Abstract

Leishmaniasis and schistosomiasis are neglected tropical diseases (NTDs) infecting the world’s poorest populations. Effectiveness of the current antileishmanial and antischistosomal therapies are significantly declining, which calls for an urgent need of new effective and safe drugs. In Ethiopia fresh leaves of Ranunculus multifidus Forsk. are traditionally used for the treatment of various ailments including leishmaniasis and eradication of intestinal worms. In the current study, anemonin isolated from the fresh leaves of R. multifidus was assessed for its in vitro antileishmanial and antischistosomal activities. Anemonin was isolated from the hydro-distilled extract of the leaves of R. multifidus. Antileishmanial activity was assessed on clinical isolates of the promastigote and amastigote forms of Leishmania aethiopica and L. donovani clinical isolates. Resazurin reduction assay was used to determine antipromastigote activity, while macrophages were employed for antiamastigote and cytotoxicity assays. Antischistosomal assays were performed against adult Schistosoma mansoni and newly transformed schistosomules (NTS). Anemonin displayed significant antileishmanial activity with IC50 values of 1.33 nM and 1.58 nM against promastigotes and 1.24 nM and 1.91 nM against amastigotes of L. aethiopica and L. donovani, respectively. It also showed moderate activity against adult S. mansoni and NTS (49% activity against adult S. mansoni at 10 µM and 41% activity against NTS at 1 µM). The results obtained in this investigation indicate that anemonin has the potential to be used as a template for designing novel antileishmanial and antischistosomal pharmacophores.

Highlights

  • Leishmaniasis is a neglected tropical disease (NTD) infecting the world’s poorest populations

  • Fresh leaves of R. multifidus were used to prepare extracts in order to mimic the form in which the plant is used in traditional medicine

  • Antileishmanial assay was done on L. aethiopica and L. donovani, which are the major causes of cutaneous leishmaniasis and visceral leishmaniasis in Ethiopia, respectively [3,6,24]

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Summary

Introduction

Leishmaniasis is a neglected tropical disease (NTD) infecting the world’s poorest populations. The effectiveness of currently available drugs is significantly declining due to increased drug resistance, emerging cross resistance, requirements for parenteral administration and/or length of treatment, lack of new drugs with novel mechanisms of action and unavailability of effective vaccine [8,9,10,11,12]. This has highlighted the urgent need to explore traditionally used medicinal plants as a source of new antileishmanial drugs in order to minimize the debilitating impact of the disease

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