title: Antileishmanial activity of verbascoside: Selective arginase inhibition of intracellular amastigotes of Leishmania (Leishmania) amazonensis with resistance induced by LPS plus IFN-γ.
abstract: 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=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.
authors.affiliation: Department of Chemistry, Universidade Federal de São Carlos, Rod. Washington Luís, Km 235, 13565-905 São Carlos, SP, Brazil. Electronic address: cmaquiaveli40@gmail.com.
authors.forename: Claudia do Carmo
authors.initials: CDC
authors.lastname: Maquiaveli
authors.affiliation: Department of Veterinary Medicine, Universidade de São Paulo, Avenida Duque de Caxias Norte, 225, 13635-900 Pirassununga, SP, Brazil.
authors.forename: Arina Lázaro
authors.initials: AL
authors.lastname: Rochetti
authors.affiliation: Department of Veterinary Medicine, Universidade de São Paulo, Avenida Duque de Caxias Norte, 225, 13635-900 Pirassununga, SP, Brazil.
authors.forename: Heidge
authors.initials: H
authors.lastname: Fukumasu
authors.affiliation: Department of Chemistry, Universidade Federal de São Carlos, Rod. Washington Luís, Km 235, 13565-905 São Carlos, SP, Brazil.
authors.forename: Paulo Cezar
authors.initials: PC
authors.lastname: Vieira
authors.affiliation: Department of Veterinary Medicine, Universidade de São Paulo, Avenida Duque de Caxias Norte, 225, 13635-900 Pirassununga, SP, Brazil.
authors.forename: Edson Roberto
authors.initials: ER
authors.lastname: da Silva
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001119:Arginase / Q000037:antagonists & inhibitors*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004351:Drug Resistance; D005960:Glucosides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects* / Q000201:enzymology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D059808:Polyphenols
chemical_list: D000981:Antiprotozoal Agents; D001119:Arginase; D016207:Cytokines; D005960:Glucosides; D007371:Interferon-gamma; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010636:Phenols; D015800:Protozoan Proteins; C058956:acteoside; D059808:Polyphenols
keywords: Arginase; Leishmania amazonensis; Nitric oxide; Polyamines; Verbascoside