Juanbi Qianggu Formula Alleviates Rheumatoid Arthritis by Suppressing the TNF-α/NF-κB Signaling Pathway

Juanbi Qianggu Formula (JBQGF) is a traditional Chinese medicine prescription with demonstrated clinical efficacy in rheumatoid arthritis (RA), yet its pharmacological mechanisms remain unclear. This study investigated whether JBQGF attenuates RA-associated inflammation by inhibiting the TNF-α/NF-κB signaling pathway. In a collagen-induced arthritis (CIA) mouse model, JBQGF significantly ameliorated joint swelling, bone erosion, and systemic inflammation, with efficacy comparable to methotrexate, and reduced serum and synovial TNF-α levels. In LPS-stimulated RAW 264.7 macrophages, JBQGF-containing serum suppressed NF-κB p65 nuclear translocation and downregulated TNF-α, iNOS, and COX-2 expression. Transcriptomic profiling of synovial tissue, coupled with functional rescue assays, revealed that JBQGF directly suppresses TNFAIP2 expression via the primary NF-κB axis rather than secondary TNF-α depletion, thereby disrupting an NF-κB/TNFAIP2/ROS inflammatory cascade. These findings indicate that JBQGF targets the TNF-α/NF-κB pathway at multiple nodes to restore cellular inflammatory and redox balance, providing a mechanistic basis for its therapeutic effects in RA.