Exploring the potential mechanism of Polygonatum sibiricum for Alzheimer's disease based on network pharmacology and...

Alzheimer's disease (AD) is a neurodegenerative disease, and there have been no systematic studies of Polygonatum against Alzheimer's disease. Therefore, our study will elucidate the mechanism of Polygonatum against AD based on network pharmacology and molecular docking. The active ingredients and corresponding targets of Polygonatum were identified using the traditional Chinese medicine systematic pharmacology database and analysis platform. Disease targets of AD were retrieved from the therapeutic target database, Online Mendelian Inheritance in Man, GeneCards, and Disgenet databases. Using the STRING database, we constructed protein interaction networks and performed gene ontology functional enrichment analysis as well as Kyoto encyclopedia of genes and genomes pathway enrichment analysis on common targets. We then drew drug-component-target-pathway-disease network maps using Cytoscape 3.10.1 software and validated the molecular docking using AutoDock4. A total of 10 active ingredients and 108 common targets were screened from Polygonatum, 29 genes (including AKT1 and STAT3) were identified as core genes. According to gene ontology analysis, the core targets were found to be mainly involved in signal transduction, positive regulation of gene expression, negative regulation of the apoptotic process, and so on. The Kyoto encyclopedia of genes and genomes analysis revealed that the signaling pathways comprised pathways in cancer, pathways of neurodegeneration - multiple diseases, and PI3K-Akt signaling pathway. The molecular docking results indicated that 10 of active ingredients from Polygonatum exhibited strong binding affinity with the 6 core targets that were screened before. The activity of Polygonatum against AD could be attributed to the regulation of multiple biological effects via multi-pathways (pathways in cancer, pathways of neurodegeneration - multiple diseases, and PI3K-Akt signaling pathway). The binding activities were estimated as good level by molecular docking. These discoveries disclosed the multi-component, multi-target, and multi-pathway characteristics of Polygonatum against AD, providing a new strategy for such medical problem.