Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus

Abstract

Chagas disease and leishmaniasis expose the need for searching more effective and safer new medicinal drugs. To broaden the knowledge about cytotoxicity and the potential of plant species is of utmost importance to obtain new therapeutic options. Plants of the genus Lonchocarpus have high medicinal potential due to the wide variety of bioactive components, presenting different biological activities, including trypanocidal and leishmanicidal activities. Lonchocarpus cultratus (L. cultratus) species features chalcones as lonchocarpine and isocordoin, steroids, and terpenes. The lack of studies on antiparasitic activity has propeled this research to investigate cytotoxicity, the action on the immunomodulation of macrophages, and the response against two parasites: Trypanosoma cruzi (T. cruzi) and Leishmania amazonensis (L. amazonensis). The extracts were obtained from the seeds of L. cultratus in vitro, focusing on in vivo use. When evaluated by the colorimetric methodology of reducing MTT tetrazolium salt to formazan, the hexanic and methanolic extracts of L. cultratus (LHS and LMS respectively) did not show cytotoxicity in murine macrophages. The dichloromethane extract of L. cultratus (LDS) was cytotoxic at the highest concentrations. The three extracts neither stimulate the release of nitric oxide nor inhibit it in macrophages under lipopolysaccharide (LPS) stimuli. The LDS and LMS extracts presented the highest activity against the tested T. cruzi forms, in their highest concentrations, with values close to those observed for Benzonidazole, used for the treatment of Chagas disease. The three extracts showed significant activity on the infection rate of T. cruzi amastigotes. The LDS and LHS extracts were the most active against the promastigote and amastigote forms of L. amazonensis, with values close to that found for Glucantime®, a positive treatment control. LDS showed low rates of selectivity for both parasites, as it was cytotoxic to murine macrophages. The three extracts did not stimulate the release of interleukin 1-beta and interleukin 10 (IL-1β and IL-10, respectively). Since they did not alter the release of NO, they may have exerted direct antiparasitic activity on parasites. There is a need to perform more in-depth tests to know the mechanisms by which the extracts exercise these actions, in order to obtain a potential therapeutic alternative for the pathologies treated in this study.