# The Confrontation between Ethnopharmacology and Pharmacological Tests of Medicinal Plants Associated with Mental and Neurological Disorders

Authors: Giovanna Felipe Cavalcante e Costa; Hisao Nishijo; Leonardo Ferreira Caixeta; Tales Alexandre Aversi-Ferreira
Journal: Evidence-Based Complementary and Alternative Medicine
 (2018)

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## Abstract

For neurological disorders, pharmacological tests have shown promising results in the reduction of side effects when using plants with known therapeutic effects in the treatment of some types of dementia. Therefore, the goals of this study are to gather data about the major medicinal plants used in the nervous system as described in ethnopharmacological surveys from South America and Brazil and to compare this data with the results from pharmacological tests on the active principles of those same plants found in the scientific literature. After collecting the data about each plant, their respective popular indication was compared with the results found through pharmacological tests. The discrepancy rate between the effects observed by ethnopharmacological and pharmacological methods in this study is greater than 50%. In conclusion, despite the importance of ethnopharmacological data, it is important to make comparisons with pharmacological tests for the same plants, since the pharmacological studies, although few, have shown a high rate of discrepancy in the results.


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## Body

## 1. Introduction

The knowledge of medicinal plants for therapeutic purposes originated from indigenous tribal cultures [1–4] or ancient civilizations such as those once found in Iran, India, or China [1–3, 5–7] and was passed from generation to generation mostly by means of oral tradition. Presently, knowledge is commonly limited to a village and rural areas or by families isolated from urban centers [8]. Most likely, original information of plants used for therapeutic purpose underwent modifications through time. This was due to their discovery by trial and error over many generations and the oral transmission of information rather than through writing.A previous study associated culturally propagated therapeutic effects of different medicinal plants obtained by ethnopharmacological/ethnobotanical means with those found in laboratory tests, showing approximately 66% discrepancy in the results [9]. Trading and distribution mistakes [10], similarity of plant names for different species [11], presence of impurities during preparation from other plants, insects, and mushrooms [12], and unexpected reactions and interactions with the active compounds [13] are all examples of commonly encountered problems in the therapeutic use of medicinal plants.It is not suggested that the medicinal use of plants should be banned, decreased, or hampered. However, there is a need for each procedure to be evaluated by government agencies, institutions, and specialists who understand the therapeutic use of biodiversity in societies with an increasing interest in alternative treatments [6, 14, 15] or in populations with limited or no access to other types of therapeutic resources. Medicinal plant-based therapy may offer benefits, like decreased side effects [16–18], higher autonomy for individuals in caring for their own health [3], reduced or nonexistent costs, and easy access for social groups located in inaccessible areas or away from urban centers and for people in poor urban areas with limited or no access to a healthcare system [6, 14, 15, 19, 20]. Indeed, those groups rely on alternative therapeutic methods for their health care, especially those derived from local medicinal plants, which is a major issue in countries with higher income gaps.Many ethnopharmacological surveys were performed in countries and regions representing the greatest biodiversity to identify plants used, with the aim of preserving the cultural heritage of the plant therapy [1–3, 5–7, 21, 22] and acquiring new active compounds for the pharmaceutical industry [8]. Brazil presents the largest biodiversity on the planet [23] and has a large amount of unexplored resources available for ethnopharmacological and herbal studies given that only 16% of Brazil’s medicinal plants or just 8% of Brazilian national flora [24] has been evaluated for therapeutic potential [25]. This country represents around 47% of all territories of the South American continent.Countries in South America present important data about medicinal plants, because of their specific locations in the Andean region, close/into the Amazon Forest [8] or the pampas. Indeed, the use of some medicinal plants was first found in the population in the Andes Ridge, in the pampas, Patagonia [10], or Brazilian’s savanna (cerrado) [9]. Probably because of the large population or size, most of the studies in South America are found in Brazil, while ethnopharmacological studies are incipient in other countries in this continent [8, 10].However, quality or reliability of medicinal plant effects cannot be ensured if ethnobotanical studies do not provide laboratory verification of the effects when prescribing compounds derived from those medicinal plants. Healthcare professionals and patients should note that studies about the correspondence or discrepancy between ethnopharmacological knowledge and laboratory tests for the same plant are lacking [9] and must be done for each class of drug.There is a growing evidence from in vitro, animal, and clinical studies reporting that medicinal plants might be beneficial for treating various mental and neurological disorders including Alzheimer disease, depression, anxiety, and insomnia [363–366]. For neurological disorders, in particular, pharmacological tests have shown promising results in the reduction of side effects when using plants with known therapeutic effects in the treatment of some types of dementia [18, 22, 367–372]. Medicinal plants have been sought as an alternative therapy [18, 373–375] owing to the inefficacy of some industrial medications on certain diseases, such as degenerative ones. Examples are the use ofMelissa officinalis, Salvia officinalis, Ginkgo biloba,andHuperzia serratafor treating the symptoms of Alzheimer disease [18, 373–375].The problem is that, especially in developing and/or populated countries, people rely on medicinal plants as primary healthcare [376]. The situation is true for mental and neurological disorders. Patient complaints associated directly or indirectly with neurological or neuropsychiatric disorders, such as headache, insomnia, amnesia, anxiety, or depression, are very common [146, 298, 377, 378], and the use of medicinal plants for these purposes is very frequent in populated countries such as Brazil, India, and China [1–3, 5–7, 22] but without support of adequate pharmacological tests.Considering the errors in the use and sale of alternative medicines as a whole, we hypothesize that the same errors could happen with plants that act directly on the nervous system. Therefore, the goal of this study is to gather data about the major medicinal plants used in the neural system, as described in ethnopharmacological surveys from South America like in Brazil and compare this data with the results from pharmacological tests on the active principles of those same plants found in the scientific literature. Specifically, this study intends to present reliable data for the use of medicinal plants in primary healthcare and assisting conventional treatments of neurological disorders.


## 2. Materials and Methods

This study was done through literature review of ethnopharmacological surveys on the medicinal plants used by groups in South America (with emphasis on Brazil) found in academic databases (MEDLINE, LILACS, Scopus, SciELO, Google Academic, and Elsevier). The terms searched were ethnobotanical studies, medicinal plants, ethnopharmacology, neural system, South America, and Brazil. The search was restricted to the most recent and classical articles/books written in Portuguese, English, or Spanish. After collecting the data about each plant, their respective popular indication was compared with the results found through pharmacological tests.For the first phase, 55 ethnobotanical survey articles were selected and then the most commonly used plants by the population for treating neural system disorders were identified. A table was prepared with data regarding family, scientific name, part of the plant utilized, preparation method, indications, and comparison with pharmacological tests.In the second phase, 181 articles in which pharmacological tests had been performed with the chosen plants were selected. Unfortunately, scientific tests for the proposed indication or toxicity for all the plants could not be found.Statistical analysis was done using central tendency measures such as modal frequency.


## 3. Results

Data on South American medicinal plants that act on the nervous system was summarized by family, scientific name, part of the plant utilized, preparation method, indications, and comparison with pharmacological tests (Table1). The most cited families were Lamiaceae (24/138), Asteraceae (16/138), and Verbenaceae (6/138), representing 33.7% of the medicinal plants analyzed (Figure 1).Table 1
Family names, forms of preparation, used part of the plants, medicinal effects cited by population, the pharmacological effects tested for cited plants with the references, and the divergence between the cited effects by population and pharmacological tests.
FamilyScientific name/common name Forms of preparation/used part Medicinal effects cited by population Pharmacological tests Divergences Acanthaceae  Hygrophila tytthaLeonard/Tame-male Infusion/Part air plant Calmative [26] Anxiolytic effect, anticonvulsant and sedative [26] No  Justicia pectoralisJacq./Anador Decoction/Leaf Headache [27] Anxiolytic and depressor Neural Central System [28], analgesic and anti-inflammatory [29], estrogenic, progestagenic and anti-inflammatory effects [30], antioxidant [31] No  Alismataceae  Echinodorus grandiflorus(Cham. & Schltdl.) Mich./Hat leatherback Decoction/Leaf Analgesic [21] Anti-inflammatory and analgesic [32, 33], diuretic [33], antihypertensive [34, 35] No  Amaranthaceae  Alternanthera paronychioidesSt-Hil./Anador Not found/Leaf, stalk Analgesic [36] Antioxidant [37] Yes  Apiaceae  Apium graveolensL./Celery Not found/Complete plant Calmative [36] Vasorelaxant and antihypertensive [38] Yes  Coriandrum sativumL./Coriander Infusion/Seed Headache [39] Antioxidant [40], anti-inflammatory [41], antibacterial [42], anxiolytic, sedative and muscle relaxant [43], antifungal [44], hypoglycemic, hypolipidemic and hepatoprotective [45], analgesic [46] No  Pimpinella anisum L./Fennel Infusion/Seed Calmative [7, 27, 39, 47–49] Antibacterial [50], neuroprotective and anticonvulsant [51], antiviral and immunostimulating [52], antioxidant [53], anticancer [54] No  Foeniculum vulgareMill./Fennel Decoction/Stalk Headache and calmative [13, 36, 55–60] Antimicrobial [61], diuretic [62], antihelminthic [63], antioxidant [64], anxiolytic [65] No  Aquifoliaceae  Ilex paraguariensis/Erva Mate Infusion/leaves, branches Stimulant [66] Stimulant [66] No  Araliaceae  Didymopanax macrocarpum(C. & S.) Seem./Five leaves Compress, bathe/Leaf Analgesic [67] Not found Not found  Hedera helix/Hiedra Cataplasm/Leaf Analgesic, neuritis, neuralgia [68] Expectorant and antitussive [69], mucolytic and bronchodilator [70], anti-inflammatory [71] No  Aristolochiaceae  Aristolochia esperanzaeO. Kuntze./Papo de peru, cipo-millhomem Decoction/Complete plant Analgesic [67] Antiophidic activity [72], antimicrobial [73] Yes  Aristolochia gilbertiiHook/Milhomem Infusion/Root Headache [7] Not found Not found  Aristolochia melastomaManso ex. Duchtra/Capitãozinho Decoction/Root, leaf Sedative [67] Not found Not found  Asteraceae  Achillea millefoliumL./Ponta-alívio Decoction/Complete plant Calmative, analgesic [21, 36, 47, 57, 74, 75] Immunostimulating [76] Yes  Achyrocline satureioidesD.C./Macela Infusion/Flower Sedative, calmative, headache [56, 67, 75, 77, 78] Anticancer [79], calmative effect, anti-inflammatory and antispasmodic [80], antiviral [81] No  Artemisia absinthiumL./Losna Decoction/Leaf Analgesic [21, 82] Anticancer [83], antifungal [84], antibacterial [85], antileishmanial [86] Yes  Artemisia camphorataVill./Camphor Infusion/Leaves Calmative [58] antiepileptic [87] Not found Not found  Artemisia vulgarisL./Artemisia Not found Headache [88] Antifungal [89] Yes  Chamomilla recutita(L.) Rauschter/Camomile Infusion/Flower Calmative, sedative [36, 39, 48, 57, 90–92] Antibacterial and anti-inflammatory [92, 93], gastroprotection [94], antihyperglycemic and antioxidant [95] Yes  Chrysanthemum partheniumBernhadi/Artemisia Decoction, infusion/Leaves Calmative [78] Not found Not found  Cynara scolymusL./Artichoke Not found Calmative [74] Diuretic [96], prolonged satiety sensation and hypoglycemic [97], antioxidant [98] Yes  Lactuca sativaL./Lettuce In nature, infusion/Leaves, root Calmative, sedative [74, 99] Antioxidant [100] Yes  Matricaria chamomilla L./Camomile Infusion/Leaves Calmative [56, 75, 78, 101, 102] Antibacterial and antioxidant [103] Yes  Mikania hirsutissima DC./Cipó-cabeludo Not found Calmative [67, 104] Antiophidic activity and antidiarrheal [105] Yes  Solidago chilensis Meyen/Arnica Compress/Complete plant Analgesic [106] Anti-inflammatory [107] Yes  Spilanthes oleracea/Anestesiol Not found Anesthetic [108] Peptic antiulcer and contraception [109] Yes  Tanacetumsp./Macelinha Decoction/Complete plant Analgesic [23] Not found Not found  Tanacetum vulgare L./Catinga-de-mulata Decoction, maceration/Leaves Analgesic [23] Antibacterial and antifungal [110], antiviral [111], cytotoxic [112], treatment of infections caused by Trypanosoma cruziand Leishmania amazonensis[113], immunomodulatory [114], antihelminthic [115] Yes  Vernoniacf. condensataBaker./Boldo do chile Infusion/Bark Calmative [57] Antitumor and anti-inflammatory [116], antioxidant [117] Yes  Bignoniaceae  Anemopaegma arvense/Catuaba Infusion, decoction/Root, bark, leaves Nervous exhaustion [118] Increased weight and testicular parenchyma [119], antifungal [120] Yes  Bombacaceae  Eriotheca candolleana(K. Schum.)/Catuaba Infusion/Root Nervous exhaustion [121] Not found Not found  Boraginaceae  Cordia verbenaceaDC./Maria preta Bathe/Leaves Analgesic [49] Antimicrobial [122], anti-inflammatory [123] No  Brassicaceae  Coronopus didymus(L.) Smith/Mastruz Maceration/Leaves Analgesic [49] Healing [124], anti-inflammatory [125] No  Bromeliaceae  Tillandsia usneoides (L.) L/Barba de velho Not found Antiepileptic [49] Abortion [126], antiviral [127] Yes  Buddlejaceae  Buddleja brasiliensisJacq./Verbasco Infusion, cataplasm/Part air plant Calmative [67] Low potential hemolytic [128] Yes  Burseraceae  Commiphora myrrha(T. Nees) Engl/Myrrh Infusion/Leaves Calmative [49] Antioxidant [117], analgesic [129] Yes  Caesalpiniaceae  Bauhinia forficataLink./Pata de vaca Decoction/Leaves Analgesic [23] Antioxidant and increased liver glycogen [130], antimutagenic [131] Yes  Bauhinia rutilans Spruce ex. Benth/Escada-de-macaco Infusion/Part air plant Analgesic [99] Not found Not found  Canellaceae  Capsicodendron dinissiOcchioni/Pepper Not found Migraine [104] Not found Not found  Capparaceae  Cleome spinosa Jacq./Mussambê Infusion/Complete plant Headache [132] Cytotoxic [49], antioxidant [133], anti-inflammatory and antinociceptive [134] No  Caprifoliaceae  Sambucus nigraL./Elderberry Decoction/Leaves Analgesic [23, 49] Anti-inflammatory and antioxidant [134], parasiticidal [135] No  Chenopodiaceae  Chenopodium ambrosioidesL./Yerba Santa Maria Maceration, infusion/Leaves, bark, seed Analgesic, calmative [23, 48, 57] Antitumor [79], hypotensive [136], antipyretic and anxiolytic [137] Yes  Compositaceae  Baccharis trimera (Less) D.C./Gorse Infusion/Leaves Headache [138] Antiulcer and antioxidant [139], anti-inflammatory [140], anti-inflammatory and analgesic [141] No  Vernonia condensataB./Boldo Infusion, decoction/Leaves Calmative [138] Antioxidant [117], analgesic [142] Yes  Cucurbitaceae  Cayaponia tayuya(Vell.) Cogn./Taiuia Infusion, decoction/Root Neuralgia [67] Hepatotoxic [142], anti-inflammatory [143] Yes  Dilleniaceae  Davilla rugosaPoir./Vine cabloco Bathe/Root Sedative [67] Antioxidant [144], antiulcer [145] Yes  Euphorbiaceae  Jatropha curcasL./Pião-bravo Infusion/Seed Headache [102, 132] Acetylcholinesterase inhibitor [146], antibacterial, antioxidant and antitumor [147, 148], cytotoxic [149] Yes  Ricinus communisL./Castor beans Infusion/Leaves Headache [77, 87] Antimicrobial and anticancer [150], antimicrobial [151] Yes  Fabaceae  Caesalpinia ferreaMart. ex. Tul./Pau ferro Not found Analgesic [57] Nutritional supplementation of iron, zinc and manganese [152] anti-inflammatory and healing [153], antihyperglycemic [154], antimicrobial [155] No  Cajanus flavus De Candolle/Andu beans Infusion/Leaves Headache [99] Not found Not found  Erythrina falcata Benth/Surina, mulungu Not found Sedative and antiepileptic [67, 104] Depressant CNS [156] No  Indigofera anil/Anil Not found Sedative [107] Not found Not found  Indigofera suffruticosaMill./Anileira Decoction, infusion/Complete plant Sedative [67] Anti-inflammatory [157], lectin activity [158], antiepileptic [159], antiparasitic [160] Yes  Pterodon emarginatus/Sucupira Infusion/leaves, fruit Headache [120] Antimicrobial [161–163], analgesic and anti-inflammatory [164]; antileishmanial, anticancer, hypoglycemic [165] No  Ginkgoaceae  Ginkgobiloba/Ginco Decoction, infusion/Leaves Vasodilator, brain dysfunction, dizziness and concentration and memory [160] Treatment of Alzheimer disease [166], prevention of dementia [167], antioxidant, vasodilator, stimulant of SNC [168] No  Geraniaceae  Pelargonium graveolensL’Her/ Mauve smelling Not found Sedative [87] Anxiolytic and antidepressant [159], antibacterial [169], hypoglycemic and antioxidant [170] No  Mimosa pudicaL./Dormideira Infusion/Complete plant Sedative [99] Reduction of fertility [171], hepatotoxic [172], lipid-lowering [173], anxiolytic and antipyretic [137], antiophidic [174] No  Iridaceae  Calydoreasp./Jabotitana Decoction/Rhizome Analgesic [23] Not found Not found  Labiatae  Agastache mexicana Kunth/Toronjil Not found Sedative [102] Antihypertensive [175], vasorelaxant [176], anti-inflammatory and antinociceptive [177], antinociceptive [178], anxiolytic [179] No  Lavandula latifolia/Lavanda Oil Stimulant [68] Anxiolytic [180], antifungal [181], antioxidant [182] Yes  Origanum vulgare/oregano Infusion/Leaf Sedative [68] Antimicrobial [183] proapoptotic effect and cytotoxic [184], antiurolithic [185] Yes  Lamiaceae  Coleus barbatusBenth./Falso-boldo Tisane mate/Leaf Headache, calmative [56] Hepatoprotective [186] Yes  Cunila microcephalaBenth./Hortelã-miúdo, hortelã-pimenta, poejo Decoction/Complete plant Analgesic [23, 58] Anti-inflammatory and antioxidant [187] No  Hyptis suaveolens Poit./Samba-coité Tea/Leaf Headache [188] Hypoglycemic and antioxidant [189], hepatoprotective and antioxidant [190], gastroprotective activity [191], neuroprotective and antioxidant [192], antifungal [193] Yes  Lavandula officinalisChaix & Kitt/Alfazema Tea/Leaf, stalk Calmative [49] Antimicrobial [194], antioxidant [195], sedative and hypnotic [196] No  Leonotis nepetifolia(L.) R. Br./Cordão de São Francisco Infusion, decoction/Leaf, branches Sedative, headache [132, 138] Antimicrobial [197], anti-inflammatory [198] Yes  MelissaofficinalisL./Erva-cidreira, melissa Decoction/Leaf Calmative, migraine, sedative [23, 36, 55, 58, 59, 87, 89, 90, 101, 102, 138, 199] Anti-inflammatory [200], calmative [201], antioxidant [202], antigenotoxic and antimutagenic [203], neuroprotective [199, 204] No  Mentha arvensisL./Hortelã-mentol Tea/Leaf Headache [188] Antibacterial [205], antifungal [206], anti-inflammatory and sedative [207], peptic antiulcer [208] Yes  Mentha cf. suaveolens Ehrh./Hortelã, hortelã-grande Decoction, maceration/Leaf Calmative, Analgesic [23, 199] Antifungal [209, 210], antioxidant [211], antibacterial [212] Yes  Mentha piperitaL./Hortelã, hortelã-roxo Decoction/Complete plant Analgesic [23, 102] Antifungal [213, 214], antioxidant [211], anthelmintic [215], hypoglycemic and hypolipidemic [216], anticancer [217] analgesic [218] No  Mentha pulegiumL./Poejo Decoction/Stalk Calmative, sedative [47, 56, 58, 78] Antioxidant [211], antimicrobial [219] Yes  Menthasp./Hortelã Decoction/Stalk Headache, Calmative [36, 47, 49, 55–57] Anthelmintic [215] Yes  Mentha spicataL./∗ ∗ ∗ ∗ Headache [87] Hypoglycemic and hypolipidemic [216], antioxidant [220], antiemetic [221] Yes  Mentha×villosaHuds./Hortelã Tea/Leaf Headache [188] Antifungal and antibacterial [222], antimicrobial and antioxidant [223], analgesic and antispasmodic [153] No  Ocimum basilicumL./Alfavaca Decoction, maceration/Leaf Calmative, analgesic [23, 39] Antidepressant and anticonvulsant [224] Yes  Ocimum gratissimumL./l Louro Tea/Leaf Headache, calmative [49, 87, 188] Anticonvulsant [225, 226], antifungal [227] Yes  Ocimum minimumL./Manjericão Maceration/Leaf Headache [94] Antiulcerogenic and antioxidant [35] Yes  Ocimum selloiBenth./Alfavaca Infusion, tea/Leaf Calmative [138] Antibacterial [219], analgesic and antidiarrheal [220] Yes  Origanum majoranaL./Manjerona Decoction/Stalk Calmative [56] Antibacterial [228], antioxidant [49], antimetastatic and antitumor [229], antihyperglycemic and antihyperlipidemic [230] Yes  Plectranthus barbatusAndr./Boldo Decoction, maceration/Leaf Analgesic [23, 57, 60] Cytotoxic [231], acetylcholinesterase inhibitor [232], antimicrobial [233] Yes  Plectranthus neochilusSchlechter/Boldo do Chile Infusion/Leaf Headache [89] Analgesic [234] No  Rosmarinus officinalisL./Alecrim Decoction/Leaf Analgesic, calmative [23, 39, 48, 58, 59, 102, 138, 235] Antibacterial [236], antioxidant [237], antifungal [238], anticancer [239], antidepressant [240], analgesic [241], antioxidant, anti-inflammatory, metal chelation [242], prevention and treatment of dementia [243], neuroprotective [244] No  Salvia lachnostachysBenth./Melissa Decoction/Leaf Somniferous [23, 78] Anti-inflammatory and analgesic [244] Yes  Salvia lavandulifoliaVahl./Mariselva Oil/∗∗ Nervous disorders [245] Hypoglycemic [245], neuroprotective [246] No  Salvia officinalisL./Salvia, barcelona Decoction/Leaf Calmative, Analgesic [23] Antibacterial [228], anti-inflammatory [247], antidiarrheal and antispasmodic [185], analgesic and anti-inflammatory [248] No  Lauraceae  Cinnamomum zeylanicumBreyn./Canela Infusion, maceration/Stalk Calmative [39] Antifungal [249] antimicrobial [250], antioxidant [251], antidiabetic [252] Yes  Nectandra megapotamica (Spreng.) Mez/Canela-preta Infusion/leaf Calmative [253] Anesthetic [254] Yes  Leguminosae  Acosmium subelegans (Mohlenbr) Yakovl/Perobinha do campo ∗ ∗ ∗ Sedative, epilepsy and nervous exhaustion [255] Depressant effect SNC and anticonvulsant [255] No  Hymenaea courbaril L./Jatobá Infusion, maceration/Bark, fruit Sedative [132] Not found. Not found  Tamarindus indica/Tamarindo Compress, bathe, infusion/Stalk, leaves, fruit Treatment of fever, stomach upset, diarrhea, jaundice and as skin cleansers [256], inflammation, urinary tract infection and laxative [257], headache and stress [258] Antibacterial [256], antihelminthic [257], antioxidant [259], antinociceptive [260], analgesic and anti-inflammatory [261], antihistaminic and antianaphylactic [262], antiulcer [263] No  Liliaceae  Allium sativumL./Alho ∗ ∗ ∗ Headache [59] Hypotensive [264], synergism with antibiotics [265], antioxidant [266] Yes  Malpighiaceae  Banisteriopsis  caapi/Mariri, ayahuasca Decoction, infusion/vine Hallucinogen, emotional and cognitive sensory changes, psychoactive [267–269] aid in treatment of abuse of other Psychoactives [270] Hallucinogen [271] inhibiting the reuptake of serotonin, in addition to inhibiting MAO [272] No  Galphimia glauca/Amarilla Maceration/Part air plants Calmative [273] Anxiolytic [273] No  Meliaceae  Cedrela fissilis/Cedro-rosa Infusion/Bark Headache [121] Not found Not found  Moraceae  Cannabis sativa/maconha, marijuana, cânhamo Oil, inhalation/Leaves, stalk, flowers Treatment of pain, nausea and vomiting, multiple sclerosis and other neurological disorders, loss of appetite and eating disorders, Insomnia, anxiety and depression, neuroprotective action [274], antiemetic, appetite stimulant [275], clinical and experimental studies in the treatment of dementias [276], schizophrenia, antipsychotic, anxiety [277], antipsychotic [278] Treatment of pain, nausea and vomiting, multiple sclerosis and other neurological disorders, loss of appetite and eating disorders, Insomnia, anxiety and depression, neuroprotective action [273], antiemetic, appetite stimulant [274], clinical and experimental studies in the treatment of dementias [275], schizophrenia, antipsychotic, anxiety [276], antipsychotic [277], psychoactive [278] No  Dorstenia brasiliensisLam./Carapiá Cataplasm/Rhizome Anesthetic [67] Anti-inflammatory [278] Yes  Myrtaceae  Eucalyptus globulusLabill./Eucalipto Infusion, Bathe/Leaf Headache [48] Toxic effect [279], antibacterial [280, 281] Yes  Eugenia unifloraL./Pitangueira Decoction/Leaf Calmative [23, 282] Antimicrobial and antioxidant [283], anti-Trypanosoma cruzi[206] Yes  Orchidaceae  Vanilla planifoliaJack. ex Andrews/Baunilha ∗ ∗ ∗ Calmative [67] Not found Not found  Oxalidaceae  Averrhoa CarambolaL./Carambola Infusion/Leaf Analgesic [99] Analgesic [284] No  Papaveraceae  Papaver somniferum/Planta do ópio ∗ ∗ ∗ Analgesic and sedative [68] Not found Not found  Passifloraceae  Passiflora alata Curtis/Maracujá Fruit Calmative [55, 59, 77, 90] Sedative [285] No  Passiflora caeruleaL./Maracujá Infusion/Part air plant Sedative and calmative [91, 286] Anxiolytic [287] No  Passiflora edulisSims./Maracujá Tea/Leaf Calmative and insomnia [39, 48, 74, 77, 78, 90, 99, 257] Anxiolytic [288] No  Passiflora miersiiMart./Maracujazinho Infusion/Leaf Calmative and antidepressant [67] Not found Not found  Pedaliaceae  Sesamum orientaleL./Gergelim Seed/Juice Anticonvulsant [99] Hypoglycemic [289] Yes  Phytolaccaceae  Petiveria alliaceaL./Guiné, tira capeta Decoction/Complete plant Analgesic [23, 74, 99, 290] Antimicrobial [291], antinociceptive, sedative, anticonvulsant and depressant [292] Yes  Piperaceae  Pothomorphe umbellataMiq./Pariparoba Infusion/Leaf Headache [121] Antioxidant [293], antitumor [294], antihelminthic [295] Yes  Poaceae  Cymbopogon citratusStapf./Capim santo, capim limão Decoction/Leaf Calmative, analgesic and sedative [7, 23, 27, 36, 39, 47–49, 55–58, 74, 77, 78, 88–90, 99, 101, 102, 138, 296] Anxiolytic, sedative and anticonvulsant [297] No  Polygalaceae  Polygala paniculataL./Arnica Decoction/Complete plant Analgesic [23] Analgesic and antidermatogenic [298], antinociceptive and gastric cytoprotective activity [299] No  Polygonaceae  Homalocladium platycladumBailey/Carquejinha Decoction/Stalk Analgesic [23] Antibacterial [300], analgesic, anti-inflammatory [301] No  Rosaceae  Rosa centifoliaL./Rosa branca Decoction/Leaf, flower Analgesic [23] Anti-inflammatory and antiarthritic [302], antioxidant [303], antiulcer and cytoprotective [304] No  Sanguisorba minorScop./Pimpinela Tea/Leaf, flower Calmative [102] Inhibitory action of acetylcholinesterase [305] Yes  Rubiaceae  Coffea arabicaL./Café Cataplasm/Leaf Headache [101] Antioxidant [306], antioxidant and stimulant [307] Yes  Cinchona officinalisL./∗ Decoction/Bark Analgesic [23] Not found Not found  Psychotria viridis/chacrona, ayahuasca Infusion/Leaves Hallucinogen, emotional and cognitive sensory changes, psychoactive [267–269] aid in treatment of abuse of other Psychoactives [268] Hallucinogen [308]  Alibertiasp./Marmelo Decoction, infusion/Root, fruit Calmative [118] Not found Not found  Rutaceae (5)  Casimiroa edulisLlave & Lex./Zapote blanco ∗ ∗ ∗ Sedative [102] Vasodilator [309, 310], anticoagulants and antimicrobial [310], anxiolytic [311], anxiolytic and antidepressant [312] No  Citrus aurantiumL./Laranja Decoction/Bark Headache and calmative [36, 48, 56, 59, 78, 90, 194] Low toxicity [313], anxiolytic [314, 315] Yes  Citrus limon(L.) Burm. f./Limão-galego, ∗ ∗ ∗ Calmative and sedative [90, 194] Neuroprotective activity and anticonvulsant [316] Yes  Citrus sinensis (L.)Osbeck Infusion/Leaf Calmative, analgesic and sedative [23, 27, 49, 74, 99, 138] Antioxidant, antithyroid and antihyperglycemic [317] Yes  Ruta graveolensL./Arruda Decoction, maceration/Leaf Calmative and headache [23, 39, 48, 57, 60, 102] Antimicrobial [318], antioxidant [319], antitumor [320], antinociceptive, anti-inflammatory and antipyretic [321] Yes  Solanaceae  Atropa belladonnaL./Beladona Decoction/Leaf Calmative [23] Healing [322] Yes  Cestrum sendtnerianumMart./Guiné-do-campo Infusion, Decoction/Leaf Sedative [67] Not found Not found  Solanum americanumMill./Maria-pretinha Decoction/Leaf, Stalk Sedative, Analgesic [45, 67] Antifungal [323], antioxidant and anticancer [324] Yes  Solanum cernuumVell/Pata de mono ∗ ∗ ∗ Calmative [87] Antiulcerogenic [325] Yes  Umbelliferae  Anethum graveolens/Eneldo ∗ ∗ ∗ Sedative [68] Antifungal [326], anticonvulsant [327], anti Helicabator pylori[328], decreased fertility rate [329], participates in the regulation of Diabetes Mellitus [330] Yes  Coriandrum sativum/Cilantro Infusion/Leaf, fruit Stimulant [68] Antioxidant [40], sedative and muscle relaxant [43], antibacterial [331], antiarthritic [332], anti-inflamatory [41], antifungal [333], hypoglycemic and hypolipidemic [334] Yes  Petroselinum hortense/Salsa da horta ∗ ∗ ∗ Sedative [107] Diuretic and hypotensive [335] Yes  Urticaceae  Urera baccifera(L.)/Urtiga Leaf Analgesic [36] Antioxidant [336], anti-inflamatory [337] No  Verbenaceae (6)  Aloysia citrodoraPalau/Erva luíza ∗ ∗ ∗ Calmative [74, 286] Not found. Not found  Aloysia triphyllaRoyle/Cidrão ∗ ∗/Leaf Sedative [55, 235] Treatment of intestinal disorders [338], anti Trypanosoma Cruzi[339], anti-Helicobacter pylori[328], antibacterial [340], spasmolytic and anti-inflammatory [341], antinociceptive [244] Yes  Lantana camaraL./Camará Infusion, Decoction/Leaf Headache [132] Antibacterial [342], antioxidant [343], anxiolytic [344] Yes  Lippia alba(Mill.) N.E. Br./Erva-cidreira Leaf/Infusion Headache and calmative [39, 49, 55, 58–61, 75, 77, 94, 97] Antimicrobial [345], antispasmodic [346], anxiolytic [347], anesthetic [348] No  Lippia gracillis Schauer/Alecrim da serra Infusion/Leaf Headache [132] Antimicrobial [349], antitumor [350], anti-inflammatory and healing [351] Yes  Verbena cf. minutifolia Phil./ ∗ Decoction/Complete plant Analgesic [23] Not found Not found  Violaceae  Viola odorataL./ ∗ ∗ ∗ Sedative [87] Antitumoral [352], antioxidant and antibacterial [353], antimicrobial [354], vasodilator and antidyslipidemic [355] Yes  Zingiberaceae  Alpinia zerumbet(Pers.) Burtt & Smith/Colônia Decoction/Leaf Calmative [39, 48, 49, 101] Hypotensive [356], vasodilator [357], antioxidant [358] Yes  Zingiber officinaleRosc./Gengibre Decoction/root Analgesic and headache [23, 57, 78] Antioxidant [359], antihyperglycemic [360], antibacterial [361], androgenic [362] Yes  Costus brasiliensisSchum./Cana-de-macaco Not found Calmative [67] Not found Not found I t   ∗ is the popular name that was quoted. It∗∗ was not mentioned how to prepare. It∗∗∗ is the portion used or how to prepare that was quoted.Figure 1
The cited families of medicinal plants according to popular knowledge.The most common indications, according to ethnopharmacological surveys, were calmative/sedative (72/167), analgesic (39/167), and headache (35/167), representing 86,2% of all indications (Figure2).Figure 2
The indications for use of the medicinal plants according to popular knowledge.Ethnobotanical surveys revealed that the leaves (70/160) and the whole plant (13/160) amounted to 51.7% of all plant parts most commonly used, but, in 18% of the studied plants, there were no citations about the used part for making medicines (Figure3).Figure 3
Part of plants used for indications according to the popular knowledge.The most common preparation methods provided in the surveys were infusion (59/167) and decoction (49/167), representing 63.7% of all the methods (Figure4).Figure 4
Preparation methods cited by population for medicinal plants.Common effects attributed to the plants in the ethnopharmacological surveys were antioxidant (42/401), anti-inflammatory (31/401), antibacterial (20/401), and antimicrobial (17/401), totaling 31.9% (Figure5).Figure 5
Attributed effects of the medicinal plants according to popular knowledge.Comparison between ethnopharmacological data and pharmaceutical tests for the same plants and compounds found differences in 52.9% (73/138) of the cases and similarities in 30.4% (42/138) (Figure6). No pharmacological tests were found for 16.9% (23/138) of the plants mentioned in the ethnopharmacological surveys (Table 1).Figure 6
Comparison between ethnopharmacological data and pharmaceutical tests for the same plants and compounds.Table1 shows a list of the medicinal plants analyzed in this study. The pharmacological effects including “anticonvulsant” and “anxiolytic” were considered to correspond to “calmative” in medicinal effects cited by population since both effects are attributed to the same action in the neural system, that is, inhibitory action. Furthermore, the pharmacological effect “anti-inflammatory” was also considered to correspond to “analgesic” in medicinal effects cited by population since anti-inflammatory agents are effective in treating pain diseases.


## 4. Discussion

The most frequent indications of medicinal plant use for neural system disorders in our survey (i.e., calmative, analgesic, headache, and insomnia) are associated with the most common occurrences seen in medical practice [7, 36, 47, 55, 68, 77, 104, 132, 235, 258] (Figure 2).The plant families analyzed (Lamiaceae and Asteraceae) are in accordance with general ethnobotanical studies [4, 7, 379–382] (Figure 1), as well as the most utilized plant parts (leaves) [1, 7, 379, 383, 384], and preparation methods (infusion and decoction) [7, 253, 379, 383, 384] (Figure 4).Despite that, the frequency of effects observed by most pharmacological tests does not coincide with those reported for the same plants when analyzed by ethnopharmacological means, (i.e., antioxidant, anti-inflammatory, antibacterial, and antimicrobial), demonstrating a high discrepancy between proven and popularly mentioned effects (Figure6).It is important to remember that results of pharmacological tests were not found for all the plants mentioned in the ethnopharmacological studies, although those represent a small minority (16.9%) (Figure5).The discrepancy rate between the effects observed by ethnopharmacological and pharmacological methods in this study is in agreement with a previous study [9] and, in both cases, a disagreement of over 50% was found. This data indicates the need for better control in the use of medicinal plants as a whole, especially in countries with a large proportion of economically backward population where such therapy is most common, such as China, India, and Brazil. However, there are possibilities that scientific studies are not enough or they are missing to corroborate the ethnopharmacological activities.Tables like the one produced in this study can be used as a basis for the indication of medications for health professionals working in the neural area who choose to substitute alternative therapies with conventional methods. The tables can be used to maintain the patient’s health and help make these treatments more accessible to people of all economic levels [385], bring medical practice closer to the care of cultural groups [386], and expand the idea of wholeness in healthcare.Performing pharmacological tests in the medicinal plants mentioned in ethnopharmacological studies will help avoid prescription errors based only on popular knowledge, which, despite the importance, exhibits extensive methodological shortcomings from its propagation through generations (see Introduction). Although the pharmacological tests cannot solve problems related to contamination during preparation and/or mistakes when identifying plants by unskilled people, performing those tests would decrease the problems caused by adverse effects and wrong prescriptions.Neurological disorders present complex etiologies often with aggravating social influences, requiring special care when making prescriptions; many critically ill patients are secluded from society and require medical monitoring and medications derived from modern pharmaceutical technology since indications for complex etiologies like dementias were not addressed in the ethnopharmacological articles analyzed in this study.In conclusion, despite the importance of ethnopharmacological data, it is important to make comparisons with pharmacological tests for the same plants, since the pharmacological studies, although few, have shown a high rate of discrepancy in the results, nevertheless, to be important to cite that the scientific studies could not be enough, or are missing, to corroborate the ethnopharmacological activities. Tables containing the plants names and their effects according to pharmacological tests should be consulted by health professionals before prescribing those medications. No medicinal plants were mentioned in ethnopharmacological data for treating complex etiology neural disorders such as dementia, indicating the need for new studies of broader geographical amplitude and pharmaceutical classes all around the world. Emphasis of these studies should occur in developing countries in order to decrease prescription errors associated with medicinal plants and increase the coverage of plant-based therapy for the global population while prioritizing people in need.



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