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

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