Immunological Modulation and Control of Parasitaemia by Ayahuasca Compounds: Therapeutic Potential for Chagas's Disease
Chemistry & Biodiversity – September 26, 2022
Source: OpenAlex
Summary
Ayahuasca shows promising potential against Chagas disease, exhibiting moderate in vitro activity against Trypanosoma cruzi with an IC50 of 95.78 μg/mL, compared to benznidazole's 2.03 μg/mL. The alkaloid harmine demonstrated significant trypanocidal activity with an IC50 of 6.37 μg/mL. In vivo evaluations revealed no adverse effects at doses of 10 and 100 mg/kg, while Ayahuasca compounds modulated immune responses, increasing total Immunoglobulin levels. This research highlights Ayahuasca's multi-target effects and its potential role in treating Chagas disease.
Abstract
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 in vitro activity against Trypanosoma cruzi trypomastigotes (IC 50 95.78 μg/mL) compared to the reference drug benznidazole (IC 50 2.03 μg/mL). The β‐carboline alkaloid harmine (HRE), isolated from B. caapi , was considered active against the trypomastigotes forms (IC 50 6.37), and the tryptamine N , N ‐dimethyltryptamine (DMT), isolated from P. viridis was also moderately active with IC 50 of 21.02 μg/mL. Regarding the in vivo evaluations, no collateral effects were observed. The HRE alone demonstrated the highest trypanocidal activity in a dose‐responsive manner (10 and 100 mg/kg). The Ayahuasca and the association between HRE and DMT worsened the parasitaemia, suggesting a modulation of the immunological response during the T. cruzi infection, especially by increasing total Immunoglobulin (IgG) and IgG1 antibody levels. The in 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 in 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.