The development of resistance by Plasmodium falciparum to conventional drugs poses a threat to malaria control. There is therefore a need to find new, effective, and affordable remedies for malaria, including those derived from plants. This study demonstrates that crude, reverse-phase high-pressure liquid chromatography (RP-HPLC)-semipurified, and RP-HPLC-purified root extracts of Fagara zanthoxyloides inhibit the growth of P. falciparum in vitro, with 50% inhibitory concentrations (IC 50 s) of 4.90, 1.00, and 0.13 g/ml, respectively. Roots of F. zanthoxyloides, known as chewing sticks, are widely used for tooth cleaning in West Africa. Microscopic examination of Giemsa-stained slides showed a virtual absence of schizonts in ring-stage synchronized cultures treated with crude extracts at concentrations of 30 to 60 g/ml during 36 to 48 h of incubation. These observations suggest that the active constituent in the extract may be cytotoxic for P. falciparum trophozoites, thereby inhibiting their development to the schizont stage. A pure bioreactive fraction was subsequently obtained from the chromatographic separations. When this fraction was mixed with pure fagaronine, the mixture coeluted as a single peak on the analytical RP-HPLC column, suggesting that fagaronine may be the active antimalarial constituent of Fagara root extracts. Additional experiments showed that fagaronine also inhibited P. falciparum growth, with an IC 50 of 0.018 g/ml. The results of this study suggest that the antimalarial activity of fagaronine deserves further investigation.Malaria represents a major cause of childhood mortality and adult morbidity in many parts of the world. Recent estimates indicate that 300 to 500 million clinical episodes of malaria occur worldwide every year (5, 25). Severe anemia, cerebral malaria, respiratory distress syndrome, and low birth weight are among the complications that contribute to the 25 to 30% malaria-attributable deaths for children under 5 years of age in Africa (13). Studies have also shown that about one million children may die each year from malaria-associated anemia alone and that up to 600,000 children succumb to cerebral malaria annually, with an estimated case fatality rate of about 20% (6, 7, 13). Low birth weight, resulting from maternal placental malaria infections, also contributes about 400,000 deaths annually to malaria mortality (19).Efforts to reduce the high malaria mortality and morbidity rates have been hampered by the development of resistance, particularly by Plasmodium falciparum, to long-standing inexpensive conventional drugs, such as chloroquine (24). It is noteworthy that quinine and qinghaosu, which are drugs derived from indigenous plants in South America and China, respectively, are relatively unlikely to induce resistance on the part of the malaria parasite. While the major proportion of malaria-attributable deaths occurs in sub-Saharan Africa, neither of these plant-derived drugs are indigenous to the region. We present here the results of a study that examined the a...
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