Mechanistic Study of Yibi Decoction in Treating Rheumatoid Arthritis via Modulating the JAK2/STAT3 Signaling Pathway.

INTRODUCTION/

OBJECTIVE

To investigate the therapeutic effects of Yibi Decoction (YBD) in rheumatoid arthritis (RA) and to elucidate the underlying mechanisms, with a particular focus on the JAK/STAT signaling pathway.

METHODS

Network pharmacology analysis was employed to predict the bioactive compounds and potential therapeutic targets of Yibi Decoction. A collagen-induced arthritis (CIA) rat model was established to validate the predicted effects in vivo. Western blotting, enzyme-linked immunosorbent assay (ELISA), and histopathological analyses were conducted to evaluate alterations in joint tissues and serum inflammatory biomarkers.

RESULTS

Network pharmacology analysis identified 128 bioactive components in YBD, among which quercetin and luteolin were predicted to be key active compounds. In CIA rats, YBD treatment significantly downregulated the expression of IL-6, IL-17, IL-23, JAK2, and STAT3 in ankle joint tissues (P < 0.05), and markedly reduced serum levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (P < 0.05). In parallel, the arthritis index was significantly decreased, and histopathological examination revealed substantial attenuation of synovial hyperplasia and cartilage destruction.

DISCUSSION: These findings suggest that YBD exerts anti-rheumatoid arthritis effects through a multi-component, multi-target regulatory mechanism involving inhibition of the JAK/STAT signaling pathway. Quercetin and luteolin may contribute to these effects by suppressing pro-inflammatory cytokine production and ameliorating joint pathological changes.

CONCLUSION

YBD ameliorates rheumatoid arthritis by suppressing the JAK/STAT signaling pathway and associated inflammatory responses, thereby providing a mechanistic basis for its potential therapeutic application in rheumatoid arthritis.