Notably, both BHGZD and the two-BAC combination of MG and CA effectively improved disease severity of active RA rats including elevating pain thresholds, relieving joint inflammation and bone erosion via inhibiting TLR4/PI3K/AKT/NFκB signaling to suppress the activation of the NLRP3 inflammasome, leading to the downregulation of downstream caspase-1, the reduced release of IL-1β, and the modulation of GSDMD-mediated pyroptosis. This evidence concerns the gene TLR4 and rheumatoid arthritis.