In-Silico unveiling of Pandanus amaryllifolius as a Cardioprotective Agent in Azithromycin-Induced Cardiotoxicity

Abstract

This study investigates the cardioprotective potential of Pandanus amaryllifolius (pandan) leaf extract against azithromycin-induced cardiotoxicity, utilizing in-silico methods to uncover its key phytochemicals and mechanisms of action. The PubChem online database was used to obtain the 3D structures of all phytocompounds, which were then optimized using the MMFF94 force field. A comprehensive screening of phytochemicals using databases such as IMPPAT identified 94 compounds present in pandan leaves, of which 9 satisfied Lipinski's rule of five, indicating strong drug-likeness. Further target prediction and network analysis revealed that 40 genes were common between the cardiotoxicity-related targets and the active compounds. Pathway enrichment analysis highlighted critical signaling pathways, including HIF-1 and PI3K-Akt, as significant modulators of the protective effects. Among the identified compounds, Pandamarilactone-1 and Pandamarine exhibited particularly strong molecular interactions with key proteins such as MAPK1 and PIK3R1. These interactions were validated through molecular docking studies, which demonstrated strong binding affinities, and molecular dynamics simulations, which confirmed stable protein-ligand complexes. The findings suggest that P. amaryllifolius may counteract cardiotoxicity by modulating oxidative stress, reducing inflammation, and targeting key pathways involved in cardiac damage. This study positions pandan leaf extract as a promising therapeutic candidate not only for drug-induced cardiotoxicity but also for broader cardiovascular conditions, providing a foundation for further research and development.