Usnic acid causes apoptotic-like death in Leishmania major, L. infantum and L. tropica.

Leishmaniasis, a deadly parasitic infection, threatens many people worldwide. Since the high cost, toxicity, and resistance are drawbacks of current treatment options, it is necessary to find safer and more effective new antileishmanial drugs. The aim of this study was to determine the antileishmanial activity of usnic acid and its apoptotic mechanism on Leishmania spp. promastigotes. The antileishmanial activity was evaluated by MTT assay and apoptosis-related gene expression was investigated by qRT-PCR. Usnic acid was to be effective against Leishmania major, L. infantum, and L. tropica promastigotes at IC50 = 10.76 µg/ml, 13.34 µg/ml, and 21.06 µg/ml, respectively. We also demonstrated a novel mechanism by which usnic acid inhibited proliferation and caused apoptosis; usnic acid upregulated p53, Bax, Casp-3, and Casp-9 gene expression and downregulated the level of Bcl-2 gene expression. Accordingly, the expression level of the P53 gene increased in L. major, L. infantum and L. tropica by 14.4-, 11.8-, and 9.5-fold, respectively, and in contrast, the Bcl-2 gene expression decreased in all three leishmaniasis by 0.8-, 0.8-, and 0.7-fold, respectively. The present study, therefore, revealed that usnic acid played a critical role in the usnic acid-induced apoptotic process in Leishmania species. Usnic acid is easily accessible and an inexpensive agent, and can be considered as an alternative therapeutic agent for Leishmania infections subject to further tests in animal models.