sisterol, Chlorogenic acid, Scopoletin, choline, Somniferiene, Somniferinine and Tropanol[4547, 153]

7Papaver somniferum1. Anticonvulsant1. SeedsAlkaloids, glycosides, tannins, Phytosterols, Terpenoids, Flavanoids and CarbohydratesMorphine, Codeine, thebaine, noscapine, papaverine, Salutarifine, meconidine, codmine, neoprene, lanthothine, rophyroxine, narcotisline and papaveramine[154159]

8Ziziphus jujube1. 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 nucleosidesZizybeoside I and II, Chryseoriol, Swertisin, Quercetin, Jujubasaponin IV, Lotoside I and II, Zizyphus saponin I and II[160]

9Tribulus terrestris1. Anxiolytic
2. Antidepressant
3. Sedative
1. Leaves
2. Whole plant
3. Whole plant
Saponins, flavonoids, glycosides, alkaloids and tanninsTigogenin, neotigogenin, rutin, chlorogenin, caffeoyl, ruscogenin, kaempferol, tribulosid, terrestribisamide, quercetin, β-sitosterol, stigmasterols, harmane, norharmane and tribulusterine[161164]

10Verbena officinalis1. Antidepressant
2.Anticonvulsant, anxiolytic and sedative
1. Leaves
2. Whole plant
Alkaloids, flavonoids, diterpenes, proteins, amino acids, tannins, saponins, phytosterols and phenolic compoundsVerbenin, oleanolic acid, verbenalin, hastatoside, alpha-sitosterol, ursolic acid, kaempferol, aucubin, luteolin, verbascoside, apigenin, scutellarein, limonene and spathulenol[42, 43]

11Albizia lebbeck1. Anticonvulsant
2. Nootropic and anxiolytic
1. Leaves
2. Leaves
Alkaloids, flavonoids, phenols, saponins; steroids and terpenoidsAlbizia saponins A, B and C, albizinin, melacacidin, catechin lebbecacidin, friedelin, and β-sitosterol[165168]

12Avena sativa1. Antidepressant
2. Anxiolytic
1. Seeds
2. Whole plant
Carbohydrates, alkaloids, flavanoids, steroids, glycosides, saponins, amino acids, gums and mucilageGramine, flavone, apigenin and luteolin, flavonolignans, saponins and ferulic acid[169171]

13Capparis decidua1. Sedative and anticonvulsant1. Flowers and fruitsAlkaloids, glycosides, terpenoids, sterols, flavanoids, phenols and fatty acidsCapparine, cappariline, capparinine, β-sitosterol, capparidisine, capparisine, codonocarpine, Capric acid, cadabacine, quercetin and rutin l-stachydrine[172, 173]

14Citrus limon1. 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 acidLimonene, α-pinene, β-pinene, linalool, α-terpineol, linalyl acetate, acetate geranyl, nerolidol, acetate neryl, farnesol, sabinene, myrcene, cineol and geranial[174176]

15Citrullus colocynthis1. Anticonvulsant
2. Antidepressant
1. Fruits
2. Fruits
Alkaloids, flavonoids, glycosides, saponosides, Phenolic compounds and ascorbic acidColocynthin, colocynthein, colocynthetin, Cucurbitane type triterpen glycoside, quercetin and Flavone[15, 16, 177]

16Datura metel1. Antiepileptic
2. Sedative and hypnotics
1. Leaves
2. Seeds
Alkaloids, resins, flavonoids, reducing sugars, tannins, terpenoids and steroid glycosidesHyoscyamine, scopolamine, atropine, daturabietatriene, daturasterol,, b-sitosterol and Melatonin and serotonin[1721]

17Hypericum perforatum1. 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 naphthodianthronesHyperoside, adhyperforin Quercitrin, Rutin, Hypericin, Kaempferol, Biapigenin and Hyperforin[2228]

18Jasminum grandiflorum1. Antidepressant
2. Anticonvulsant
1. Essential oil of plant
2. Leaves
Coumarins, steroids, cardiac glycosides, essential oils, flavonoids, phenolics and saponinsRutin, kaempferol, quercetin, β-primeveroside, kaempferol, hesperidin Methyl jasmonate, methyl anthranilate, linalool β-rutinoside, oleuropein and daucosterol[2931]

19Lycopersicon esculentum1. 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 proteinsChlorogenic acid, rutin, naringenin, noradrenaline lycopene, dopamine, tomatin, tomatoside-A, ascorbic acid, bergapten, serotonin and adrenaline[32, 178180]

20Ocimum basilicum1. 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 flavonoidsCineole, geraniol, linalool, cadinol and sabinene, methyl chavicol, β-caryophyllene and neral, quercetin, myricetin, kaempferol, catechin and eugenol[181184]

21Punica granatum1. 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 triterpenoidCatechin, rutin, quercetin epicatechin, estriol, luteolin kaempferol, anthocyanins, gallagyldilacton, stigmasterol, β-sitosterol, testosterone, tocopherols and isoflavones[185188]

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 [3336].

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 [3741].

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 [4244].

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 [4548].

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).


Sr #PhytochemicalsSourceFamilyDiseaseMechanismDevelopment stageTrade NameReference

1CannabidiolCannabis sativaCannabaceaeEpilepsyModulation of intracellular calcium and neuronal inhibitionFDA approved, 2018Epidiolex as 5- 10 mg/kg/day[189]

2CannabidolCannabis sativa L.CannabaceaeChronic Neuropathic painCB1 and CB2 receptor activationFDA approved, 2005Sativex Spray (CBD 25mg/ml + THC27mg/ml)[190]

3CapsaicinCapsicum annum L.SolanaceaePostherpetic neuralgiaTRPV1 activatorFDA approved, 2010Qutenza as Patch (179mg capsacin)[190]

4CurcuminCurcuma longaZingiberaceaeDementiaAnti-amyloid, AChEIphase II[191]

5GalantamineGalanthus nivalisAmaryllidaceaeAlzheimerAChEI, allosteric modulation of nicotinic ACh receptorFDA approved, 2004Razadyne as 8-12 mg BD[192]

6Huperzine AHuperzia serrataHuperziaceaeAlzheimerAChEI, inhibits NMDA and glutamate toxicityapproved in China[193]

7IbogaineTabernanthe ibogaApocynaceaeParkinsonDopaminergic agonist, NMDA antagonismpreclinical[193]

8PsychollatinePsychotria umbellateRubiaceaeParkinsonMAO inhibitorpreclinical[193]

9ResveratrolVitis vinifera L.VitaceaeAlzheimerReduces Aβ formation and promote Aβ decompositionphase II[194]

10Scyllo-InositolCornus florida L.CornaceaeAlzheimerBreakdown of neurotoxic fibrils, allowing amyloid peptides to clear the body rather than form amyloid plaquesphase 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.

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.

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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.


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