Ribeiro Tatiana G, Chávez-Fumagalli Miguel A, Valadares Diogo G, Franca Juçara R, Lage Paula S, Duarte Mariana C, Andrade Pedro H R, Martins Vivian T, Costa Lourena E, Arruda Ana L A, Faraco André A G, Coelho Eduardo A F, Castilho Rachel O
Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
Exp Parasitol. 2014 Aug;143:60-8. doi: 10.1016/j.exppara.2014.05.004. Epub 2014 May 17.
Leishmaniasis is a major public health problem, and the alarming spread of parasite resistance has increased the importance of discovering new therapeutic products. The present study aimed to investigate the in vitro leishmanicidal activity from 16 different Brazilian medicinal plants. Stationary-phase promastigotes of Leishmania amazonensis and murine macrophages were exposed to 44 plant extracts or fractions for 48 h at 37°C, in order to evaluate their antileishmanial activity and cytotoxicity, respectively. The most potent extracts against L. amazonensis were the hexanic extract of Dipteryx alata (IC50 of 0.08 μg/mL), the hexanic extract of Syzygium cumini (IC50 of 31.64 μg/mL), the ethanolic and hexanic extracts of leaves of Hymenaea courbaril (IC50 of 44.10 μg/mL and 35.84 μg/mL, respectively), the ethanolic extract of H. stignocarpa (IC50 of 4.69 μg/mL), the ethanolic extract of Jacaranda caroba (IC50 of 13.22 μg/mL), and the ethanolic extract of J. cuspidifolia leaves (IC50 of 10.96 μg/mL). Extracts of D. alata and J. cuspidifolia presented higher selectivity index, with high leishmanicidal activity and low cytotoxicity in the mammalian cells. The capacity in treated infected macrophages using the extracts and/or fractions of D. alata and J. cuspidifolia was also analyzed, and reductions of 95.80%, 98.31%, and 97.16%, respectively, in the parasite burden, were observed. No nitric oxide (NO) production could be observed in the treated macrophages, after stimulation with the extracts and/or fractions of D. alata and J. cuspidifolia, suggesting that the biological activity could be due to mechanisms other than macrophage activation mediated by NO production. Based on phytochemistry studies, the classes of compounds that could contribute to the observed activities are also discussed. In conclusion, the data presented in this study indicated that traditional medicinal plant extracts present effective antileishmanial activity. Future studies could focus on the identification and purification of the antileishmanial compounds within these plants for analysis of their in vivo antileishmanial activity.
利什曼病是一个重大的公共卫生问题，而寄生虫耐药性的惊人传播增加了发现新治疗产品的重要性。本研究旨在调查16种不同巴西药用植物的体外杀利什曼原虫活性。将亚马逊利什曼原虫的静止期前鞭毛体和小鼠巨噬细胞分别在37°C下暴露于44种植物提取物或馏分48小时，以分别评估它们的抗利什曼原虫活性和细胞毒性。对亚马逊利什曼原虫最有效的提取物是双翼豆的己烷提取物（IC50为0.08μg/mL）、乌墨的己烷提取物（IC50为31.64μg/mL）、孪叶豆叶的乙醇提取物和己烷提取物（分别为IC50为44.10μg/mL和35.84μg/mL）、硬果苏木的乙醇提取物（IC50为4.69μg/mL）、巴西紫薇的乙醇提取物（IC50为13.22μg/mL）和尖叶紫薇叶的乙醇提取物（IC50为10.96μg/mL）。双翼豆和尖叶紫薇的提取物表现出更高的选择性指数，在哺乳动物细胞中具有高杀利什曼原虫活性和低细胞毒性。还分析了使用双翼豆和尖叶紫薇的提取物和/或馏分处理感染巨噬细胞的能力，观察到寄生虫负荷分别降低了95.80%、98.31%和97.16%。在用双翼豆和尖叶紫薇的提取物和/或馏分刺激后，处理过的巨噬细胞中未观察到一氧化氮（NO）产生，这表明其生物活性可能归因于除由NO产生介导的巨噬细胞激活之外的机制。基于植物化学研究，还讨论了可能导致观察到的活性的化合物类别。总之，本研究提供的数据表明传统药用植物提取物具有有效的抗利什曼原虫活性。未来的研究可以集中于鉴定和纯化这些植物中的抗利什曼原虫化合物，以分析它们的体内抗利什曼原虫活性。
