Plantas medicinais da Bacia do Rio das Velhas: avaliação das condições para produção e uso em saúde pública / Medicinal plants of the Rio das Velhas watershed region: potential for production and use in public health

RESUMO O desenvolvimento de projetos que contemplem o cultivo e beneficiamento de plantas medicinais, com qualidade, é urgente e necessário, especialmente quando se considera a expansão da oferta desses produtos para o Sistema Único de Saúde (SUS). Nesta pesquisa, foi avaliada a existência de iniciativas que produzem e disponibilizam plantas medicinais de interesse do SUS, em municípios que compõem a Bacia Hidrográfica do Rio das Velhas (BHRV), em Minas Gerais. Foram visitados 45 municípios da Bacia buscando informações sobre atividades já existentes de produção e uso coletivo de plantas medicinais. Os dados sobre plantas medicinais já existentes foram posteriormente confrontados com informações epidemiológicas, como as principais causas de internações hospitalares e cobertura de equipes da Estratégia da Saúde da Família (ESF). A pesquisa evidenciou a existência de atividades filantrópicas e comerciais, relativas à utilização coletiva de plantas medicinais, apenas em Belo Horizonte, Capim Branco, Curvelo, Lassance, Nova Lima e Sete Lagoas. Vinte e sete espécies, nativas e exóticas, presentes na RDC 10/2010 da Anvisa são produzidas nessas iniciativas, e elas ocorrem tanto de forma espontânea como por meio de cultivo. A correlação das principais causas de internação hospitalar com as espécies vegetais disponíveis revelou potenciais locais de aproveitamento das plantas, inclusive pela ESF. O desenvolvimento da cadeia produtiva, trabalhando desde o cultivo até a dispensação aos usuários do SUS, pode representar uma oportunidade de integração de diferentes atores e instituições da região, além de incrementar o desenvolvimento econômico-social e a preservação da biodiversidade local.

ABSTRACT The development of projects that include the cultivation and processing of medicinal plants with quality is urgent and necessary, especially when considering the offer increase of these products to the Unified Health System (SUS). In this study, we evaluated the potential of the Rio das Velhas" watershed region (BHRV) in producing and using medicinal plants. We visited 45 cities of the watershed, seeking information about existing production and collective use of medicinal plants. Afterwards, the data obtained in the fieldwork were confronted with epidemiological information, such as hospitalization rates and coverage of the Family Health Strategy. The research showed the existence of commercial and philanthropic activities in Belo Horizonte, Capim Branco, Curvelo, Lassance, Nova Lima and Sete Lagoas. Twenty-seven species, native and exotic ones, included in the 10/2010 Resolution edited by the Brazilian Health Surveillance Agency (Anvisa), are produced in these initiatives, and they occur both spontaneously and through cultivation. The correlation of the leading causes for hospitalization and the available plant species showed potential use of local plants, including by the Family Health Strategy. The development of the production chain, from the plants" cultivation to the medicines" dispensation for the SUS users, may represent an opportunity of integration of different actors and institutions in the region, besides increasing the economic and social development and contributing to the preservation of local biodiversity.

Ampelozyziphus amazonicus Ducke (Rhamnaceae), a medicinal plant used to prevent malaria in the Amazon Region, hampers the development of Plasmodium berghei sporozoites.

Most medicinal plants used against malaria in endemic areas aim to treat the acute symptoms of the disease such as high temperature fevers with periodicity and chills. In some endemic areas of the Brazilian Amazon region one medicinal plant seems to be an exception: Ampelozyziphus amazonicus, locally named "Indian beer" or "Saracura-mira", used to prevent the disease when taken daily as a cold suspension of powdered dried roots. In previous work we found no activity of the plant extracts against malaria blood parasites in experimentally infected animals (mice and chickens) or in cultures of Plasmodium falciparum. However, in infections induced by sporozoites, chickens treated with plant extracts were partially protected against Plasmodium gallinaceum and showed reduced numbers of exoerythrocytic forms in the brain. We now present stronger evidence that the ethanolic extract of "Indian beer" roots hampers in vitro and in vivo development of Plasmodium berghei sporozoites, a rodent malaria parasite. Some mice treated with high doses of the plant extract did not become infected after sporozoite inoculation, whereas others had a delayed prepatent period and lower parasitemia. Our data validates the use of "Indian beer" as a remedy for malaria prophylaxis in the Amazon, where the plant exists and the disease represents an important problem which is difficult to control. Studies aiming to identify the active compounds responsible for the herein described causal prophylactic activity are needed and may lead to a new antimalarial prophylactic.

Assessment of the antimicrobial activity of Casearia sylvestris extract against oral pathogenic microorganisms

An ethanolic extract of leaves from the tree Casearia sylvestris, known as guaçatonga in Brazil, was tested for in vitro activity against oral pathogenic bacteria and fungi. The results showed susceptibility of all the microorganisms tested. This study suggests a potential use of ethanolic extract of C. sylvestris as a novel treatment of oral infectious conditions, such as denture stomatitis, periodontitis and dental caries.

New evidences of antimalarial activity of Bidens pilosa roots extract correlated with polyacetylene and flavonoids.

Bidens pilosa is among the several plants used in Brazil to treat malaria. It was demonstrated that crude extracts from roots prepared with 80% ethanol by percolation are active in vitro against Plasmodium falciparum and the activity is correlated with the presence of polyacetylene and flavonoids. This extract was submitted to column chromatography with ether and ether methanol (1:1) and two fractions, enriched in polyacetylene and flavonoids, respectively, were obtained. The extract and the fractions were assessed by HPLC/DAD analysis and antimalarial tests in vivo. Ethanol extract showed by HPLC the presence of several peaks for polyacetylene and flavonoids, compounds corresponding to quercetin-3,3'-dimethoxy-7-0-rhamnoglucopyranose and the acetylene 1-phenyl-1,3-diyn-5-en-7-ol-acetate, previously identified in this extract. The peaks for flavonoids were absent in ether fraction and those ones for polyacetylene in ether:methanol. In in vivo tests, ethanol extract caused 36% of reduction of parasitaemia at fifth day, and 29% at seventh day. Ether:methanol fraction caused 38% of reduction at fifth day but was inactive at day 7. The survival of the animals treated with 80% ethanol extract was higher than in the fractions. The results showed that the in vivo activity of ethanol extract depends on the presence of polyacetylene and flavonoids.

Caracterização botânica e química de Rudgea viburnoides (Cham.) Benth., (Rubiaceae) / Morphological and chemical diagnosis of Rudgea viburnoides (Cham.) Benth., (Rubiaceae)

Congonha, congonha-de-bugre e bugre são nomes populares atribuídos a várias espécies medicinais, incluindo Rudgea viburnoides (Cham.) Benth. (Rubiaceae), cujas folhas são utilizadas na medicina popular como diuréticas, hipotensoras, antireumáticas e depurativas do sangue. Esta espécie vem sendo comercializada como porangaba e utilizada em regimes de emagrecimento, substituindo Cordia ecalyculata Vell. (Boraginaceae). Neste estudo, foram determinadas as características botânicas, fisico-químicas e químicas para R. viburnoides com o objetivo de auxiliar sua identificação taxonômica e o controle de qualidade de produtos preparados com esta planta. Uma amostra referência foi coletada e submetida à caracterização macroscópica, microscópica e organoléptica, determinação de cinzas totais e umidade, prospecção fitoquímica e determinação dos perfis cromatográficos em CCD. Amostras de R. viburnoides podem ser reconhecidas pela epiderme pilosa com marcantes estrias cuticulares, estômatos paracíticos, presença de idioblastos com ráfides no mesofilo e pela configuração em arco dos tecidos vasculares da nervura de primeira ordem, caracteres ausentes em C. ecalyculata. A presença de cistólitos e canais mucilaginosos na medula diferem prontamente C. ecalyculata de R. viburnoides. A análise por CCD evidenciou a presença de flavonóides e saponinas. Amostras adquiridas no comércio e submetidas aos mesmos ensaios permitiram validar os métodos propostos e confirmaram a ampla comercialização de R. viburnoides em Minas Gerais.

Congonha, congonha-de-bugre and bugre are popular names for several medicinal plant species, including Rudgea viburnoides (Cham.) Benth. (Rubiaceae), whose leaves are widely used in popular medicine as diuretic, hypotensive, antirheumatic, and blood depurative. This species has been commercialized as porangaba, and used for diet purposes in substitution of Cordia ecalyculata Vell. (Boraginaceae). This study determines botanical, physico-chemical and chemical characteristics of R. viburnoides with the objective of providing tools for its taxonomical identification and the quality control of derived products. A reference sample was collected and submitted to macroscopical, microscopical and organoleptical characterization, total ash and water content, phytochemical screening, and TLC profile determination. Samples of Rudgea viburnoides can be easily distinguished from those of Cordia ecalyculata by the pilose epidermis with paracytic stomata, outstanding cuticularized striation, the presence of cristalliferous idioblasts, and by the arc pattern of the midvein vascular tissues. Furthermore, C. ecalyculata presents cystoliths and medullary mucilaginous channels differing from R. viburnoides. TLC analysis demostrated the presence of flavonoids and saponins. Commercially acquired samples submitted to the same assays have therefore validated the proposed methods, and confirmed the wide commercialization of R. viburnoides in the state of Minas Gerais, Brazil.

Antimalarial activity of Cinchona-like plants used to treat fever and malaria in Brazil.

For centuries, malaria was treated with the bark of Cinchona calisaya and Cinchona succirubra plants named "quinas" in Brazil, from which the quinine molecule was isolated. Other plant species known also as "quinas" are used to treat fever and malaria, like Deianira erubescens (roots and leaves), Strychnos pseudoquina (bark), and Remijia ferruginea (bark). Based on this popular knowledge, we evaluated the in vivo antimalarial activity of the ethanol crude extracts of these plant species in mice infected with Plasmodium berghei. Only Remijia ferruginea showed antimalarial activity, reducing parasitaemia and mortality at the highest dose tested. Its phytochemical analysis showed the presence of alkaloids but not quinine. The other two plant species were inactive.

The starch from Solanum lycocarpum St. Hill. fruit is not a hypoglycemic agent.

We have investigated the hypoglycemic effect induced by the starch obtained from the unripe fruits of Solanum lycocarpum (Solanaceae). Per os administration of the starch (1000 or 2000 mg/kg, twice daily for 7 days, N = 6) did not change glycemia levels of nondiabetic female Swiss mice weighing 25-30 g. In streptozotocin-induced diabetic mice, similar treatment with the starch did not change the elevated glycemia 3 h after the last dose (diabetic treated with saline = 288 17/309 18; starch 1000 mg/kg = 295 +/- 33; starch 2000 mg/kg = 258 +/- 37; N = 5). In animals fasted for 15 h, per os administration of glucose (600 mg/kg) significantly increased glycemia 1 h later. Previous (-30 min) treatment of the animals with the starch (1000 or 2000 mg/kg; N = 5) did not change the increase of glycemia. Per os administration of the starch (1000 or 2000 mg kg-1 day-1, twice daily for 7 days) did not induce body weight gain or loss. The chemical analysis of the starch indicated the presence of glycoalkaloids, a finding that represents a reason for concern since many of these substances are generally toxic. In interviews with 56 diabetic patients, 29 medicinal plants were reported as useful in their treatment of diabetes and S. lycocarpum was the sixth most frequently mentioned. All patients interviewed reported that they also used insulin or oral hypoglycemic drugs. The results of the present study do not provide evidence for a hypoglycemic effect associated with the polysaccharide fraction of S. lycocarpum in either normal or hyperglycemic mice. These data demonstrate the need for adequate pharmacological investigation of the natural products widely used in folk medicine.

The starch from Solanum lycocarpum St. Hill. fruit is not a hypoglycemic agent

We have investigated the hypoglycemic effect induced by the starch obtained from the unripe fruits of Solanum lycocarpum (Solanaceae). Per os administration of the starch (1000 or 2000 mg/kg, twice daily for 7 days, N = 6) did not change glycemia levels of nondiabetic female Swiss mice weighing 25-30 g. In streptozotocin-induced diabetic mice, similar treatment with the starch did not change the elevated glycemia 3 h after the last dose (diabetic treated with saline = 288 ± 17/309 ± 18; starch 1000 mg/kg = 295 ± 33; starch 2000 mg/kg = 258 ± 37; N = 5). In animals fasted for 15 h, per os administration of glucose (600 mg/kg) significantly increased glycemia 1 h later. Previous (-30 min) treatment of the animals with the starch (1000 or 2000 mg/kg; N = 5) did not change the increase of glycemia. Per os administration of the starch (1000 or 2000 mg kg-1 day-1, twice daily for 7 days) did not induce body weight gain or loss. The chemical analysis of the starch indicated the presence of glycoalkaloids, a finding that represents a reason for concern since many of these substances are generally toxic. In interviews with 56 diabetic patients, 29 medicinal plants were reported as useful in their treatment of diabetes and S. lycocarpum was the sixth most frequently mentioned. All patients interviewed reported that they also used insulin or oral hypoglycemic drugs. The results of the present study do not provide evidence for a hypoglycemic effect associated with the polysaccharide fraction of S. lycocarpum in either normal or hyperglycemic mice. These data demonstrate the need for adequate pharmacological investigation of the natural products widely used in folk medicine

Preparação e caracterização de extratos glicólicos enriquecidos em taninos a partir das cascas de Stryphnodendron adstringens (Mart. ) Coville (Barbatimão) / Preparation and characterization of propylene glicol extracts obtained from dried stem barks of Stryphnodendron adstringens (Mart. ) Coville (barbatimão)

Neste estudo, foram preparados e caracterizados extratos glicólicos de cascas de Stryphnodendron adstringens (barbatimão), visando a obtenção de extratos enriquecidos em taninos. Os extratos foram preparados, em triplicata, por meio de maceração estática da droga vegetal pulverizada, seguida de percolação, com diferentes misturas de 90 por cento (PGL90), 80 por cento (PGL80) e 70 por cento (PGL70) de propilenoglicol em água. Os extratos foram recolhidos de forma fracionada. Cada fração obtida foi submetida a análises de pH, densidade, determinação de resíduo seco, e dos teores de taninos e de polifenóis. Os resultados dessas análises demonstraram que o solvente PGL70 extraiu maior quantidade de constituintes químicos da droga vegetal, a partir das primeiras frações. No entanto, as análises revelaram que o solvente PGL80 foi mais seletivo ao extrair, especificamente, os taninos da planta. Os resultados indicaram que a incorporação de 20 por cento de água ao propilenoglicol deve conduzir a extratos mais enriquecidos em taninos, a partir das cascas de barbatimão.

Extracts from dried stem barks of Stryphnodendron adstringens (barbatimão) were prepared with 90 percent, 80 percent and 70 percent of propylene glycol and water (PGL90, PGL80 and PGL70, respectively). The extract was prepared by percolation and collected as fractions of 100mL. The pH, density, dry residue and tannin and polyphenolic contents were determined for each fraction. The results showed that the extraction of chemical compounds was more efficient with PGL70, but PGL80 was more selective for extraction of tannins, the active compounds.

The search for new antimalarial drugs from plants used to treat fever and malaria or plants ramdomly selected: a review.

In this review we discuss the ongoing situation of human malaria in the Brazilian Amazon, where it is endemic causing over 610,000 new acute cases yearly, a number which is on the increase. This is partly a result of drug resistant parasites and new antimalarial drugs are urgently needed. The approaches we have used in the search of new drugs during decades are now reviewed and include ethnopharmocology, plants randomly selected, extracts or isolated substances from plants shown to be active against the blood stage parasites in our previous studies. Emphasis is given on the medicinal plant Bidens pilosa, proven to be active against the parasite blood stages in tests using freshly prepared plant extracts. The anti-sporozoite activity of one plant used in the Brazilian endemic area to prevent malaria is also described, the so called "Indian beer" (Ampelozizyphus amazonicus, Rhamnaceae). Freshly prepared extracts from the roots of this plant were totally inactive against blood stage parasites, but active against sporozoites of Plasmodium gallinaceum or the primary exoerythrocytic stages reducing tissue parasitism in inoculated chickens. This result will be of practical importance if confirmed in mammalian malaria. Problems and perspectives in the search for antimalarial drugs are discussed as well as the toxicological and clinical trials to validate some of the active plants for public health use in Brazil.

Interesse dos estudantes de Farmácia e Biologia por plantas medicinais e fitoterapia

Este trabalho descreve os resultados obtidos em um levantamento realizado com 262 estudantes dos cursos de Farmácia e Biologia, de várias partes do Brasil, sobre o tema Plantas Medicinais e Fitoterapia. Foram aplicados questionários com questões relativas aos dados pessoais de cada estudante e questões relacionadas a temas, como por exemplo: a) por que o estudante se interessava por Plantas Medicinais e Fitoterapia? e b) estudante deveria citar cinco plantas que mais conhecia e/ou utilizava. Os resultados da pesquisa demonstraram que os estudantes de Farmácia e Biologia reconhecem a importância das Plantas Medicinais e da Fitoterapia para o seu futuro desempenho como profissionais e têm interesse em se aprimorar nessa área de conhecimento. A alta freqüência de estudantes que consideraram a fitoterapia mais eficaz do que os medicamentos convencionais e a baixa freqüência daqueles que associaram plantas medicinais à riqueza da biodiversidade brasileira foram resultados preocupantes. Um ponto positivo foi o grande número de citações de plantas medicinais que contam com algum estudo de validação, como sendo as mais conhecidas e utilizadas. Consideramos interessante que as disciplinas dos Cursos de Farmácia e Biologia, envolvidas com o tema, concentrem‑se no estudo de plantas medicinais já conhecidas e utilizadas pelos estudantes, capacitando‑os nos aspectos técnico‑científicos de cada espécie e seus produtos.

[Surveillance of phytotherapeutic drugs in the state of Minas Gerais. Quality assessment of commercial samples of chamomile]. / Vigilância de fitoterápicos em Minas Gerais. Verificação da qualidade de diferentes amostras comerciais de camomila.

Marketing of medicinal plants and phytotherapeutic products is spreading all over the world. In order to assess the commercialization of medicinal plants and phytotherapeutic products in the State of Minas Gerais, we identified and tested for the presence of adulterants and active ingredients in 27 samples of chamomile. All the samples consisted of Matricaria recutita flowers, but they were badly fragmented, a result of excessive handling and poor preservation. All samples contained contaminants, and insects were observed in 63% of the samples sold in drugstores. Only 50% of the samples in each group had the essential oils needed to produce antiinflammatory activity. Flavonoids and other phenolic constituents with a spasmolytic effect were detected in only 20% of the samples from each group. Results with chamomile indicated the poor quality with which medicinal plants and phytotherapeutic products are marketed and confirm the need for surveillance of such products in Brazil.

Antimalarial activity of extracts and fractions from Bidens pilosa and other Bidens species (Asteraceae) correlated with the presence of acetylene and flavonoid compounds.

After interviewing natives and migrants from the Amazon region of Brazil about plants traditionally used for treatment of malaria fever and/or liver disorders, we selected and identified 41 different species, including the native Bidens (Asteraceae). We have undertaken an antimalarial study of Bidens pilosa and other species of Bidens from abroad. The crude ethanol extracts (whole plant, leaves and roots) and the chloroform and butanol fractions from B. pilosa at concentrations of 50 microg/ml caused up to 90% inhibition of Plasmodium falciparum growth in vitro. In vivo the fractions caused partial reduction of Plasmodium berghei parasitemia in mice. The ethanol extracts from nine different Bidens species collected outside Brazil were tested, and seven inhibited parasite growth in vitro by 65-91%. As B. pilosa appears to be a promising antimalarial agent, we further characterized the substances responsible for such activity. HPLC analysis using a photo diode-array detector showed phenyl acetylene and flavonoids in the ethanol extract from the leaves and roots. The chloroform fractions from the roots, which caused 86% inhibition of parasite growth in vitro, contained a major component identified as 1-phenyl-1,3-diyn-5-en-7-ol-acetate. The association of antimalarial activity and the presence of acetylene compounds is discussed. In summary, all species of Bidens which had aliphatic acetylenes (6-14 each) were also very active, whereas extracts of B. parriflora and of B. bitternata with none or the three acetylenes, respectively as reported in literature, were inactive or had a borderline activity in vitro.

A dammarane-type saponin from the roots of Ampelozizyphus amazonicus.

A new C31 dammarane-type triterpenoid saponin has been isolated from the roots of Ampelozizyphus amazonicus. Its structure was elucidated to be ampelozigenin-15 alpha-O-acetyl- 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside by 1D and 2D NMR spectroscopic methods, and by chemical transformations. Ampelozigenin is a novel triterpene, (20R,22R)-16 beta,22:16 alpha, 30-diepoxydammar-24(24')- methylene-3 beta, 15 alpha, 20-triol.

Survey of medicinal plants used as antimalarials in the Amazon.

Plants traditionally employed for the treatment of malaria in certain areas of Brazil, where this disease is prevalent, were surveyed by interviewing natives and migrants in the Amazon Region. Forty-one plants used for malarial treatment and/or for the related symptoms (fever and liver disorders) were collected and identified. Given the potential of Brazil's forests and medicinal plants, research on traditional plant-based remedies in this country may lead to the development of new drugs.

Triterpene saponins from the roots of Ampelozizyphus amazonicus.

A new triterpene saponin was isolated from the roots of Ampelozizyphus amazonicus together with the known 3-O-beta-D-glucopyranosyl-20-O-alpha-L-rhamnopyranosyljujubogenin and the known triterpenes melaleucic acid, 3 beta,27 alpha-dihydroxylup-20(29)-en-28 beta-oic acid, betulinic acid, betulin, lupeol. The structure of this saponin was elucidated as 3-O-[beta-D-glucopyranosyl(1----2)alpha-L-arabinopyranosyl]- 20-O-alpha-L-rhamnopyranosyljujubogenin by spectral analysis and chemical transformations.

Antimalarial activity of crude extracts from Brazilian plants studied in vivo in Plasmodium berghei-infected mice and in vitro against Plasmodium falciparum in culture.

1. Ninety-five crude extracts obtained with either organic solvents or water from 48 Brazilian plants or parts of plants were evaluated experimentally as blood schizontocides. Seventy-three extracts were obtained from 33 plants randomly collected using an empirical approach, and 22 from 15 "medicinal" plants. 2. The crude extracts were screened in vivo at up to 1.0 g/kg, po, for 4 days in mice infected with blood forms of Plasmodium berghei and parasitemia was determined on the fifth day. 3. Six plants, 2 randomly collected, Vernonia brasiliana and Eupatorium squalidum, and 4 "medicinal" plants, Acanthospermum australe, Esenbeckia febrifuga, Lisianthus speciosus, and Tachia guianensis, were partly active against the rodent malaria, i.e., they showed 40-50% inhibition of P. berghei multiplication. Forty-two plants whose extracts presented no antimalarial activity are reported. 4. Four extracts with antimalarial activity were also tested in vitro using P. falciparum cultures and two of them, V. brasiliana and A. australe, were active. Extracts of V. brasiliana caused about 50% inhibition of parasite multiplication at relatively low doses (40 ng/ml) as compared to chloroquine (30 ng/ml) and quinine (50 ng/ml). 5. The relatively high percentage of positive results obtained here for "medicinal" plants vs randomly chosen plants demonstrates the effectiveness of the ethnopharmacological approach to drug testing.

Antimalarial activity of crude extracts from Brazilian plants studied in vivo in Plasmodium berghei-infected mice and in vitro against Plasmodium falciparum in culture

1. Ninety-five crude extrat obtained with either organic solvents or water from 48 Brazilian plants or parts of plants were evaluated experimentally as blood schizontocides. Seventy-three extracts wee obtained from 33 plants randomly collected using an empirical approach, and 22 from 15 "medicinal" plants. 2. The crude extracts were screened in vivo at up to 1.0g/Kg, po, for 4 days in mice infected with blood forms of Plasmodium berghei and parasitemia was determined on the fifth day. 3. Six plants, 2 randomly collected, Vernonia brasiliana and Eupatorium squalidum, and 4 "medicinal" plants, Acanthospermum australe, Esenbeckia febrifuga, Lisianthus speciosus, and Tachia guianensis, were partly active aginst the rodent malaria, i.e., they showed 40-50% inhibition of P. berghei multiplication. Forthy-two plants whose extracts presented no antimalarial activity are reported. 4. Four extracts with antimalarial activity were also tested in vitro using P. falciparum cultures and two of them, V. brasiliana and A. australe, were active. Extracts of V. brasiliana caused about 50% inhibition of parasite multiplication at relatively low doses (40ng/ml) as compared to chloroquine (30ng/ml) and quinine (50ng/ml). The relatively high percentage of positive results obtained here for "medicinal" plants vs randomly chosen plants demonstrates the effectiveness of the ethnopharmacological approach to drug testing