Quercetin promotes antipromastigote effect by increasing the ROS production and anti-amastigote by upregulating Nrf2/HO-1 expression, affecting iron availability.

American cutaneous leishmaniasis is a zoonotic disease caused by protozoans of the genus Leishmania. The treatment of cutaneous leishmaniasis is unsatisfactory, thus, much research effort has been focused on investigating new compounds with lower collateral effects to the patients and derived from low-cost sources, such as natural products. In the present study, we evaluated the in vitro directly effect of the flavonoid quercetin against Leishmania (Viannia) braziliensis. Quercetin inhibited the proliferation of promastigote forms at all tested concentrations, these effect were due to increasing the reactive oxygen species (ROS) production, phosphatidylserine exposure and loss of plasma membrane integrity. Moreover, quercetin reduced the number of parasites in L. braziliensis-infected macrophages, reducing the levels of TNF-α and increasing IL-10 synthesis without modulate nitric oxide (NO) production. In addition, quercetin upregulated Nrf2/HO-1 expression and modulated the labile iron pool in infected macrophages, culminating in a depletion of available iron for L. braziliensis replication.