Integration of phytochemical profiling and computational approaches to evaluate the neuroprotective potential of Nardostachys jatamansi in Alzheimer's disease

Despite broad spectrum utility of Nardostachys jatamansi (D. Don) DC, little is known about the molecular processes that underlie its anti-Alzheimer action. To investigate the molecular targets and therapeutic potential of N. jatamansi for Alzheimer's disease (AD), we used Gas Chromatography-Mass Spectrometry (GC-MS), ADMET analysis, network pharmacology, differential gene expression analysis, molecular docking, and molecular dynamics (MD) simulations. The STITCH database was used for network creation and protein-protein interaction analysis, while Cytoscape was used for network visualization and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) for term enrichment. Additionally, to investigate the intermolecular interactions between the active chemicals and target proteins, molecular docking experiments were conducted using the Blind docking on the Achilles server. The stability of the PS1 gene complex with Spirojatamol, was further evaluated using MD simulations. With Spirojatamol showing the highest binding energy scores against PS1 (−6.9 kcal/mol), molecular docking confirmed the activity of this metabolite against AD targets PS1 and Spirojatamol formed a stable complex at 100 nanoseconds, according to additional investigation using MD simulations. Significant ligand-protein interactions were verified by binding free energy calculations using the MM/GBSA technique. The PS1-Spirojatamol complex had a binding energy of ΔG: −36.95 ± 5.00 kcal/mol. By focusing on several genes and pathways, involved in AD, this work reveals the molecular underpinnings behind N. jatamansi possible use in the treatment of AD.