Effects of Melia azedarach extract on T. cruzi epimastigotes proliferation

L. FRACCAROLI; MD. RUIZ; P. TORRES; L. LAROCCA; C. CARRILLO; V. DE PINO

Congreso; Reunión Anual de Sociedades Biocientíficas 2019; 2019

Chagas disease is an endemic parasitosis caused by the protozoan Trypanosoma cruzi (T. cruzi). The current therapies are limited in efficacy and show multiple side effects. Thus, there is a need to identify new effective and specific trypanocidal strategies. Melia azedarach (MA), native of Asia but widely distributed in several countries, known as ?Paraíso?, has been described to have therapeutic properties such as antifungal and antihelmintic.The aim of this work was to evaluate the effect of extracts obtained from ripe fruits from MA in the proliferation of T. cruzi epimastigotes. To approach this aim we performed MA extracts using water, ethanol and DMSO as solvents. We tested the extracts in cultures of epimastigotes from the Y-GFP strain in concentrations between 0 and 6 mg/ml. We observed that only DMSO extracts dose dependently decreased the proliferation of the parasites. The IC50 calculated at day 4 of culture was 0.94 mg/ml (0.81-1.09 mg/ml). To evaluate the stability, we stored the extract at 4ºC and -20ºC during 15 days. Then, we calculated the IC50 of both in Y-GFP epimastigotes observing that the storage at -20ºC maintained the activity while the extract at 4ºC decreased its activity by half. We tested the citotoxicity of the DMSO extract in Vero cell line with MTT assay, calculating a selectivity index of 1.2. While it is not optimal, it is proximal to those obtained for Nifurtimox or Benznidazole. We performed an HPLC separation of the extract recollecting different fractions. Preliminary results showed that the individual fractions did not decrease epimastigotes proliferation, while the pool of those fractions restored the effect. The results present herein propose that the extracts obtained from ripe fruits of MA have bioactive compounds that affect the proliferation and viability of T. cruzi epimastigotes suggesting that the citotoxic activity may be the result of the interaction of different compounds present in the extract.