Fengshi gutong capsules attenuates CIA-induced RA bone destruction in rats by targeting TNF-α inhibition: Integration and experimental validation of network pharmacology and proteomics.

ETHNOPHARMACOLOGICAL RELEVANCE

Fengshi Gutong Capsule (FSGT) is a proprietary Chinese medicine with established clinical efficacy in Rheumatoid arthritis (RA); however, its underlying mechanisms remain unclear.

AIM

This study aims to elucidate the mechanisms by which FSGT alleviates RA.

MATERIALS AND METHODS

A collagen-induced arthritis (CIA) rat model was employed to assess the therapeutic effects of FSGT in RA. Network pharmacology and proteomics were integrated to identify potential mechanism and molecular targets, which were further validated via Western blot analysis. Molecular docking and microscale thermophoresis (MST) were utilized to assess the binding affinities of FSGT's active components to key proteins.

RESULTS

FSGT (280 and 840 mg/kg) alleviated CIA-induced RA in rats without significant side effects. Network pharmacology and label-free proteomic analysis displayed that FSGT exerted its therapeutic effects by modulating inflammation and bone destruction. FSGT significantly reduced serum levels of inflammatory cytokines and their protein expression in the ankle joints and synovial tissues. Additionally, FSGT attenuated bone destruction and significantly reversed the expression of bone destruction-related proteins. Molecular docking revealed that 18 active compounds in FSGT exhibited strong binding affinity for TNF-α, with hypaconitine, 18α-glycyrrhizic acid, and naringenin further validated by MST assays.

CONCLUSION

FSGT improved CIA-induced RA in rats by targeting TNF-α to reduce inflammation and inhibit bone destruction, offering insights into its therapeutic mechanisms in RA.