Antimicrobial peptides (AMPs) are multifunctional components of the innate immune system. Chemotherapeutic agents used for treatment of
visceral leishmaniasis (VL) are now threatened due to the emergence of acquired drug resistance and toxicity. AMPs are attractive alternative to conventional
pharmaceuticals. In this study, first time we explored the antileishmanial activity of
spinigerin originally derived from Pseudacanthotermes spiniger. Leishmania donovani promastigotes present apoptosis-like cell death upon exposure to
spinigerin (IC50, 150 μM). The
infection rate was reduced by 20% upon exposure to 150 μM
spinigerin but no cytotoxicity on host macrophages was observed. Elevation of intracellular ROS level and down-regulation of two ROS detoxifying
enzymes,
ascorbate peroxidase (APx) and
trypanothione reductase (TR) suggested essential role of ROS machinery during
spinigerin mediated cell death. About 97% cell population was found to be
Annexin-V positive; 44% cells being highly
Annexin-V positive. Moreover, we observed morphological changes like cell rounding, nuclear condensation, oligonucleosomal
DNA degradation and TUNEL positive cells without loss of membrane integrity upon
spinigerin exposure, suggests apoptosis-like death. Interestingly, collapse in mitochondrial membrane potential and increased level of intracellular ROS and
calcium were not associated with
caspase like activity. Computational analysis suggests spiningerin interacts with
trypanothione reductase and thus probably interferes its function to detoxify the toxic ROS level. Therefore,
spinigerin induces apoptosis-like cell death in L. donovani in a
caspase-independent manner. The study elucidates the antileishmanial property of
spinigerin that may be considered for future chemotherapeutic option alone or adjunct with other
drug regimens for improved treatment of
visceral leishmaniasis.