Department of Chemistry, Universidade Federal de São Carlos, Rod. Washington Luís, Km 235, 13565-905 São Carlos, SP, Brazil.
Department of Veterinary Medicine, Universidade de São Paulo, Avenida Duque de Caxias Norte, 225, 13635-900 Pirassununga, SP, Brazil.
Biochem Pharmacol. 2017 Mar 1;127:28-33. doi: 10.1016/j.bcp.2016.12.018. Epub 2016 Dec 23.
Verbascoside is the main component of the traditional medicinal plants that were used against protozoa parasites that cause malaria and leishmaniasis. Previously, we have described verbascoside inhibition of Leishmania amazonensis arginase as well as its antileishmanial action against extracellular promastigotes. In this study, we have assessed arginase parasite inhibition in intracellular amastigotes. In addition, we verified whether verbascoside can influence the host defense against the parasite by measuring gene expression of cytokines IL-1b, IL-10, IL-18, TNF-α and murine macrophage arginase as well as nitric oxide synthase enzymes. Our results show that verbascoside acts on intracellular amastigotes of L. amazonensis (EC=32μM) by selectively inhibiting the parasite arginase. Verbascoside did not affect the expression of cytokines or enzymes by murine macrophages. However, verbascoside was active against L. (L.) amazonensis amastigotes that were resistant to treatment with LPS and IFN-γ. Verbascoside action on L. amazonensis can be associated with reduction of the protective oxidative mechanism of the parasite leading to impaired trypanothione synthesis that is induced by the parasite arginase inhibition.
毛蕊花糖苷是传统药用植物的主要成分，这些植物曾被用于治疗引起疟疾和利什曼病的原生动物寄生虫。此前，我们已经描述了毛蕊花糖苷对莱什曼原虫精氨酸酶的抑制作用及其对细胞外前鞭毛体的抗利什曼作用。在这项研究中，我们评估了毛蕊花糖苷对细胞内无鞭毛体寄生虫抑制作用。此外，我们还通过测量细胞因子 IL-1b、IL-10、IL-18、TNF-α 和鼠巨噬细胞精氨酸酶以及一氧化氮合酶的基因表达，来验证毛蕊花糖苷是否可以影响宿主对寄生虫的防御。我们的结果表明，毛蕊花糖苷通过选择性抑制寄生虫精氨酸酶来作用于 L. amazonensis 的细胞内无鞭毛体（EC=32μM）。毛蕊花糖苷不影响鼠巨噬细胞中细胞因子或酶的表达。然而，毛蕊花糖苷对 LPS 和 IFN-γ 处理耐药的 L.（L.）amazonensis 无鞭毛体具有活性。毛蕊花糖苷对 L. amazonensis 的作用可能与降低寄生虫的保护性氧化机制有关，这导致寄生虫精氨酸酶抑制诱导的三肽硫醇合成受损。
