Aspidosperma (Apocynaceae) plant cytotoxicity and activity towards malaria parasites. Part I: Aspidosperma nitidum (Benth) used as a remedy to treat fever and malaria in the Amazon

Julia Penna Coutinho,Maria De Meneses Pereira,Tania Maria Almeida Alves,Anna Caroline Campos Aguiar,Antoniana Ursine Krettli,Antonio Euzebio Goulart Santana,Maria Gabrielle Lima Rocha,Joaquim Corsino Lima,Pierre Alexandre Dos Santos,Carlos Leomar Zani

doi:10.1590/0074-0276130246

Abstract

Infusions of Aspidosperma nitidum (Apocynaceae) wood bark are used to treat fever and malaria in the Amazon Region. Several species of this family are known to possess indole alkaloids and other classes of secondary metabolites, whereas terpenoids, an inositol and the indole alkaloids harmane-3 acid and braznitidumine have been described in A. nitidum . In the present study, extracts from the wood bark, leaves and branches of this species were prepared for assays against malaria parasites and cytotoxicity testing using human hepatoma and normal monkey kidney cells. The wood bark extracts were active against Plasmodium falciparum and showed a low cytotoxicity in vitro, whereas the leaf and branch extracts and the pure alkaloid braznitidumine were inactive. A crude methanol extract was subjected to acid-base fractionation aimed at obtaining alkaloid-rich fractions, which were active at low concentrations against P. falciparum and in mice infected with and sensitive Plasmodium berghei parasites. Our data validate the antimalarial usefulness of A. nitidum wood bark, a remedy that can most likely help to control malaria. However, the molecules responsible for this antimalarial activity have not yet been identified. Considering their high selectivity index, the alkaloid-rich fractions from the plant bark might be useful in the development of new antimalarials.

Highlights

Infusions of Aspidosperma nitidum (Apocynaceae) wood bark are used to treat fever and malaria in the Amazon Region
Extracts from the wood bark, leaves and branches were prepared and evaluated in biological assays with P. falciparum and mice infected with P. berghei in addition to assays to evaluate cytotoxicity
These are the same extracts and fractions used in a previous chemical investigation that resulted in the identification of several compounds, including harman-3-carboxylic acid and braznitidumine (Meneses-Pereira et al 2006) which was inactive against P. falciparum in vitro

Summary

Introduction

Infusions of Aspidosperma nitidum (Apocynaceae) wood bark are used to treat fever and malaria in the Amazon Region. Medicinal plants afforded the discovery in the XIX century of the first remedies from the bark of Cinchona spp, later shown to be rich in alkaloids, quinine, the basis of such aminoquinoline synthetic drugs as chloroquine, amodiaquine and mefloquine. Another class of important antimalarials is based on artemisinin, a compound found in Artemisia annua, a medicinal plant native to China (WHO 2006). Other examples include Aspidosperma nitidum (Benth) and Aspidosperma excelsum (Muell Arg), widely cited as remedies in the treatment of malaria, among other species of the genus Aspidosperma (Apocynaceae), which comprises various medicinal species used as bark infusions against malaria and other diseases (Brandão et al 1992, Weniger et al 2001, Ferreira et al 2004, Tanaka et al 2007, de Oliveira et al 2011)

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