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来自巴西东北部植物(樟科)的新木脂素具有抗恰加斯病(克氏锥虫)活性。

Neolignans from plants in northeastern Brazil (Lauraceae) with activity against Trypanosoma cruzi.

机构信息

Laboratório de Diptera, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil, 4365, 21045-900 Rio de Janeiro, RJ, Brazil.

出版信息

Exp Parasitol. 2010 Mar;124(3):319-24. doi: 10.1016/j.exppara.2009.11.007. Epub 2009 Nov 26.

Abstract

Trypanosoma cruzi is the ethiological agent for Chagas disease in Latin America. This study aimed to test the trypanocidal effect of licarin A and burchellin isolated from plants in northeastern Brazil. These neolignans were tested on T. cruzi and on peritoneal macrophages, to evaluate drug toxicity. Epimastigote growth was inhibited in 45% with licarin A and 20% with burchellin with an IC(50)/96 h of 462.7 microM and 756 microM, respectively. Epimastigotes treated with licarin A presented swollen mitochondria and disorganized mitochondrial cristae, kDNA and Golgi complex. When treated with burchellin, they presented enormous autophagosomes and chromatin disorganization. Licarin A and burchellin were able to induce trypomastigote death with IC(50)/24 h of 960 microM and 520 microM, respectively. Although licarin A presented an IC(50) for trypomastigotes higher than for epimastigotes, both substances acted as therapeutic trypanocidal agents, because they were able to kill parasites without affecting macrophages. Due to our results, burchellin and licarin A need to be further analysed to observe if they may be used as alternative blood additive prophylaxis against Chagas disease, since it has been established that blood transfusion is an important mechanism in the transmission process.

摘要

克氏锥虫是拉丁美洲恰加斯病的病原体。本研究旨在测试从巴西东北部植物中分离出的利卡里亚 A 和伯切尔林的杀锥虫作用。在 T. cruzi 和腹腔巨噬细胞上测试了这些新木脂素,以评估药物毒性。利卡里亚 A 抑制 45%的滋养体生长,伯切尔林抑制 20%的滋养体生长,IC(50)/96 h 分别为 462.7 μM 和 756 μM。用利卡里亚 A 处理的滋养体呈现肿胀的线粒体和线粒体嵴排列紊乱、kDNA 和高尔基体复合物。用伯切尔林处理时,它们呈现出巨大的自噬体和染色质紊乱。利卡里亚 A 和伯切尔林能够诱导锥虫死亡,IC(50)/24 h 分别为 960 μM 和 520 μM。尽管利卡里亚 A 对锥虫的 IC(50)高于对滋养体的 IC(50),但这两种物质都可以作为治疗性杀锥虫药物,因为它们能够杀死寄生虫而不影响巨噬细胞。鉴于我们的结果,需要进一步分析伯切尔林和利卡里亚 A,以观察它们是否可用作治疗恰加斯病的替代血液添加剂预防剂,因为已经确定输血是传播过程中的一个重要机制。

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