Bioassay-based Corchorus capsularis L. leaf-derived β-sitosterol exerts antileishmanial effects against Leishmania donovani by targeting trypanothione reductase
| Autor: | Angshuman Bagchi, Sajal Chakraborti, Pijush Kanti Pramanik, Tapati Chakraborti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Models Molecular Corchorus Protein Conformation Science 030106 microbiology Leishmania donovani Antiprotozoal Agents Protozoan Proteins Pharmacology Mechanism of action Chemical Fractionation Biochemistry Article 03 medical and health sciences chemistry.chemical_compound medicine Bioassay NADH NADPH Oxidoreductases IC50 Natural products Multidisciplinary Binding Sites biology Chemistry Drug discovery Plant Extracts Leishmaniasis Phosphatidylserine biology.organism_classification medicine.disease Chemical biology Sitosterols Computational biology and bioinformatics Molecular Docking Simulation Plant Leaves 030104 developmental biology Visceral leishmaniasis Corchorus capsularis Mitochondrial Membranes Medicine Reactive Oxygen Species Intracellular |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-15 (2020) |
| ISSN: | 2045-2322 |
| Popis: | 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-sitosterolCCL) were observed by spectroscopic analysis (FTIR, 1H NMR, 13C NMR and GC–MS). The inhibitory efficacy of this β-sitosterolCCL against L. donovani promastigotes was measured (IC50 = 17.7 ± 0.43 µg/ml). β-SitosterolCCL 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-sitosterolCCL was validated by enzyme inhibition and an in silico study in which β-sitosterolCCL was found to inhibit Leishmania donovani trypanothione reductase (LdTryR). Overall, β-sitosterolCCL appears to be a novel inhibitor of LdTryR and might represent a successful approach for treatment of VL in the future. |
| Databáze: | OpenAIRE |
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