Integrated in vivo and in silico validation of Corchorus olitorius seed-mediated cardioprotection against doxorubicin-induced cardiotoxicity via network pharmacology, molecular docking, and molecular dynamics.

BACKGROUND: Corchorus olitorius L., known in Arab countries as molokhia, is a leafy plant rich in many carotenoids, minerals, and vitamins; its seeds are also reported to offer cardioprotective effects. Although the cardioprotective effects of molokhia are ascribed to the presence of cardiac glycoside compounds, the exact action mechanisms remain uninvestigated. METHODS: In this study, we examined the potential of molokhia seeds to protect against cardiopathy by isolating the major constituents of C. olitorius seeds, analyzing its gene expression in vivo, and conducting computational studies to demonstrate the cardioprotective activities of these constituents. RESULTS: Crude extracts of C. olitorius seeds were found to reduce the expression of IL-1β, IL-6, TNF-α, NF-κB, ICAM-1, and MMP-9 that had increased upon the administration of doxorubicin (DOX). Electrocardiographic studies showed reduced heart rate along with prolongation of the PR interval, QRS complex, and ST segment upon Corchorus administration. CONCLUSION: The findings of this study demonstrate that the cardioprotective effects of molokhia seeds against DOX-induced cardiotoxicity are probably mediated via anti-inflammatory actions.