Assessment of sesquiterpene lactones isolated from Mikania plants species for their potential efficacy against Trypanosoma cruzi and Leishmania sp.

LAURELLA CECILIA; CERNY N.; BIVONA A.; SANCHEZ ALBERTI ANDRÉS; GIBERTI, GUSTAVO; MALCHIODI, E; MARTINO, VIRGINIA; CATALAN, CESAR; ALONSO MARÍA ROSARIO; CAZORLA, S.; SULSEN, VALERIA

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2018 vol. 11

1932-6203

Four sesquiterpene lactones, mikanolide, deoxymikanolide, dihydromikanolide and scandenolide were isolated by bioassay guided fractionation from Mikania variifolia and Mikania micrantha dichloromethane extracts. Mikanolide and deoxymikanolide were the major compounds in both extracts 2.2and 0.4.for Mikania variifolia and 21.0 and 6.4% for Mikania micrantha, respectively. Mikanolide, deoxymikanolide, dihydromikanolide were active against Trypanosoma cruzi epimastigotes with 50% inhibitory concentrations of 0.7, 0.08 and 2.5 µg/ml, respectively. These compounds were also active against the infective forms of the parasites, with 50% inhibitory concentrationsof 2.1, 1.5 and 0.3 µg/ml for bloodstream trypomastigotes, and against amastigotes with 50% inhibitory concentrations of 4.5, 6.3 and 8.5 µg/ml against amastigotes, respectively. By contrast, scandenolide showed no activity against Trypanosoma. cruziparasite. Besides, mikanolide and deoxymikanolide were also active compounds against Leishmania braziliensis promastigotes with 50% inhibitory concentrations of 5.1 and 11.5 µg/ml. The four sesquiterpene lactones were tested for their cytotoxicity on Vero cells. Deoxymikanolide presented the highest selectivity indexes (SI = 54) for trypomastigotes and amastigotes (SI=12.5) in an in vivo model of Trypanosoma cruzi infection. deoxymikanolide treatment was able to decrease the parasitemia and the weight lost associated to the acute phase of the parasite infection. More importantly, while 100% of control mice died at day 22 post infection, 70% of mikanolide-treated mice survived to a lethal T. cruzi infection. We also observed that deoxymikanolide increased TNF-α and IL-12 production by macrophages, which could contribute to the control of the T. cruzi infection.