ABSTRACT
Ayahuasca is a psychoactive and psychedelic decoct composed mainly of Banisteriopsis caapi and Psychotria viridis plant species. The beverage is rich in alkaloids and it is ritualistically used by several indigenous communities of South America as a natural medicine. There are also reports in the literature indicating the prophylaxis potential of Ayahuasca alkaloids against internal parasites. In the present study, Ayahuasca exhibited moderate inâ vitro activity against Trypanosoma cruzi trypomastigotes (IC50 95.78â µg/mL) compared to the reference drug benznidazole (IC50 2.03â µg/mL). The ß-carboline alkaloid harmine (HRE), isolated from B.â caapi, was considered active against the trypomastigotes forms (IC50 6.37), and the tryptamine N, N-dimethyltryptamine (DMT), isolated from P.â viridis was also moderately active with IC50 of 21.02â µg/mL. Regarding the inâ vivo evaluations, no collateral effects were observed. The HRE alone demonstrated the highest trypanocidal activity in a dose-responsive manner (10 and 100â mg/kg). The Ayahuasca and the association between HRE and DMT worsened the parasitaemia, suggesting a modulation of the immunological response during the T.â cruzi infection, especially by increasing total Immunoglobulin (IgG) and IgG1 antibody levels. The inâ silico molecular docking revealed HRE binding with low energy at two sites of the Trypanothione reductase enzyme (TR), which are absent in humans, and thus considered a promissory target for drug discovery. In conclusion, Ayahuasca compounds seem to not be toxic at the concentrations of the inâ vivo evaluations and can promote trypanocidal effect in multi targets, including control of parasitaemia, immunological modulation and TR enzymatic inhibition, which might benefit the treatments of patients with Chagas' disease. Moreover, the present study also provides scientific information to support the prophylactic potential of Ayahuasca against internal parasites.