Survey of plants popularly used for pain relief in Rio Grande do Sul, southern Brazil

Abstract

Ethnobotanical data can be an important tool in the search for new drugs. The Brazilian Health Surveillance Agency accepts the registration of herbal medicines based on ethnopharmacological and ethnobotanical studies. With the purpose of increasing the knowledge of potentially useful plants for the treatment of painful conditions, we analyzed the ethnobotanical studies carried out in Rio Grande do Sul state (RS-Southern Brazil); we had access to nineteen studies.To our knowledge, this is the first compilation of ethnobotanical studies that focus on pain relief carried out in RS. The species native to RS cited in at least nine (about 50%) of these studies were selected. The search retrieved 28 native species cited as used to alleviate painful conditions, which are distributed in eighteen botanical families, being Asteraceae the most mentioned. The species more frequently cited for pain relief were Achyrocline satureioides, Baccharis articulata, Baccharis crispa, Lepidium didymum, Eugenia uniflora and Maytenus ilicifolia. The only species not reported in any pre-clinical study associated with pain relief was B. articulata. Among the six species cited, no studies on clinical efficacy were found. In conclusion, the folk use of native plants with therapeutic purposes is widespread in RS State (Brazil), being pain relief an important property.

Ethnobotany ; Folk medicine ; Pain; South Brazil

Introduction

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage (IASP, 1986). It affects approximately 70% of world population and is associated with deficit in quality of life (WHO, 2007). The Brazilian Society for Pain Study estimates that pain prevalence in the country is of 30% (around 50 million of people) (SBED, 2012).

Despite significant efforts and investments from academia and the pharmaceutical industry, very few new therapies for pain treatment have been introduced to clinical practice (Hruby et al., 2006). As a consequence, pain treatment continues to depend on therapeutic modalities that present limited efficacy and/or important adverse effects, such as respiratory depression, constipation, tolerance, dependence, gastritis and ulcers (Brunton et al., 2011).

In this context, medicinal plants may be expected to contribute to the search of new therapeutic strategies, as well as for new molecular patterns with antinociceptive activity, due to chemical diversity (Phillipson, 2007).

The main example of natural compounds relevance in analgesic drug development is the potent opioid alkaloid morphine isolated from Papaver somniferum L.; other important plant contributions are salicin and colchicine. Salicin, isolated from Salix alba L., is the precursor molecule to acetylsalicylic acid, a nonsteroidal analgesic, antipyretic and anti-inflammatory drug (Brunton et al., 2011). Colchicine is an alkaloid of Colchicum autumnale L., largely effective for the treatment of gouty arthritis, a painful inflammatory disease (Brunton et al., 2011). In addition, several other secondary metabolites derived from plants, such as phloroglucinols, alkaloids, terpenoids, methylxanthines and flavonoids have been evaluated in pre-clinical studies on antinociceptive activity (Calixto et al., 2000; Sardella et al., 2008; Galeotti et al., 2010; Haas et al., 2011; Sawynok, 2011; Silva et al., 2011; Radulovic et al., 2012).

The approach for drug development from plant resources depends on defined purposes. Different strategies yield particular active compounds or phytomedicines. The most common strategy is the careful observation of the use of natural resources in the folk medicine of different cultures. The traditional use of plants in primary health care is recognized by WHO (1992) and has increased significantly over the past 20 years (Calixto, 2000; Rates, 2001; Dhanani et al., 2011; Kumar et al., 2011; WHO, 2008). Besides contributing to primary health care, herbal medicine can be used as indicator of pharmacologically relevant activities in drugs development approaches (Rates, 2001).

By the year 2007, herbal medicine revenue in Brazil earned US$160 million (WHO, 2008). Ethnobotanical studies demonstrate the popular use of plants for pain relief, as it was the case in Rio Grande do Sul state (Garlet, 2000; Marodin, 2000; Di Stasi, 2002; Agra et al., 2007; Matos, 2007). The Brazilian National Health Surveillance Agency (Anvisa) accepts the traditional uses reported by ethnopharmacological and/or ethnically oriented studies as evidence of efficacy of phytopharmaceuticals or herbal drugs used with therapeutic purpose (Anvisa, 2010; 2014). Furthermore, the Brazilian government has expressed interest in including phytotherapy in the public health system, and published a list of species considered relevant for research aiming at future therapeutic use (MS, 2009).

In the light of the above, a compilation of ethnobotanical studies carried out in the state of Rio Grande do Sul, Brazil, was performed with special focus on the knowledge of the plants potentially useful for the treatment of painful conditions, with special focus on native species.

Materials and methods

The present study comprises nineteen ethnobotanical studies (including original articles, theses and dissertations), which present data from communities living in Rio Grande do Sul (RS) state. The studies were found by performing searches within virtual databases (PubMed, SciELO and Portal de Periódicos CAPES), using the following keywords: folk medicine, medicina popular, ethnobotany, etnobotânica; combined with Rio Grande do Sul, southern Brazil and sul do Brasil. Regional university libraries were also assessed. The criteria for selection were: accessibility, presence of a botanist in the team of researchers, publication time interval from 1997 to 2009.

These studies were grouped according to the eleven physiographic regions of RS territory defined by Fortes (1959) (Fig. 1): Depressão Central - Possamai (2000), Soares et al. (2004), Vendruscolo (2004) and Casagrande (2009); Encosta do Sudeste - Martha (2003), Veiga (2003), Zanandrea (2003) and Ceolin (2009); Litoral - Marodin (2000) and Haas (2003); Encosta Inferior do Nordeste - Sebold (2003) and Barbosa (2005); Alto Uruguai -Kubo (1997) and Löwe (2004); Serra do Sudeste - Fernandes (2001) and Leitzke (2003); Missões - Barros et al. (2007); Campos de Cima da Serra - Ritter et al. (2002); Planalto Médio - Garlet (2000); Campanha and Encosta Superior do Noroeste - no studies were found.

Figure 1
Physiographic regions of the Rio Grande do Sul state (southern Brazil) defined by Fortes (1959). The number of studies found in each region is in parentheses.

The species (native and exotics) cited in at least nine (about 50%) of the nineteen studies were listed; furthermore, those cited as useful for alleviating painful conditions were selected. The search terms considered as related to painful conditions were: pain (dor), headache/migraine (dor de cabeça/enxaqueca), sore throat (dor de garganta), stomachache (dor de estômago) and backache (dor nas costas), abdominal pain (dor abdominal), kidney pain/inflammation (dor/inflamação nos rins), leg pain (dor nas pernas), bellyache (dor de barriga), sprain pain (dor de entorse); or related ones, like colics (cólica), baby's colics (cólica de bebê), and rheumatism and pain of the joints (reumatismo/dor nas articulações). From the cited species, we selected the native ones cited in at least five (about 50%) of the eleven RS physiographic regions, in order to analyze published scientific data related to their antinociceptive activity and toxicity.

Pre-clinical and clinical studies were searched in PubMed, SciELO, Scopus and Portal de Periódicos CAPES. The scientific name of the plant combined with the terms "pain", "antinociceptive", "analgesic", "toxicity", "dor", "analgesia" and "toxicidade" were used as keywords. Additionally, the total number of publications for each species in Pubmed and SciELO Brazil was registered. In the Banco de Teses CAPES only the number of theses was considered. All these searches covered studies published until January 2013.

The valid names of the species and the authors were confirmed using The Plant List (2014) and Lista da Flora do Brasil (2014) databases. The botanical families were updated based on the APG III classification system (Stevens, 2012).

Results and discussion

From the nineteen ethnobotanical studies consulted, 625 species were collected. All species were mentioned in at least one study and some of them were cited in more than one study, which resulted in a total of 2,208 plant cited. Seventy-four species (natives, exotics, and subspontaneous) were mentioned as having some traditional use in at least nine (about 50%) of the ethnobotanical studies, which constitutes 42.3% (934) of the total citations. Out of these 74 species, 70 species were mentioned for relieving some kind of symptom related to pain, confirming that painful conditions represent an important health complaint in the state. Sixty percent (60%) of the species used for pain relief are exotic (Chart 1) and 40% native (Chart 2). We speculate that the process of population formation in Southern Brazil, which results from the miscegenation between original inhabitants (amerindians), Europeans and Africans, could be one factor that contributes to the widespread use of exotic plants. The African slaves and European immigrants brought several species considered to have a medicinal or ritualistic value in their original countries, which were acclimated and incorporated to the Brazilian folk medicine (Brandão et al., 2008).

Chart 1
Exotic and subspontaneous species used for pain relief mentioned in ethnobotanical studies in Rio Grande do Sul, Brazil.

Chart 2
Native species used for pain-relief mentioned in ethnobotanical studies in Rio Grande do Sul (RS) - Brazil were distributed by family, part of plant used and preparation form reported by each studied region with references. The physiographic regions of RS territory: DC-Depressão Central; ES-Encosta do Sudeste; LT-Litoral; EN-Encosta Inferior do Nordeste; AU-Alto Uruguai; SS-Serra do Sudeste; MS-Missões; CS- Campos de Cima da Serra; PM-Planalto Médio.

In Chart 2, the native species are listed by popular name, botanical family, part of plant used, form of preparation and symptom/claim reported in each studied region (with respective authors) are shown. Native species were identified as members of 18 botanical families, and Asteraceae (n = 7) the family more frequently cited. These results are in accordance to those previously published by Giulietti et al. (2005) who demonstrated that Asteraceae is the second largest family in Brazil, comprising 1900 species. Some studies reported the antinociceptive activity of species belonging to Asteraceae family, including RS native plants (Conde et al., 2011; Figueredo et al., 2011).

Leaves are the most frequently utilized part of the plant (45%), followed by aerial parts (11%), flowers (11%), roots (8%), stems (8%), whole plant (4%), inflorescences (5%), fruits (4%), buds (2%), barks (1%) and rhizomes (1%). The preference for leaves has been previously reported by others (Garlet, 2000; Borba and Macedo, 2006).

The predominant preparation form cited was tea (including decoction and infusion) (63%) followed by ethanolic extract (8%) and syrup (6%). The use of plants combined with chimarrão (6%) was also cited. Chimarrão (also known as "mate") is an aqueous beverage of Ilex paraguariensis St. Hill. leaves prepared with water at 70ºC, which is largely consumed in southern Brazil. In general, this beverage is taken daily and represents an important social habit inherited from South American Indians (Lessa, 1986; MTG, 2014).

The native species more frequently mentioned (cited in at least five of nine RS physiographic regions) for treating pain were Achyrocline stureioides (Lam.) DC., Baccharis articulata (Lam.) Pers,Baccharis crispa Spreng, Lepidium didymum L., Eugenia uniflora L. and Maytenus ilicifolia Mart. ex. Reissek. Eugenia uniflora, popularly known as pitanga, was the only one mentioned for pain relief in all studied regions, demonstrating its widespread folk use.

A brief numerical analysis of the scientific data regarding the six species above-mentioned (Table 1) has shown that the majority of studies are indexed in the Banco de Teses CAPES, a Brazilian database that embraces all theses and dissertations submitted throughout the country. Only part of these studies is indexed in the Brazilian database SciELO as well as in the international database PubMed.

Table 1
Number of scientific studies on Eugenia uniflora, Achyrocline satureioides, Maytenus ilicifolia, Baccharis articulata, Baccharis trimera and Coronopus didymus indexed in Brazilian (Banco de Teses CAPES and SciELO Brazil) and international (PubMed) databases.

Species	Scientific literature (publication number)
	Banco de Teses CAPES	SciELO Brazil	PubMed
Achyrocline satureioides	52	16	40
Baccharis articulata	12	5	6
Baccharis crispa	70	33	21
Lepidium didymum	4	8	11
Eugenia uniflora	118	66	54
Maytenus ilicifolia	87	46	61

In the next paragraphs we present a summary of the scientific studies (related to pain and toxicity) on these species indexed in the consulted databases.

Achyrocline satureioides (Lam.) DC.

A. satureioides is widely used in southern Brazil, as it is in South America since ancient times (Mercosur, 1993). This species is described in The Brazilian Pharmacopoeia (Farm. Bras., 2001) and is considered the medicinal plant, symbol of Rio Grande do Sul (Assembléia Legislativa do Estado do Rio Grande do Sul, 2002). It is known as "marcela/macela", traditionally used to treat several diseases besides pain and inflammation. Anti-inflammatory, analgesic, antispasmodic and myorelaxant properties of aqueous (macerate and decoction) and ethanolic extracts of inflorescences, leaves and stems were demonstrated by pre-clinical studies (Langeloh and Schenkel, 1985; Simões et al., 1986a, 1988a, 1988b; Filot da Silva and Langeloh, 1994; De Souza et al., 2007); these effects were attributed to the flavonoids, especially quercetin, 3-O-methylquercetin and luteolin (Simões et al., 1986a, 1988c; De Souza et al., 2007). Several reports demonstrate that A. satureoides does not seem to be associated with toxicity (Carney et al., 2002; Arredondo et al., 2004; Bettega et al., 2004; Polydoro et al., 2004; Rivera et al., 2004; Fachinetto et al., 2007). Nevertheless, European standards prohibit its use in food products (EFSA, 2007; 2009). A review regarding phytochemical and pharmacological data on A. satureioideswas published by Retta et al. (2012). Clinical studies were not found.

Baccharis articulata (Lam.) Pers. and Baccharis crispa Spreng

Species of the Baccharis genus, popularly known as carqueja, are traditionally used in folk medicine of southern Brazil, Uruguay and Argentina (Simões et al., 1986b). The Baccharis genus comprises around 400 species (Bremer, 1984), and the differentiation between species is somewhat complex due to the presence of winged stems and branches (Barroso and Bueno, 2002). This fact leads people to indiscriminately use Baccharis species as medicinal plants (Gianello et al., 2000).

Scientific reports on analgesic or anti-inflamatory properties of B. articulata were not found. Recently, some authors demonstrated that the aqueous extract of aerial parts of B. articulata increases the number of micronucleated human peripheral blood mononuclear cells (PBMC) in vitro and exerts low mutagenic effects in mice (Cariddi et al., 2010). Also, aqueous extract of the aerial parts of B. articulata induces apoptosis in human PBMC in vitro and genotoxic effects on erythrocytes from bone marrow of mice (Cariddi et al., 2012). These results suggest that B. articulata should be used with caution as it may cause cell damage.

B. crispa is cited in the Brazilian Pharmacopoeia (Farm. Bras., 2010) and in the RENISUS (MS, 2009). It is popularly used to treat gastrointestinal, liver and kidney diseases, and inflammation (Verdi et al., 2005). The antinociceptive and anti-inflammatory properties of the crude aerial parts aqueous extract (Gené et al., 1996; Paul et al., 2009) and butanolic fraction (Nogueira et al., 2011) of B. crispa were demonstrated in pre-clinical studies. It has been proposed that these properties may be related to the presence of saponins (echinocystic acid), rutin and other phenolic compounds (Gené et al., 1996; Oliveira et al., 2012). No mutagenic effect of aqueous extract and ethanolic fraction of the aerial parts of B. crispa was observed on the Salmonella typhimurium microsomal activation assay (Nogueira et al., 2011). However, mice treatment with the same extracts induced in vivo and in vitrotoxicological effects to kidney cells (Nogueira et al., 2011). Likewise, the aqueous extract of the aerial parts of B. crispa increased the frequency of micronucleated cells in bone marrow of treated mice, indicating a mutagenic effect at chromosomal level (Rodrigues et al., 2009). Moreover, the hydroethanolic extract of B. crispa aerial parts was toxic kidney and liver cells in pregnant rats, but did not cause changes in hematological parameters nor in maternal body weight (Grance et al., 2008). Pinho et al. (2010)demonstrated that aerial parts infusion of B. crispa presented dose-dependent mutagenic effects in the Allium cepa L. assay and induced chromosomal aberrations in human lymphocytes cultures. Also, the essential oil inhibits the differentiation of neuronal cells in vitro and reduces the survival of neurons as well as glial cells proliferation (Losqui et al., 2009). However, clinical studies were not found.

Lepidium didymum L.

L. didymum is popularly known as mentruz, mastruço or mentruz-rasteiro. It is used in folk medicine to treat several diseases, among them rheumatism (Mahmood et al., 2011) and headache (Rajan et al., 2005); it has been also reported antipyretic, wound healing and anti-inflammatory activities (Prabhakar et al., 2002; Mantena et al., 2005). The anti-inflammatory effect of L. didymum seems to be linked to several mechanisms, including the inhibition of enzymes (myeloperoxidase and adenosine-deaminase) and action on mediators (bradykinin, histamine, substance P, prostaglandin E2 and nitric oxide) (Busnardo et al., 2010). The hepatoprotective effect of L. didymum in rats has demonstrated to reverse the elevation in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic lipid peroxide levels induced by CCl4 hepatotoxin. These activities may be due to the presence of flavonoids, saponins and tannins (Mantena et al., 2005). However, clinical studies were not found.

Eugenia uniflora L.

This species is cited in the RENISUS (MS, 2009) list. Pre-clinical data suggest the efficacy of pitanga leaves infusion (Schapoval et al., 1994) and essential oil (Amorim et al., 2009) as antinociceptive; terpenoids (furanosesquiterpenes) seem to contribute to this effect (Amorim et al., 2009). Schapoval et al. (1994) also demonstrated the potential of E. uniflora leaves infusion as anti-inflammatory in the carrageenan induced rat paw edema test.

The aqueous extract of E. uniflora leaves did not display genotoxic nor clastogenic effects in the Allium cepa L. assay (Yajı́a et al., 1997). Nevertheless, Lora (2007) demonstrated the hydroethanolic extract of E. uniflora leaves induces hepatotoxicity in mice. In addition, the crude ethanol extract and ethyl acetate, n-hexane and chloroform fractions obtained from E. uniflora leaves, induced vasodilation, vascular congestion and toxicity in the hepatopancreas of Oreochromis niloticus L. (Fiuza et al., 2009). However, clinical studies were not found.

Maytenus ilicifolia Mart. ex Reissek

M. ilicifolia is cited in the RENISUS (MS, 2009) list. It is known as espinheira-santa or cangorosa, found in the southern region of Brazil (Tropical Atlantic Forest), Paraguay, Uruguay and Argentina. Traditionally it is used as anti-inflammatory, analgesic and antiulcerogenic. The main compounds identified were phenolic metabolites, such as terpenoids (Shirota et al., 1994; Ohsaki et al., 2004; Gutiérrez et al., 2007), tannins (Gonzalez et al., 2001) and flavonoids (Leite et al., 2001). The pre-clinical studies showed that extract of M. ilicifolia has an anti-inflammatory effect in carrageenan or formaldehyde induced rat paw edema test (Jorge et al., 2004). The anti-inflammatory activity was associated to friedelin, a terpenoid isolated to M. ilicifolia (Schimizu and Tomoo, 1994), and according to Oliveira et al. (1991) the acute and chronic extract administration did not induce any apparent toxicity. In pregnant rodents, the extract caused a pre-implantation embryonic loss, but had no effect on implantation or organogenesis; did not induce morphological alterations of the reproductive system, embryotoxic effects, nor external malformations; and it did not alter the development of the pups (righthing reflex, ambulation, eye-opening), general activity and learning when adults (Oliveira et al., 1991; Montanari and Bevilacqua, 2002). Clinical studies were not found.

As far as we know this is the first study aiming at gathering the use of native species for pain treatment in southern Brazil. It agrees with other reports that document the widespread use of native species as homemade remedies (ethnobotanical studies came from nine out of eleven physiographic regions) that integrate a portrait of the main medicinal plants popularly used for treating pain in the state of Rio Grande do Sul, Brazil. It might contribute to the selection of plants to further studies or include in programs of drug development and public health system. A. satureioides, B. articulata, B. crispa, L. didymum, E. uniflora and M. ilicifolia were the native species most cited for pain relief purposes. However, scientific data are still insufficient to guarantee the efficacy and safety of these plants.

Acknowledgment

The authors thank CAPES and CNPq Brazilian agencies for the financial aid. This paper is the contribution number seven supported by CAPES/PNADB through the project "Knowledge, use and conservation of plant biodiversity in Atlantic Forest and Caatinga" (UFSC/UFRPE/UFRGS).

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• #
  These authors collaborated equally to this study.

Publication Dates

• Publication in this collection
  Mar-Apr 2014

History

• Received
  08 Jan 2014
• Accepted
  17 Mar 2014