Ethanolic extract of Croton blanchetianus Ball induces mitochondrial defects in Leishmania amazonensis promastigotes

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 c...

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Published in:Anais da Academia Brasileira de Ciências 2020, Vol.92 (suppl 2), p.e20180968-e20180968
Main Authors: PEREIRA, KATILY L.G., VASCONCELOS, NANCY B.R., BRAZ, JULIANA V.C., INÁCIO, JOB D.F., ESTEVAM, CHARLES S., CORREA, CRISTIANE B., FERNANDES, ROBERTA P.M., ALMEIDA-AMARAL, ELMO E., SCHER, RICARDO
Format: Article
Language:English
Subjects:
Leishmania amazonensi
Leishmania infantum
mitochondrial metabolism
MULTIDISCIPLINARY SCIENCES
natural products
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Summary: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.
ISSN:0001-3765
1678-2690
1678-2690
DOI:10.1590/0001-3765202020180968