Effects of piperovatine and piperlonguminine on mitochondrial function and integrity of the cell membrane in Trypanosoma cruzi

The search for therapeutic agents effective and less toxic for the treatment of Chagas' disease is increasing. Due to the wide diversity of molecular structures found in natural products, they have become targets for new drug discovery. Although the literature reports many studies with extracts and pure compounds obtained from plants with a good potential for treating infection, little is known about their mechanism of action. Thus, the main of this study was to evaluate the alterations caused by piperovatine and piperlonguminine, compounds isolated from Piper ovatum Vahl, on mitochondrion function and cell membrane plasma integrity of T. cruzi in a way to try to elucidate possible mechanism of action. For this, epimastigotes were treated for 24h, using IC₅₀ and IC₉₀ (41.5 and 178.4µM for piperovatine; 54 and 163.6µM for piperlonguminine) and incubated with Rh123. Epimastigotes were also treated with high concentrations of piperovatine (256µM) and piperlonguminine (220.5µM) and incubated with propidium iodide. Both assays were then evaluated by flow cytometry. The treatment with piperovatine and piperlonguminine with IC₉₀ caused decrease in fluorescence intensity total of Rh123 of 53.3% for piperlonguminine and 30.3% for piperovatine, indicating mitochondria depolarization. Additionally, an increase of 62.4% only for piperlonguminine was observed in treated cells, indicate alteration in cell membrane integrity. It is possible to suppose that the tripanocidal action of piperovatine and piperlonguminine maybe involve its effect on the mitochondrial function leading to cell death of the parasite.