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Medicinal plants with popular names associated with manufactured drugs in Rio Grande do Sul state, Brazil

Abstract

Medicinal plants used by the population in southern Brazil have been observed to be popularly referred to by the names of manufactured drugs. This study aimed to find a connection between the use of medicinal plant species with popular names associated with manufactured drugs and the actual biomedical system. A database regarding such medicinal plants was established based on thirty-four ethnobotanical studies undertaken in the state of Rio Grande do Sul, Brazil, and chemical and pharmacological information was collected from a scientific article database and crossed referenced to determine whether folk information was correlated. Thirty-one species with a total of twenty-five different popular names of manufactured drugs were found. The greatest number of popular names of manufactured drugs was for Alternanthera brasiliana with eight names, followed by Achillea millefolium with six. The therapeutic indication of the species used in the manufactured formulas was found to differ from the indications of popular use. However, the therapeutic indication of both were correlated for digestive disorders, as well as for popularly named phytotherapic species. Cultural adoption of popular names may be influenced by the biomedical system and the flow of knowledge arising from conventional medicine toward popular medicine.

Key words:
commercial drug; digestive disorders; ethnobotany; phytotherapics

Resumo

Observou-se que as plantas medicinais utilizadas pela população do sul do Brasil têm sido referidas popularmente pelos nomes dos medicamentos industrializados. Este estudo visou encontrar uma ligação entre o uso de espécies de plantas medicinais com os nomes populares associados a medicamentos industrializados e o sistema biomédico atual. Foi criada uma base de dados sobre estas plantas medicinais com base em 34 estudos etnobotânicos realizados no estado do Rio Grande do Sul, Brasil, e foram buscadas informações químicas e farmacológicas a partir de uma base de dados de artigos científicos, e cruzadas para determinar se as informações populares estavam correlacionadas. Foram encontradas 31 espécies com um total de 25 nomes populares de medicamentos industrializados diferentes. O maior número de nomes populares de medicamentos industrializados foi para Alternanthera brasiliana com oito nomes, seguido de Achillea millefolium com seis. Verificou-se que a indicação terapêutica das espécies utilizadas nas fórmulas industrializadas era diferente das indicações de uso popular. No entanto, a indicação terapêutica de ambas foram correlacionadas para distúrbios digestivos, bem como para as espécies designadas popularmente por fitoterápicos. A adoção cultural de nomes populares pode ser influenciada pelo sistema biomédico e pelo fluxo de conhecimento decorrente da medicina convencional em direção à medicina popular.

Palavras-chave:
medicamento comercial; problemas digestivos; etnobotânica; fitoterápicos

Introduction

Interactions between biomedicine and local medical systems of different human groups have been an important focus of ethnobiological research (Mignone et al. 2007Mignone J, Bartlett J, O’Neil J & Orchard T (2007) Best practices in intercultural health: five case studies in Latin America. Journal of Ethnobiology and Ethnomedicine 3: 31. Available at <Available at https://ethnobiomed.biomedcentral.com/articles/10.1186/1746-4269-3-31 >. Access on 17 March 2019. DOI: 10.1186/1746-4269-3-31.
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; Vandebroek 2013Vandebroek I (2013) Intercultural health and ethnobotany: how to improve healthcare for underserved and minority communities? Journal of Ethnopharmacology 148: 746-754.). Even though some studies have observed that the biomedical system affects local knowledge negatively, evidencing an incompatibility between the two types of knowledge (Ragupathy et al. 2008Ragupathy S, Steven NG, Maruthakkutti M, Velusamy V & Ul-Huda MM (2008) Consensus of the ‘Malasars’ traditional aboriginal knowledge of medicinal plants in the Velliangiri holy hills, India. Journal of Ethnobiology and Ethnomedicine 4: 8. Available at <Available at https://ethnobiomed.biomedcentral.com/track/pdf/10.1186/1746-4269-4-8.pdf >. Access on 10 January 2018. DOI: 10.1186/1746-4269-4-8
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; Hoa et al. 2009Hoa NP, Chuc NT & Thorson A (2009) Knowledge, attitudes, and practices about tuberculosis and choice of communication channels in a rural community in Vietnam. Health Policy 90: 8-12.), others have shown integration between the two systems, leading to what is known as “intermedicality” (Greene 1998Greene S (1998) The shaman’s needle: development, shamanic agency, and intermedicality in Aguaruna lands, Peru. American Ethnologist 25: 634-658.), that is, people of a group use local and biomedical knowledge complementarily (see Soldati & Albuquerque 2012Soldati GT & Albuquerque UP (2012) Ethnobotany in intermedical spaces: the case of the Fulni-ô Indians (Northeastern Brazil). Evidence-Based Complementary and Alternative Medicine 2012: 648469. DOI: 10.1155/2012/648469
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). It has often been revealed that natural resources and industrialized medicines are used that are not mutually exclusive and do not necessarily compete with one another (Giovannini et al. 2011Giovannini P, Reyes-García V, Waldstein A & Heinrich M (2011) Do pharmaceuticals displace local knowledge and use of medicinal plants? Estimates from a cross-sectional study in a rural indigenous community, Mexico. Social Science & Medicine 72: 928-936.).

In countries such as Cameroon, Kenya and Uganda, carriers of the human immunodeficiency virus (HIV) use both conventional medical treatments and medicinal plants (Noumi & Manga 2011Noumi E & Manga P (2011) Traditional medicines for HIV/AIDS and opportunistic infections in north-west Cameroon: case of skin infections. American Journal of Tropical Medicine and Public Health 1: 44-46.). In other cases, plants serve as a substitute for conventional medicines, with this substitution providing carriers an easily accessible treatment with fewer side effects and less social exposure to stigmatization (Noumi & Manga 2011). An interesting example of the integration of biomedical and local medical systems is the use by some human groups of the names of manufactured medicines to designate medicinal plants, as observed by various studies in different regions of Brazil, such as in the South (Kubo 1997Kubo RR (1997) Levantamento das plantas de uso medicinal em Coronel Bicaco, RS. Dissertação de Mestrado. Universidade Federal do Rio Grande do Sul, Porto Alegre . 163p.; 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. ; Marodin & Baptista 2001Marodin SM & Baptista LRM (2001) O uso de plantas com fins medicinais no município de Dom Pedro de Alcântara, Rio Grande do Sul. Revista Brasileira de Plantas Medicinais 4: 57-68.; 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.; Trojan-Rodrigues et al. 2012Trojan-Rodrigues MR, Alves TLS, Soares GLG & Ritter MR (2012) used as antidiabetics in popular medicine in Rio Grande do Sul, Southern Brazil. Journal of Ethnopharmacology 139: 155-163. ; 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.), Southeast (Martins et al. 2005Martins LGS, Senna-Valle L & Pereira NA (2005) Princípios ativos e atividades farmacológicas de 8 plantas popularmente conhecidas por nome de medicamentos comerciais. Revista Brasileira de Plantas Medicinais 7: 73-76.; Pilla et al. 2006Pilla MAC, Amorozo MCM & Furlan A (2006) Obtenção e uso das plantas medicinais no distrito de Martim Francisco, município de Mogi-Mirim, SP, Brasil. Acta Botanica Brasilica 20: 789-802.) and the Northeast (Soldati & Albuquerque 2012Soldati GT & Albuquerque UP (2012) Ethnobotany in intermedical spaces: the case of the Fulni-ô Indians (Northeastern Brazil). Evidence-Based Complementary and Alternative Medicine 2012: 648469. DOI: 10.1155/2012/648469
https://doi.org/10.1155/2012/648469...
), as well as in the country in general (Siqueira et al. 2017Siqueira BVL, Soares BE, Oliveira DR & Sakuragui CM (2017) The regionalization of medicalized vernacular names of medicinal plants in Brazil. Scientometrics 110: 945-966. DOI: 10.1007/s11192-016-2184-y
https://doi.org/10.1007/s11192-016-2184-...
). Indicating medicinal plants using the names of manufactured medicines represents an interesting case to observe the phenomenon of intermedicality of medical systems because it reveals a way that the integration of biomedicine and local systems can occur, evolve and structure local medical systems. Casagrande (2009Casagrande A (2009) Plantas medicinais e ritualísticas utilizadas pela comunidade do Morro da Cruz, Porto Alegre - RS. Monografia de Conclusão de Curso. Universidade Federal do Rio Grande do Sul, Porto Alegre. 139p.) demonstrated the interconnection between scientific and traditional knowledge in a popular community in the metropolitan region of Porto Alegre, Brazil, recovering the use of plants such as Alternanthera brasiliana (L.) Kuntze (popularly called ampicillin, penicillin) and Sphagneticola trilobata (L.) Pruski (popularly called insulin), indicating the use of manufactured drug names for plants intended for the same symptoms and diseases.

We investigated the use of names of medicines of biomedical origin as names of medicinal plants by human communities in the state of Rio Grande do Sul, Brazil, to better understand some aspects of the integration of biomedicine and local systems. Specifically, we aimed to answer the following questions: (1) Which species of medicinal plants with a popular name associated with a manufactured drug are used in the state of Rio Grande do Sul? (2) Are plants of native or exotic (cultivated and naturalized) origin in Brazil more widely used? (3) Are species with a popular name associated with a manufactured phytotherapic medicine also found in the formulation of the medicine? (4) Is there correspondence between the use of plants with names from manufactured medicines and the use of the manufactured medicine by the biomedical system? These questions are important for determining the aspects of the medical system that have greater interaction between local and biomedical systems regarding medicinal plant nomenclature and if the use of medicine names for medicinal plants has a biomedical rational.

Materials and Methods

Information was obtained from ethnobotanical studies on the use of medicinal plants, such those reported in articles, doctoral theses, master’s theses and monographs, conducted in different regions of the state of Rio Grande do Sul, Brazil.

Studies were found through searches in databases, such as Google Scholar (2021), Portal CAPES (2021) and PUBMed (2021), using the following keywords: “ethnobotanical survey” and “medicinal plants” crossed with the word “Rio Grande do Sul”. The criteria for selection were: accessibility, presence of a botanist in the research team, study focus about the knowledge and/or use of medicinal plants by local communities, and with methods characteristic of ethnobotanical research (mainly interviews). The following thirty-four ethnobotanical surveys were recovered (from 1997 to 2020) and assessed: Kubo (1997Kubo RR (1997) Levantamento das plantas de uso medicinal em Coronel Bicaco, RS. Dissertação de Mestrado. Universidade Federal do Rio Grande do Sul, Porto Alegre . 163p.); Zucchetti et al. (1997Zucchetti AM (1997) Levantamento das plantas medicinais mais usadas por ervateiros na zona norte de Porto Alegre para doenças ginecológicas. Monografia de Conclusão de Curso. Universidade Luterana do Brasil, Canoas. 189p.); Froehlich (1998Froehlich NMS (1998) Plantas medicinais utilizadas na comunidade rural de Fortaleza campo, município de Cidreira, RS. Monografia de Conclusão de Curso. Universidade Luterana do Brasil, Canoas. 59p.); Briani Neto (1999Briani Neto ML (1999) Levantamento etnobotânico de plantas medicinais dos distritos de Cazuza Ferreira e Lageado Grande, no município de São Francisco de Paula - RS, Brasil. Monografia de Conclusão de Curso. Universidade Luterana do Brasil, Canoas. 100p. ); Koch (2000Koch V (2000) Estudo etnobotânico das plantas medicinais na cultura ítalobrasileira no Rio Grande do Sul - um modelo para o cultivo comercial na agricultura familiar. Dissertação de Mestrado. Universidade Federal do Rio Grande do Sul, Porto Alegre . 152p.); Possamai (2000Possamai RM (2000) Levantamento etnobotânico das plantas de uso medicinal em Mariana Pimentel, Rio Grande do Sul. Dissertação de Mestrado. Universidade Federal do Rio Grande do Sul, Porto Alegre . 108p.); Fernandes (2001Fernandes AA (2001) Levantamento etnobotânico na região da Pedra do Segredo, Caçapava do Sul, RS. Monografia de conclusão de curso. Universidade Federal de Pelotas, Pelotas . 54p.); 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. ); Marodin & Baptista (2001Marodin SM & Baptista LRM (2001) O uso de plantas com fins medicinais no município de Dom Pedro de Alcântara, Rio Grande do Sul. Revista Brasileira de Plantas Medicinais 4: 57-68.); 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.); Hass (2003Hass APS (2003) Categorização tóxico-terapêutica das plantas medicinais usadas no município de Maquiné - Rio Grande do Sul. Monografia de Conclusão de Curso. Universidade Federal do Rio Grande do Sul, Porto Alegre . 56p.); Leitzke (2003Leitzke ZCS (2003) Levantamento das plantas medicinais da comunidade Nossa Senhora da Conceição - Canguçu-RS. Trabalho de Conclusão de Curso. Universidade Federal de Pelotas, Pelotas . 128p.); Martha (2003Martha EM (2003) O uso das plantas medicinais pela comunidade da associação dos agricultores construtores da Palma - assentamento 24 de Novembro. Trabalho de Conclusão do Curso. Universidade Federal de Pelotas, Pelotas . 79p.); Sebold (2003Sebold DF (2003) Levantamento etnobotânico de plantas de uso medicinal no município de Campo Bom, Rio Grande do Sul, Brasil. Dissertação de Mestrado. Universidade Federal do Rio Grande do Sul, Porto Alegre . 107p.); 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 Marcela (Achyrocline satureioides) e Capim-limão (Cymbopogon citratus), Camomila (Matricaria chamomilla). Monografia de Conclusão de Curso. Universidade Federal de Pelotas, Pelotas . 42p.); Zanandrea (2003Zanandrea I (2003) Estudo etnobotânico das plantas medicinais mais utilizadas pelos moradores do bairro Santa Terezinha. Pelotas, RS. Monografia de conclusão de curso. Universidade Federal de Pelotas, Pelotas . 68p.); Löwe (2004Löwe TR (2004) Estudo etnobotânico em uma área rural do município de Três de Maio, RS. Trabalho de Conclusão de Curso. Universidade Federal de Pelotas, Pelotas . 45p.); Silveira (2004Silveira YL (2004) Estudo etnobotânico das plantas medicinais utilizadas pelos índios Mbyá-Guarani da Terra Indígena de Cantagalo, Viamão, RS, para a saúde bucal. Dissertação de Mestrado. Universidade Luterana do Brasil, Canoas. 152p.); 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.); 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 Sul. Monografia de Conclusão de Curso. Universidade do Vale do Rio dos Sinos, São Leopoldo. 53p.); 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, Brasil. Iheringia 61: 83-103.); Barros et al. (2007Barros 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 265: 652-662. ); Schwambach (2007Schwambach KH (2007) Utilização de plantas medicinais e medicamentos no autocuidado no município de Teutônia, RS. Dissertação de Mestrado. Universidade Federal do Rio Grande do Sul, Porto Alegre . 97p.); Ramos (2008Ramos AJK (2008) Plantas com potencial medicinal na Floresta Nacional de Canela e comunidades do entorno, Canela, Rio Grande do Sul. EMATER/RS-ASCAR, Porto Alegre. 90p.); Casagrande (2009Casagrande A (2009) Plantas medicinais e ritualísticas utilizadas pela comunidade do Morro da Cruz, Porto Alegre - RS. Monografia de Conclusão de Curso. Universidade Federal do Rio Grande do Sul, Porto Alegre. 139p.); Ceolin (2009Ceolin T (2009) Conhecimento sobre plantas medicinais entre agricultores de base ecológica da região sul do Rio Grande do Sul. Dissertação de Mestrado. Universidade Federal de Pelotas, Pelotas. 108p.); Vanini (2010Vanini M (2010) Uso de plantas medicinais em um território quilombola do município de Mostardas - Rio Grande do Sul. Dissertação de Mestrado. Universidade Federal de Pelotas, Pelotas . 90p.); Baptista et al. (2013); 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. ); Hentges (2015Hentges AM (2015) Dados socioculturais de usuários de plantas medicinais e plantas utilizadas como medicinais no município de Cândido Godói, Rio Grande do Sul. Trabalho de Conclusão de Curso, Universidade Federal da Fronteira Sul, Cerro Largo. 55p.); Brião et al. (2016Brião D, Artico LL, Líma LFP & Menezes APS (2016) Utilização de plantas medicinais em um município inserido no bioma Pampa brasileiro. Revista da Universidade Vale do Rio Verde 14: 206-219.); Delfim (2019Delfim TF (2019) Uso e conservação de plantas bioativas em comunidades quilombolas da mesorregião do sudeste Rio-grandense. Tese de Doutorado. Universidade Federal de Pelotas, Pelotas . 91p.) and Bremm et al. (2020Bremm N, Ramos RF, Nilles JH, Pivetta CP & Pelegrin CMG (2020) Plantas medicinais usadas em uma comunidade do noroeste do Rio Grande do Sul, Brasil. Revista Thema 17: 765-781.).

These surveys were used to construct a database of species that were popularly named by using a name of a manufactured drug or active substance, along with their therapeutic indications. World Flora Online (WFO) (2022) and Flora e Funga do Brasil 2022 (continuously updated) were used to confirm valid and current scientific names and their synonymies while the classification system used was that of APG IV (2016). Original popular names traditionally used in southern Brazil were used and Flora Digital do Rio Grande do Sul and Santa Catarina (2021) and Flora e Funga do Brasil 2022 (continuously updated) were used to categorize the origin of species as native to Brazil, cultivated exotics or naturalized exotics.

The therapeutic classes of the studied species were standardized using the therapeutic classes of the medicines (Brasil 1984) and manufactured drug package inserts. The medicinal species associated with drugs were determined by consulting package inserts and their therapeutic class was indicated and confirmed in ANVISA (Brasil 2021).

All species addressed by this study were compiled with their respective therapeutic uses, which were categorized according to the International Classification of Diseases (ICD-11) (WHO 2020), as presented in Table 1.

Our question about the correspondence between medicinal applications of plants with drug names and the use of the drug by the biomedical system was addressed by first recording the popular uses of each plant. This was then followed by checking for the occurrence of the popular uses in the indications that appeared in the package insert of the manufactured drug. Thus, it was possible to determine if the name adopted by popular medicine was related to the effects for which the manufactured drug is used.

Our question about whether species with names associated with a manufactured phytotherapic medicine are also used in the medicine was addressed by checking for the occurrence of the species in the formula of the medicine. The package insert was used as a source of information to verify whether the species are indeed the same.

Chemical data and pharmacological activities of the studied species were surveyed by consulting published articles using the valid scientific name or synonyms of the species found in searches of ISI Web of Knowledge (2021), Portal CAPES (2021) and PUBMed (2021) databases up to the year 2021. The articles selected were those that contained, in the title or in the abstract, the scientific binomial or a synonym of a studied species and its chemical characterization and pharmacological activity.

Table 1
Classification of the popular therapeutic indications found in ethnobotanical surveys conducted in Rio Grande do Sul state, Brazil, according to ICD-11 (WHO 2020).

Results and Discussion

Medicinal plant species and their popular names

Thirty-four ethnobotanical studies were assessed, revealing thirty-one species with a total of twenty-five different popular names of manufactured drugs (Tab. 2). The studies were performed in municipalities located in different regions of the state of Rio Grande do Sul.

The species belong to the families Asteraceae (32.3%), Amaranthaceae (16.1%), Lamiaceae (16.1%) and 10 other families (35.5%). Asteraceae was the most representative family as it presents great morphological and geographic diversity among its species that is reflected in their ability to produce a range of secondary metabolites (Calabria et al. 2009Calabria LM, Emerenciano VP, Scotti MT & Mabry TJ (2009) Secondary chemistry of Compositae. In: Funk VA, Susanna A, Stuessy TF & Bayer RJ (eds.) Systematics, evolution and biogeography of Compositae. International Association for Plant Taxonomy, Vienna. Pp. 73- 88.). Asteraceae stands out with regard to medicinal use in other parts of the world, beyond Rio Grande do Sul (Saslis-Lagoudakis et al. 2011).

Among the species, 48.4% are native to Brazil, 38.7% are cultivated exotics and 12.9% are naturalized exotics. The species with the greatest number of popular names from manufactured drugs were Alternanthera brasiliana L. (Kuntze) (native) with eight, Achillea millefolium L. (cultivated exotic) with six and Salvia microphylla Kunth. (cultivated exotic) with four. Thus, manufactured drug names are attributed to both native and exotic species.

Asteraceae was the botanical family with the greatest representation in terms of species in this research, which may be due to it being the most diverse and prolific plant family in the world. According to Chadwick et al. (2013Chadwick M, Trewin H, Gawthrop F & Wagstaff C (2013) Sesquiterpenoids lactones: benefits to plants and people. International Journal of Molecular Sciences 14: 12780-12805.), the families Asteraceae and Euphorbiaceae produce secondary metabolites, such as sesquiterpene lactones, that are responsible for bitter taste. These phytochemicals represent a significant proportion of the dry weight (around 3%) of species of Asteraceae.

According to the Brazilian National Program of Medicinal Plants, folk medicinal plants, especially native ones, are valued because they are local and thus easily available to users (Brasil 2015). Moreover, locals tend to prefer native over exotic plants for medicinal application (Albuquerque 2006Albuquerque UP (2006) Re-examining hypotheses concerning the use and knowledge of medicinal plants: a study in the Caatinga vegetation of NE Brazil. Available at <Available at http://www.ethnobiomed.com/content/2/1/30 >. Access on 10 July 2020. DOI: 10.1186/1746-4269-2-30
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; Estomba et al. 2006Estomba D, Ladio A & Lozada M (2006) Medicinal wild plant knowledge and gathering patterns in a Mapuche community from North-western Patagonia. Journal of Ethnopharmacology 103: 109-119.). However, exotic plants were found to be preferred medicinal plants for digestive disorders, which is probably explained by the low specificity of the action of exotic plants. In other words, many substances might present similar effects, allowing for the replacement of native species with exotics (Estomba et al. 2006).

Table 3 lists the twenty-five names of drugs and/or active substances used as plant names found by the present study and their respective therapeutic medicinal classes. Analgesic and antipyretic are the most frequent therapeutic class, with nine manufactured drug names, followed by antispasmodic and digestive with five and antibiotic also with five. Achillea millefolium was the species with the highest number of therapeutic classes, that is, it had broader use.

The popular name Anador (analgesic and antipyretic) was mentioned for eight different species, Infalivina (digestive) for seven and Novalgina (analgesic and antipyretic) for four. There is one group of species whose names are of phytotherapics that are all related to digestive problems.

The case of species popularly named for phytotherapics and digestive disorders

The therapeutic indications of the species used in manufactured formulas were generally found to differ from the indications of popular use. However, therapeutic indications for both popular use and manufactured formulas were correlated when it came to the therapeutic indication of digestive disorders. For example, the species Cynara scolymus L., called alcachofra, and Peumus boldus Molina, called boldo-do-chile, are plants contained in the formula of the phytotherapic Figatil®, while Gymnanthemum amygdalinum (Delile) Sch.Bip. ex Walp. (= Vernonia condensata Baker), also popularly called boldo (Lorenzi & Matos 2008Lorenzi H & Matos FJA (2008) Plantas medicinais no Brasil. 2a ed. Instituto Plantarum, Nova Odessa. 576p.), is the species indicated by the ethnobotanical studies as Figatil. Ten species in total were mentioned as having the folk names Figatil, Infalivina or Olina (Tab. 4).

Table 2
Species, family, popular names and popular name associated with manufactured drugs, obtained in ethnobotanical surveys in Rio Grande do Sul state, Brazil.

According to Medeiros et al. (2015Medeiros PM, Ladio AH & Albuquerque UP (2015) Local criteria for medicinal plant selection. In: Albuquerque U, Medeiros P & Casas A (eds.) Evolutionary ethnobiology. Springer, Cham. Pp 149-162. Available at <Available at https://ethnobioconservation.com/index.php/ebc/article/view/641 >. Access on 15 July 2018. DOI: 10.1007/978-3-319-19917-7_11
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), traditional pharmacopoeias follow criteria for introducing plants for medicinal purposes. It is not a random process and may be determined by chemoreceptor system (flavor/odor) and/or cultural information (good or bad, useful or not useful, and values, symbolism, etc.). Taste might be a good principle, called an ethnopharmacophore descriptor (Gilca & Barbulescu 2015Gilca M & Barbulescu A (2015) Taste of medicinal plants: a potential tool in predicting ethnopharmacological activities? Journal of Ethnopharmacology 174: 464-473.), for decision-making regarding the beneficial properties that specific medicinal plants provide for specific illnesses (Heinrich et al. 1992Heinrich M, Rimpler H & Barrera NA (1992) Indigenous phytotherapy of gastrointestinal disorders in a lowland Mixe community (Oaxaca, Mexico): Ethnopharmacologic evaluation. Journal of Ethnopharmacology 36: 63-80. ).

Following this concept, organoleptic properties could serve as cues for identifying the most efficient plants (Medeiros et al. 2015Medeiros PM, Ladio AH & Albuquerque UP (2015) Local criteria for medicinal plant selection. In: Albuquerque U, Medeiros P & Casas A (eds.) Evolutionary ethnobiology. Springer, Cham. Pp 149-162. Available at <Available at https://ethnobioconservation.com/index.php/ebc/article/view/641 >. Access on 15 July 2018. DOI: 10.1007/978-3-319-19917-7_11
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). Thusly, herbs can be classified according to their major constituents, taste and actions as bitter (amara), aromatic and aromatic-bitter (Kelber et al. 2018Kelber O, Bauer R & Kubelka W (2018) Phytotherapy in functional gastrointestinal disorders. Digestive Diseases 35: 36-42.). Heinrich et al. (1992Heinrich M, Rimpler H & Barrera NA (1992) Indigenous phytotherapy of gastrointestinal disorders in a lowland Mixe community (Oaxaca, Mexico): Ethnopharmacologic evaluation. Journal of Ethnopharmacology 36: 63-80. ) found bitter, aromatic and aromatic-bitter plants to be particularly valued for the treatment of gastrointestinal cramps and pain. In addition, astringent drugs were valued to treat diarrhea and dysentery by an indigenous population in Mexico (Leonti et al. 2002Leonti M, Sticher O & Heinrich M (2002) Medicinal plants of the Popoluca, México: organoleptic properties as indigenous selection criteria. Journal of Ethnopharmacology 81: 307-315.).

Bitter substances stimulate gastric secretion and gastrointestinal motility (Kelber et al. 2018Kelber O, Bauer R & Kubelka W (2018) Phytotherapy in functional gastrointestinal disorders. Digestive Diseases 35: 36-42.), promoting the flow of saliva, gastric juices and bile (Van Wyk & Wink 2004Van Wyk BE & Wink M (2004) Medicinal plants of the world. Briza Publications, Arcadia. 480p.; Kelber et al. 2018) and thus enhance the function of the digestive system (Olivier & Van Wyk 2013Olivier DK & Van Wyk B-E (2013) Bitterness values for traditional tonic plants of Southern Africa. Journal of Ethnopharmacology 147: 676-679.). Evidence of a bitter taste was found for Gymnanthemum amydalinum (Kaur et al. 2019Kaur D, Kaur N & Chopra A (2019) A comprehensive review on phytochemistry and pharmacological activities of Vernonia amygdalina. Journal of Pharmacognosy and Phytochemistry 8: 2629-2636.; Awwad et al. 2020Awwad A, Pouchereta P, Idresa AY, Bidelb L & Touscha D (2020) The bitter Asteraceae: an interesting approach to delay the metabolic syndrome progression. NFS Journal 18: 29-38.) due to the presence of tannins and saponins (Kaur et al. 2019). Moreover, as stated earlier, this plant is popularly called boldo (Lorenzi & Matos 2008Lorenzi H & Matos FJA (2008) Plantas medicinais no Brasil. 2a ed. Instituto Plantarum, Nova Odessa. 576p.), and so it makes sense for it to be popularly called Figatil when compared with the commercialized phytotherapic Figatil®, which in turn contains the species Peumus boldus Molina, also popularly called boldo, however boldo-do-chile. Other species with bitter taste as a common feature were found, including Calea serrata Less., named ‘bitter tea’ (Ribeiro et al. 2008Ribeiro VLS, Avancini C, Gonçalves K, Toigo E & von Poser G (2008) Acaricidal activity of Calea serrata (Asteraceae) on Boophilus microplus and Rhipicephalus sanguineus. Veterinary Parasitology 151: 351-354.), and Artemisia absinthium L. (Awwad et al. 2020).

Aromatic plants are those that have significant essential oil content. For digestive disorders they present spasmolytic activity or stimulatory effects on peristalsis. Volatile oil and flavonoids are common chemicals of the genus Croton (Magalhães et al. 1998Magalhães PJC, Criddle DN, Tavares RA, Melo EM, Mota TL & Leal-Cardoso JH (1998) Intestinal myorelaxant and antispasmodic effects of the essential oil of Croton nepetaefolius and its constituents Cineole, Methyl-eugenol and Terpineol. Phytotherapy Research 12: 172-177.), many species of which are used in folk medicine for digestive treatments, such as C. eluteria Bennertt. and C. nepetaefolius Baill. The volatile oil of these species is composed mainly of monoterpenes (cineol, linalol), propanoids (eugenol, anetol) (Magalhães et al. 1998; Matos 2011Matos LMM (2011) Química de espécies nativas de Croton (Euphorbiaceae). Dissertação de Mestrado. Universidade de São Paulo, São Paulo. 132p.) and sesquiterpenes (cariofileno) (Matos 2011), compounds that possess relaxant and antispasmodic activities (Magalhães et al. 1998). Volatile oils of some South American Croton species especially have antispasmodic and anti-diarrheic activities (Salantino et al. 2007). Evidence indicates that C. gnaphalii Baill., an endemic species of South America that is used by folk medicine for digestive disorders, has potential to be explored due to the history of genus for medicinal therapeutic use.

There are also bitter-aromatic plants, featured in this survey by Achillea millefolium and Artemisias (Artemisia absinthium, A. verlotiorum Lamotte and A. vulgaris L.), which have both bitter compounds and volatile oil in their composition. The species A. absinthium, for example, has sesquiterpene lactones, such as absinthin and artabsin, as bitter substances (Kelber et al. 2018Kelber O, Bauer R & Kubelka W (2018) Phytotherapy in functional gastrointestinal disorders. Digestive Diseases 35: 36-42.), while saponins are the bitter compound of A. vulgaris (Kumar & Kumud 2010Kumar AP & Kumud U (2010) Preliminary phytochemical screening and physic-chemical parameters of aerial parts of Artemisia vulgaris. International Journal of Research in Ayurveda and Pharmacy 1: 206-211.). In general, the genus Artemisia has flavonoids (Valant-Vetschera et al. 2003Valant-Vetschera KM, Fischer R & Wollenweber E (2003) Exudate flavonoids in species of Artemisia (Asteraceae - Anthemideae): new results and chemosystematic interpretation. Biochemical Systematics and Ecology 31: 487-498.) and essential oil (Biondi et al. 2000Biondi E, Valentini G & Bellomaria B (2000) Essential oil of some halophyle and subhalophyle taxa Artemisia L. from the Central European Mediterranean. Journal of Essential Oil Research 12: 365-371.; Bellomaria et al. 2001Bellomaria B, Valentini G & Biondi E (2001) Chemotaxonomy of Artemisia variabilis Ten. and A. campestris L. ssp. glutinosa (Ten.) Briq. et Cavill. (Asteraceae) from Italy. Journal of Essential Oil Research 13: 90-94. ) as common phytochemicals, at least mostly at the species and subspecies level. All species of Artemisia in the present survey (A. absinthium, A. verlotiorum and A. vulgaris) contain the secondary metabolite flavonoid (see Tab. 1), with A. verlotiorum being an exception to having a bitter substance in its composition. Three important phytochemical components (bitter substances, essential oil and flavonoids) for digestive disorders are present in A. absinthium and A. vulgaris; Achillea millefolium also possesses those same three phytochemicals (Benedek et al. 2006BENEDEK B, Geisz N, Jäger W, Thalhammer T & Kopp B (2006) Choleretic effects of yarrow (Achillea millefolium s.l.) in the isolated perfused rat liver. Phytomedicine 13: 702-706. ; Lemmens-Gruber et al. 2006Lemmens-Gruber R, Marchart E, Rawnduzi P, Engel N, Benedek B & Kopp B (2006) Investigation of the spasmolytic activity of the flavonoid fraction of Achillea millefolium s.l. on isolated guinea-pig ilea. Arzneimittelforschung 56: 582-588. ; Pires et al. 2009Pires JM, Mendes FR, Negri G, Duarte-Almeida JM & Carlini EA (2009) Antinociceptive peripheral effect of Achillea millefolium L. and Artemisia vulgaris L.: both plants known popularly by brand names of analgesic drugs. Phytotherapy Research 23: 212-219. ).

Table 3
Popular name associated with manufactured drugs of medicinal plants mentioned in ethnobotanical surveys in Rio Grande do Sul state, Brazil, with number of species cited for each name and the therapeutic classes associated with medicalized names.

Table 4
Commercial name of phytotherapics with species/family contained in the formulas and the species indicated in ethnobotanical surveys with the same name of the phytotherapic.

Lepidium bonariensis L. was the only species that could not be classified according to the three taste groups. This lack of information may be due to the fact that Lepidium is an endemic genus for which there has not been significant research, even at the genus level. Further studies are recommended for the genus.

From the phytochemical perspective applied to digestive disorders, bitterness is due to the presence of secondary substances such as saponins (Kaur et al. 2019Kaur D, Kaur N & Chopra A (2019) A comprehensive review on phytochemistry and pharmacological activities of Vernonia amygdalina. Journal of Pharmacognosy and Phytochemistry 8: 2629-2636.), sesquiterpene lactones (Chadwick et al. 2013Chadwick M, Trewin H, Gawthrop F & Wagstaff C (2013) Sesquiterpenoids lactones: benefits to plants and people. International Journal of Molecular Sciences 14: 12780-12805.) and caffeine (Yamanishi 1995Yamanishi T (1995) Flavor of tea. Food Reviews International 11: 477-525.). Other substances related to digestive disorders include tannins, present in astringent plants (Heinrich et al. 1992Heinrich M, Rimpler H & Barrera NA (1992) Indigenous phytotherapy of gastrointestinal disorders in a lowland Mixe community (Oaxaca, Mexico): Ethnopharmacologic evaluation. Journal of Ethnopharmacology 36: 63-80. ; Leonti et al. 2002Leonti M, Sticher O & Heinrich M (2002) Medicinal plants of the Popoluca, México: organoleptic properties as indigenous selection criteria. Journal of Ethnopharmacology 81: 307-315.) and used to treat diarrhea and dysentery; flavonoids, which have a broad spectrum of relevant actions, such as spasmolytic, anti-inflammatory, and anti-oxidative properties; and essential oil, responsible for spasmolytic activity or stimulatory effects on peristalsis (Kelber et al. 2018Kelber O, Bauer R & Kubelka W (2018) Phytotherapy in functional gastrointestinal disorders. Digestive Diseases 35: 36-42.).

Chemical and pharmacological information

Seven species, among those representing the 25 denominated manufactured drug names, have been pharmacologically studied with regard to at least one of the eight therapeutic classes suggested by popular knowledge: digestive, antispasmodic, analgesic, antipyretic, anti-inflammatory, expectorant, topical analgesic and antidiabetic (Tab. 5). The species Achillea millefolium, Eucalyptus cinerea F. Muell. ex Benth. and Sphagneticola trilobata were studied by laboratory tests for 100% of the classes indicated by the popular name evaluated, while Alternanthera brasiliana was in 75% and Artemisia absinthium, A. verlotiorum and A. vulgaris in 50%.

The anti-inflammatory action popularly attributed to Alternanthera brasiliana and Achillea millefolium can be attributed to the presence of phenolic derivatives and flavonoids. Other species that have also presented this activity in pharmacological tests are: Alternanthera ficoidea (L.) P. Beauv. (Guerra et al. 2003Guerra RNM, Pereira HAW, Silveira LMS & Olea RSG (2003) Immunomodulatory properties of Alternanthera tenella Colla aqueous extracts in mice. Brazilian Journal of Medical and Biological Research 36: 1215-1219.; Biella et al. 2008Biella CA, Salvador MJ, Dias DA, Dias-Baruffi M & Pereira-Crott LS (2008) Phytochemical screening of Alternanthera tenella Colla (Amaranthaceae) aqueous extracts. Memórias do Instituto Oswaldo Cruz 103: 569-577.), Artemisia vulgaris (flavonoids and terpenoids) (Kumar & Kumud 2010Kumar AP & Kumud U (2010) Preliminary phytochemical screening and physic-chemical parameters of aerial parts of Artemisia vulgaris. International Journal of Research in Ayurveda and Pharmacy 1: 206-211.), Gymnanthemum amygdalinum (Valverde et al. 2001Valverde AL, Cardoso GL, Pereira NA, Silva AJ & Kuster RM (2001) Analgesic and antiinflammatory activities of vernonioside B2 from Vernonia condensata. Phytotherapy Research 15: 263-264.), Mentha arvensis L. (Verma et al. 2003Verma SM, Arora H & Dubey R (2003) Anti-inflammatory and sedative-hypnotic activity of the methanolic extract of the leaves of Mentha arvensis. Ancient Science of the Life 23: 95-99.) and Sphagneticola trilobata (Maldini et al. 2009Maldini M, Sosa S, Montoro P , Giangaspero A, Balick MJ, Pizza C , Della Loggia R (2009) Screening of the topical anti-inflammatory activity of the bark of Acacia cornigera Willdenow, Byrsonima crassifolia Kunth, Sweetia panamensis Yakovlev and the leaves of Sphagneticola trilobata Hitchcock. Journal of Ethnopharmacology 122: 430-433. ).

The species Artemisia vulgaris, Alternanthera brasiliana and Achillea millefollium have been shown to present analgesic activity. Rutin (glycosylated flavonol) and caffeic acid derivatives with analgesic activity were identified in Achillea millefolium (Pires et al. 2009Pires JM, Mendes FR, Negri G, Duarte-Almeida JM & Carlini EA (2009) Antinociceptive peripheral effect of Achillea millefolium L. and Artemisia vulgaris L.: both plants known popularly by brand names of analgesic drugs. Phytotherapy Research 23: 212-219. ), as previously indicated by Gené et al. (1996Gené RM, Cartaña C, Adzet T, Marín E, Parella T & Cañigueral S (1996) Anti-inflammatory and analgesic activity of Bacharis trimera: identification of its active constituents. Planta Medica 62: 232-235.) and Ficarra et al. (1995Ficarra R, Ficarra P, Tommasini S, Calabrò ML, Ragusa S, Barbera R & Rapisarda A (1995) Leaf extracts of some Cordia species - analgesic and antiinflammatory activities as well as their chromatographic analysis. Farmaco 50: 245-256.).

Gymnanthemum amygdalinum presented hypocholesterolemic (Arantes et al. 2016Arantes AA, Falé PL, Costa LCB, Pacheco R, Ascensão L & Serralheiro ML (2016) Inhibition of HMG-CoA reductase activity and cholesterol permeation through Caco-2 cells by caffeoylquinic acids from Vernonia condensata leaves. Brazilian Journal of Pharmacognosy 26: 738-743. ) and gastroprotective (Boeing et al. 2016Boeing T, Silva LM, Somensi LB, Cury BJ, Costa APM, Petreanu M, Niero R & Andrade SF (2016) Antiulcer mechanisms of Vernonia condensata Baker: a medicinal plant used in the treatment of gastritis and gastric ulcer. Journal of Ethnopharmacology 184: 196-207.) activities.

Diterpenes (caurenoic acid) were found in Sphagneticola trilobata, with hypoglycemic activity confirmed by laboratory tests (Bresciani et al. 2004Bresciani LFV, Yunes RA, Burger C, Oliveira LE, Bóf KL & Cechinel-Filho V (2004) Seasonal variation of kaurenoic acid, a hypoglycemic diterpene present in Wedelia paludosa (Acmela brasiliensis) (Asteraceae). A Journal of Biosciences: Zeitschrift für Naturforschung C 59: 229-232.).

Table 5
Phytochemical and pharmacological information for plant species with popular names associated with manufactured drugs used by popular medicine in southern Brazil.

Correspondence between popular uses and the biomedical system

The medicinal species popularly known as anador, doril, figatil and melhoral showed 100% agreement between the popular indications, which were compared with all the indications on the drug’s package insert. It should be noted that this percentage does not consider the versatility of uses of the species and of the drug package insert and that those with 100% concordance of uses may only have one use and that this use is indicated by the insert of the manufactured drugs. Although all the popular indications were found in the package insert, some of the indications in the leaflet may not have been reported by the population.

This finding suggests that the use of the name of a drug for the name of a medicinal plant may be associated with the uses that are indicated by manufactured drugs, regardless of the origin of the species (native or exotic). This “hybridization” (see Ladio & Albuquerque 2014Ladio AH & Albuquerque UP (2014) The concept of hybridization and its contribution to urban ethnobiology. Ethnobiology and Conservation 3. Available at <Available at http://ethnobioconservation.com/index.php/ebc/article/view/59 >. Access on 20 May 2019. DOI: 10.15451/ec2014-11-3.6-1-9
http://ethnobioconservation.com/index.ph...
) involving biomedicine and the local medical system, in the context of this research, expresses a double movement with the decontextualization of the names of medicines and their recontextualization in the names of medicinal plants. This process is particularly important for the species of the present study since it is possible that these species have been named after manufactured drugs because their therapeutic effects may be compatible with the medicines. In fact, people name plants after medicines manufactured to treat the same symptoms and illnesses, while the use of the previous popular name gradually ceases. Such a new name is often only known regionally and used for different species.

Physical, psychic, and social aspects are considered important in the healing process in medical systems (Kleinman 1978Kleinman A (1978) Concepts and a model for the comparison of medical systems as cultural systems. Social Science & Medicine 12: 85-93. ). Thus, psychosocial needs (a group’s idea about the feeling of “comfort”) represented by the popular names based on medicines attributed to medicinal plants may be a symbolic representation, given by the ‘status syndrome’ (see Marmot 2004Marmot M (2004) Status syndrome. Bloomsbury Publishing, London. 288p.), recontextualizing the names of medicinal products from medicinal plants. Semantic analysis of the nomenclature employed can demonstrate links and implications that the dominant medical system (Western medicine) establishes (Kleinman 1978; Helman 2009Helman CG (2009) Cultura, saúde e doença. 5a ed. Artmed, Porto Alegre. 431p.). These vernacular assignments may induce safety or credibility in their efficacy by assigning to the available resource a nomenclature belonging to the current biomedical system, that is, a cultural legitimization of biomedical treatment with popular therapeutics. This process is a two-way street, because just as the biomedical system influences popular use, popular medicine, based on this initial recontextualization, can increase the process of experimentation by incorporating new therapeutic properties.

Regarding the symptoms that marketed phytotherapeutics and folk therapeutics are prescribed for, the main activities prescribed by the former were spasmodic, choleretic and carminative. These activities were correlated with the studied species: (1) the majority of the species of the present research have flavonoids in their composition (Tab. 3), which, as mentioned previously, have spasmolytic activity for digestive disorders (Kelber et al. 2018Kelber O, Bauer R & Kubelka W (2018) Phytotherapy in functional gastrointestinal disorders. Digestive Diseases 35: 36-42.) acting as an antispasmodic agents they promote muscle (gastrointestinal and abdominal) relaxation, thereby reliving the discomfort associated with indigestion, diarrhea, etc., and decreasing the pain and spasms related to muscle contraction (Hicks 2007Hicks GA (2007) Irritable bowel syndrome. In: Williams M (ed.) Comprehensive medicinal chemistry II. Therapeutic areas I: central nervous system, pain, metabolic syndrome, urology, gastrointestinal and cardiovascular. Vol. 6. Elsevier, Oxford. Pp. 643-670. ); (2) bitter plants have substances that stimulate gastric secretion and gastrointestinal motility (Kelber et al. 2018); (3) aromatic plants possess volatile oil that stimulates gastric secretions and antispasmodic activity (Magalhães et al. 1998Magalhães PJC, Criddle DN, Tavares RA, Melo EM, Mota TL & Leal-Cardoso JH (1998) Intestinal myorelaxant and antispasmodic effects of the essential oil of Croton nepetaefolius and its constituents Cineole, Methyl-eugenol and Terpineol. Phytotherapy Research 12: 172-177.); (4) aromatic-bitter plants, such as Achillea millefolium as representative of the group, have been shown by pharmacological studies to have choleretic (Benedek et al. 2006BENEDEK B, Geisz N, Jäger W, Thalhammer T & Kopp B (2006) Choleretic effects of yarrow (Achillea millefolium s.l.) in the isolated perfused rat liver. Phytomedicine 13: 702-706. ), antispasmodic (Lemmens-Gruber et al. 2006Lemmens-Gruber R, Marchart E, Rawnduzi P, Engel N, Benedek B & Kopp B (2006) Investigation of the spasmolytic activity of the flavonoid fraction of Achillea millefolium s.l. on isolated guinea-pig ilea. Arzneimittelforschung 56: 582-588. ; Kelber et al. 2018) and carminative activities (Kelber et al. 2018). The last is related to Infalivina®, which is prescribed for intestinal gas reduction. Interestingly, the genus Achillea is popularly named as Infalivina and has the same therapeutic use, demonstrating that folk names have been influenced by the medical system.

The present ethnobotanical survey conducted in Rio Grande do Sul, southern Brazil, revealed an interaction between the biomedical system and popular medicine, namely the use of medicine names for medicinal plants. Two important observations were made: (1) this phenomenon is independent of plant origin (native or exotic) and (2) a correspondence exists between the therapeutic use of plants and that of the manufactured medicines for which they are named.

Species with popular names associated with commercialized phytotherapeutics were not given these names at random. The names were found to be correlated, with both being prescribed for digestive disorders. Findings here indicate that taste might be a criterion for folk plant selection, resulting in three groups: bitter, aromatic and aromatic-bitter plants. The phytochemical substances responsible for digestive treatment are saponins, caffeine, sesquiterpene lactones, tannins, flavonoids and essential oil, the main actions of which are spasmodic, choleretic and carminative activities.

The cultural aspects of this phenomenon, its origin and its meaning to the population still remain unclear, and so further and more extensive research at the sites where the present surveys were conducted are needed in order to better understand its significance and cultural dynamics. These future investigations can clarify aspects of the dynamics and evolution of local medical systems and generate implications for bioprospection, including the search for plants with potential to reveal new bioactive compounds of pharmacological interest.

Acknowledgements

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

Data availability statement

In accordance with Open Science communication practices, the authors inform that all data are available within the manuscript.

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Publication Dates

  • Publication in this collection
    20 May 2024
  • Date of issue
    2024

History

  • Received
    05 May 2022
  • Accepted
    07 Dec 2023
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