<i>Seco</i>-limonoid 11<i>α</i>,19<i>β</i>-dihydroxy-7-acetoxy-7- deoxoichangin promotes the resolution of <i>Leishmania panamensis</i> infection

Abstract

The high morbidity generated by the infection caused by parasites of the genus Leishmania , make of this infection into one of the vector-borne infectious diseases most relevant worldwide, which added to the fact that the drugs used for its treatment are far from be optimal and considering that prophylactic approaches (such as the development of a vaccine) still seems far from being achieved, make of the search for new therapeutic alternatives for safe and effective treatment of this disease one of the most accurate approaches to the control of this disease. In this study we evaluated the antileishmanial and immunomodu- latory activity of the compound 11 α ,19 β -dihydroxy- 7-acetoxy-7-deoxoichangin (a seco -limonid molecule) through: 1) evaluation of its cytotoxicity over promastigotes and axenic amastigotes of L . (V) panamensis , 2) determination of its ability to induce the control of in vitro infection, using infected murine cells (J774.2) and human dendritic cells (hDCs), 3) quantifying the levels of pro-inflammatory cytokines, (iv) evaluating the expression of cell markers associated with hDCs maturation, and (v) determinating the production of nitric oxide free radicals (NO). In this regard, this seco -limonoid exhibited an antileishmanial activity represented in the reduction of in vitro infection in J774.2 cells and hDCs, with a EC 50 of 7.9 μM (4.48 μg/mL) and 25.5 μM (14.39 μg/mL), respectively, and additionally, we observed an increase on the production of IL-12p70, TNF- α and NO, as also, in the number of hDCs HLA-DR-positive in treated infected hDCs. These findings suggest that anti-lei- shmanial activity of this compound could be associated with the potential “reactivation” of phagocytic cell that is “paralyzed” by the infection, generating an immune phenotype associated with protection.