Topical Application of Oxylipin (3S)-16,17-Didehydrofalcarinol in Mice Infected with Leishmania mexicana: A Possible Treatment for Localized Cutaneous Leishmaniasis.

Abstract

Pentavalent antimonials are the first-line treatment for localized cutaneous leishmaniasis. However, they have disadvantages such as their elevated toxicity, high costs, and parenteral application. Plant-derived compounds may be an alternative treatment against this disease. Previous in vitro studies have shown that (3S)-16,17-didehydrofalcarinol (1), a polyacetylene oxylipin isolated from Tridax procumbens, is active against Leishmania mexicana. We have analyzed the mechanism of action of compound 1, evaluating reactive oxygen species production, apoptosis of L. mexicana, cytotoxicity in murine macrophages, and its efficacy in controlling the disease progression and parasite load when applied topically in C57BL/6 mice infected with L. mexicana. Results show that parasites incubated with 1.6 μM compound 1 significantly increased reactive oxygen species production (p ≤ 0.05). The percentage of apoptosis also increased significantly (p ≤ 0.05) and did not affect the viability of macrophages. The application of the topical formulations with 0.5% and 0.75% compound 1 for 7 weeks reduced disease progression and parasite load. We demonstrate that compound 1 generates the death of L. mexicana by apoptosis through reactive oxygen species production. We conclude that compound 1 can be used a possible alternative treatment for localized cutaneous leishmaniasis, enabling a less painful and more accessible therapy.