Chemosensitizing action of cepharanthine against drug-resistant human malaria, Plasmodium falciparum.

J Ethnopharmacol

Program for Collaborative Research in the Pharmaceutical Sciences (M/C 877), College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA.

Published: April 2005

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.

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http://dx.doi.org/10.1016/j.jep.2005.01.015DOI Listing

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