Wittm. fruit extracts as inhibitors: and approaches.

Leishmaniasis is a group of neglected diseases caused by parasites of the genus. The treatment of Leishmaniasis represents a great challenge, because the available drugs present high toxicity and none of them is fully effective. is a botanical genus rich in phenolic compounds, which leaves extracts have already been described by its antileishmanial action. Thus, we investigated the effect of pulp and peel extracts of the fruit on promastigote and amastigote forms of . Both extracts had antipromastigote effect after 24, 48, and 72 h, and this effect was by apoptosis-like process induction, with reactive oxygen species (ROS) production, damage to the mitochondria and plasma membrane, and phosphatidylserine exposure. Knowing that the fruit extracts did not alter the viability of macrophages, we observed that the treatment reduced the infection of these cells. Thereafter, in the infection context, the extracts showed antioxidant proprieties, by reducing NO, ROS, and MDA levels. Besides, both peel and pulp extracts up-regulated Nrf2/HO-1/Ferritin expression and increase the total iron-bound in infected macrophages, which culminates in a depletion of available iron for replication. , the molecular modeling experiments showed that the three flavonoids presented in the extracts can act as synergistic inhibitors of proteins, and compete for the active site. Also, there is a preference for rutin at the active site due to its greater interaction binding strength.Communicated by Ramaswamy H. Sarma.