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(Lamiaceae): Revisão Dos Trabalhos Publicados De 1970 a 2003

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(Lamiaceae): Revisão Dos Trabalhos Publicados De 1970 a 2003 81 REVISÃO Uso popular e ações farmacológicas de Plectranthus barbatus Andr. (Lamiaceae): revisão dos trabalhos publicados de 1970 a 2003 COSTA, M.C.C.D. Departamento de Biologia, Universidade Católica de Pernambuco, Rua do Príncipe, 526, Boa Vista, Recife, PE, Brasil. CEP 50.050-900 Tel.: (081) 3216-4181; E-mail address: [email protected] RESUMO: Embora seja principalmente utilizado pela população para distúrbios gástricos, um grande número de ações farmacológicas já foram testadas e comprovadas para Plectranthus barbatus Andr., envolvendo compostos isolados de suas folhas, caule e raízes. Entre os aspectos farmacológicos estudados e comprovados destacam-se: ação hipotensiva, inotrópica positiva, cardiovascular, bronco-dilatadora, ativação da adelilato ciclase, inibição da agregação de plaquetas (antimetastase), antitumoral, antinociceptivo e antiinflamatório. Visando contribuir para um maior conhecimento da espécie apresentamos uma revisão das principais publicações envolvendo estudos químico e farmacológico publicados no período de 1970 a 2003. Palavras-chave: Plectranthus barbatus, plantas medicinais, farmacologia ABSTRACT: Popular use and pharmacological actions of Plectranthus barbatus Andr. (Lamiaceae): revision of the works published from 1970 to 2003. Despite the main use of Plectranthus barbatus Andr by the population for gastric disturbances, a great number of pharmacological actions were already tested and proved for this species; such actions involve compounds segregated from their leaves, stems, and roots. Among the pharmacological actions studied and proved, we highlight the followings: hypotensive and positive inotropic actions, cardiovascular action, bronchodilator activity, stimulatory action of adenylate cyclases, inhibition of platelet aggregation (antimetastasis), antitumoral, anti-nociceptive and anti-inflammatory activities. Aiming to contribute for the enrichment of the knowledge regarding this species, a revision of the main publications involving chemical and pharmacological studies published in the period from 1970 to 2003 is presented. Key words: Plectranthus barbatus, medicinal plants, pharmacology INTRODUÇÃO amboinicus), pode ser facilmente confundido por O Plectranthus barbatus Andr. (Coleus leigos. Embora sendo espécies pertencentes ao barbatus Benthan; Coleus forskohlii Briq.), mesmo gênero, P. barbatus e P. amboinicus, exibem provavelmente originário da África, é amplamente propriedades químicas e farmacológicas distintas cultivado em todo o Brasil e utilizado como planta (Albuquerque, 2000). medicinal, com propriedades analgésica e anti- Carriconde et al. (1996) relata que P. dispéptica (Carriconde et al., 1996). barbatus constitui uma das plantas mais citadas em Trata-se de um arbusto aromático perene, levantamentos etnobotânicos de plantas medicinais de ramos eretos e sub-lenhosos, que atinge de 1,0 a do Brasil, para a qual muitos estudos visando detectar 1,5m de altura. As folhas são ovado-oblongas, pilosas ações farmacológicas foram desenvolvidos. Todavia e grossas com bordos denteados. As flores de faltam informações sobre riscos à saúde, decorrentes coloração azulada crescem em racemos (espigas) do uso prolongado de doses repetidas de preparados que surgem na estação chuvosa. Vulgarmente é à base dessa espécie. conhecido como boldo nacional, boldo do Brasil, Entre os estudos químicos, merecem malva santa, sete-dores e tapete-de-Oxalá. Muito destaque aqueles realizados por Zelnik et al. (1977), semelhante ao hortelã da folha grande (P. que estudaram a composição química das folhas de Recebido para publicação em 10/01/2004 Aceito para publicação em 14/10/2005 Rev. Bras. Pl. Med., Botucatu, v.8, n.2, p.81-88, 2006. 82 P. barbatus e estabeleceram a estrutura química de interna do caule de P. barbatus, coletado no Rio de três diterpenos isolados: o barbatusin, presente em Janeiro. Do extrato foram isolados além do barbatusol, maior quantidade, com fórmula molecular C24H30O8, o o ferruginol. O barbatusol, foi considerado como um 3 β-hydroxy-3-deoxybarbatusin com fórmula molecular novo diterpeno bioativo com um esqueleto abietano C24H32O8 e o ciclobutatusin, em menor quantidade, com fórmula empírica C20H28O2. O autor refere que com fórmula C22H28O5. vários diterpenos abietanos têm sido isolado das Tandon et al. (1977) isolaram das raízes de folhas de plantas crescendo no Brasil, enquanto P. barbatus um composto ao qual chamaram de folhas de plantas do Quênia apresentaram rearranjos coleonol. Referiram tratar-se de um diterpeno com abietanos altamente insaturados. Raízes de P. atividades espasmolítica e hipotensiva, com fórmula barbatus da Índia forneceram diterpenos labdanos C22H34O7, cuja atividade biológica foi encontrada na polihidroxilados, dois dos quais, forskolin e coleonol, fração solúvel benzeno. com potente atividade antihipertensiva. Bhat et al. (1977) isolaram, também, das Kelecom et al. (1987) isolaram e raízes de P. barbatus cinco diterpenos, três dos quais determinaram a estrutura de dois componentes com propriedades cardioativa e hipotensiva. Os menores presentes no extrato do caule de P. maiores constituintes isolados do extrato metanólico barbatus. Ambos os componentes já haviam sido das raízes foram identificados como 7 â-acetoxi-8,13- relatados pelo autor em 1983 e em 1985, como sendo epoxi-6â-hidroxi labd-14-en-11-one, com fórmula o cariocal, preservando o grupo metil. Após purificação molecular C22H34O5 e 1á, 9á-dihidroxi derivativo, por acetilação e cromatografia de coluna em sílica idêntico ao coleonol de fórmula C22H34O7, já isolado gel, os dois compostos puderam ser identificados. O anteriormente por Tandon et al. (1977). primeiro deles exibiu a fórmula C24H32O6 e o segundo Lindner et al. (1978) definiram a estrutura a fórmula C24H30O6. química e a atividade farmacológica do forskolin, Valdés et al. (1987) consideraram o forskolin isolado anteriormente por Bhat et al. (1977), com e coleonol como um mesmo composto, presente fórmula molecular C22H34O7. Posteriormente, o apenas nas raízes de P. barbatus. Referem, forskolin foi definido por Dubey et al. (1981), como entretanto, que inicialmente, estruturas químicas um diasteroisômero do coleonol. diferentes foram propostas para esses compostos e Tandon et al. (1979) fizeram análises que a diferença restringia-se apenas a configuração cromatográficas de extratos de exemplares de P. do grupo acetato (-OAc) do carbono 7, que no forskolin barbatus coletados no Brasil, África e Índia. Os seria â acima, enquanto no coleonol seria á abaixo. resultados indicaram que as plantas produziam Todavia o grupo de pesquisadores que isolou o diferentes compostos, conforme sua procedência, forskolin, percebeu que ambos os compostos eram levantando a questão se essas diferenças eram o mesmo (Bhat et al., 1977), e estudos farmacológicos genéticas ou determinadas pelo clima. Se fossem posteriores (Valdés et al., 1987) indicaram que genéticas, então mais investigações deveriam ser coleonol e forskolin têm propriedades idênticas. feitas para determinar se as variações são Ambos os compostos têm a mesma estrutura, sendo intraespecíficas ou se mais de uma espécie estaria correta aquela proposta para o forskolin. Assim, envolvida. Resolver essa questão foi considerado pelos embora o nome coleonol tenha precedido o nome autores como sendo da maior importância para decidir forskolin, está ligado a uma estrutura química errada. se o cultivo de P. barbatus, para produção de No mesmo ano, Valdés et al. (1987) isolaram forskolin, poderia ser realizado em outras áreas, que o forskolin de C. forskohlii e determinaram sua não a Índia. configuração absoluta. Além disso promoveram Bhat et al. (1983) referiram que o composto estudos fitoquímicos de 12 espécies de Plectranthus, 7â-acetoxi-8,13-epoxi- 1á, 6â, 9á-hidroxi labd-14-en- não encontrando nenhuma outra fonte de forskolin 11-one, isolado das raízes de P. barbatus e nessas espécies. A despeito das considerações feitas denominado forskolin, foi o principal princípio ativo por Tandon et al. (1979), sobre os diferentes com ação hipotensiva em animais de laboratório e compostos obtidos de representantes da espécie que quatro outros compostos análogos do forskolin, cultivados em diferentes países, referem que plantas também presentes nas raízes, foram isolados. cultivadas em Michigan a partir de sementes coletadas Quarenta e nove derivados semissintéticos foram na Índia, produziram boas quantidades de forskolin elaborados, incorporando-se alterações estruturais excedendo os registros prévios feitos por Bhat et al. nas posições 1-, 6-, 7-, 9-, 11-, 14/15 e tiveram suas (1977) e por Tandon et al. (1977). Admitem que o alto propriedades inotrópica e hipotensiva comparadas. rendimento do forskolin pode ser atribuído ao uso de No mesmo ano, Kelecom (1983) promoveu plantas jovens, com menos de um ano, ao cuidado a elucidação da estrutura química, a configuração com a coleção e à preservação dos tubérculos. absoluta e a síntese parcial do barbatusol isolado do Roy et al. (1993) isolaram dois componentes extrato bruto diclorometano da casca e da parte presentes em menores quantidades que o coleonol Rev. Bras. Pl. Med., Botucatu, v.8, n.2, p.81-88, 2006. 83 nas raízes de C. forskohlii (1kg) extraídas com 1,2- obtenção de todos os dados espectrais. Segundo o dicloroetano (3x3l). Os componentes tiveram a autor, o composto parece ser a primeira substância estrutura química elucidada correspondendo ao 1,9- natural, da classe dos diterpenos, com a presença dideoxy coleonol e ao 1-acetoxy coleonol, com de anel de
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