Introduction:
Emodin (EMO), a natural derivative of the
anthraquinone family mainly extracted from rhubarb (Rheum palmatum), has previously been demonstrated to possess superior anti-inflammatory properties from a single target or pathway. In order to explore the underlying mechanism of action of EMO against
rheumatoid arthritis (RA), a network pharmacology approach was employed. Methods: A gene expression profile from GSE55457 available from the Gene Expression Omnibus (GEO) database was used to identify the targets of EMO action. Further, single cell
RNA sequencing data from GEO database of RA patients (GSE159117) were downloaded and analysed. To further investigate the anti-RA effect of EMO on MH7A cells, the expression of
IL-6 and IL-1β were monitored. Finally,
RNA-seq analyses were conducted on synovial fibroblasts from EMO-treated. Result: We screened the key targets of EMO against RA using network pharmacology methods, including
HMGB1, STAT1, EGR1, NR3C1, EGFR,
MAPK14,
CASP3, CASP1,
IL4,
IL13,
IKBKB and FN1, and their reliability was verified using ROC curve. Single-cell
RNA sequencing data analysis showed that these core target
proteins mainly played a role by modulating monocytes. The anti-RA effect of EMO was further verified with MH7A cells, which showed that EMO could block cell differentiation and reduce the expression of
IL-6 and IL-1β. WB experiments confirmed that EMO could affect the expression of COX2, HMBG1 and the phosphorylation of p38. Finally, sequencing of synovial fibroblasts from rats treated with EMO showed consistent results with those predicted and verified, further proving the anti-inflammatory effect of EMO. Conclusion: Our research shows that EMO inhibits inflammatory response of
rheumatoid arthritis (RA) by targeting
HMGB1, STAT1, EGR1, NR3C1, EGFR,
MAPK14,
CASP3, CASP1,
IL4,
IL13,
IKBKB, FN1 and Monocytes/macrophages.