In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa

Ana Carolina Av Kayano,Fabio Tm Costa,Wanessa C Souza-Neiras,João Carlos P Mello,Fernanda G Bueno,Elaine C Cabral,Stefanie Cp Lopes,Lucy M Yamauchi,Marcos N Eberlin,Mary A Foglio

doi:10.1186/1475-2875-10-112

Abstract

BackgroundTo overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity.MethodsCrude extract (CE) was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7) and -resistant (S20) strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted.ResultsAt non-toxic concentrations, the 100% ethanolic (F4) and 50% methanolic (F5) fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153.ConclusionsThe findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.

Highlights

To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials
At 100 μg/mL the F4 and the F7 fractions did not significantly reduce cell growth compared to the control
To determine if this low toxicity could be extant to non-infected erythrocytes (niE), the red blood cell density (RBCD) percentage of plant crude extract (CE) and fractions relative to the control was determined at concentrations varying from 0.19 to 25 μg/mL

Summary

Introduction

To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named “sibipiruna”, originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. Quinine was the first drug successfully used to treat malaria This alkaloid has a high level of toxicity and a short pharmacological half-life, which limit its use [2,3]. Caesalpinia pluviosa, commonly named “sibipiruna”, is a leguminous of the Fabaceae family that is originated from Brazil. This genus is a rich source of furanoditerpenoids and has demonstrated multiple therapeutic properties, including antiviral [12,13,14], antimicrobial [15,16], anti-inflammatory [17,18], and antioxidant [19,20] activities. The in vitro anti-malarial activities of C. pluviosa extracts and the fractions effective against CQ- resistant and -sensitive P. falciparum strains, alone or in combination with artesunate, have been evaluated and identified

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