Antileishmanial activity of verbascoside: Selective arginase inhibition of intracellular amastigotes of Leishmania (Leishmania) amazonensis with resistance induced by LPS plus IFN-γ

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• 作者：Claudia do Carmo Maquiaveli^a ; ^{cmaquiaveli40@gmail.com} ; ^{cmaquiaveli@usp.br} ; Arina Lá ; zaro Rochetti^b ; Heidge Fukumasu^b ; Paulo Cezar Vieira^a ; Edson Roberto da Silva^b
• 关键词：Leishmania amazonensis ; Polyamines ; Arginase ; Nitric oxide ; Verbascoside
• 刊名：Biochemical Pharmacology
• 出版年：2017
• 出版时间：1 March 2017
• 年：2017
• 卷：127
• 期：Complete
• 页码：28-33
• 全文大小：812 K
• 卷排序：127

文摘

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 (EC50 = 32 μM) 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.