Systemic mechanism of Panax noteginseng saponins in antiaging based on network pharmacology combined with experimental validation

Abstract

This study aims to investigate the systemic mechanism of Panax notoginseng saponins (PNS) in antiaging using network pharmacology combined with experimental validation. String database and Cytoscape3.7.2 were used to perform the protein–protein interaction (PPI) and construct genes network. The key target genes were analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, the aging-related genes were verified by reverse-transcription polymerase chain reaction in SAM-P/8 mice, and performed molecular docking with the main components of PNS. Moreover, it produced cluster between Hub genes and differential genes. A total of 169 crossover genes were obtained, and the results of GO and KEGG indicated that the antiaging effect of PNS was mediated by apoptosis, cancer, and neurodegeneration and that five of the eight Hub genes had good binding activity with the main components of PNS. In addition, animal experiments reported that MAP2, MAPKK4, RAB6A, and Sortilin-1 have different levels of expression in the brain tissues of aging mice, and bind well docking with the main active components of PNS. However, there was no crossover between the 169 PNS intersecting genes and the four differential genes, while they yielded a link from PPI in which MAP2K4 was only linked to AKT1 and CASP3; MAP2 was only linked to AKT1 and CASP3; RAB6A was only linked to AKT1; but Sortlin-1 did not link to the Hub genes. In summary, the antiaging effect of PNS is associated with the eight Hub genes and four differential genes. All of them consist of a cluster or group that is possibly related to the antiaging effect of PNS.