Defining the Role of Isoeugenol from Ocimum tenuiflorum against Diabetes Mellitus-Linked Alzheimer’s Disease through Network Pharmacology and Computational Methods

Abstract

The present study involves the integrated network pharmacology and phytoinformatics-based investigation of phytocompounds from <i>Ocimum tenuiflorum</i> against diabetes mellitus-linked Alzheimer's disease. It aims to investigate the mechanism of the <i>Ocimum tenuiflorum</i> phytocompounds in the amelioration of diabetes mellitus-linked Alzheimer's disease through network pharmacology, druglikeness and pharmacokinetics, molecular docking simulations, GO analysis, molecular dynamics simulations, and binding free energy analyses. A total of 14 predicted genes of the 26 orally bioactive compounds were identified. Among these 14 genes, GAPDH and AKT1 were the most significant. The network analysis revealed the AGE-RAGE signaling pathway to be a prominent pathway linked to GAPDH with 50.53% probability. Upon the molecular docking simulation with GAPDH, isoeugenol was found to possess the most significant binding affinity (-6.0 kcal/mol). The molecular dynamics simulation and binding free energy calculation results also predicted that isoeugenol forms a stable protein-ligand complex with GAPDH, where the phytocompound is predicted to chiefly use van der Waal's binding energy (-159.277 kj/mol). On the basis of these results, it can be concluded that isoeugenol from <i>Ocimum tenuiflorum</i> could be taken for further in vitro and in vivo analysis, targeting GAPDH inhibition for the amelioration of diabetes mellitus-linked Alzheimer's disease.