Ursolic acid promotes Trypanosoma cruzi clearance in macrophages by multiple mechanisms

MARTINEZ, SANTIAGO J.; ROMANO, PATRICIA S.; MUÑOZ LUCILA I; VANRELL, MARÍA CRISTINA; SALASSA, BETIANA NEBAÍ

California

Conferencia; 1st International Electronic Conference on Biomolecules: Natural and Bio-Inspired Therapeutics for Human Diseases session The natural and bio-inspired drug universe; 2020

MDPI

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 and its possible mechanism of action.To test this, we infected cells with T. cruzi for 24 hours, and then treated the samples with UA (5-10 μM) for different times. Our data showed that UA significantly decreased the amount of amastigotes compared to non-treated cells. We also studied the effect of UA on the autophagy response and other possible mechanisms of action we observed that UA induces the autophagy pathway, and that LC3, the marker of autophagy, is recruited around amastigotes, indicating xenophagy of these parasites. A cytotoxic effect was observed on T. cruzi trypomastigotes while epimastigotes displayed more resistance to this drug. 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.