Laboratório de Patologia de Moléstias Infeciosas, Departamento de Patologia da Faculdade de Medicina, da Universidade de São Paulo, Av. Dr. Arnaldo, 455, Cerqueira César, 01246-000, São Paulo, Brazil.
Parasitol Res. 2014 Jan;113(1):333-9. doi: 10.1007/s00436-013-3659-x. Epub 2013 Oct 31.
The current medications used to treat leishmaniasis have many side effects for patients; in addition, some cases of the disease are refractory to treatment. Therefore, the search for new leishmanicidal compounds is indispensable. Recently, it was demonstrated that oleanolic- and ursolic-containing fraction from Baccharis uncinella leaves eliminated the promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and L. (Viannia) braziliensis without causing toxic effects for J774 macrophages. Thus, the aim of the present work was to characterize the therapeutic effect of the triterpenic fraction in L. (L.) amazonensis-infected BALB/c mice. Oleanolic- and ursolic acid-containing fraction was extracted from B. uncinella leaves using organic solvents and chromatographic procedures. L. (L.) amazonensis-infected BALB/c mice were treated intraperitoneally with triterpenic fraction during five consecutive days with 1.0 and 5.0 mg/kg of triterpenic fraction, or with 10.0 mg/kg of amphotericin B drug. Groups of mice treated with the triterpenic fraction, presented with decreased lesion size and low parasitism of the skin-both of which were associated with high amounts of interleukin-12 and interferon gamma. The curative effect of this fraction was similar to amphotericin B-treated mice; however, the final dose, required to eliminate amastigotes, was lesser than amphotericin B. Moreover, triterpenic fraction did not cause microscopic alterations in liver, spleen, heart, lung, and kidney of experimental groups. This work suggests that this fraction possesses compounds that are characterized by leishmanicidal and immunomodulatory activities. From this perspective, the triterpenic fraction can be explored as a new therapeutic agent for use against American Tegumentar Leishmaniasis.
目前用于治疗利什曼病的药物对患者有许多副作用;此外,有些病例对治疗有抗药性。因此,寻找新的杀利什曼原虫化合物是必不可少的。最近,研究表明,从 Baccharis uncinella 叶中提取的含有齐墩果酸和熊果酸的部分消除了 Leishmania (Leishmania) amazonensis 和 L. (Viannia) braziliensis 的前鞭毛体和无鞭毛体形式,而对 J774 巨噬细胞没有毒性作用。因此,本工作的目的是表征齐墩果酸部分在感染 L. (L.) amazonensis 的 BALB/c 小鼠中的治疗效果。从 Baccharis uncinella 叶中用有机溶剂和色谱程序提取齐墩果酸和熊果酸部分。用齐墩果酸部分对感染 L. (L.) amazonensis 的 BALB/c 小鼠进行腹腔内治疗,连续 5 天用 1.0 和 5.0 mg/kg 的齐墩果酸部分或用 10.0 mg/kg 的两性霉素 B 药物进行治疗。用齐墩果酸部分治疗的小鼠组,皮肤病变面积减小,寄生虫数量减少-这两者都与高水平的白细胞介素-12 和干扰素 γ有关。该部分的疗效与两性霉素 B 治疗的小鼠相似;然而,消除无鞭毛体所需的最终剂量小于两性霉素 B。此外,齐墩果酸部分不会引起实验组肝、脾、心、肺和肾的显微镜改变。这项工作表明,该部分具有杀利什曼原虫和免疫调节活性的化合物。从这个角度来看,齐墩果酸部分可以作为一种新的治疗剂来对抗美洲皮肤利什曼病。