生薬学および天然物ジャーナル

Leishmanicidal Activity of Oleuropein: Leishmania donovani Promastigote Cell Death through a Possibly ROS-Independent Mechanism

Abstract

ID Kyriazis, D Smirlis, A Papadaki, O Koutsoni, N Aligiannis, AL Skaltsounis and E Dotsika*

The development of potent and inexpensive antiparasitic agents for common use is imperative due to the absence of an effective and safe treatment for visceral leishmaniasis, a devastating parasitic disease. Oleuropein, a secoiridoid, exerts an antileishmanial effect on promastigotes of Leishmania infantum, L. major and L. donovani, as well as on amastigotes of L. donovani in in vitro and in vivo experimental models. In this study, our aim was to characterize how oleuropein drives parasites into cell death. Our hypothesis is that oleuropein promotes an apoptotis-like cell death which restrains the inflammatory processes that facilitate parasitic dissemination.

Logarithmic-phase L. donovani promastigotes were treated with oleuropein for 24, 48 and 72 h, and parasitic cell cycle, parasitic membrane asymmetry and intracellular generalized oxidative stress were assessed via flow cytometry. Morphological alterations were analyzed with confocal microscopy.

Cell-cycle analysis revealed that oleuropein fragmented parasite DNA within the first 24 h of incubation. In vitro treatment of promastigotes with oleuropein resulted in several morphological alterations and significant annexin V binding. Interestingly, oleuropein treatment did not increase the levels of intracellular reactive oxygen species until 48 h of incubation.

Our findings suggest that oleuropein promotes apoptosis-like cell death in L. donovani promastigotes that is not being mediated by an induced endoparasitic oxidative stress.