RESUMO
Background: The current study was aimed to evaluate the chemical composition, as well as antileishmanial and cytotoxic effects of the essential oil of Ferula macrecolea and its main compound, terpinolene, against promastigotes and amastigotes of Leishmania tropica. Methods: The chemical composition of the essential oil was analyzed by a gas chromatograph connected to a mass spectrometer (GC/MS). The MTT (3-(4.5-dimethylthiazol-2-yl) - 2.5-diphenyl tetrazolium bromide) assay was used to study the effects of the essential oil and terpinolene against promastigotes while the macrophage model was used for evaluating the effect of F. macrecolea essential oil against amastigotes of L. tropica as well as assessing cytotoxicity. The Griess reaction assay was employed to study the nitric oxide (NO) produced by treating macrophage cells with the essential oil and terpinolene. Furthermore, the effect of the essential oil and terpinolene on plasma membrane permeability and inhibition of infection in macrophages was evaluated. Results: The main compounds were terpinolene (77.72%), n-nonanal (4.47%), and linalool (4.35%), respectively. The 50% inhibitory concentrations (IC50) of the essential oil, terpinolene, and glucantime against promastigotes were 27.6, 11.6, and 32.8 µg/mL, respectively; however, their IC50 values against amastigotes were 42.3, 19.6, and 56.9 µg/mL, respectively. The 50% cytotoxic concentrations of the essential oil, terpinolene, and glucantime were 471.3, 207.3, and 1165.3 µg/mL, respectively. The production of NO in macrophage cells after treatment with the essential oil and terpinolene was increased in a dose-dependent manner (p < 0.001). The results revealed that by increasing the concentration of the essential oil and terpinolene, the permeability of the parasites' plasma membrane was significantly changed (p < 0.001). The pre-incubation of Leishmania parasites with F. macrecolea essential oil and terpinolene significantly declined the rate of cell infection by 74.8% and 79.4%, respectively (p < 0.001). Conclusion: The results of the present study indicated that F. macrecolea essential oil, especially its main compound, i.e., terpinolene, has a potent antiparasitic effect on the promastigote and amastigote stages of L. tropica. Considering the advantages of medicinal plant products over their chemical counterparts, it is suggested that in the continuation of this study, the effect of F. macrecolea essential oil, especially terpinolene, on laboratory animals, and in case of high efficiency, in humans be evaluated.
