Trypanocidal activity of guaianolide obtained from Tanacetum parthenium (L.) Schultz-Bip. and its combinational effect with benznidazole.
In the present study, we evaluated the in vitro antiprotozoal activity of a guaianolide (11,13-dehydrocompressanolide) isolated from Tanacetum parthenium against Trypanosoma cruzi and investigated the possible combinational effect of guaianolide and benznidazole. The isolated compound was shown to be effective against T. cruzi, with IC₅₀ values of 18.1±0.8 and 66.6±1.3 μM against the multiplicative epimastigote and amastigote forms, respectively. The best results were obtained against trypomastigotes, with an EC₅₀ of 5.7±0.7 μM. The guaianolide presented no toxicity in LLCMK₂ cells (CC₅₀ of 93.5 μM) and was 16.4-fold more selective for trypomastigotes. The study of the combinational effect of benznidazole and guaianolide revealed the presence of a synergistic effect against the epimastigote form and marginal additive effect against the trypomastigote form. Striking morphological changes were observed in epimastigotes treated with guaianolide, such as thinning and stretching of the cell body and flagellum and changes in the format of the cell body with apparent leakage of the cytoplasmic content in trypomastigote forms. The ultrastructural analysis of epimastigotes revealed the presence of membranes that involved organelles and formation of myelin-like figures. Flow cytometry revealed a cell volume reduction and decrease in mitochondrial membrane potential. However, no major changes in cell membrane integrity were found in the epimastigote form treated with guaianolide.
Programa de Pós graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
Juliana
J
Cogo
Angelo de Oliveira
Ade O
Caleare
Tânia
T
Ueda-Nakamura
Benedito Prado Dias
BP
Filho
Izabel Cristina Piloto
IC
Ferreira
Celso Vataru
CV
Nakamura
D004357:Drug Synergism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009593:Nitroimidazoles / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D045789:Sesquiterpenes, Guaiane / Q000302:isolation & purification / Q000494:pharmacology*; D031203:Tanacetum / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure
D009593:Nitroimidazoles; D010936:Plant Extracts; D045789:Sesquiterpenes, Guaiane; D014344:Trypanocidal Agents; C009999:benzonidazole