LAUSR

Total saponins of Panax japonicus (TSPJ) are extracted from Panax japonicus (T.Nees) C.A.Mey and have achieved a good therapeutic effect in the treatment of rheumatoid arthritis (RA). Unfortunately, the mechanism of TSPJ acting on RA is not clear.To investigate the potential mechanisms and key targets of TSPJ on RA.The raw data were downloaded from the Gene Expression Omnibus (GEO) database, and the RStudio3.6.1 software was used to identify differentially expressed genes (DEGs). The potential targets of active compounds from TSPJ were predicted by the Pharmmapper and SwissTargetPrediction databases. Based on the overlapping genes, we used Cytoscape 3.7.2 software to construct a protein-protein interactions (PPI) network and to determine the mechanisms of the treatment by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Collagen-induced arthritis (CIA) model was established and treated with different doses of TSPJ. Arthritis index (AI) and histology score were used to evaluate the symptoms of CIA. The levels of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1 (HIF-1), IL-1β, and IL-17A tested by enzyme linked immunosorbent assay and real time-quantitative Polymerase Chain Reaction.A total of 2670 DEGs and 371 TSPJ targets were obtained, including 52 overlapping genes. 41 genes had protein interactions that are used to build the PPI network. The results of the KEGG enrichment analysis included VEGF and HIF-1 signaling pathway. Seven negative correlation genes and 16 positive correlation genes were obtained by correlational analysis of DEGs in VEGF and HIF-1 signaling pathway. SRC proto-oncogene, nonreceptor tyrosine kinase (SRC), and the signal transducer and the activator of transcription 3 (STAT 3) had a higher value of degree in PPI and showed a significant correlation in the pathways; they were regarded as key targets. Compared with the CIA model group, TSPJ significantly decreased the AI and histology scores. Moreover, the expression of VEGF-A, HIF-1α, IL-1β, and IL-17A in serum or spleens significantly reduced in a dose-dependent.Present study show that SRC and STAT 3 may be the key targets of TSPJ acting on the VEGF and HIF-1 signaling pathways, thus inhibiting angiogenesis and improving RA.None declared