Computational and experimental approaches manifest the leishmanicidal potential of α-mangostin resourced from Garcinia cowa

Abstract

Owing to the persistent number of parasitic deaths, Visceral leishmaniasis continues to haunt several economically weaker sections of India. The disease causes over 30,000 deaths and threatens millions annually on a global scale. The standard pentavalent antimonials, on the other hand, are associated with health adversities and disease relapse. The current study is focused on the search for the most potential natural bioactive phytocompound from the bark extract of the Northeastern Indian plant, Garcinia cowa, that shows potent anti-leishmanial properties. The High Resonance Liquid Chromatography followed by Mass Spectrometry (HR-LCMS) study followed by an in silico molecular docking using computational tools revealed that α-mangostin might potentially possess antiparasitic activity. To validate the anti-leishmanial efficacy of the compound, a cell viability assay was performed, which demonstrated the parasite-specific inhibitory activity of α-mangostin; with IC50 values ranging from 4.95 - 7.37 µM against the different forms of Leishmania donovani parasite. The flow cytometric analysis of the phytocompound treated parasites indicated an oxidative and nitrosative stress-mediated apoptotic cell death in the parasites, by the suggestive surge in nuclear fragmentation and mitochondrial dysfunction. Simultaneously, a cytokine profiling study suggested approximate two-to-three-fold upregulated levels of pro-inflammatory cytokines post-compound treatment, which is predicted to actively contribute to parasite-killing. α-mangostin was also found to reduce the chances of parasite survival by inhibiting arginase enzyme activity, which in favorable conditions facilitates its sustenance. This study thereby substantiates that α-mangostin significantly possesses anti-leishmanial potentiality that can be developed into a cure for this infectious disease.