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

## TL;DR

A plant compound called (3S)-16,17-didehydrofalcarinol shows promise as a topical treatment for a skin infection caused by Leishmania mexicana in mice.

## Contribution

The study demonstrates the efficacy of a plant-derived oxylipin as a topical treatment for cutaneous leishmaniasis in mice.

## Key findings

- Compound 1 increased reactive oxygen species production and apoptosis in Leishmania mexicana parasites.
- Topical application of compound 1 reduced disease progression and parasite load in infected mice.
- The compound did not affect the viability of murine macrophages.

## 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.