Academic Editor: Elisa Belluzzi
Objective: The aim of this study was to identify potentially important
Rheumatoid arthritis (RA) targets related to immune cells based on bioinformatics
analysis, and to identify small molecules of traditional Chinese medicine (TCM)
associated with these targets that have potential therapeutic effects on RA.
Methods: Gene expression profile data related to RA were downloaded from
the Gene Expression Omnibus (GSE55235, GSE55457, and GSE77298), and datasets were
merged by the batch effect removal method. The RA key gene set was identified by
protein-protein interaction network analysis and machine learning-based feature
extraction. Furthermore, immune cell infiltration analysis was carried out on all
DEGs to obtain key RA markers related to immune cells. Batch molecular docking of
key RA markers was performed on our previously compiled dataset of small
molecules in TCM using AutoDock Vina. Moreover, in vitro experiments
were performed to examine the inhibitory effect of screened compounds on the
synovial cells of an RA rat model. Results: The PPI network and feature
extraction with machine learning classifiers identified eight common key RA
genes: MYH11, CFP, LY96, IGJ,
LPL, CD48, RAC2, and CSK. RAC2 was
significantly correlated with the infiltration and expression of five immune
cells, with significant differences in these immune cells in the normal and RA
samples. Molecular docking and in vitro experiments also showed that
sanguinarine, sesamin, and honokiol could effectively inhibit the proliferation
of RA rat synovial cells, also could all effectively inhibit the secretion of
TNF-