Abstract
BackgroundVisceral leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani (L. donovani), is the most severe form of leishmaniasis. It is largely responsible for significant morbidity and mortality in tropical and subtropical countries. Currently, available therapeutics have lots of limitations including high-cost, adverse side-effects, painful route of administration, less efficacy, and resistance. Therefore, it is time to search for cheap and effective antileishmanial agents. In the present work, we evaluated the antileishmanial potential of sesamol against promastigotes as well as intracellular amastigotes. Further, we tried to work out its mechanism of antileishmanial action on parasites through different assays.Methodology In vitro and ex vivo antileishmanial assays were performed to evaluate the antileishmanial potential of sesamol on L. donovani. Cytotoxicity was determined by MTT assay on human THP-1-derived macrophages. Sesamol-induced morphological and ultrastructural changes were determined by electron microscopy. H2DCFDA staining, JC-1dye staining, and MitoSOX red staining were performed for reactive oxygen assay (ROS), mitochondrial membrane potential, and mitochondrial superoxide, respectively. Annexin V/PI staining for apoptosis, TUNEL assay, and DNA laddering for studying sesamol-induced DNA fragmentation were performed.ConclusionsSesamol inhibited the growth and proliferation of L. donovani promastigotes in a dose-dependent manner. It also reduced the intracellular parasite load without causing significant toxicity on host-macrophages. Overall, it showed antileishmanial effects through induction of ROS, mitochondrial dysfunction, DNA fragmentation, cell cycle arrest, and apoptosis-like cell death to parasites. Our results suggested the possible use of sesamol for the treatment of leishmaniasis after further in vivo validations.
Highlights
Leishmaniasis is caused by the protozoan parasite L. donovani
Sesamol effectively inhibited the viability of promastigote parasites in a dose-dependent manner in comparison to untreated parasite control
A substantial amount of inhibition was observed at higher concentrations, and the parasite did not revert to normal shape post-incubation
Summary
Leishmaniasis is caused by the protozoan parasite L. donovani. It has three main clinical forms: visceral leishmaniasis (VL), cutaneous leishmaniasis (CL), and mucocutaneous leishmaniasis (MCL). It stays in sand flies as well as in mammals, including human. It exists in two major forms, extracellular promastigote and intramacrophagic amastigote. The drugs used for the treatment of VL include pentavalent antimonial, liposomal amphotericin B, paromomycin, and miltefosine These treatments have several limitations due to their non-specificity, toxicity, painful route of administration, and high cost (Sundar et al, 2019). Visceral leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani (L. donovani), is the most severe form of leishmaniasis. It is largely responsible for significant morbidity and mortality in tropical and subtropical countries. We tried to work out its mechanism of antileishmanial action on parasites through different assays
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