Work

Fraxetin inhibits TNFα-mediated synoviocyte activation and attenuates disease progression in a rat model of rheumatoid arthritis

Year: 2025

Type: article

Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease that profoundly affects patients' lives. Developing new treatments by screening small molecule compounds targeting RA-related signaling pathways is a key area of research. This study employs bioinformatics analysis, Western blotting, and cellular thermal shift assay (CETSA) to demonstrate, for the first time, that fraxetin may function as a novel natural MEK inhibitor, modulating RA pathogenesis via the MEK/ERK signaling pathway. We further evaluated fraxetin's therapeutic effects on collagen-induced arthritis (CIA) in rats in vivo and its inhibitory effects on TNFα-induced arthritic fibroblast-like synoviocytes (FLSs) in vitro. The results showed that fraxetin significantly alleviated ankle joint inflammation and bone destruction in CIA rats and markedly suppressed TNFα-induced proliferation, migration, and cytokine secretion (IL-1β, IL-6, and TNFα) in arthritic FLSs. These findings highlight fraxetin's potential as a promising therapeutic agent for RA.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2025.115391