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Bioassay-based Corchorus capsularis L. leaf-derived β-sitosterol exerts antileishmanial effects against Leishmania donovani by targeting trypanothione reductase
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Bioassay-based Corchorus capsularis L. leaf-derived β-sitosterol exerts antileishmanial effects against Leishmania donovani by targeting trypanothione reductase
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Journal Article
Bioassay-based Corchorus capsularis L. leaf-derived β-sitosterol exerts antileishmanial effects against Leishmania donovani by targeting trypanothione reductase
2020
Overview
Leishmaniasis, a major neglected tropical disease, affects millions of individuals worldwide. Among the various clinical forms, visceral leishmaniasis (VL) is the deadliest. Current antileishmanial drugs exhibit toxicity- and resistance-related issues. Therefore, advanced chemotherapeutic alternatives are in demand, and currently, plant sources are considered preferable choices. Our previous report has shown that the chloroform extract of
Corchorus capsularis
L. leaves exhibits a significant effect against
Leishmania donovani
promastigotes. In the current study, bioassay-guided fractionation results for
Corchorus capsularis
L. leaf-derived β-sitosterol (β-sitosterol
CCL
) were observed by spectroscopic analysis (FTIR,
1
H NMR,
13
C NMR and GC–MS). The inhibitory efficacy of this β-sitosterol
CCL
against
L. donovani
promastigotes was measured (IC
50
= 17.7 ± 0.43 µg/ml). β-Sitosterol
CCL
significantly disrupts the redox balance via intracellular ROS production, which triggers various apoptotic events, such as structural alteration, increased storage of lipid bodies, mitochondrial membrane depolarization, externalization of phosphatidylserine and non-protein thiol depletion, in promastigotes. Additionally, the antileishmanial activity of β-sitosterol
CCL
was validated by enzyme inhibition and an in silico study in which β-sitosterol
CCL
was found to inhibit
Leishmania donovani
trypanothione reductase (
Ld
TryR). Overall, β-sitosterol
CCL
appears to be a novel inhibitor of
Ld
TryR and might represent a successful approach for treatment of VL in the future.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/154
/ 631/45
/ 631/92
/ Antiprotozoal Agents - chemistry
/ Antiprotozoal Agents - isolation & purification
/ Antiprotozoal Agents - pharmacology
/ Binding Sites - drug effects
/ Humanities and Social Sciences
/ Leaves
/ Leishmania donovani - drug effects
/ Leishmania donovani - enzymology
/ Molecular Docking Simulation
/ NADH, NADPH Oxidoreductases - chemistry
/ NADH, NADPH Oxidoreductases - metabolism
/ NMR
/ Protozoan Proteins - antagonists & inhibitors
/ Reactive Oxygen Species - metabolism
/ Science
/ Sitosterols - isolation & purification
/ Toxicity
