Wenyang Yishen Tongluo prescription synergizes with bone marrow mesenchymal stem cells to alleviate rheumatoid arthritis via inhibiting IL-6.

This study investigated the synergistic anti-arthritic effects of Wenyang Yishen Tongluo Prescription (TLP) combined with bone marrow mesenchymal stem cells (BMSCs) in rheumatoid arthritis (RA). A collagen-induced arthritis (CIA) rat model was established, and animals were divided into groups receiving TLP, BMSCs, or combination therapy. Network pharmacology identified IL-6 as a core target of TLP, which was further validated by molecular docking and cellular thermal shift assay (CETSA). The combination therapy reduced arthritis index score by 34.41% compared with the model group, alleviated synovial hyperplasia and fibrosis, synergistically downregulated autoantibody rheumatoid factor (RF), pro-inflammatory factors (TNF-α, MMP-9, VEGFA), and bone-resorptive factor RANKL, while upregulating bone-protective factors (BMP-7, OPG) and immunosuppressive molecules (TGF-β1, PD-1, FOXP3). Mechanistically, TLP restored BMSC function by inhibiting IL-6 and its downstream phosphorylation of NF-κB, STAT3, and Akt pathways, as demonstrated by IL-6 overexpression experiments. These findings demonstrate that TLP combined with BMSCs synergistically ameliorates the inflammatory microenvironment, restores immune balance, and reduces bone damage in RA by targeting IL-6 and its downstream signaling, offering a safe and effective integrative treatment strategy.