Analysis of the anti-Alzheimer potential of bioactive compounds from DC. peel, leaf, and essential oil by network pharmacology.

Alzheimer's disease (AD) is the most known neurodegenerative disease, and its prevalence is predicted to increase significantly. Discovering novel drugs and treatments for AD is urgently needed. Drugs from natural products have been preferred lately due to their high potential and low toxicity. DC. (kaffir lime; KL) is one such herbal plant that is found abundantly in Southeast Asia with many biological activities. In this study, the potential of bioactive compounds from KL peel, leaf, and essential oil as anti-AD agents was explored using network pharmacology. First, the compounds were identified with KNApSAcK database and related literature. Subsequently, the targets of each corresponding compound were determined with SEA Search Server and Swiss Target Prediction, while the proteins associated with AD were identified using OMIM, GenCLiP3, and DisGeNET. Furthermore, a protein-protein interaction network and a compound-target interaction network were constructed to identify the most crucial proteins and compounds in the network by employing Cytoscape v3.9.1. The study continued with pathway enrichment analysis using STRING v1.7.1, molecular docking with PyRx and SwissDock, and molecular dynamics simulation with YASARA for further confirmation. Our results showed that almost all the secondary metabolites of KL targeted AD-associated genes, with oxypeucedanin and citrusoside A showing the highest anti-AD potential and targeting essential genes, EGFR and MAPK14, respectively. These targets were associated with inflammatory and oxidative stress pathways, indicating the potential mechanism of KL in attenuating AD clinical manifestation.