Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, 58051-970 João Pessoa, Paraíba, Brazil.
Exp Parasitol. 2011 Jan;127(1):215-21. doi: 10.1016/j.exppara.2010.07.020. Epub 2010 Aug 5.
We have previously demonstrated that yangambin, a lignan obtained from Ocotea duckei Vattimo (Lauraceae), shows antileishmanial activity against promastigote forms of Leishmania chagasi and Leishmania amazonensis. The aim of this study was to determine the in vitro effects of yangambin against these parasites using electron and confocal microscopy. L. chagasi and L. amazonensis promastigotes were incubated respectively with 50 μg/mL and 65 μg/mL of pure yangambin and stained with acridine orange. Treated-parasites showed significant alterations in fluorescence emission pattern and cell morphology when compared with control cells, including the appearance of abnormal round-shaped cells, loss of cell motility, nuclear pyknosis, cytoplasm acidification and increased number of acidic vesicular organelles (AVOs), suggesting important physiological changes. Ultrastructural analysis of treated-promatigotes showed characteristics of cell death by apoptosis as well as by autophagy. The presence of parasites exhibiting multiples nuclei suggests that yangambin may also affect the microtubule dynamic in both Leishmania species. Taken together our results show that yangambin is a promising agent against Leishmania.
我们之前已经证明，yangambin 是从瓦蒂莫奥克泰树（Lauraceae）中提取的木脂素，对美洲锥虫和亚马逊利什曼原虫的前鞭毛体具有抗利什曼原虫活性。本研究的目的是使用电子显微镜和共聚焦显微镜来确定 yangambin 对这些寄生虫的体外作用。用 50μg/ml 和 65μg/ml 的纯 yangambin 分别孵育 L. chagasi 和 L. amazonensis 前鞭毛体，并使用吖啶橙染色。与对照细胞相比，处理后的寄生虫在荧光发射模式和细胞形态方面显示出明显的变化，包括出现异常圆形细胞、丧失细胞运动性、核固缩、细胞质酸化和酸性囊泡细胞器 (AVOs) 数量增加，表明发生了重要的生理变化。处理后的前鞭毛体的超微结构分析显示出细胞凋亡和自噬的特征。表现出多个核的寄生虫的存在表明 yangambin 也可能影响两种利什曼原虫的微管动态。综上所述，我们的研究结果表明，yangambin 是一种有前途的抗利什曼原虫药物。
