Visceral leishmaniasis
(VL) or kala-azar is a vector-borne dreaded
protozoal infection that is caused by the parasite
Leishmania donovani
. With increases in the dramatic
infection rates, present drug toxicity, resistance, and the absence
of an approved vaccine, the development of new antileishmanial compounds
from plant sources remains the keystone for the control of visceral
leishmaniasis. In this study, we evaluated the leishmanicidal effect
of thymoquinone against
L. donovani
with an
in vitro
and
ex vivo
model.
Thymoquinone exhibited potent antipromastigote activity with IC
50
and IC
90
concentrations achieved at 6.33 ±
1.21 and 20.71 ± 2.15 μM, respectively, whereas the IC
50
and IC
90
concentrations were found to be 7.83
± 1.65 and 27.25 ± 2.20 μM against the intramacrophagic
form of amastigotes, respectively. Morphological changes in promastigotes
and growth reversibility study following treatment confirmed the leishmanicidal
effect of thymoquinone. Further, thymoquinone exhibited leishmanicidal
activities against
L. donovani
promastigote
through cytoplasmic shrinkage, membrane blebbing, chromatin condensation,
cellular and nuclear shrinkage, and DNA fragmentation, as observed
under scanning and transmission electron microscopy analyses. The
antileishmanial activity was exerted via programmed cell death as
proved by exposure of phosphatidylserine, DNA nicking by TUNEL assay,
and loss of mitochondrial membrane potential. Thymoquinone at a concentration
of 200 μM was devoid of any cytotoxic effects against mammalian
macrophage cells. Thymoquinone showed strong leishmanicidal activity
against
L. donovani
, which is mediated
via an apoptosis mode of parasitic cell death, and accordingly, thymoquinone
may be the source of a new lead molecule for the cure of VL.