title: In vitro evaluation of (-)α-bisabolol as a promising agent against Leishmania amazonensis.
abstract: Current treatments for leishmaniasis present some difficulties due to their toxicity, the use of the intravenous route for administration and therapy duration, which may lead to treatment discontinuation. The aim of this study is to investigate new treatment alternatives to improve patients well being. Therefore, we evaluated the inhibitory effect of (-)α-bisabolol, a sesquiterpene alcohol found in various essential oils of different plant species, against the promastigotes and intracellular amastigotes forms of Leishmania amazonensis, as well as the cytotoxic, morphological and ultrastructural alterations of treated cells. Promastigotes forms of L. amazonensis were incubated with (-)α-bisabolol to determine the antileishmanial activity of this compound. The cytotoxicity effect was evaluated by testing against J774.G8 cells. After these tests, the infected and uninfected cells with L. amazonensis were used to determine if the (-)α-bisabolol was able to kill intracellular parasites and to cause some morphological changes in the cells. The (-)α-bisabolol compound showed significant antileishmanial activity against promastigotes with a 50% effective concentration of 8.07 µg/ml (24 h) and 4.26 µg/ml (48 h). Against intracellular amastigotes the IC50 (inhibitory concentration) of (-)α-bisabolol (24 h) was 4.15 µg/ml. The (-)α-bisabolol also showed a cytotoxic effect against the macrophage strain J774.G8. The value of 50% cytotoxic concentration was 14.82 µg/ml showing that (-)α-bisabolol is less toxic to macrophages than to the parasite. Ultrastructural studies of treated promastigotes and amastigotes showed several alterations, such as loss of cytoplasmic organelles, including the nucleus, and the presence of lipid inclusions. This study showed that (-)α-bisabolol has promising antileishmanial properties, as it can act against the promastigote forms and is able to penetrate the cell, and is also active against the amastigote forms. About 69% of the promastigotes forms suffered mitochondrial membrane damage after treatment with IC50 of (-)α-bisabolol, suggesting inhibition of the metabolic activity of parasites. These results open new prospects for research that can contribute to the development of products based on essential oils or isolated compounds from plants for the treatment of cutaneous leishmaniasis.
authors.affiliation: Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Mariana Margatto
authors.initials: MM
authors.lastname: Rottini
authors.affiliation: Laboratório de Plantas Medicinais e Derivados, Farmanguinhos, FIOCRUZ, Manguinhos, RJ, Brazil.
authors.forename: Ana Claudia Fernandes
authors.initials: AC
authors.lastname: Amaral
authors.affiliation: Laboratório de Plantas Medicinais e Derivados, Farmanguinhos, FIOCRUZ, Manguinhos, RJ, Brazil.
authors.forename: Jose Luiz Pinto
authors.initials: JL
authors.lastname: Ferreira
authors.affiliation: Lab. de Cromatografia, Departamento de Quimica, UFAM, Manaus, AM, Brazil.
authors.forename: Jefferson Rocha de Andrade
authors.initials: JR
authors.lastname: Silva
authors.affiliation: Núcleo de Microscopia Eletrônica, Instituto Adolfo Lutz, São Paulo, SP, Brazil.
authors.forename: Noemi Nosomi
authors.initials: NN
authors.lastname: Taniwaki
authors.affiliation: Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Celeste da Silva Freitas de
authors.initials: Cda S
authors.lastname: Souza
authors.affiliation: Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Luiz Ney
authors.initials: LN
authors.lastname: d'Escoffier
authors.affiliation: Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Almeida-Souza
authors.affiliation: Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Daiana de Jesus
authors.initials: Dde J
authors.lastname: Hardoim
authors.affiliation: Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Sylvio Celso
authors.initials: SC
authors.lastname: Gonçalves da Costa
authors.affiliation: Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. Electronic address: calabrese@ioc.fiocruz.br.
authors.forename: Kátia da Silva
authors.initials: Kda S
authors.lastname: Calabrese
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000981:Antiprotozoal Agents; D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes; C004497:bisabolol
keywords: (−)α-bisabolol; Cutaneous leishmaniasis; Leishmania amazonensis; Promastigotes