Abstract
Leishmaniasis is a neglected disease caused by Leishmania. Chemotherapy remains the mainstay for leishmaniasis control; however, available drugs fail to provide a parasitological cure, and are associated with high toxicity. Natural products are promising leads for the development of novel chemotherapeutics against leishmaniasis. This work investigated the leishmanicidal properties of ethanolic extract of Croton blanchetianus (EECb) on Leishmania infantum and Leishmania amazonensis, and found that EECb, rich in terpenic compounds, was active against promastigote and amastigote forms of both Leishmania species. Leishmania infantum promastigotes and amastigotes presented IC50 values of 208.6 and 8.8 μg/mL, respectively, whereas Leishmania amazonensis promastigotes and amastigotes presented IC50 values of 73.6 and 3.1 μg/mL, respectively. Promastigotes exposed to EECb (100 µg/mL) had their body cellular volume reduced and altered to a round shape, and the flagellum was duplicated, suggesting that EECb may interfere with the process of cytokinesis, which could be the cause of the decline in the parasite multiplication rate. Regarding possible EECb targets, a marked depolarization of the mitochondrial membrane potential was observed. No cytotoxic effects of EECb were observed in murine macrophages at concentrations below 60 µg/mL, and the CC50 obtained was 83.8 µg/mL. Thus, the present results indicated that EECb had effective and selective effects against Leishmania infantum and Leishmania amazonensis, and that these effects appeared to be mediated by mitochondrial dysfunction.
Highlights
Leishmaniasis is a disease caused by protozoan parasites from more than 20 Leishmania species (WHO 2016)
After 30 min in the presence of the essential oil, the parasites were completely destroyed. These data show that the genus Croton is a source of promising leads for novel leishmaniasis chemotherapeutics
These findings encouraged our study of the antileishmanial activity of ethanolic extract of C. blanchetianus (EECb) on L. amazonensis and L. infantum
Summary
Leishmaniasis is a disease caused by protozoan parasites from more than 20 Leishmania species (WHO 2016). This work presents, for the first time, the leishmanicidal activity of C. blanchetianus bark extract, and its effect on mitochondrial metabolism in L. amazonensis promastigotes. Cellular membrane integrity assessment L. amazonensis promastigotes (5 x 105 cells/mL) were cultivated in Schneider’s insect medium supplemented with HIFCS, as previously described, in either the absence or presence of 70.0 μg/mL and 140.0 μg/mL of C. blanchetianus extract, at 26°C for 24 h.
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