Zhuangdu Quhan Mixture Alleviates Ankylosing Spondylitis in Mice by Inhibiting the Interleukin‐17 Signaling

This study aimed to elucidate the therapeutic effect and mechanism of Zhuangdu Quhan Mixture (ZDQHM) in ankylosing spondylitis (AS). An AS mouse model was established in mice using β-glucan. Therapeutic efficacy was assessed through arthritis scores, histopathology, serum cytokine measurement by ELISA, and bone metabolism-related protein analysis via Western blot. Active compounds were identified by UHPLC-MS, with targets predicted using network pharmacology and validated by molecular docking and molecular dynamics simulations. ZDQHM significantly ameliorated spinal inflammation and histopathological damage, reduced serum IL-6 and TNF-α levels, and modulated bone metabolism proteins. Network pharmacology identified 45 intersecting targets between ZDQHM compounds and AS, predominantly enriched in IL-17, Toll-like receptor, and NOD-like receptor pathways. Molecular docking and dynamics demonstrated binding of key compounds to IL-17A. In vivo validation revealed that ZDQHM suppressed IL-17A, Act1, and IL-17RA expression, and recombinant IL-17A partially reversed its therapeutic effects. ZDQHM alleviates inflammation and abnormal bone metabolism in AS mice, potentially through inhibition of the IL-17 signaling pathway. Beyond confirming the established role of IL-17 in AS, this study provides an integrated pharmacological framework explaining how ZDQHM exerts its effects via regulation of the IL-17A/IL-17RA/Act1 axis, offering mechanistic insights and experimental support for TCM in AS therapy.