Antimalarial Activity of Compounds and Mixed Fractions of Cecropia pachystachya

Extracts from Cecropia pachystachya (Cecropiaceae), a medicinal plant used in Brazil, were tested for their antimalarial activity against Plasmodium falciparum and/or Plasmodium berghei in mice. The ethanol extracts of wood, root, and leaves reduce parasitemia of malaria-infected mice from 35-66% in relation to nontreated control mice. The plant roots extracts, with stronger activity, were further analyzed and provided subfractions also active in vivo from which two compounds were isolated and chemically characterized as beta-sitosterol and tormentic acid. Although both compounds were active in mice malaria, only the tormentic acid inhibited P. falciparum chloroquine-resistant parasites (W2) growth in cultures, reducing parasitemia dose-responsively (IC50 = 11-15 mu g/ml). The antimalarial activity of the plant extracts kept refrigerated 7 years after the initial isolation, when tested in parallel with new extracts freshly isolated from plants collected at the same geographical site, was similar, confirming the superiority of the plant roots and the stability of the active extracts. In these experiments, inhibition of parasite growth was measured by hypoxanthine incorporation and by immunoenzymatic assay (ELISA) with monoclonal antibodies against the P. falciparum histidine-rich protein (HRP2), expressed by the erythrocytic forms. The plant roots showed the lowest IC50 value and displayed the lowest toxicity, thus having the best therapeutic index. C. pachystachya species is therefore a good candidate for phytotherapeutic use against malaria. Further studies are ongoing to isolate new active compounds through bioguided fractionation analysis, in an effort to develop a new drug prototype against P. falciparum erythrocytic parasites. Drug Dev Res 71:82-91, 2010. (C) 2009 Wiley-Liss, Inc.