Sesamol Induces Apoptosis-Like Cell Death in Leishmania donovani

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.MethodologyIn 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.

Direct In Vitro Comparison of the Anti-Leishmanial Activity of Different Olive Oil Total Polyphenolic Fractions and Assessment of Their Combined Effects with Miltefosine

“…promastigotes and provoked the generation of intracellular ROS [ 28 ]. These findings are consistent with other studies which also demonstrated the contribution of ROS production and mitochondrial dysfunction to Leishmania death induced by natural products, such as sesamol, carajurin, apigenin, and quercetin [ 37 , 38 , 39 , 40 ].…”

A Core‐Linker‐Polyamine (CLP) Strategy Enables Rapid Discovery of Antileishmanial Aminoalkylquinolinecarboxamides That Target Oxidative Stress Mechanism

“…These justify that low cell count at 48 h is due to cell death caused by compounds 9 a and 9 b . Therefore, all these results together clearly indicate that the investigated compounds show antileishmanial activity by generating mitochondrial superoxide radicals [24] …”

“…Therefore, all these results together clearly indicate that the investigated compounds show antileishmanial activity by generating mitochondrial superoxide radicals. [24]…”

Chrysin and Capsaicin induces premature senescence and apoptosis via mitochondrial dysfunction and p53 elevation in Cervical cancer cells

“…Cells were seeded in six well plates and after the indicated doses treatment for 24 h. Added 10 µM H 2 DCFDA in dark for 45 mins at 37 °C ( Ali et al, 2021 ). Change in Mitochondrial membrane potential was detected using 10 μM Rhodamine 123 solution in media in dark condition for 30 mins at 37 °C.…”