Federal University of Pará, Institute of Biological Sciences, Laboratory of Structural Biology, Belém, Pará, Brazil; National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro, Brazil.
Federal University of Pará, Institute of Biological Sciences, Laboratory of Molecular Pharmacology, Belém, Pará, Brazil.
Biomed Pharmacother. 2018 Jan;97:1613-1621. doi: 10.1016/j.biopha.2017.11.089. Epub 2017 Nov 28.
Leishmania (Leishmania) amazonensis and Leishmania infantum (=Leishmania chagasi) are protozoa that cause American cutaneous and visceral leishmaniasis, respectively. These diseases show a high incidence in developing countries such as Brazil. The treatments used for leishmaniasis are still limited due to their high cost and toxicity. Currently, some natural products are considered an important alternative source of new leishmanicidal agents. Euterpe oleracea Martius, a palm producing black fruits, is frequently consumed in the Amazon region, as a juice, known as açai, with potent antioxidant, anti-inflammatory and anticonvulsant properties. Interestingly, the biological activity of clarified açai juice (EO) on L. (L.) amazonensis and L. infantum (=L. chagasi) is unknown. Therefore, the mechanism of anti-leishmanial action of EO has been evaluated on L. (L.) amazonensis and L. infantum (=L. chagasi). EO reduced the number of promastigotes and caused morphological alterations, increased the production of reactive oxygen species (ROS) and induced cell death phenotypes probably seems by apoptosis in the promastigotes of L. (L.) amazonensis (IC = 1:40) and L. infantum (=L. chagasi) (IC= 1:38). EO also presented activity against Leishmania amastigotes. Treatment with EO for 72 h strongly reduced IL-17 cytokine levels at all tested concentrations and decreased the number of intracellular amastigotes in macrophages infected with L. (L.) amazonensis (IC= 1:30) and L. infantum (=L. chagasi) (IC= 1:38). Additionally, no cytotoxic effect was observed in murine macrophages treated with EO (72 h - CC > 1:1). Our results demonstrated that EO has leishmanicidal activity against two different species that cause American visceral and cutaneous leishmaniasis without cytotoxic effects for the host cell.
嗜中性白血球无形体(Leishmania)亚马逊亚种和婴儿利什曼原虫(=利什曼原虫恰加斯亚种)分别是导致美洲皮肤和内脏利什曼病的原生动物。这些疾病在巴西等发展中国家的发病率很高。由于成本高和毒性大,目前用于治疗利什曼病的药物仍然有限。目前,一些天然产物被认为是新的杀利什曼原虫药物的重要替代来源。产黑色果实的掌状棕榈树(Euterpe oleracea Martius)在亚马逊地区常被制成果汁,即被称为“acai”的果汁,具有强大的抗氧化、抗炎和抗惊厥特性。有趣的是,澄清的 acai 果汁(EO)对 L.(L.)亚马逊亚种和 L. 婴儿利什曼原虫(=利什曼原虫恰加斯亚种)的生物活性尚不清楚。因此,评估了 EO 对 L.(L.)亚马逊亚种和 L. 婴儿利什曼原虫(=利什曼原虫恰加斯亚种)的抗利什曼原虫作用机制。EO 减少了前鞭毛体的数量并引起形态改变,增加了活性氧物质(ROS)的产生,并在 L.(L.)亚马逊亚种(IC=1:40)和 L. 婴儿利什曼原虫(=利什曼原虫恰加斯亚种)(IC=1:38)的前鞭毛体中诱导细胞死亡表型,可能通过凋亡。EO 也对利什曼内阿米巴原虫具有活性。用 EO 处理 72 小时强烈降低了所有测试浓度下的白细胞介素-17 细胞因子水平,并减少了感染 L.(L.)亚马逊亚种(IC=1:30)和 L. 婴儿利什曼原虫(=利什曼原虫恰加斯亚种)(IC=1:38)的巨噬细胞内的内阿米巴数量。此外,在用 EO 处理的鼠巨噬细胞中未观察到细胞毒性作用(72 小时-CC>1:1)。我们的结果表明,EO 对导致美洲内脏和皮肤利什曼病的两种不同物种具有杀利什曼原虫活性,而对宿主细胞没有细胞毒性作用。