In OA models, U50,488H attenuates M1 macrophage polarization through NF-κB inhibition (Shi et al., 2024), whereas the non-selective antagonist naltrexone exerts similar anti-inflammatory effects by targeting the Toll-like receptor 4 (TLR4)/NF-κB axis in rheumatoid arthritis (Xu et al., 2020). This evidence concerns the gene TLR4 and rheumatoid arthritis.