Abstract
BACKGROUND: Panax ginseng C. A. Mey (ginseng) is a traditional Chinese medicinal herb used for the treatment of nervous system disorders, such as Alzheimer's disease (AD). However, the pharmacological mechanisms of ginseng involved in AD have not been systematically investigated. Here, a network pharmacology approach was adopted to explore the effective components, core targets, and key pathways of ginseng against AD. METHODS: TCMSP database was used to screen the active ingredients of ginseng. Prediction of the targets of ginseng and AD-related genes was performed using online public databases. "Compound-Target," "Compound-Target-Disease," "Protein-Protein Interaction (PPI)," "Compound-Target-Pathway," and "Compound-Target-GO-Pathway" networks were constructed with Cytoscape 3.7.2 software. Gene Ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed by using the DAVID database. RESULTS: A total of 22 bioactive compounds were identified from ginseng, and 481 targets of ginseng and 763 AD-related targets were obtained from public databases. The PPI network screened out 19 hub genes of ginseng against AD. According to GO function enrichment, ginseng influenced cell proliferation, death, the nitric oxide biosynthetic process, hypoxia response, and synaptic transmission. Neuroactive ligand-receptor interaction, serotonergic synapse, calcium signaling, cAMP signaling, FoxO signaling, Ras signaling, and PI3K-AKT signaling were among the most key regulatory pathways. The compound-target-GO-route network found EGFR, MAPK1, MAPK14, AKT1, CASP3, and PRKACA as key genes, with PI3K-AKT signaling being the most important pathway for ginseng's anti-AD activity. CONCLUSION: Ginseng exerts neuroprotective effects in AD patients through multicomponent, multitarget, and multipathway modes, providing novel insight into the pharmacological and experimental research on ginseng against AD.