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Medicinal plants for the "nerves": a review of ethnobotanical studies carried out in South Brazil

ABSTRACT

Among the medicinal purposes for which plants have been used is the treatment of “nerves". The objective of this study was to search for species of plants used in the state of Rio Grande do Sul (South Brazil) for the relief of symptoms related to central nervous system (CNS) disorders. Twenty-seven ethnobotanical studies were compiled, in which a total of 94 species were cited. The five most cited species were Cymbopogon citratus (81.5 %), Melissa officinalis (77.7 %), Aloysia citriodora (66.6 %), Matricaria chamomilla (62.9 %) and Passiflora edulis (51.8 %). Scientific studies have corroborated the popular use of these plants as sedatives, but most studies are preclinical and very few have been clinical (M. chamomilla and M. officinalis), and these were mainly exploratory or were performed against placebo. In addition to efficacy data, there are also indications of toxicity for M. chamomilla and P. edulis. In conclusion, there is a great diversity of plant species used in the treatment of symptoms related to CNS disorders, and they are most frequently used as a sedative. Data indicate that M. officinalis possesses clinical efficacy in the treatment of symptoms associated with anxiety without signs of toxicity.

Keywords:
central nervous system disorders; ethnobotany; popular medicine; sedative; toxicity

Introduction

Brazil is rich in ethnic and cultural diversity and holds valuable traditional knowledge associated with the use of herbal medicines (Brasil 2006Brasil. 2006. Política Nacional de Plantas Medicinais e Fitoterápicos. Brasília, Ministério da Saúde. http://bvsms.saude.gov.br/bvs/publicacoes/politica_nacional_fitoterapicos.pdf. 22 Jan. 2016.
http://bvsms.saude.gov.br/bvs/publicacoe...
). Such popular medicine is widespread in the South Region of the country, especially in rural areas where the population faces difficulties in accessing primary care services (Souza et al. 2004Souza GC, Haas APS, Poser G, Elisabetsky E. 2004. Farmácias caseiras comunitárias do município de Maquiné (RS): uma avaliação etnofarmacológica. Revista Brasileira de Plantas Medicinais 6: 83-91.) and uses alternative therapeutic resources including medicinal plants. Consumption is also favored by a widespread popular belief that medicinal plants and byproducts do not present adverse effects or toxicity, and thus are beneficial and safe products for health (Mengue et al. 2001Mengue SS, Mentz LA, Schenkel EP. 2001. Uso de plantas medicinais na gravidez. Revista Brasileira de Farmacognosia 11: 21-35.). However, there is also evidence that plants may be toxic and that in certain situations even plants considered safe may cause adverse (in some cases, serious) events or loss of efficacy (Moreira et al. 2014 Moreira DL, Teixeira SS, Monteiro MHD, Oliveira ACAX, Paumgartten FJR. 2014. Traditional use and safety of herbal medicines. Revista Brasileira de Farmacognosia 24: 248-257.; Lorenzo et al. 2015Lorenzo C, Ceschi A, Kupferschmidt H, et al. 2015. Adverse effects of plant food supplements and botanical preparations: a systematic review with critical evaluation of causality. British Journal of Clinical Pharmacology 79: 578-92. ). Thus, knowledge about the use, pharmacological properties and toxicology of plants and products derived from them is fundamental to assure their safety and effectiveness (Rates 2001Rates SMK. 2001. Plants as source of drugs. Toxicon 39: 603-613. ; Moreira et al. 2014 Moreira DL, Teixeira SS, Monteiro MHD, Oliveira ACAX, Paumgartten FJR. 2014. Traditional use and safety of herbal medicines. Revista Brasileira de Farmacognosia 24: 248-257.; Lorenzo et al. 2015Lorenzo C, Ceschi A, Kupferschmidt H, et al. 2015. Adverse effects of plant food supplements and botanical preparations: a systematic review with critical evaluation of causality. British Journal of Clinical Pharmacology 79: 578-92. ; Braga et al. 2017Braga FC, Rates SMK, Simões CMO. 2017. Avaliação da eficácia e segurança de produtos naturais candidatos a fármacos e medicamentos. In: Simões CMO, Schenckel EP, Mello JCP, Mentz LA, Petrovick PR. (orgs.) Farmacognosia: do produto natural ao medicamento. 1st. edn. Porto Alegre, Artmed. p. 53-68.). The main objective of ethnobotanical research is to recover knowledge and the use of medicinal plants in communities (Rodrigues et al. 2011Rodrigues E, Giorgetti M, Rossi, L. 2011. Brazilian plants with possible action on the Central Nervous System: a study of historical sources from the 16th to 19th century. Revista Brasileira de Farmacognosia 21: 537-555.). Besides being important for the acquisition of knowledge of the flora and for preserving the cultural identity of communities, such studies also provide important elements for the rational and sustainable use of these resources, including the development of herbal medicines and the discovery of bioactive molecules, with consequent drug development (Rates 2001Rates SMK. 2001. Plants as source of drugs. Toxicon 39: 603-613. ; Braga et al. 2017Braga FC, Rates SMK, Simões CMO. 2017. Avaliação da eficácia e segurança de produtos naturais candidatos a fármacos e medicamentos. In: Simões CMO, Schenckel EP, Mello JCP, Mentz LA, Petrovick PR. (orgs.) Farmacognosia: do produto natural ao medicamento. 1st. edn. Porto Alegre, Artmed. p. 53-68.). In fact, many drugs used in current therapy were originally obtained or developed from plant products (Cragg & Newman 2013Cragg GM, Newman DJ. 2013. Natural products: A continuing source of novel drug leads Biochimica et Biophysica Acta 1830: 3670-3695. ).

Previous compilations of ethnobotanical surveys conducted in the Brazilian state of Rio Grande do Sul focused on plants used for the treatment of diabetes (Trojan-Rodrigues et al. 2012Trojan-Rodrigues M, Alves TLS, Soares GLG, Ritter MR. 2012. Plants used as antidiabetics in popular medicine in Rio Grande do Sul, Southern Brazil. Journal of Ethnopharmacology 139: 155- 163.) and pain (Stolz et al. 2014Stolz ED, Müller LG, Trojan-Rodrigues M, et al. 2014. Survey of plants popularly used for pain relief in Rio Grande do Sul, southern Brazil. Brasilian Journal of Pharmacognosy 24: 185-196.) and demonstrated that the use of medicinal plants is a widespread practice in the state. Neverthless, no compilation has been performed for plants used for the relief of symptoms related to central nervous system (CNS) disorders cited in ethnobotanical surveys in Rio Grande do Sul. Such plants are popularly denominated as medicinal plants for the "nerves".

Knowledge of the use of plants in popular medicine for treating CNS disorders is relevant, given the epidemiology of these diseases and the difficulty in establishing effective and safe pharmacological therapies. About 5.8 % of the Brazilian population lives with depression, and it has the greatest prevalence of anxiety disorders among countries of the world, with about 9.3 % of the population (WHO 2017WHO - World Health Organization. 2017. Depression and other common mental disorders: Global health estimates. http://www.who.int/mental_health/management/depression/ prevalence_global_health_estimates/en/. 10 Oct. 2017.
http://www.who.int/mental_health/managem...
).

There are different pharmacological treatments for depressive disorders and anxiety. However, the available therapeutic arsenal has important limitations: benzodiazepine anxiolytics cause dependence and develop tolerance (Rates & Salles 2012Rates SMK, Salles LA. 2012. Os medicamentos para a ansiedade e a insônia. In: Schenkel EP, Mengue SS, Petrovick PR. (org.) Cuidados com os medicamentos. 5th. edn. Porto Alegre/ Florianópolis, UFRGS/ UFSC. p. 149-156. ; Murrough et al. 2015Murrough JW, Yaqubi S, Sayed S, Dennis S. Charney. 2015. Emerging drugs for the treatment of anxiety. Expert Opinion Emerging Drugs 20: 393-406. ); antidepressants have low adherence due to adverse effects and long latency, about 30 uninterrupted days, to treatment efficacy. In addition, about 33 % of patients do not respond to antidepressants (Stahl 2014Stahl SM. 2014. Psicofarmacologia. Bases Neurocientíficas e Aplicações Práticas. 4th. edn. Rio de Janeiro, Guanabara Koogan.; Murrough et al. 2015Murrough JW, Yaqubi S, Sayed S, Dennis S. Charney. 2015. Emerging drugs for the treatment of anxiety. Expert Opinion Emerging Drugs 20: 393-406. ). The contribution of plants to the development of drugs for the treatment of mental disorders can be exemplified by the species Rauwolfia serpentina, from which reserpine was isolated; although now in disuse, this drug was important in the early stages of the pharmacological treatment of schizophrenia. Species such as Hypericum perforatum and Piper methysticum, currently serve as raw material for the production of herbal medicines for the treatment of depression and anxiety, respectively. Valeriana officinalis, a species with millennial use, is recgonized by WHO as a sedative in replacement of benzodiazepines (WHO 2017WHO - World Health Organization. 2017. Depression and other common mental disorders: Global health estimates. http://www.who.int/mental_health/management/depression/ prevalence_global_health_estimates/en/. 10 Oct. 2017.
http://www.who.int/mental_health/managem...
).

Studies involving the use of plants to treat some CNS dysfunctions have been undertaken in different cultures, such as Andean (Lozada et al. 2006Lozada M, Ladio A, Weigandt M. 2006. Cultural transmission of ethnobotanical knowledge in a rural community of northwestern Patagonia, Argentina. Economic Botany 60: 374-385.; Vidaurre et al. 2006Vidaurre JPR, Saucedo RMP, Veja IS, Cunya JS. 2006. Etnobotánica de la valeriana (Valeriana spp.) en la Jalca de Cajamarca, Perú. Arnaldoa 13: 370-381.; Bussmann et al. 2010Bussmann RW, Glenn A, Sharon D. 2010. Healing the body and soul: Traditional remedies for “magical” ailments, nervous system and psychosomatic disorders in Northern Peru. African Journal of Pharmacy and Pharmacology 4: 580-629.), Mexican (Gutierrez et al. 2014Gutiérrez SLG, Chilpa RR, Jaime HB. 2014. Medicinal plants for the treatment of “nervios”, anxiety, and depression in Mexican Traditional Medicine. Revista Brasileira de Farmacognosia 24: 591-608.), Spanish (Calvo & Cavero 2015Calvo MI, Cavero RY. 2015. Medicinal plants used for neurological and mental disorders in Navarra and their validation from official sources. Journal of Ethnopharmacology 169: 263-268. ) and Iranian (Saki et al. 2014Saki K, Bahmani M, Rafieian-Kopaei M, et al. 2014. The most common native medicinal plants used for psychiatric and neurological disorders in Urmia city, northwest of Iran. Asian Pacific Journal of Tropical Disease 4: 895-901.) peoples. Many species of plants are used to treat some CNS dysfunctions in Brazil, as evidenced by the large number of herbal medicines registered by the National Health Surveillance Agency (ANVISA): about 146 used to treat mood disorders, approximately 80 simple herbal medicines, and 66 herbal compounds (Montezolli & Lopes 2015Montezolli AP, Lopes GC. 2015. Phytotherapics use in mood disorders: myth or reality? Brazilian Journal of Surgery and Clinical Research 12: 38-44.).

In this context, the objective of the present work was to compile plants used to treat symptoms related to mental disorders, such as depression and anxiety, mentioned in ethnobotanical studies carried out in the state of Rio Grande do Sul, and to perform a bibliographic survey of chemical, biological and toxicity data of the most cited species.

Materials and methods

The compiled etnonobotanical studies were found by performing searches within virtual databases (PubMed - http//www.pubmed.com, SciELO - http//www.SciELO.org/php/index.php and Portal de Periódicos CAPES - http//www.periodicos.capes.gov.br), using the following keywords: folk medicine, medicina popular, ethnobotany, and etnobotânica combined with Rio Grande do Sul, South Brazil and sul do Brasil. Regional university libraries were also surveyed.

The criteria for selecting ethnobotanical studies were: publication up to and including 2017, accessibility, presence of at least one citation of a plant species used to treat CNS disorders (tranquilizer, sedative, for nerves, depression, anxiety, nervousness). In addition, studies were only considered if authored by at least one botanist or if they mentioned plant identification by a botanist(s). Thusly, a total of 27 ethnobotanical studies performed in Rio Grande do Sul were consulted. These studies took place in different physiographic regions of Rio Grande do Sul as defined by Fortes (1959Fortes AB. 1959. Geografia física do Rio Grande do Sul. Porto Alegre, Editora Globo.): Alto Uruguai - Battisti et al. (2013Battisti C, Garlet TMB, Essi L, Horbach RK, Andrade A, Badke MR. 2013. Plantas medicinais utilizadas no município de Palmeira das Missões, RS, Brasil. Revista Brasileira de Biociências 11: 338-348.), Kubo (1997Kubo RR. 1997. Levantamento das plantas de uso medicinal em Coronel Bicaco, RS. MSc Thesis, Universidade Federal do Rio Grande do Sul, Porto Alegre.), Löwe (2004Löwe TR. 2004. Estudo etnobotânico em uma área rural do município de Três de Maio, RS. Monograph, Universidade Federal de Pelotas, Pelotas.); Campanha - Löbler et al. (2014Löbler L, Santos D, Rodrigues ES, Santos NRZ. 2014. Levantamento etnobotânico de plantas medicinais no bairro Três de Outubro, da cidade de São Gabriel, RS, Brasil. Revista Brasileira de Biociências 12: 81-89.); Campos de Cima da Serra - Ritter et al. (2002Ritter MR, Sobierajski GR, Schenkel EP, Mentz LA. 2002. Plantas usadas como medicinais no município de Ipê, RS, Brasil. Revista Brasileira de Farmacognosia 12: 51-62. ); Depressão Central - Baldauf et al. (2009Baldauf C, Kubo RR, Silva F, Irgang BE. 2009. “Ferveu, queimou o ser da erva”: conhecimentos de especialistas locais sobre plantas medicinais na região sul do Brasil. Revista Brasileira de Plantas Medicinais 11: 282-291.), Koch (2000Koch I. 2000. Estudo etnobotânico de plantas medicinais na cultura ítalo brasileira, no Rio Grande do Sul. MSc Thesis, Universidade do Vale do Rio dos Sinos, São Leopoldo.), Possamai (2000Possamai RM. 2000. Levantamento etnobotânico das plantas de uso medicinal em Mariana Pimentel, RS. MSc Thesis, Universidade Federal do Rio Grande do Sul, Porto Alegre.), Soares et al. (2004Soares ELC, Vendruscolo GS, Eisinger SM, Záchia RA. 2004. Estudo etnobotânico do uso dos recursos vegetais em São João do Polêsine, RS, Brasil, no período de outubro 1999 a junho de 2001. I - Origem e fluxo do conhecimento. Revista Brasileira de Plantas Medicinais 6: 69-95.), Somavilla & Canto-Dorow (1996Somavilla N, Canto-Dorow TS. 1996. Levantamento das plantas medicinais utilizadas em bairros de Santa Maria-RS. Ciência e Natura 18: 131-148.), Souza (2007Souza MB. 2007. O uso medicinal e místico de plantas por moradores do bairro Morretes, município de Nova Santa Rita, Rio Grande do Sul. Monograph, Universidade La Salle, Canoas.), Vendruscolo & Mentz (2006Vendruscolo GS, Mentz LA. 2006. Levantamento etnobotânico das plantas utilizadas como medicinais por moradores do bairro Ponta Grossa, Porto Alegre, Rio Grande do Sul. Iheringia, Série Botânica 61: 83-103. ); Encosta do Sudeste - Borba (2008Borba ICG. 2008. Estudo etnobotânico de plantas bioativas: uso pela comunidade quilombola do Monjolo do município de São Lourenço do Sul - RS. Monograph, Universidade Católica de Pelotas, Pelotas.), Ceolin et al. (2009Ceolin T, Heck RM, Barbieri RL, et al. 2009. Plantas medicinais utilizadas como calmantes por agricultores ecológicos da região Sul do Rio Grande do Sul, Brasil. Revista de Enfermagem 3: 1034-1041.), Martha (2003Martha EM. 2003. O uso das plantas medicinais pela comunidade da Associação dos Agricultores Construtores da Palma - Assentamento 24 de Novembro. Monograph, Universidade Federal de Pelotas, Pelotas.), Veiga (2003Veiga APF. 2003. Levantamento das espécies de plantas medicinais usadas pela população do bairro Cohab-Fragata e comparação entre os usos popular e científico da Macela (Achyrocline satureioides) e Capim-limão (Cymbopogon citratus), Camomila (Matricaria chamomilla). Monograph, Universidade Federal de Pelotas, Pelotas.), Zanandrea (2003Zanandrea I. 2003. Estudo etnobotânico das plantas medicinais mais utilizadas pelos moradores do bairro Santa Terezinha, Pelotas, RS. Monograph, Universidade Federal de Pelotas, Pelotas. ); Encosta Inferior do Nordeste - Barbosa (2005Barbosa JF. 2005. Estudo etnobotânico das plantas de uso medicinal e místico utilizadas na comunidade Quilombola de Nova Real, Bom Retiro do Sul, Estado do Rio Grande do SulMonograph, Universidade do Vale do Rio dos Sinos, São Leopoldo.), Sebold (2003Sebold DF. 2003. Levantamento etnobotânico de plantas de uso medicinal no município de Campo Bom, RS, Brasil. MSc Thesis, Universidade Federal do Rio Grande do Sul, Porto Alegre.); Encosta Superior do Nordeste - Piva (1998Piva MG. 1998. Estudio Etnobotánico del Municipio de Caxias do Sul/RS- Brasil. PhD Thesis, Universidade de León, León.); Litoral - Borges (2010Borges AM. 2010. Plantas medicinais no cuidado em saúde de moradores da Ilha dos Marinheiros: contribuições à enfermagem. MSc Thesis, Universidade Federal de Pelotas, Pelotas.), Froehlich (1998Froehlich NMS. 1998. Plantas medicinais utilizadas na comunidade rural de Fortaleza, Município de Cidreira, RS. Monograph, Universidade Luterana do Brasil, Canoas.), Sperry et al. (1999Sperry A, Coelho GP, Kubo RR, Poser G. 1999. O sistema de saúde da Comunidade de Solidão, município de Maquiné, RS, Brasil. Monograph, Universidade Federal do Rio Grande do Sul, Porto Alegre.); Missões - Barros et al. (2007)Barros FMC, Pereira KN, Zanetti GD, Heinzmann BM. 2007. Plantas de uso medicinal no município de São Luiz Gonzaga, RS, Brasil. Latin American Journal of Pharmacy 26: 652-662.; Planalto Médio - Garlet & Irgang (2001Garlet TMB, Irgang BE. 2001. Plantas medicinais utilizadas na medicina popular por mulheres trabalhadoras rurais de Cruz Alta, Rio Grande do Sul, Brasil. Revista Brasileira de Plantas Medicinais 4: 9-18.); and Serra do Sudeste - Fernandes (2001Fernandes AA. 2001. Levantamento etnobotânico na região da Pedra do Segredo, Caçapava do Sul, RS. Monograph, Universidade Federal de Pelotas, Pelotas.), Leitzke (2003Leitzke ZCS. 2003. Levantamento das plantas medicinais da comunidade Nossa Senhora da Conceição - Canguçu - RS. Monograph, Universidade Federal de Pelotas, Pelotas. ).

Plant popular names cited in the original studies were preserved in the current work. The origin (native of Rio Grande do Sul or exotic), valid scientific names and possible synonymies of each plant were obtained from the databases of Flora do Brasil (2018)Flora do Brasil 2020 [em construção]. 2018. Angiospermas. Rio de Janeiro, Jardim Botânico do Rio de Janeiro. http://floradobrasil.jbrj.gov.br/. 18 Jul. 2018.
http://floradobrasil.jbrj.gov.br/...
, The Plant List (2018)The Plant List. 2018. A working list of all plant species. http://www.theplantlist.org/. 22 Apr. 2018.
http://www.theplantlist.org/...
and Tropicos (http://www.mobot.org). The botanical families were updated according to the APG IV (2016)APG IV - Angiosperm Phylogeny Group. 2016. An update of the Angiosperm Phylogeny Group classification for the orders and families of flowering plants: APG IV. Botanical Journal of the Linnean Society 181: 1-20.. The habit and form of preparation, as they are given in the studies, were compiled. Terms such as infusion and decoction were standardized as “tea”. Citation frequency was calculated as follows: number of studies that cite the species ×(100)/total number of studies.

The species cited in more than half of the compiled ethnobotanical studies were selected for further searches for scientific data about chemical constitution, biological properties and evidence of toxicity. For this, clinical and preclinical studies were searched in the PubMed (http//www.pubmed.com), SciELO (http//www.SciELO.org/php/index.php), Scopus (https://www.scopus.com/home.uri) and Portal de Periódicos CAPES (http//www.periodicos.capes.gov.br). The scientific name of the plant was combined with the terms "depression", "sedative", "anxiety", "nervousness", "biological activity", "chemical composition" and "toxicity", as well as their corresponding words in Portuguese, and used as keywords in the searches.

Results and discussion

Twenty-seven ethnobotanical studies were assessed. The studies were performed in municipalities located in different physiographic regions of Rio Grande do Sul. The Depressão Central was the region with the greatest number of studies (07), which is likely due to its proximity to the most important universities. It should be noted that currently the Fortes’s classification (Fortes 1959Fortes AB. 1959. Geografia física do Rio Grande do Sul. Porto Alegre, Editora Globo.) is mainy of historical value. In fact, the diversity of climate, soil and landforms in Rio Grande de Sul generates distinct ecosystems included in two biomes: the Atlantic Forest and the Pampa. The Atlantic Forest biome is characterized by the predominance of forest vegetation. It originally encompassed about 37 % of the state of Rio Grande do Sul, occupying the northern half of the state, although only 7.5 % of the area of the biome in the state remains, with high a degree of fragmentation relative to the original vegetation cover (Brasil 2018aBrasil. 2018a. Biomas. Brasília, Ministério do Meio Ambiente. http://www.mma.gov.br/biomas . 02 Jun. 2018.
http://www.mma.gov.br/biomas...
; Rio Grande do Sul 2018Rio Grande do Sul . 2018. Atlas sócio econômico do RS. Secretaria de Planejamento, Governança e Gestão Secretaria de Planejamento, Governança e Gestãohttp://www.atlassocioeconomico.rs.gov.br/ 12 Jun. 2018.
http://www.atlassocioeconomico.rs.gov.br...
). The Pampa biome in Brazil is restricted to the southern half of Rio Grande do Sul, and encompasses over 63% of the state. This biome is characterized by the predominance of a set of lowland vegetation that extends through Uruguay and Argentina, and possesses a great diversity of fauna and flora that is still poorly known (Brasil 2018aBrasil. 2018a. Biomas. Brasília, Ministério do Meio Ambiente. http://www.mma.gov.br/biomas . 02 Jun. 2018.
http://www.mma.gov.br/biomas...
; Rio Grande do Sul 2018Rio Grande do Sul . 2018. Atlas sócio econômico do RS. Secretaria de Planejamento, Governança e Gestão Secretaria de Planejamento, Governança e Gestãohttp://www.atlassocioeconomico.rs.gov.br/ 12 Jun. 2018.
http://www.atlassocioeconomico.rs.gov.br...
).

Ninety-four plant species were indicated to treat CNS dysfunctions (Tab. 1). Reports that provided only the genus or popular name were not considered. The families with the greatest number of species cited were Lamiaceae, with twenty-four species, Asteraceae, with thirteen species, and Rutaceae, with eight species.

Table 1
Medicinal plants used as antidepressants. tranquilizers or sedatives. mentioned in the ethnobotanical surveys carried out in Southern Brazil. Origin: E=exotic, N=native, Habit: C=climber, H=herb, S=shrub, T=tree.

Out of all the species cited (94), 73.4 % (69 species) were exotic and 26.6 % (25 species) were native to Rio Grande do Sul. This finding differs somewhat from that reported by Trojan-Rodrigues et al. (2012Trojan-Rodrigues M, Alves TLS, Soares GLG, Ritter MR. 2012. Plants used as antidiabetics in popular medicine in Rio Grande do Sul, Southern Brazil. Journal of Ethnopharmacology 139: 155- 163.) and Stolz et al. (2014Stolz ED, Müller LG, Trojan-Rodrigues M, et al. 2014. Survey of plants popularly used for pain relief in Rio Grande do Sul, southern Brazil. Brasilian Journal of Pharmacognosy 24: 185-196.), who found parity in the popular use of native and exotic plants for treating diabetes and pain, respectively. The use of exotic species, which are frequently cultivated in domestic gardens, points to the influence of different cultures coming from several ethnic groups. European, Asian and African descendants have integrated with indigenous peoples in Brazil, which is responsible for originating the current tradition of popular use of medicinal plants in the country (Ceolin et al. 2009Ceolin T, Heck RM, Barbieri RL, et al. 2009. Plantas medicinais utilizadas como calmantes por agricultores ecológicos da região Sul do Rio Grande do Sul, Brasil. Revista de Enfermagem 3: 1034-1041.; Battisti et al. 2013Battisti C, Garlet TMB, Essi L, Horbach RK, Andrade A, Badke MR. 2013. Plantas medicinais utilizadas no município de Palmeira das Missões, RS, Brasil. Revista Brasileira de Biociências 11: 338-348.; Löbler et al. 2014Löbler L, Santos D, Rodrigues ES, Santos NRZ. 2014. Levantamento etnobotânico de plantas medicinais no bairro Três de Outubro, da cidade de São Gabriel, RS, Brasil. Revista Brasileira de Biociências 12: 81-89.).

Regarding plant habit, 50.0 % (47 species) of the species were herbaceous, 21.3 % (20 species) arboreal, 19.1 % (18 species) shrubby and 9.6 % (nine species) climbing. About 60 % of the cited species had their leaves used while 17 % had the flowers or inflorescences used. These data are in agreement with other ethnobotanical studies of medicinal plants, which also found the flora to be mostly of herbaceous habit, a common occurrence for the Atlantic Forest biome. The commonality of the herbaceous habit may be related to the traditional practice of cultivation in backyards, since small plants are more easily cultivated in these smaller areas and backyard cultivation facilitates access to plants (Medeiros et al. 2004Medeiros MFD, Fonseca VS, Andreata RHP. 2004. Plantas medicinais e seus usos pelos sitiantes da Reserva Rio das Pedras, Mangaratiba, RJ, Brasil. Acta Botanica Brasilica 18: 391-399. ; Pinto et al. 2006Pinto EPP, Amorozo MCM, Furlan A. 2006. Conhecimento popular sobre plantas medicinais em comunidades rurais de mata atlântica - Itacaré, BA, Brasil. Acta Botanica Brasilica 20: 751-762. ; Giraldi & Hanazaki 2010Giraldi M, Hanazaki N. 2010. Uso e conhecimento tradicional de plantas medicinais no Sertão do Ribeirão, Florianópolis, SC, Brasil. Acta Botanica Brasilica 24: 395-406.). The use of leaves is predominant in Rio Grande do Sul since they are abundantly availability in the typical vegetation of southern Brazil, while the use of other plant parts is more characteristic of other regions, such as the Cerrado and Caatinga biomes, where the availability of leaves is more limited (Baldauf et al. 2009Baldauf C, Kubo RR, Silva F, Irgang BE. 2009. “Ferveu, queimou o ser da erva”: conhecimentos de especialistas locais sobre plantas medicinais na região sul do Brasil. Revista Brasileira de Plantas Medicinais 11: 282-291.). The form of preparation cited for treating CNS dysfunctions for all species was tea (including decoction and infusion), although several speices were cited for other uses including as food and as a conndiment. Tea was also the predominant form of preparation cited in research on general medical use (Trojan-Rodrigues et al. 2012Trojan-Rodrigues M, Alves TLS, Soares GLG, Ritter MR. 2012. Plants used as antidiabetics in popular medicine in Rio Grande do Sul, Southern Brazil. Journal of Ethnopharmacology 139: 155- 163.; Stolz et al. 2014Stolz ED, Müller LG, Trojan-Rodrigues M, et al. 2014. Survey of plants popularly used for pain relief in Rio Grande do Sul, southern Brazil. Brasilian Journal of Pharmacognosy 24: 185-196.).

Five species were cited in more than half of the studies surveyed: Cymbopogon citratus, with a 81.5 % citation frequency; Melissa officinalis, with 77.7 %; Aloysia citriodora, with 66.6 %; Matricaria chamomilla, with 62.9 %, and Passiflora edulis, with 51.8 %. Of these, only P. edulis is native to the study area. The use indicated for these five most cited species was as a sedative. Cymbopogon citratus, M. officinalis and M. chamomilla have been used as sedatives in other regions of Brazil, such as the states of Mato Grosso (Bieski et al. 2012Bieski IGC, Santos FR, Oliveira RM,et al. 2012. Ethnopharmacology of medicinal plants of the Pantanal region (Mato Grosso, Brazil). Evidence-Based Complementary and Alternative Medicine 2012: 1-36.), Minas Gerais (Costa & Mayworm 2011Costa VP, Mayworm MAS. 2011. Plantas medicinais utilizadas pela comunidade do bairro dos Tenentes - município de Extrema, MG, Brasil. Revista Brasileira de Plantas Medicinais 13: 282-292.), Rio de Janeiro (Medeiros et al. 2004Medeiros MFD, Fonseca VS, Andreata RHP. 2004. Plantas medicinais e seus usos pelos sitiantes da Reserva Rio das Pedras, Mangaratiba, RJ, Brasil. Acta Botanica Brasilica 18: 391-399. ), and Rondônia (Santos et al. 2008Santos MRA, Lima MR, Ferreira MGR. 2008. Uso de plantas medicinais pela população de Ariquemes, em Rondônia. Horticultura Brasileira 26: 244-250.). Indigenous peoples of Tocantins (Rodrigues & Carlini 2006Rodrigues E, Carlini EA. 2006. Plantas com possíveis ações psicoativas utilizadas pelos índios Krahô, Brasil. Revista Brasileira de Psiquiatria[online] 28(4): 277-282.) and quilombolas communities of Mato Grosso (Rodrigues & Carlini 2003Rodrigues E, Carlini EA. 2003. Possíveis efeitos sobre o sistema nervoso central de plantas utilizadas por duas culturas brasileiras (quilombolas e índios). Arquivos Brasileiros de Fitomedicina Científica 1: 147-154.) use C. citratus as a sedative. Indigenous communities living in cerrado savannahs and/or Pantanal wetlands use M. officinalis “to calm nervs” (Rodrigues & Carlini 2006Rodrigues E, Carlini EA. 2006. Plantas com possíveis ações psicoativas utilizadas pelos índios Krahô, Brasil. Revista Brasileira de Psiquiatria[online] 28(4): 277-282.). C. citratus, M. officinalis, M. chamomilla and P. edulis are used for the tratament of “nervios”, anxiety and depression in Mexico (Gutiérrez et al. 2014Gutiérrez SLG, Chilpa RR, Jaime HB. 2014. Medicinal plants for the treatment of “nervios”, anxiety, and depression in Mexican Traditional Medicine. Revista Brasileira de Farmacognosia 24: 591-608.), while M. officinalis and M. chamomilla are used for psychosomatic disorders in Peru (Bussmann et al. 2010Bussmann RW, Glenn A, Sharon D. 2010. Healing the body and soul: Traditional remedies for “magical” ailments, nervous system and psychosomatic disorders in Northern Peru. African Journal of Pharmacy and Pharmacology 4: 580-629.).

Cymbopogon citratus is indicated by the Formulário de Fitoterápicos da Farmacopéia Brasileira (Pharmacotherapeutic Formulary of the Brazilian Pharmacopoeia) as an antispasmodic, anxiolytic and mild sedative, and that it may potentiate the effect of sedative drugs (Brasil 2011Brasil. 2011. Formulário de Fitoterápicos da Farmacopéia Brasileira /Agência Nacional de Vigilância Sanitária. Brasília, ANVISA . ; 2016Brasil. 2016. Lista de fitoterápicos regulamentados pela ANVISA. Brasília, ANVISA . http://g1.globo.com/Noticias/Brasil/2010/03/drgvege.pdf 05 Mar. 2016.
http://g1.globo.com/Noticias/Brasil/2010...
). Citral is the main chemical constituent of the volatile oil of the plant, accounting for at least 60 % of its composition (Brasil 2010Brasil. 2010. Farmacopéia Brasileira. Vol. 2. Brasília, ANVISA.). Studies have suggested that the anxiolytic effect of the essential oil of this species is mediated by the GABAA receptor-benzodiazepine complex (Costa et al. 2011Costa CA, Kohn DO, Lima VM,et al. 2011. The GABAergic system contributes to the anxiolytic-like effect of essential oil fromCymbopogon citratus (lemongrass). Journal of Ethnopharmacology 137: 828-836.).

Melissa officinalis has been historically used as an anxiolytic (Wong et al. 1998Wong AH, Smith M, Boon HS. 1998. Herbal remedies in psychiatric practice. Archives of General Psychiatry 55: 1033-1046.). It is indicated in the Formulário de Fitoterápicos da Farmacopéia Brasileira as an antispasmodic, anxiolytic and mild sedative, with the warning that it should not be used in cases of hypothyroidism and used with caution with people with hypotension (Brasil 2011Brasil. 2011. Formulário de Fitoterápicos da Farmacopéia Brasileira /Agência Nacional de Vigilância Sanitária. Brasília, ANVISA . ; 2018bBrasil. 2018b. Formulário de Fitoterápicos da Farmacopéia Brasileira /Agência Nacional de Vigilância Sanitária. 1st. edn. Brasília, ANVISA . ). According to the Brazilian Pharmacopoeia, M. officinalis must possess at least 4.0 % of total hydroxycinnamic derivatives, at least 2.0 % of rosmarinic acid and at least 0.6 % of volatile oil (Brasil 2010Brasil. 2010. Farmacopéia Brasileira. Vol. 2. Brasília, ANVISA.). Citral, geranial, neral and β-caryophyllene have been suggested as the main compounds responsible for actions of M. officinalis on the CNS (Tagashira & Ohtake 1998Tagashira M, Ohtake Y. 1998. A new antioxidative 1, 3-benzodioxole from Melissa officinalis. Planta Medica 64: 555-558.; Wake et al. 2000Wake G, Court J, Pickering A, et al. 2000. CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory. Journal of Ethnopharmacology 69: 105-114.; Vale et al. 2002Vale TG, Furtado EC, Santos JG, Viana GSB. 2002. Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) NE Brown. Phytomedicine 9: 709-714.).

Matricaria chamomillais among the most important medicinal plants native to southern and eastern Europe (Singh et al. 2011Singh O, Khanam Z, Misra N, Srivastava MK. 2011. Chamomile (Matricaria chamomilla L.): an overview. Pharmacognosy Reviews 5: 82-95.; Telesinski et al. 2013Telesinski A, Grzeszczuk M, Jadczak D, Zakrzewska H. 2013. Fluoride content and biological value of flowers of some chamomile (Matricaria recutita L.) cultivars. Journal of Elementology 17: 703-712. ). Singh & Aishwarya (2017)Singh CE, Aishwarya J. 2017. Chamomile an Ancient Aromatic Plant - A Review. Journal of Ayurveda Medical Sciences 2: 251-255. recently published a review on the biological properties of this species. It is indicated in the Formulário de Fitoterápicos da Farmacopéia Brasileira as antispasmodic, anxiolytic and mild sedative. The formulary also includes information on occasional allergic reactions and possible occurrence of nervous excitement and insomnia in cases of overdose, and that its use should be avoided with people that are allergic or hypersensitive to chamomile or plants of the family Asteraceae (Brasil 2011Brasil. 2011. Formulário de Fitoterápicos da Farmacopéia Brasileira /Agência Nacional de Vigilância Sanitária. Brasília, ANVISA . ). Camazulene, coumarin and trans-caryophyllene have been suggested as the compounds responsible for the effects of M. chamomilla on the CNS (Hajjaj et al. 2013Hajjaj G, Bounihi A, Tajani M, Cherrah Y, Zellou A. 2013. Evaluation of CNS activities of Matricaria chamomilla L. essential oil in experimental animals from Morocco. International Journal of Pharmacy and Pharmaceutical Sciences 5: 530-534.; Keefe et al. 2016Keefe JR, Mao JJ, Soeller I, Li QS, Amsterdam JD. 2016. Short-term open-label chamomile (Matricaria chamomilla L.) therapy of moderate to severe generalized anxiety disorder. Phytomedicine 23: 1699-1705. ; Mao et al. 2016Mao JJ, Xie SX, Keefe JR, Soeller I, Li QS, Amsterdam JD. 2016. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial. Phytomedicine 23: 1735-1742. ).

Passiflora edulis is indicated in the Formulário de Fitoterápicos da Farmacopéia Brasileira as an anxiolytic and mild sedative, with the warning that its use may cause somnolence and that it should not be used chronically or concomitantly with other sedatives and depressants of the nervous system (Brasil 2011Brasil. 2011. Formulário de Fitoterápicos da Farmacopéia Brasileira /Agência Nacional de Vigilância Sanitária. Brasília, ANVISA . ; 2018bBrasil. 2018b. Formulário de Fitoterápicos da Farmacopéia Brasileira /Agência Nacional de Vigilância Sanitária. 1st. edn. Brasília, ANVISA . ).

Aloysia citriodora is traditionally used in France as a sedative and muscle relaxant for newborns (Makram et al. 2015Makram S, Alaoui K, Benabboyha T, Faridi B, Cherrah Y, Zellou A. 2015. Extraction et activité psychotrope de l’huile essentielle de la verveine odorante Lippia citriodora. Phytothérapie 13: 163-167.). This species is native to South America and has been cultivated into Europe since 1784 (Pio Corrêa 1931Pio Corrêa M. 1931. Dicionario das plantas úteis do Brasil e das exóticas cultivadas. Vol. 2. Rio de Janeiro, Imprensa Nacional.). According to Ragone et al. (2010Ragone MI, Sella M, Pastore A, Consolini AE. 2010. Sedative and cardiovascular effects of Aloysia citriodora Palau, on mice and rats. Latin American Journal of Pharmacy 29: 79-86.), the effect of this plant is similar to the effect of benzodiazepines. Citral is its main constituent (Ponce-Monter et al. 2010Ponce-Monter H, Fernández-Martínez E, Ortiz MI, et al. 2010. Spasmolytic and anti-inflammatory effects of Aloysia triphylla and citral, in vitro and in vivo studies. Journal of Smooth Muscle Research 46: 309-319.).

Scientific studies on the efficacy of the five most frequently mentioned species (Tab. 2) are mostly preclinical; that is, they were carried out with non-human animal models (rodents, fish, crustaceans), or were cellular or biochemical tests. Among the activities demonstrated by these studies, we highlight antimicrobial, antioxidant and anti-inflammatory properties and depressant of central nervous system (mainly, sedative effect). Clinical studies (i.e., on humans) were found only for Matricaria chamomilla and Melissa officinalis. Several clinical trials have suggested a modest beneficial action by M. chamomilla in relieving symptoms of anxiety (Amsterdam et al. 2009Amsterdam JD, Li Y, Soeller I, et al. 2009. A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy of generalized anxiety disorder. Journal of Clinical Psychopharmacology 29: 378-382.; 2012Amsterdam JD, Shults J, Soeller I, et al. 2012. Chamomile (Matricaria recutita) may have antidepressant activity in anxious depressed humans-an exploratory study. Alternative Therapies in Health and Medicine 18: 44-49.;Zick et al. 2011Zick SM, Wright BD, Sen A, Arnedt JT. 2011. Preliminary examination of the efficacy and safety of a standardized chamomile extract for chronic primary insomnia: a randomized placebo-controlled pilot study. Evidence-Based Complementary and Alternative Medicine 22: 78. doi: 10.1186/1472-6882-11-78
https://doi.org/10.1186/1472-6882-11-78...
; Keefe et al. 2016Keefe JR, Mao JJ, Soeller I, Li QS, Amsterdam JD. 2016. Short-term open-label chamomile (Matricaria chamomilla L.) therapy of moderate to severe generalized anxiety disorder. Phytomedicine 23: 1699-1705. ; Mao et al. 2016Mao JJ, Xie SX, Keefe JR, Soeller I, Li QS, Amsterdam JD. 2016. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial. Phytomedicine 23: 1735-1742. ). A randomized double-blind clinical study of M. officinalis found indications of positive action for agitation and cognitive impairment in Alzheimer's patients (Akhondzadeh et al. 2003Akhondzadeh S, Noroozian M, Mohammadi M, et al. 2003. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind, randomised, placebo controlled trial. Journal of Neurology, Neurosurgery and Psychiatry 74: 863-866.). Two other studies found positive action for anxiety. One, an open prospective study, indicated efficacy for insomnia and symptoms associated with stress and anxiety (Cases et al. 2011Cases J, Ibarra A, Feuillère N, Roller M, Sukkar SG. 2011. Pilot trial of Melissa officinalisL. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances. Mediterranean Journal of Nutrition Metabolism 4: 211-218.), while the other, a double-blind randomized placebo study, demonstrated efficacy in relieving anxiety-related heart palpitations (Alijaniha et al. 2015Alijaniha F, Naseri M, Afsharypuor S, et al. 2015. Heart palpitation relief withMelissa officinalisleaf extract: double blind, randomized, placebo controlled trial of efficacy and safety. Journal of Ethnopharmacology 164: 378-384.).

Table 2
Chemical composition, biological activities and toxicity of medicinal species with CNS action cited in at least fourteen ethnobotanical surveys.

Indications regarding safety were found for two of the five most cited plants. Studies were found that reported genotoxicity of Matricaria chamomilla (Vieira et al. 2009Vieira A, Guimarães MDA, David GQ, Karsburg IV, Campos ANR. 2009. Efeito genotóxico da infusão de capítulos florais de camomila. Revista Trópica. Ciências Agrárias e Biológicas 3: 8-13.; Delarmelina et al. 2012Delarmelina JM,Batitucci L, Gonçalves JLO. 2012. Efeitos citotóxico, genotóxico e mutagênico da tintura de Matricaria chamomilla L. in vivo. Revista Cubana de Plantas Medicinales 17: 149-159.) and hepatobiliary and pancreatic (in rodents and humans) toxicity of Passiflora edulis (Maluf et al. 1991Maluf E, Barros HMT, Frochtengarten ML, Benti R, Leite JR. 1991. Assessment of the hypnotic sedative effects and toxicity of Passiflora edulis aqueous extract in rodents and humans. Phytotherapy Research 5: 262-266.). These findings are matter for some concern, and indicate a need for additional research including long-term studies to establish the safety of these plants.

Conclusion

The present study demonstrates that there is a great diversity of plant species used by the population of the state of Rio Grande do Sul for treating symptoms related to disorders of the central nervous system, with use as a sedative being the most frequent indication. The use of exotic species was predominant. The five most cited species have broad traditional use as sedative agents in Brazil and Europe, four of which are accepted by the National Health Surveillance Agency (ANVISA) for therapeutic use: Matricaria chamomilla, Melissa officinalis, Cymbopogon citratus and Passiflora edulis. Scientific studies corroborate popular use as a sedative, but most studies are preclinical, with the few clinical studies (M. chamomilla and M. officinalis) being mainly exploratory and/or performed against placebo. Among the most cited species, M. chamomilla and P. edulis possess potential long-term toxicity. The present study finds M. officinalis to be the species with the best indications of clinical efficacy in the treatment of symptoms associated with anxiety, with an absence of toxicity data. Taken together, the results presented here evidence the need for further research on the plant species mentioned in ethnobotanical surveys carried out in the state of Rio Grande do Sul.

Acknowledgements

The authors wish to thank Erik Russell Wild for revising the English. This research was carried out with financial support from the Universidade Federal do Rio Grande do Sul.

References

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Publication Dates

  • Publication in this collection
    19 June 2019
  • Date of issue
    Apr-Jun 2019

History

  • Received
    31 Oct 2018
  • Accepted
    19 Feb 2019
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