Laboratório de Biologia de Tripanosomatídeos, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, Manguinhos, 21045-900 Rio de Janeiro, Rio de Janeiro, Brazil.
Parasitol Res. 2010 Oct;107(5):1193-204. doi: 10.1007/s00436-010-1988-6. Epub 2010 Aug 3.
Croton cajucara is a plant found in the Amazon region and is known for its medicinal properties. The effects of the methanolic extract of the stem bark of C. cajucara (MCC) and of the isolated terpenes, trans-dehydrocrotonin (t-DCTN) and acetyl aleuritolic acid (AAA), were investigated using four isolates of Trypanosoma cruzi. In assays with trypomastigotes, the extract was more active than the isolated compounds, presenting IC(50) in the range of 10 to 50 μg/mL. The trypanocidal effect of MCC, AAA and benznidazole was significantly higher in the GLT291 and C45 strains, which were recently isolated from wild animals. MCC and AAA caused a dose-dependent inhibition of epimastigote proliferation. In assays using intracellular amastigotes, AAA and MCC reduced the percent of infection and the endocytic index after 96 h of treatment, at concentrations that were non-toxic to the host cells. MCC inhibited the trypanothione reductase pathway in both epimastigotes and trypomastigotes of all the subpopulations. The absence of AAA activity on the trypanothione reductase pathway in epimastigotes of Dm28c suggests heterogeneity of the biochemical profile between this clone and the three strains. Epimastigotes and trypomastigotes (GLT291) were treated for 24 h with MCC or AAA, and both induced alterations of the plasma membrane, while AAA-treated epimastigotes also displayed mitochondrial damage.
刺果番荔枝是一种生长在亚马逊地区的植物，以其药用特性而闻名。本研究采用四种克氏锥虫分离株，考察了刺果番荔枝茎皮甲醇提取物（MCC）和分离得到的萜类化合物，反式-脱氢巴豆酰（t-DCTN）和乙酰阿魏酸（AAA）的作用。在对游离鞭毛体的实验中，提取物比分离化合物更具活性，其 IC50 范围为 10-50μg/mL。MCC、AAA 和苯并硝哒唑对 GLT291 和 C45 这两种最近从野生动物中分离出的分离株的杀锥虫效果明显更高。MCC 和 AAA 可剂量依赖性地抑制体外培养的前鞭毛体的增殖。在使用细胞内无鞭毛体的实验中，AAA 和 MCC 可降低感染率和内吞指数，在不损伤宿主细胞的浓度下，作用 96 小时。MCC 可抑制所有亚群的前鞭毛体和游离鞭毛体中的硫氧还蛋白还原酶途径。在 Dm28c 株的前鞭毛体中，AAA 对硫氧还蛋白还原酶途径没有活性，这表明该克隆与 3 株分离株之间的生化特征存在异质性。用 MCC 或 AAA 处理 24 小时后，可使前鞭毛体和游离鞭毛体（GLT291）发生质膜改变，而 AAA 处理的前鞭毛体还显示出线粒体损伤。
