Danggui Beimu Kushen Pill Alleviates Colitis-Induced Inflammation in Mice by Regulating the IL-6/IL-6R and...

Background/Objectives: Danggui Beimu Kushen pill (DBK) is a traditional Chinese medicine renowned for its efficacy in the treatment of inflammatory conditions. It has been used in the modern clinical treatment of ulcerative colitis (UC). Further research is required to clarify its underlying mechanisms. Methods: DBK compounds were analyzed using UPLC-ESI-MS/MS. A mouse model of Dextran sulfate sodium (DSS)-induced UC was used to assess the efficacy of DBK. Network pharmacology identified DBK targets in UC, which were validated by molecular docking simulations. Cytokine levels were quantified using ELISA. Western blotting, immunofluorescence (IF), and immunohistochemistry (IHC) were employed to explore its underlying molecular mechanisms. Results: DBK treatment enhanced body weight and colon length in mice with DSS-induced colitis. Inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IL-23, and IL-17A) were notably decreased in both serum and colon tissues. Network pharmacology and molecular docking analyses identified the IL-6/IL-6R and IL-17A/IL-17RA signaling pathways as crucial for the DBK treatment of UC. Additional validation using WB, IHC, and IF analyses demonstrated that DBK alleviated UC by suppressing the IL-6/STAT3 and IL-17/TRAF6/NF-κB pathways. Conclusions: DBK mitigates intestinal injury in mice with DSS-induced colitis and exerts therapeutic effects on UC by inhibiting the IL-6/IL-6R and IL-17A/IL-17RA signaling pathways to reduce inflammation. These findings provide significant insights into the mechanism of DBK treatment for UC.