Ursolic acid‐rich extract presents trypanocidal action in vitro but worsens mice under experimental acute Chagas disease

Abstract

Chagas disease is a neglected tropical disease with only two drugs available for treatment and the plant Cecropia pachystachya has several compounds with antimicrobial and anti‐inflammatory activities. This study aimed to evaluate a supercritical extract from C. pachystachya leaves in vitro and in vivo against Trypanosoma cruzi. A supercritical CO2 extraction was used to obtain the extract (CPE). Cytotoxicity and immunostimulation ability were evaluated in macrophages, and the in vitro trypanocidal activity was evaluated against epimastigotes and trypomastigotes forms. In vivo tests were done by infecting BALB/c mice with blood trypomastigotes forms and treating animals orally with CPE for 10 days. The parasitemia, survival rate, weight, cytokines and nitric oxide dosage were evaluated. CPE demonstrated an effect on the epi and trypomastigotes forms of the parasite (IC50 17.90 ± 1.2 μg/mL; LC50 26.73 ± 1.2 μg/mL) and no changes in macrophages viability, resulting in a selectivity index similar to the reference drug. CPE‐treated animals had a worsening compared to non‐treated, demonstrated by higher parasitemia and lower survival rate. This result was attributed to the anti‐inflammatory effect of CPE, demonstrated by the higher IL‐10 and IL‐4 values observed in the treated mice compared to the control ones. CPE demonstrated a trypanocidal effect in vitro and a worsening in the in vivo infection due to its anti‐inflammatory activity.

Nonsteroidal Anti‐Inflammatory Drugs and Experimental Chagas Disease: An Unsolved Question

“…Observing the mortality rate, the ASA‐treated animals had the worst scenario and began to die 20 days post infection at the acute phase, showing 25% of mortality on the 30th day, while until day 180 post infection, the mortality rate reached 60% [13]. In a study using an extract rich in ursolic acid (a natural substance with anti‐inflammatory activity), BALB/c mice elevated the parasitemia and mortality in comparison with non‐treated mice, corroborating with the previous studies [67].…”