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526731 
Journal Article 
Chemosensitizing action of cepharanthine against drug-resistant human malaria, Plasmodium falciparum 
Tamez, PA; Lantvit, D; Lim, E; Pezzuto, JM 
2005 
Yes 
Journal of Ethnopharmacology
ISSN: 0378-8741 
98 
1-2 
137-142 
English 
We have established a system of in vitro and in vivo assays to prioritize plant extracts that can serve as a source of drug candidates for the treatment of malaria, an infectious disease that affects nearly 40% of the world's population. In the present study, we have investigated the biological potential of one such plant-derived drug lead, cepharanthine. In vitro growth inhibition studies indicated this compound possessed good antiplasmodial activity without mediating a cytotoxic response. Based on this selectivity, evaluations were performed with an in vivo mouse model. Moderate activity was observed, inhibiting parasite growth by 46% at a dose of 100 mg/kg body weight (BW). We further assessed the ability of cepharanthine to serve as a drug in combination with a standard antimalarial regimen. Like chloroquine, cepharanthine inhibited the trophozoite stage of parasite growth. Isobolographic analyses revealed synergism with chloroquine, but only with the drug-resistant malaria clone, and single-dose drug-interaction studies demonstrated that cepharanthine lowered the half-maximal inhibitory concentration of chloroquine from 148.5 to 37.8 nM. In summary, since activity in the mouse model was only moderate, cepharanthine may be of greater value as a modulator of resistance, capable of prolonging the clinical utility of chloroquine. (c) 2005 Elsevier Ireland Ltd. All rights reserved. 
Plasmodium falciparum; Plasmodium berghei; in vitro; in vivo; cepharanthine; bisbenzylisoquinoline alkaloid; bisbenzylisoquinoline alkaloids; rhaphidophora-decursiva; multidrug-resistance; cancer-cells; agents; antimalarials; plants