Departamento de Biologia Animal - Parasitologia, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, São Paulo, Brazil.
Divisão de Química Orgânica e Farmacêutica, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Universidade Estadual de Campinas, UNICAMP, Paulínia, São Paulo, Brazil.
Parasitol Res. 2021 Feb;120(2):705-713. doi: 10.1007/s00436-020-07019-1. Epub 2021 Jan 8.
Leishmaniasis is one of the most neglected parasitic infections of the world and current therapeutic options show several limitations. In the search for more effective drugs, plant compounds represent a powerful natural source. Artemisinin is a sesquiterpene lactone extracted from Artemisia annua L. leaves, from which dihydroartemisinin (DQHS) and artesunic acid (AA)/artesunate are examples of active derivatives. These lactones have been applied successfully on malaria therapy for decades. Herein, we investigated the sensitivity of Leishmania braziliensis, one of the most prevalent Leishmania species that cause cutaneous manifestations in the New World, to artemisinin, DQHS, and AA. L. braziliensis promastigotes and the stage that is targeted for therapy, intracelular amastigotes, were more sensitive to DQHS, showing EC of 62.3 ± 1.8 and 8.9 ± 0.9 μM, respectively. Cytotoxicity assays showed that 50% of bone marrow-derived macrophages cultures were inhibited with 292.8 ± 3.8 μM of artemisinin, 236.2 ± 4.0 μM of DQHS, and 396.8 ± 6.7 μM of AA. The control of intracellular infection may not be essentially attributed to the production of nitric oxide. However, direct effects on mitochondrial bioenergetics and HO production appear to be associated with the leishmanicidal effect of DQHS. Our data provide support for further studies of artemisinin and derivatives repositioning for experimental leishmaniasis.
利什曼病是世界上最被忽视的寄生虫感染之一，目前的治疗选择存在多种局限性。在寻找更有效的药物时，植物化合物是一种强大的天然来源。青蒿素是从青蒿叶中提取的一种倍半萜内酯，二氢青蒿素（DQHS）和青蒿琥酯（AA）/青蒿琥酯是其活性衍生物的例子。这些内酯已成功应用于疟疾治疗数十年。在此，我们研究了巴西利什曼原虫对青蒿素、DQHS 和 AA 的敏感性，巴西利什曼原虫是引起新世界皮肤病变的最常见利什曼原虫之一。巴西利什曼原虫前鞭毛体和针对治疗的阶段，即细胞内无鞭毛体，对 DQHS 更为敏感，EC 分别为 62.3±1.8 和 8.9±0.9 μM。细胞毒性试验表明，骨髓来源的巨噬细胞培养物的 50%被青蒿素抑制，浓度为 292.8±3.8 μM，DQHS 为 236.2±4.0 μM，AA 为 396.8±6.7 μM。细胞内感染的控制可能不是本质上归因于一氧化氮的产生。然而，对线粒体生物能学和 HO 产生的直接影响似乎与 DQHS 的杀利什曼原虫作用有关。我们的数据为进一步研究青蒿素及其衍生物在实验性利什曼病中的重新定位提供了支持。
