Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
Department of Veterinarian Sciences, Ceará State University, Fortaleza, Ceará, Brazil.
Biomed Pharmacother. 2018 Feb;98:662-672. doi: 10.1016/j.biopha.2017.12.083. Epub 2018 Jan 4.
Leishmania (L.) amazonensis is the American Cutaneous Leishmaniasis-causing agents, and the available drugs for this disease present toxicity, low efficiency and difficulty of administration. Plants belong23ing to the Caryocar genus are found in Brazilian Cerrado, where fruits are used as food and in folk medicine, and previous studies showed several biological effects of extracts of this plant. The present work evaluated the leishmanicidal and immunomodulatory activity of ethyl acetate (EAC) and methanol (MET) C. coriaceum leaf extracts EAC and MET showed an antipromastigote effect after 24, 48 and 72 h. The extracts also induced loss of mitochondrial membrane potential, reactive oxygen species (ROS) production, damage to the plasma membrane, and phosphatidylserine exposure on promastigote forms, and most parasites were going through a late apoptosis-like process. The range of concentrations used did not alter the viability of peritoneal macrophages of BALB/c mice; therefore, we observed that the treatment with extracts was able to reduce the infection of this cells. Thereafter, the extracts were able to significantly improve the levels of TNFα, IL-6, MCP-1, and IL-10, and reduced the levels of MDA and ROS without interfering on NO levels released by infected macrophages. In addition, both EAC and MET up-regulated Nrf2/HO-1/Ferritin expression and reduced the labile iron pool in infected macrophages. Based on the data obtained, it is possible to infer that different solvent extracts of the C. coriaceum leaves exert leishmanicidal effect, acting on promastigote forms through apoptosis-like mechanisms and intracellular amastigote forms involving a Nrf2/HO-1 dependent antioxidant response, which culminates in a depletion of available iron for L. amazonensis replication.
莱什曼原虫（L.）亚马逊是引起美洲皮肤利什曼病的病原体，而这种疾病的可用药物存在毒性、效率低和给药困难等问题。属于卡里奥卡属的植物分布在巴西的塞拉多，其果实被用作食物和民间药物，先前的研究表明该植物的提取物具有多种生物效应。本研究评估了乙酸乙酯（EAC）和甲醇（MET）C. coriaceum 叶提取物的杀利什曼原虫和免疫调节活性，EAC 和 MET 在 24、48 和 72 小时后对前鞭毛体表现出抗增殖作用。提取物还诱导了线粒体膜电位丧失、活性氧（ROS）产生、质膜损伤和前鞭毛体上的磷脂酰丝氨酸暴露，大多数寄生虫经历了晚期凋亡样过程。使用的浓度范围没有改变 BALB/c 小鼠腹腔巨噬细胞的活力；因此，我们观察到提取物处理能够降低这些细胞的感染。之后，提取物能够显著提高 TNFα、IL-6、MCP-1 和 IL-10 的水平，并降低 MDA 和 ROS 的水平，而不干扰感染巨噬细胞释放的 NO 水平。此外，EAC 和 MET 均上调了 Nrf2/HO-1/铁蛋白的表达，并减少了感染巨噬细胞中不稳定铁池的含量。根据获得的数据，可以推断出 C. coriaceum 叶的不同溶剂提取物具有杀利什曼原虫作用，通过类似于细胞凋亡的机制作用于前鞭毛体，并通过依赖 Nrf2/HO-1 的抗氧化反应作用于细胞内无鞭毛体形式，最终导致用于 L. amazonensis 复制的可用铁耗尽。
