TITLE:
Seco-limonoid 11α,19β-dihydroxy-7-acetoxy-7- deoxoichangin promotes the resolution of Leishmania panamensis infection
AUTHORS:
Diana Granados-Falla, Carlos Coy-Barrera, Luis Cuca, Gabriela Delgado
KEYWORDS:
Leishmaniasis; Treatment; Immunomodulation; Seco-Limonoid
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.2A,
February
28,
2013
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 11α,19β-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 EC50 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.