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
Universidade Federal de Sergipe, Av. Marechal Rondon, s/n, Rosa Elze, 49000-000 São Cristóvão, SE, Brazil.
Instituto Oswaldo Cruz/FIOCRUZ, Av. Brasil, 4365, Manguinhos, 21040-900 Rio de Janeiro, Brazil.
An Acad Bras Cienc. 2020 Oct 28;92(suppl 2):e20180968. doi: 10.1590/0001-3765202020180968. eCollection 2020.
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.
利什曼病是一种由利什曼原虫引起的被忽视疾病。化疗仍然是控制利什曼病的主要手段；然而，现有的药物无法实现寄生虫学治愈，且具有高毒性。天然产物是开发抗利什曼病新型化疗药物的有前景线索。这项工作研究了巴豆叶乙醇提取物（EECb）对婴儿利什曼原虫和亚马逊利什曼原虫的杀利什曼原虫特性，发现富含萜类化合物的EECb对这两种利什曼原虫的前鞭毛体和无鞭毛体均有活性。婴儿利什曼原虫前鞭毛体和无鞭毛体的IC50值分别为208.6和8.8μg/mL，而亚马逊利什曼原虫前鞭毛体和无鞭毛体的IC50值分别为73.6和3.1μg/mL。暴露于EECb（100μg/mL）的前鞭毛体其体细胞体积减小并变为圆形，且鞭毛加倍，这表明EECb可能干扰胞质分裂过程，这可能是寄生虫繁殖率下降的原因。关于EECb可能的作用靶点，观察到线粒体膜电位有明显去极化。在浓度低于60μg/mL时，未在小鼠巨噬细胞中观察到EECb的细胞毒性作用，获得的CC50为83.8μg/mL。因此，目前的结果表明EECb对婴儿利什曼原虫和亚马逊利什曼原虫具有有效且选择性的作用，并且这些作用似乎是由线粒体功能障碍介导的。
