Exploring the Mechanism of Saponins from Panax japonicus in Improving Alzheimer's Disease Based on Network Pharmacology and Molecular Docking.

Abstract

Introduction: To study the mechanism of saponins from Panax japonicus (SPJ) in improving Alzheimer's disease based on network pharmacology and molecular docking technology.

Methods: The active components in the SPJ were obtained from the databases of CNKI, PubMed, and PubChem. The active component targets were retrieved from the databases of Swiss Target Prediction and Super-PRED. The disease targets were retrieved from the databases GeneCards, OMIM, and PharmGKB. Drug-disease intersection targets were obtained via Venny 2.1.0. The String database was utilized to establish the protein network. The drug- active ingredient- target network was constructed by Cytoscape 3.10.1 software. The Metascape database was employed to conduct the gene ontology function enrichment analysis and KEGG pathway enrichment analysis. AutoDock Tools 1.5.7 was used to perform the molecular docking analysis.

Results: A total of 57 active components were obtained from the SPJ, and 438 drug targets and 2294 disease targets were identified, including 169 identical targets. The key targets were SRC, STAT3, PIK3R1, AKT1, ESR1, EGFR, and JUN. Pseudoginsenoside F11, Vina-ginsenoside R2, and Chikusetsusaponin III might be the key active components of SPJ in improving Alzheimer's disease. The key active components showed good binding energy and better binding affinity within the active targets.

Discussion: Network pharmacology has screened out 57 potential active components of SPJ, including pseudo ginsenoside F11, ginsenoside R2, and III, which may exert therapeutic effects by acting on key targets such as SRC, STAT3, PIK3R1, AKT1, ESR1, EGFR, and JUN. These targets are closely related to core pathological processes of AD, such as Aβ production, Tau protein phosphorylation, neuroinflammation, neuronal survival, and synaptic plasticity. Functional analysis indicates that SPJ may act on multiple cellular sites, such as receptor complexes and synaptic membranes, by influencing biological processes such as cell migration, inflammatory response, and membrane potential regulation. Pathway enrichment suggests that its mechanism of action may be related to Alzheimer's disease pathways, the NF-κB signaling pathway, and the calcium signaling pathway. The continuous activation of NF-κB can exacerbate neuroinflammation and oxidative damage, while the disorder of the calcium signaling pathway will lead to intracellular calcium overload, mitochondrial dysfunction, and synaptic damage, all of which play key roles in the progression of AD.

Conclusion: SPJ exerts a therapeutic effect and provides the basis for Alzheimer's disease through multiple components, targets, and pathways.