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Background  Leishmaniasis, a parasitic disease caused by protozoa of the genus  Leishmania , affects more than 12 million people worldwide. Quercetin has generated considerable interest as a pharmaceutical compound with a wide range of therapeutic activities. One such activity is exhibited against the bloodstream parasite  Trypanosoma brucei  and amastigotes of  Leishmania donovani . However, the mechanism of protozoan action of quercetin has not been studied.    Methodology/Principal Findings  In the present study, we report here the mechanism for the antileishmanial activity of quercetin against  Leishmania amazonensis  promastigotes. Quercetin inhibited  L. amazonensis  promastigote growth in a dose- and time- dependent manner beginning at 48 hours of treatment and with maximum growth inhibition observed at 96 hours. The IC 50  for quercetin at 48 hours was 31.4 µM. Quercetin increased ROS generation in a dose-dependent manner after 48 hours of treatment. The antioxidant GSH and NAC each significantly reduced quercetin-induced cell death. In addition, quercetin caused mitochondrial dysfunction due to collapse of mitochondrial membrane potential.    Conclusions/Significance  The effects of several drugs that interfere directly with mitochondrial physiology in parasites such as  Leishmania  have been described. The unique mitochondrial features of  Leishmania  make this organelle an ideal drug target while minimizing toxicity. Quercetin has been described as a pro-oxidant, generating ROS which are responsible for cell death in some cancer cells. Mitochondrial membrane potential loss can be brought about by ROS added directly  in vitro  or induced by chemical agents. Taken together, our results demonstrate that quercetin eventually exerts its antileishmanial effect on  L. amazonensis  promastigotes due to the generation of ROS and disrupted parasite mitochondrial function.

Reactive Oxygen Species Production and Mitochondrial Dysfunction Contribute to Quercetin Induced Death in Leishmania amazonensis