dos Santos Aliança Amanda Silva, dos Anjos Keicyanne Fernanda Lessa, de Vasconcelos Reis Thiago Nogueira, Higino Taciana Mirely Maciel, Brelaz-de-Castro Maria Carolina Accioly, Bianco Éverson Miguel, de Figueiredo Regina Celia Bressan Queiroz
Departamento de Microbiologia, Centro de Pesquisa Aggeu Magalhães (CPqAM-FIOCRUZ), Av. Moraes Rego s/n Cidade Universitária, Campus da UFPE, Recife 50670-420, Brazil.
Departamento de Oceanografia, Universidade Federal de Pernambuco (UFPE), Recife 50740-550, Brazil.
Molecules. 2014 Sep 9;19(9):14052-65. doi: 10.3390/molecules190914052.
Seaweeds present a wide variety of interesting bioactive molecules. In the present work we evaluated the biological activity of the dichloromethane/methanol (2:1) extract (DME) from the brown seaweed Dictyota mertensii against Leishmania amazonensis and its cytotoxic potential on mammalian cells. The extract showed significant inhibitory effect on the growth of promastigote forms (IC50=71.60 μg/mL) and low toxicity against mammalian cells (CC50=233.10 μg/mL). The DME was also efficient in inhibiting the infection in macrophages, with CC50 of 81.4 μg/mL and significantly decreased the survival of amastigote forms within these cells. The selectivity index showed that DME was more toxic to both promastigote (SI=3.25) and amastigote (SI=2.86) forms than to macrophages. Increased NO production was observed in treated macrophages suggesting that besides acting directly on the parasites, the DME also shows an immunomodulatory effect on macrophages. Drastic ultrastructural alterations consistent with loss of viability and cell death were observed in treated parasites. Confocal microscopy and cytometry analyzes showed no significant impairment of plasma membrane integrity, whereas an intense depolarization of mitochondrial membrane could be observed by using propidium iodide and rhodamine 123 staining, respectively. The low toxicity to mammalian cells and the effective activity against promastigotes and amastigotes, point to the use of DME as a promising agent for the treatment of cutaneous leishmaniasis.
海藻呈现出各种各样有趣的生物活性分子。在本研究中,我们评估了褐藻网胰藻二氯甲烷/甲醇(2:1)提取物(DME)对亚马逊利什曼原虫的生物活性及其对哺乳动物细胞的细胞毒性潜力。该提取物对前鞭毛体形式的生长显示出显著的抑制作用(IC50 = 71.60 μg/mL),并且对哺乳动物细胞的毒性较低(CC50 = 233.10 μg/mL)。DME在抑制巨噬细胞感染方面也很有效,CC50为81.4 μg/mL,并显著降低了这些细胞内无鞭毛体形式的存活率。选择性指数表明,DME对前鞭毛体(SI = 3.25)和无鞭毛体(SI = 2.86)形式的毒性比对巨噬细胞更大。在经处理的巨噬细胞中观察到一氧化氮产生增加,这表明除了直接作用于寄生虫外,DME还对巨噬细胞显示出免疫调节作用。在经处理的寄生虫中观察到与活力丧失和细胞死亡一致的剧烈超微结构改变。共聚焦显微镜和细胞分析表明,质膜完整性没有明显受损,而分别使用碘化丙啶和罗丹明123染色可观察到线粒体膜的强烈去极化。对哺乳动物细胞的低毒性以及对前鞭毛体和无鞭毛体的有效活性,表明DME有望成为治疗皮肤利什曼病的药物。