Unraveling the therapeutic mechanism of Azadirachta indica phytocompounds against hypertension: an integrated network pharmacology, molecular simulation, and DFT studies

Hypertension is a major cardiovascular disease that contributes to various deadly diseases in humans. This study elucidated the mechanism by which A. indica regulates high blood pressure approaches. Phytochemicals from A. indica were screened with drug likeness properties, and then their significant genes were obtained from the SwizzTargetPrediction database. Protein–protein interaction and the Cytoscape tool were used to identify the top 10 targets. GO and KEGG enrichment studies were performed, followed by molecular docking of the targets with selected A. indica phytochemicals. The top-ranked molecules were subjected to molecular dynamics simulation and DFT studies. Of the ten hub genes identified, AKT1, EGFR, ESR1, PPARG, MAPK3 and SRC were directly implicated in hypertension. Molecular docking showed that vilasinin gave the best binding affinity against AKT1, meliantrol against PPARG and EGFR, nimbiol against MAPK3, and flowerone against ESR1 and SRC. The 100 ns MD simulation of these complexes suggested that the ligand exhibited stability and established important interactions. The electronic properties of the chemical compounds showed that the phytochemical exhibit good stability, reactivity, and electrophilicity index. Comprehensive in vivo and in vitro antihypertensive studies of the A. indica phytochemicals are recommended for further studies.