Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceum

Malaria Journal

Research

Arildo JB de Oliveira¹  Talita PC Chierrito¹  Regina AC Gonçalves¹  Antoniana U Krettli²  Anna CC Aguiar²  Isabel M de Andrade³  Isabela P Ceravolo³ 

[1] Centro de Ciências da Saúde, de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Avenida Colombo, 5790, CEP 87.020-900, Maringá, PR, Brazil;Faculdade de Medicina, Programa de Pós-Graduação em Medicina Molecular, Universidade Federal de Minas Gerais, Prof. Alfredo Balena, 190, 30130-100, Belo Horizonte, MG, Brazil;Laboratório de Malária, Centro de Pesquisas René Rachou, FIOCRUZ, Av. Augusto de Lima 1715, 30190-002, Belo Horizonte, MG, Brazil;Laboratório de Malária, Centro de Pesquisas René Rachou, FIOCRUZ, Av. Augusto de Lima 1715, 30190-002, Belo Horizonte, MG, Brazil;

关键词: Aspidosperma olivaceum;    Indole alkaloids;    Aspidoscarpine;    Medicinal plants;    Antimalarial;    Plasmodium falciparum;   

DOI  :  10.1186/1475-2875-13-142

 received in 2013-10-17, accepted in 2014-01-21,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundSeveral species of Aspidosperma (Apocynaceae) are used as treatments for human diseases in the tropics. Aspidosperma olivaceum, which is used to treat fevers in some regions of Brazil, contains the monoterpenoid indole alkaloids (MIAs) aspidoscarpine, uleine, apparicine, and N-methyl-tetrahydrolivacine. Using bio-guided fractionation and cytotoxicity testing in a human hepatoma cell line, several plant fractions and compounds purified from the bark and leaves of the plant were characterized for specific therapeutic activity (and selectivity index, SI) in vitro against the blood forms of Plasmodium falciparum.MethodsThe activity of A. olivaceum extracts, fractions, and isolated compounds was evaluated against chloroquine (CQ)-resistant P. falciparum blood parasites by in vitro testing with radiolabelled [3H]-hypoxanthine and a monoclonal anti-histidine-rich protein (HRPII) antibody. The cytotoxicity of these fractions and compounds was evaluated in a human hepatoma cell line using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, and the SI was calculated as the ratio between the toxicity and activity. Two leaf fractions were tested in mice with Plasmodium berghei.ResultsAll six fractions from the bark and leaf extracts were active in vitro at low doses (IC50 < 5.0 μg/mL) using the anti-HRPII test, and only two (the neutral and basic bark fractions) were toxic to a human cell line (HepG2). The most promising fractions were the crude leaf extract and its basic residue, which had SIs above 50. Among the four pure compounds evaluated, aspidoscarpine in the bark and leaf extracts showed the highest SI at 56; this compound, therefore, represents a possible anti-malarial drug that requires further study. The acidic leaf fraction administered by gavage to mice with blood-induced malaria was also active.ConclusionUsing a bio-monitoring approach, it was possible to attribute the anti-P. falciparum activity of A. olivaceum to aspidoscarpine and, to a lesser extent, N-methyl-tetrahydrolivacine; other isolated MIA molecules were active but had lower SIs due to their higher toxicities. These results stood in contrast to previous work in which the anti-malarial activity of other Aspidosperma species was attributed to uleine.

【 授权许可】

Unknown   
© Chierrito et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.