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龙葵甾体诱导恶性疟原虫无性血液阶段细胞死亡

Induction of cell death on Plasmodium falciparum asexual blood stages by Solanum nudum steroids.

作者信息

López Mary Luz, Vommaro Rossiane, Zalis Mariano, de Souza Wanderley, Blair Silvia, Segura Cesar

机构信息

Grupo Malaria, Universidad de Antioquia, Sede de Investigación Universitaria-SIU, Medellín, Colombia.

出版信息

Parasitol Int. 2010 Jun;59(2):217-25. doi: 10.1016/j.parint.2010.02.002. Epub 2010 Feb 11.

Abstract

Solanum nudum Dunal (Solanaceae) is a plant used in traditional medicine in Colombian Pacific Coast, from which five steroids denominated SNs have been isolated. The SNs compounds have antiplasmodial activity against asexual blood stages of Plasmodium falciparum strain 7G8 with an IC(50) between 20-87microM. However, their mode of action is unknown. Steroids regulate important cellular functions including cell growth, differentiation and death. Thus, the aim of this work was to determine the effects of S. nudum compounds on P. falciparum asexual blood stages and their association with cell death. We found that trophozoite and schizont stages were the most sensitive to SNs. By Giemsa-stained smears, induction of crisis forms was observed. Transmission electron microscopy of treated parasites showed morphological abnormalities such as a cytoplasm rich in vesicles and myelinic figures. The Mitochondria presented no morphological alterations and the nuclei showed no abnormal chromatin condensation. By the use of S. nudum compounds, cell death in P. falciparum was evident by a decrease in mitochondrial membrane potential, DNA fragmentation and cytoplasmic acidification. The asexual blood stages of P. falciparum showed some apoptotic-like and autophagic-like cell death characteristics induced by SNs treatment.

摘要

光花茄(茄科)是一种在哥伦比亚太平洋沿岸用于传统医学的植物,已从中分离出五种名为SNs的甾体。SNs化合物对恶性疟原虫7G8株的无性血液阶段具有抗疟原虫活性,IC(50)在20 - 87微摩尔之间。然而,它们的作用方式尚不清楚。甾体调节包括细胞生长、分化和死亡在内的重要细胞功能。因此,本研究的目的是确定光花茄化合物对恶性疟原虫无性血液阶段的影响及其与细胞死亡的关联。我们发现滋养体和裂殖体阶段对SNs最为敏感。通过吉姆萨染色涂片,观察到了危机形式的诱导。经处理的疟原虫的透射电子显微镜显示出形态异常,如富含囊泡和髓样结构的细胞质。线粒体没有呈现形态改变,细胞核也没有显示异常的染色质凝聚。通过使用光花茄化合物,恶性疟原虫的细胞死亡通过线粒体膜电位降低、DNA片段化和细胞质酸化得以显现。恶性疟原虫的无性血液阶段表现出一些由SNs处理诱导的凋亡样和自噬样细胞死亡特征。

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