The anti-leishmanial effect of Kalanchoe is mediated by nitric oxide intermediates

We have previously shown that oral treatment with the leaf extract of the p lant Kalanchoe pinnata (Kp) significantly decreases the lesion size and the parasite load in BALB/c mice infected with Leishmania amazonensis. Here we report on the mode of action of Kp, particularly on the induction of nitri c oxide (NO) production by macrophages. We observed that Kp has no direct i nhibitory activity on extracellular promastigotes, but effectively decrease s the intracellular amastigote growth in a dose-related fashion. A 58 % red uction in amastigote growth induced by 500 mu g/ml Kp was associated with a 6-fold increase in the production of NO by the macrophages. IFN-gamma syne rgistically enhanced the NO-stimulating effect of Kp in culture. Go-treatme nt with the inducible NO synthase enzyme inhibitor L-N-G-monomethyl-arginin e abolished the antileishmanial effect of Kp in vitro and in L. amazonensis -infected BALB/c mice. These results indicate that the protective effect of Kp in leishmaniasis may not be due to a direct effect on the parasite itse lf but rather to activation of the reactive nitrogen intermediates pathway of macrophages.