Therefore, we pretreated RA synovial fibroblasts with 4-HMC for 1 h and stimulated them with TNF-α for different durations; the cells were stimulated with TNF-α for 15 min (PI3K and Akt), 30 min (IKKα/β, N-NF-κB, and IκBα), or 18 h (MMP-1 and MMP-3). This evidence concerns the gene MMP1 and rheumatoid arthritis.