Trypanocidal and leishmanicidal activities of flavonoids isolated from Stevia satureiifolia var. satureiifolia.

Context Chagas' disease and leishmaniasis produce significant disability and mortality with great social and economic impact. The genus Stevia (Asteraceae) is a potential source of antiprotozoal compounds. Objective Aerial parts of four Stevia species were screened on Trypanosoma cruzi. Stevia satureiifolia (Lam.) Sch. Bip. var. satureiifolia (Asteraceae) dichloromethane extract was selected for a bioassay-guided fractionation in order to isolate its active compounds. Additionally, the antileishmanial activity and the cytotoxicity of these compounds on mammalian cells were assessed. Materials and methods The dichloromethane extract was fractionated by column chromatography. The isolated compounds were evaluated using concentrations of 0-100 µg/mL on T. cruzi epimastigotes and on Leishmania braziliensis promastigotes for 72 h, on trypomastigotes and amastigotes of T. cruzi for 24 h and 120 h, respectively. The compounds' cytotoxicity (12.5-500 µg/mL) was assessed on Vero cells by the MTT assay. The structure elucidation of each compound was performed by spectroscopic methods and HPLC analysis. Results The dichloromethane extracts of Stevia species showed significant activity on T. cruzi epimastigotes. The flavonoids eupatorin (1.3%), cirsimaritin (1.9%) and 5-desmethylsinensetin (1.5%) were isolated from S. satureiifolia var. satureiifolia extract. Eupatorin and 5-desmethylsinensetin showed IC50 values of 0.2 and 0.4 µg/mL on T. cruzi epimastigotes and 61.8 and 75.1 µg/mL on trypomastigotes, respectively. The flavonoid 5-desmethylsinensetin showed moderate activity against T. cruzi amastigotes (IC50 value = 78.7 µg/mL) and was the most active compound on L. braziliensis promastigotes (IC50 value = 37.0 µg/mL). Neither of the flavonoids showed cytotoxicity on Vero cells, up to a concentration of 500 µg/mL.

Vaccination approaches against Trypanosoma cruzi infection.

In natural infection, the survival of Trypanosoma cruzi, despite the complex immune response elicited including several humoral and cellular components of innate and acquired immunity, suggests that the immune system's natural responses are inherently inadequate. Consequently, it is of paramount importance to find alternatives to direct the immune system before infection, and redirect it after infection, to obtain a prophylactic and therapeutic vaccine. Herein, we review the recent advances in vaccine research and the development of the major antigen candidates, including cruzipain, trans-sialidase, amastigote surface protein, paraflagellar rod protein, among others. In the last 5 years, experimental works have been conducted to analyze DNA delivery systems, including viruses and bacteria, as well as immunomodulators such as CpG-oligodeoxynucleotide, macrophage-activating lipopeptide from Mycoplasma fermentans, glycolipid alpha-galactosylceramide, granulocyte-macrophage colony-stimulating factor, IL-12 and other cytokines and chemokines. The review also covers articles that shed light on some mechanisms of innate and adaptive immunity against T. cruzi, which improved our knowledge and provided potentially useful tools to fight infection. A better understanding of the protective immune responses that can effectively arrest T. cruzi survival in the mammalian host is critical for the development of vaccines against Chagas disease.