Ursolic acid promotes clearance of Trypanosoma cruzi amastigotes in the host cell

Trypanosoma cruzi is the etiological agent of Chagas disease, which is endemic in Latin America. Ursolic acid (UA) is a natural pentacyclic triterpene which has been shown to reduce the peak of parasitemia in T. cruzi infected mice. Due to UA was described as an inducer of autophagy and having into account that our previous work established the protective role of this process on in vivo infections, we decided to study the possible involvement of UA in the elimination of parasites in macrophages and cardiac cells. To test this, we infected cells with T. cruzi for 24 hours, and then treated the samples for 24, 48 or 72 hours under both control and UA (10 µM) conditions, and evaluated the amount of amastigotes. Both xenophagy (by IFI) and ROS generation (by 2',7'-dichlorodihydrofluorescein diacetate reaction) were also tested as two possible mechanisms of action of this drug. Our data showed that UA decreased the amount of amastigotes in cells. We also observed that UA induces the autophagy pathway, and that LC3, the marker of autophagy, is recruited around amastigotes, indicating xenophagy of these parasites. Moreover, the production of ROS after 24 hours of treatment is increased on infected cells but, interestingly, UA does not have this effect on non-infected cells. We conclude that this natural compound promotes parasite death through induction of autophagy and other host cell responses.