Abstract
BackgroundStephania rotunda is used by traditional health practitioners in Southeast Asia to treat a wide range of diseases and particularly symptoms related to malaria. Cepharanthine (CEP) is an alkaloid isolated from this plant with potential innovative antiplasmodial activity. The analysis of interactions between antiplasmodial drugs is necessary to develop new drugs combinations to prevent de novo emergence of resistance. The objective of this study was to evaluate the anti-malarial activity of CEP in combination with usual anti-malarial compounds, both in vitro and in vivo.MethodsA fixed ratio method using the isotopic micro test was performed on the chloroquine-resistant plasmodial strain W2 to build isobolograms from eight CEP-based combinations with standard anti-malarial drugs. The efficacy of two combinations was then evaluated in the BALB/c mouse infected with Plasmodium berghei ANKA strain.ResultsIn vitro, efficiency gains were observed when CEP was combined with chloroquine (CQ), lumefantrine (LUM), atovaquone (ATO), piperaquine (PPQ) and particularly monodesethylamodiaquine (MdAQ), whereas an antagonistic interaction was observed with dihydroartemisinin (DHA) and mefloquine (MQ). In vivo, the combination of CEP with CQ or amodiaquine (AQ) improved significantly the survival of mice and extended the delay for parasitic recrudescence.ConclusionAll these observations suggest that CEP could be an interesting lead compound in the development of a combination therapy against malaria.
Highlights
Stephania rotunda is used by traditional health practitioners in Southeast Asia to treat a wide range of diseases and symptoms related to malaria
The spread of resistance of Plasmodium falciparum to most anti-malarial drugs is an important difficulty in the treatment of this disease
The use of artemisinin combination therapy (ACT) as first-line treatment of uncomplicated malaria caused by P. falciparum was officially recommended by the World Health Organization (WHO) in 2006 [2]
Summary
Stephania rotunda is used by traditional health practitioners in Southeast Asia to treat a wide range of diseases and symptoms related to malaria. The emergence of resistance to artemisinin derivatives was recently reported from the Southeast Asia [3,4]. In this context, new anti-malarial compounds are urgently needed to treat this major. New anti-malarial compounds are urgently needed to treat this major In this context, four surveys were performed between 2002 and 2004 on plants used in Cambodian traditional medicine. Stephania rotunda (Menispermaceae) is a plant growing on calcareous cliffs and rainforest areas [7], used in traditional medicine to treat malaria and fevers [8]
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