The effect of the phytol-rich fraction from Lacistema pubescens against Leishmania amazonensis is mediated by mitochondrial dysfunction

Abstract Leishmaniasis is a complex disease caused by protozoan parasite Leishmania and the treatment remains a serious problem since the available drugs exhibited high toxicity and side effects. Plant-derived natural products are promising leads for the development of novel chemotherapeutics. In this work the phytol-rich hexane fraction (PRF) from the leaves of Lacistema pubescens was obtained and identified by GC–MS analysis. When assayed for antileishmanial effects, PRF was active against promastigote and amastigote forms of Leishmania amazonensis (IC 50 values of 44.0 and 25.8 μg/mL respectively). Furthermore, PRF did not show significant cytotoxicity on peritoneal macrophages being more destructive to the intracellular parasite than to mammalian cells. In addition, possible targets of PRF were investigated against L. amazonensis promastigotes. The results showed that PRF exerted its antipromastigote activity by marked depolarization of the mitochondrial membrane potential followed by the increase of ROS levels in L. amazonensis promastigotes. During these events, no rupture of the cell membrane integrity was observed. Our results indicated that PRF was effective and selective against L. amazonensis, and that this effect was mainly mediated by mitochondrial dysfunction associated to ROS production.