Caracterização inicial dos extratos de Tephrosia toxicaria (Sw.) Pers. quanto a atividade leishmanicida e toxicidade

Abstract

Leishmaniasis is a complex zoonosis caused by protozoa of the genus Leishmania, vectored by sandflies that affect humans and other vertebrates. Of the available therapeutic options, pentavalent antimonials are the first-choice interventions. However, its use is associated with a high cost, requires hospitalization and long-term medical follow-up, adverse events to patients and the occurrence of parasite resistance. Thus, new chemotherapeutic adjuvants need to be made available and plant extracts have been reported as strong candidates for pharmacological therapies, as they concentrate biomolecules capable of manifesting numerous biological activities. The present study had as objective to evaluate the leishmanicidal potential of the organs of the legume Tephrosia toxicaria (Sw.) Pers (roots, stems, leaves and seeds) against promastigotes of Leishmania amazonensis, using aqueous and hydroethanolic extracts. Increasing concentrations of extracts (0.01 to 1.0 mg/mL) were incubated with the parasites to determine their growth inhibition and analysed some classes of chemical compounds present in the extracts, with emphasis on proteins and investigated the toxic effects of the extracts. in cell culture assays. Among the extracts obtained, the hydroethanolic extract of leaves (FHA) stands out as the most active as it inhibits approximately 30% of parasite growth at the lowest concentration investigated (0.01 mg/mL), yielding an IC50 = 0.47 mg/mL . Cytotoxicity assays suggest that FHA does not induce toxic events in mouse embryonic fibroblasts, cell line 3T3 (CC50 = 2.66 mg/mL) and in immortalized hepatocyte lineage, HepG2 (CC50 = 1.60 mg/mL). Preliminary chemical analyses suggest that FHA extraction conditions favored the concentration of carbohydrates, phenolic compounds and proteins, mainly protease inhibitors, with estimated molecular masses between 13 and 45 kDa. The results indicate the potential of T. toxicaria and its extracts, mainly FHA, as candidates for study for the development of formulations for therapeutic interventions in leishmaniasis, due to their ability to inhibit the growth of parasites in a concentration range without toxic events against HepG2 and 3T3