Several studies have demonstrated that celastrol has cellular targets in the context of RA, such as TAK1/IKK and MAPK/MEK pathways as well as MMP-9, STAT3, RANKL, and MD2/TLR4, interfering with the production of cytokines, chemokines, and inflammatory mediators; inhibiting cell invasion and proliferation; and suppressing bone resorption (5, 9, 14, 47). This evidence concerns the gene TLR4 and rheumatoid arthritis.