In vitro antiplasmodial activity of cepharanthine

Malaria Journal

Research

Aurélie Pascual¹  Christelle Travaille²  Nicolas Taudon³  Charles Chapus³  Daniel Parzy⁴  Jérôme Desplans⁴  Camille Desgrouas⁴  Evelyne Ollivier⁵  Béatrice Baghdikian⁵ 

[1] Département d’Infectiologie de Terrain, Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France;Trypanosome Cell Biology Unit, CNRS URA2581 and Parasitology Department, Institut Pasteur 25 rue du Docteur Roux, 75015, Paris, France;UMR-MD3, Institut de recherche biomédicale des armées, BP73 91223, Brétigny-sur-Orge, France;UMR-MD3, Institut de recherche biomédicale des armées, Faculté de Pharmacie, Aix-Marseille Université, 27 Bd Jean Moulin CS30064 13385, Marseille cedex 5, Marseille, France;UMR-MD3, Laboratoire de Pharmacognosie et Ethnopharmacologie, Faculté de Pharmacie, Aix-Marseille Université, 27 Bd Jean Moulin, 13385, Marseille Cedex 5, Marseille, France;

关键词: Stephania rotunda;    Cepharanthine;    Plasmodium falciparum;    Antiplasmodial activity;    Transcriptomic analysis;   

DOI  :  10.1186/1475-2875-13-327

 received in 2014-05-01, accepted in 2014-08-07,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundNew classes of anti-malarial drugs are needed to control the alarming Plasmodium falciparum resistance toward current anti-malarial therapy. The ethnopharmacological approach allows the discovery of original chemical structures from the vegetable biodiversity. Previous studies led to the selection of a bisbenzylisoquinoline, called cepharanthine and isolated from a Cambodian plant: Stephania rotunda. Cepharanthine could exert a mechanism of action different from commonly used drugs. Potential plasmodial targets are reported here.MethodsTo study the mechanism of action of cepharanthine, a combined approach using phenotypic and transcriptomic techniques was undertaken.ResultsCepharanthine blocked P. falciparum development in ring stage. On a culture of synchronized ring stage, the comparisons of expression profiles showed that the samples treated with 5 μM of cepharanthine (IC90) were significantly closer to the initial controls than to the final ones. After a two-way ANOVA (p-value < 0.05) on the microarray results, 1,141 probes among 9,722 presented a significant differential expression.A gene ontology analysis showed that the Maurer’s clefts seem particularly down-regulated by cepharanthine. The analysis of metabolic pathways showed an impact on cell-cell interactions (cytoadherence and rosetting), glycolysis and isoprenoid pathways. Organellar functions, more particularly constituted by apicoplast and mitochondrion, are targeted too.ConclusionThe blockage at the ring stage by cepharanthine is described for the first time. Transcriptomic approach confirmed that cepharanthine might have a potential innovative antiplasmodial mechanism of action. Thus, cepharanthine might play an ongoing role in the progress on anti-malarial drug discovery efforts.

【 授权许可】

Unknown   
© Desgrouas 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/4.0), 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.