Investigation of the Role and Mechanism of Euonymus alatus (Thunb.) Siebold in the Treatment of Rheumatoid Arthritis Through Comprehensive Bioinformatic and Experimental Analyses

Background: This study aimed to investigate the main active ingredients and potential mechanism of action of Euonymus alatus (Thunb.) Siebold (EA), a traditional Chinese medicine that is used to alleviate symptoms of rheumatoid arthritis (RA). Methods: Potential targets of EA and related pathways in the treatment of RA were identified using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis tools, SymMap, GeneCards, Swiss Target Prediction database, Metascape, and molecular docking. The anti-inflammatory effect of the predicted core active ingredient in EA was validated using lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro. Results: The main active ingredients in EA that are influential in the treatment of RA are likely to be flavonoids and polyphenols, such as kaempferol, quercetin, baicalein, wogonin, and oroxylin A. These active ingredients may target AKT1, BCL2, IGF1R, SRC, PTGS2, and EGFR to affect the NF-κB, mTOR, and related signaling pathways, as determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Meanwhile, the molecular docking results suggested that these active ingredients most likely target AKT1, BCL-2, and PTGS-2. Experimental studies have shown that the EA active ingredient, baicalein, can suppress macrophage proliferation, TNF-α expression, and reactive oxygen species (ROS) production. Conclusion: The active ingredients in EA may target AKT, BCL-2, and PTGS-2 to mediate the regulation of the PI3K/AKT signaling pathway in RA treatment.