Icariin decreases cell proliferation and inflammation of rheumatoid arthritis-fibroblast like synoviocytes via GAREM1/MAPK signaling pathway.

Objective: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation and joint damage, leading to pain and reduced joint function. Icariin, a flavonoid compound, has been studied for its potential therapeutic role in RA due to its anti-inflammatory and anti-proliferative effects. Here, we aimed to investigate the action mechanism of icariin in regulating RA.

Materials and methods: Fibroblast-like synoviocytes (FLS) were obtained from RA and trauma patients, generating RA-FLS and normal FLS. The cells were treated with varying concentrations of icariin (0, 10, 20, 40, 80 μM). We assessed the effects of icariin on cell proliferation, apoptosis, and levels of inflammatory factors using the CCK-8 assay, flow cytometry, and enzyme-linked immunosorbent assay, qRT-PCR, and western blotting.

Results: Icariin treatment had no significant impact on the cell proliferation of normal FLS. However, it dose-dependently repressed cell proliferation, reduced TNF-α, IL-6, and IL-1β levels, and increased apoptosis in RA-FLS. The expression of GAREM1, p-p38, and p-ERK1/2 was upregulated in RA-FLS, which was reversed by icariin treatment. Overexpression of GAREM1 reversed the inhibitory effects of icariin on cell proliferation and inflammatory factor levels in RA-FLS.

Conclusion: Our findings suggest that icariin treatment can alleviate the development of RA by reducing cell proliferation and inflammation in RA-FLS through the regulation of the GAREM1/MAPK signaling pathway. These results support the potential of icariin as a therapeutic agent for RA treatment. As icariin is safe and well-tolerated in previous studies, further research is warranted to explore its efficacy in clinical settings.