Essential Oils from Croton Species: Chemical Composition, in vitro and in silico Antileishmanial Evaluation, Antioxidant and Cytotoxicity Activities

Selene Morais,Nadja Vila-Nova,Oriel Bonilla,Antonio Silva,Maria Teixeira,Manoel De Moraes,Valdir De Paula,Danyelle Cossolosso,Claudio Campello

doi:10.21577/0103-5053.20190155

Abstract

Chemotherapy treatment of leishmaniasis is based on the use of pentavalent antimonials, but these drugs present low efficacy and high toxicity. In the search for new antileishmanial agents, essential oils (EOs) from four Croton species (C. argyrophylloides, C. jacobinensis, C. nepetifolius and C. sincorensis) were evaluated against Leishmania infantum chagasi, L. amazonensis and L. braziliensis. EOs were analyzed by gas chromatography combined with mass spectrometry. Spathulenol, β-caryophyllene, β-caryophyllene oxide, 1,8-cineole and methyl eugenol were the major constituents. The evaluation of antioxidant activity by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) method showed that all EOs have moderate antioxidant activity. All oils were similarly active against L. i. chagasi, and C. nepetifolius EO showed the best result against L. amazonensis, with median inhibitory concentrations (IC50) of 9.87 μg mL-1, similar to amphotericin B (IC50 = 7.38 μg mL-1). The oils presented low cytotoxicity in macrophages. The in silico analysis revealed that spathulenol and 1,8-cineole were active against the enzyme Leishmania infantum trypanothione reductase (LiTR), showing excellent interaction energies, making them promising agents for leishmaniasis control.

Highlights

Leishmaniasis is a growing public health problem in many countries of the Americas, Asia, Europe and Africa
Due to several biological activities of Croton essential oils (EOs), four species from the Caatinga biome of northeastern Brazil were chosen for investigation of their potential as antileishmanial agents. We evaluated their chemical composition, antioxidant action, antileishmanial activities against promastigotes of Leishmania infantum chagasi, L. braziliensis and L. amazonensis, toxicity in macrophages AMJ2-C11, and performed computational analysis of essential oil constituents in relation to Leishmania infantum trypanothione reductase (LiTR)
The IC50 values were calculated from linear regression curves using the statistical software Graph Pad Prism 4.0.32 The data were initially submitted to the Shapiro-Wilk and Bartlett tests for confirmation of normal distribution and homogeneity of variance between treatments, respectively

Summary

Introduction

Leishmaniasis is a growing public health problem in many countries of the Americas, Asia, Europe and Africa. We evaluated their chemical composition, antioxidant action, antileishmanial activities against promastigotes of Leishmania infantum chagasi, L. braziliensis and L. amazonensis, toxicity in macrophages AMJ2-C11, and performed computational analysis of essential oil constituents in relation to Leishmania infantum trypanothione reductase (LiTR). The IC50 (inhibitory concentration which inhibits 50% of Leishmania promastigotes) values were calculated from linear regression curves using the statistical software Graph Pad Prism 4.0.32 The data were initially submitted to the Shapiro-Wilk and Bartlett tests for confirmation of normal distribution and homogeneity of variance between treatments, respectively.

Results

Conclusion