In vitro activity of the hydroethanolic extract and biflavonoids isolated from Selaginella sellowii on Leishmania (Leishmania) amazonensis.

Yasmin Silva Rizk,Maria Carolina Silva Marques,Marillin De Castro Cunha,Patrik Oening Rodrigues,Carla Cardozo Pinto De Arruda,Alice Fischer,Maria De Fátima Cepa Matos,Mônica Cristina Toffoli Kadri,Carlos Alexandre Carollo

doi:10.1590/0074-0276140312

Yasmin Silva Rizk, Maria Carolina Silva Marques + Show 7 more

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https://doi.org/10.1590/0074-0276140312

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Abstract

This study is the first phytochemical investigation of Selaginella sellowii and demonstrates the antileishmanial activity of the hydroethanolic extract from this plant (SSHE), as well as of the biflavonoids amentoflavone and robustaflavone, isolated from this species. The effects of these substances were evaluated on intracellular amastigotes of Leishmania (Leishmania) amazonensis, an aetiological agent of American cutaneous leishmaniasis. SSHE was highly active against intracellular amastigotes [the half maximum inhibitory concentration (IC50) = 20.2 µg/mL]. Fractionation of the extract led to the isolation of the two bioflavonoids with the highest activity: amentoflavone, which was about 200 times more active (IC50 = 0.1 μg/mL) and less cytotoxic than SSHE (IC50 = 2.2 and 3 μg/mL, respectively on NIH/3T3 and J774.A1 cells), with a high selectivity index (SI) (22 and 30), robustaflavone, which was also active against L. amazonensis (IC50 = 2.8 µg/mL), but more cytotoxic, with IC50 = 25.5 µg/mL (SI = 9.1) on NIH/3T3 cells and IC50 = 3.1 µg/mL (SI = 1.1) on J774.A1 cells. The production of nitric oxide (NO) was lower in cells treated with amentoflavone (suggesting that NO does not contribute to the leishmanicidal mechanism in this case), while NO release was higher after treatment with robustaflavone. S. sellowii may be a potential source of biflavonoids that could provide promising compounds for the treatment of cutaneous leishmaniasis.

Highlights

Leishmaniases are a group of infectious diseases caused by protozoan parasites of the genus Leishmania transmitted by the bite of sandflies
The aim of this study was to evaluate the activity of the hydroethanolic extract and of the biflavonoids isolated from S. sellowii on intracellular amastigotes of L. amazonensis
The plant was identified by Dr Arnildo Pott of the Botany Laboratory, Centre for Biological and Health Sciences (CCBS) of the Federal University of Mato Grosso do Sul (UFMS) and voucher material was deposited in the CG/MS Herbarium under registration 27218

Summary

Introduction

Leishmaniases are a group of infectious diseases caused by protozoan parasites of the genus Leishmania transmitted by the bite of sandflies. The cutaneous diffuse manifestation is associated, in Brazil, with Leishmania (Leishmania) amazonensis, a form in which anergic individuals develop numerous parasite-rich nodules. Amphotericin B and pentamidine are used as alternative therapeutic options All of these drugs have important limitations as to the safety of use, presenting relevant toxicity and a high frequency of side effects (Croft & Coombs 2003, Sundar & Chatterjee 2006, Oliveira et al.2011). The antimonials require long-term use and parenteral administration, resulting in treatment failure and resistant parasites (Sundar et al 2000), facts which reinforce the urgent need for new therapeutic agents. Studies have explored the biological activities of compounds present in their species, including anticancer, antifungal (Mishra et al 2011) and antiviral activities (Ma et al 2001). The aim of this study was to evaluate the activity of the hydroethanolic extract and of the biflavonoids (amentoflavone and robustaflavone) isolated from S. sellowii on intracellular amastigotes of L. amazonensis

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