Sulforaphane targets Leishmania promastigotes to inhibit parasite motility and alters host autophagy to suppress parasite replication in macrophages

Visceral leishmaniasis (VL) is a neglected tropical disease caused by protozoan parasites Leishmania infantum and Leishmania donovani. Affected populations in extreme poverty and those impacted by climate change suffer limited treatment options that are both costly and toxic. The disease's prevalence is rising even in affluent countries, making the search for new, accessible treatments crucial.

Sulforaphane (SFN) has demonstrated anti-parasitic effects against various Leishmania species, including L. tropica, L. mexicana, L. panamensis, and L. amazonesis. SFN was also effective post-infection, reducing infected cells and amastigotes in macrophages infected with Leishmania species causing both VL and cutaneous leishmaniasis (CL).

A synthetic derivative of SFN, Alkyne SFN (A-SFN), showed even greater efficacy in reducing parasite viability and inhibiting motility. SFN treatment enhanced nonselective macroautophagy in infected macrophages by increasing lysosomal acidification and upregulating protective, antioxidant, and autophagy-related genes via the NRF2 transcription factor.

These findings provide evidence that SFN and its derivatives could be promising lead compounds for treating Leishmania infections through multiple innate immune pathways.