Fractions of an antimalarial neem-leaf extract have activities superior to chloroquine, and are gametocytocidal

Abstract

The antimalarial activities of two fractions (IRDN-A and IRDN-B) of an extract from the leaves of the neem tree (Azadirachta indica) were compared with those of chloroquine, in in-vitro assays against Plasmodium falciparum. The asexual stages of a chloroquine-sensitive clone (ITG2F6) and a chloroquine-resistant isolate (W2) and the gametocytes of the NF 54 (BD-7) isolate of P. falciparum were used as the drug targets. Activity against the asexual stages was generally evaluated as the concentrations inhibiting the parasitaemias recorded in the control cultures, after an incubation of 48–72 h, by 50% (IC₅₀) or 100% (IC₁₀₀). For the ITG2F6 strain, the IC₅₀ and IC₁₀₀ (in μg/ml) were, respectively, 10⁻⁵ and 10⁻⁴ for IRDN-A, 10⁻³ and 10⁻² for IRDN-B, and 10⁻² and 1.0 for chloroquine. The corresponding values for the W2 strain were 10⁻⁵ and 1.0 for IRDN-A, and 10.0 and >100 for chloroquine (even at 100 μg/ml, chloroquine only inhibited the parasitaemia by 85%).

Each of the two neem-leaf fractions lysed 50% and 100% of developing gametocytes, at 10⁻³ and 1.0 μg/ml, respectively; and 50% and 100% of mature gametocytes at 10⁻³ and 10² μg/ml, respectively. If they are found safe and effective in vivo, the neem-leaf fractions may form the basis of new antimalarial drugs that not only cure chloroquine-sensitive and chloroquine-resistant malaria but also markedly reduce transmission.