In Vitro Antioxidant and Antitrypanosomal Activities of Extract and Fractions of Terminalia catappa

SIMPLE SUMMARY: Chagas disease is a serious infection caused by an intracellular parasite and transmitted primarily through an infected insect. Despite available treatments, the disease continues to cause countless deaths around the world due to the ineffectiveness of drugs. Medicinal plants have been used as an alternative and effective treatment against various diseases. In this work, we verified the antioxidant properties of the extract and fractions obtained from the plant species Terminalia catappa and its action against the parasite responsible for Chagas disease, Trypanosoma cruzi. Initially, we observed that the ethyl acetate and aqueous fraction demonstrated antioxidant activity. In addition, the ethyl acetate fraction showed the best inhibitory activity against all cellular forms of the parasite (epimastigotes, trypomastigotes and intracellular amastigotes), and did not present toxicity to host cells. We also observed that the ethyl acetate fraction induced several morphological changes to the parasite, such as cytoplasmic disruption, cell disorganization, morphological variation and loss of integrity. In this sense, we conclude that the ethyl acetate fraction obtained from T. catappa leaves can be an effective alternative in the treatment and control of Chagas disease. ABSTRACT: Chagas disease is a severe infectious and parasitic disease caused by the protozoan Trypanosoma cruzi and considered a public health problem. Chemotherapeutics are still the main means of control and treatment of the disease, however with some limitations. As an alternative treatment, plants have been pointed out due to their proven pharmacological properties. Many studies carried out with Terminalia catappa have shown several biological activities, but its effect against T. cruzi is still unknown. The objective of this work is to evaluate the therapeutic potential of extracts and fractions obtained from T. catappa on the parasite T. cruzi, in addition to analyzing its antioxidant activity. T. catappa ethyl acetate fraction were produced and submitted the chemical characterization by Liquid Chromatography Coupled to Mass Spectrometry (LC-MS). From all T. catappa extracts and fractions evaluated, the ethyl acetate and the aqueous fraction displayed the best antioxidant activity by the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging method (IC(50) of 7.77 ± 1.61 and 5.26 ± 1.26 µg/mL respectively), and by ferric ion reducing (FRAP) method (687.61 ± 0.26 and 1009.32 ± 0.13 µM of Trolox equivalent/mg extract, respectively). The ethyl acetate fraction showed remarkable T. cruzi inhibitory activity with IC(50) of 8.86 ± 1.13, 24.91 ± 1.15 and 85.01 ± 1.21 µg/mL against epimastigotes, trypomastigotes and intracellular amastigotes, respectively, and showed no cytotoxicity for Vero cells (CC(50) > 1000 µg/mL). The treatment of epimastigotes with the ethyl acetate fraction led to drastic ultrastructural changes such as the loss of cytoplasm organelles, cell disorganization, nucleus damage and the loss of integrity of the parasite. This effect could be due to secondary compounds present in this extract, such as luteolin, kaempferol, quercetin, ellagic acid and derivatives. The ethyl acetate fraction obtained from T. catappa leaves can be an effective alternative in the treatment and control of Chagas disease, and material for further investigations.