Unveiling the Mechanism of Cibotium barometz in the Treatment of Rheumatoid Arthritis: A Study Based on Network Pharmacology and Experimental Validation.

OBJECTIVE: Cibotium barometz, a perennial arborescent fern of the family Cibotiaceae widely distributed in tropical and subtropical mountainous regions of China, exhibits significant therapeutic efficacy against Rheumatoid Arthritis (RA). This study aims to reveal the key molecular mechanisms underlying Cibotium barometz in the treatment of RA through an integrated approach combining network pharmacology and experimental validation. METHODS: Active components and targets of Cibotium barometz were identified using Herb and TCMSP databases, and RA-related targets from GeneCards. A compound-target network was constructed, followed by PPI and KEGG analyses. Aqueous Extract of Cibotium barometz (AECB) was prepared and analyzed by LC-MS. RA-derived Fibroblast- like Synoviocytes (RA-FLS) were isolated and treated with AECB for in vitro validation. RESULTS: Network pharmacology identified 7 active components and 104 RA-related targets. LC-MS confirmed the presence of all 7 components in AECB. PPI highlighted IL-6 as a key target, and KEGG pointed to inflammation-related pathways. TNF-α stimulation enhanced IL-6 expression and activated NF-κB, p38 MAPK, and AKT signaling in RA-FLS, whereas AECB dose-dependently suppressed these responses. DISCUSSION: This study predicted the molecular mechanisms of Cibotium barometz in treating RA through network pharmacology and identified its key bioactive components and core hub targets. Experimental results showed that AECB can effectively downregulate the expression of pro-inflammatory cytokines by modulating inflammation-related pathways. CONCLUSION: Network pharmacology and experimental validation demonstrate that the therapeutic effect of Cibotium barometz on RA is closely associated with inhibition of inflammatory pathways and cytokine release.