Efficacy and potential pharmacological mechanisms of total glucosides of paeony in treating ankylosing spondylitis in Asian populations: a meta-analysis, network pharmacology, and molecular dynamics simulation

Background Ankylosing spondylitis (AS) is a chronic autoimmune disorder, accompanied by a notably high disability rate and limited treatment options. White peony root is a classic nourishing Chinese medicinal herb with immune-modulating effects. Its glycoside components-Total glucosides of paeony (TGP), a natural compound, exhibits anti-inflammatory and immunomodulatory effects. However, little is currently known about the efficacy and safety of TGP therapy for treating AS. Purpose This study aimed to provide evidence-based support for the efficacy and safety of TGP in treating ankylosing spondylitis and to explore the potential mechanisms underlying TGP therapy for this disease. Methods A search strategy combining keywords and free-text terms was employed to retrieve studies from eight databases: CBM, CNKI, VIP, Wanfang, Embase, PubMed, Cochrane Library, and Web of Science. Statistical analysis was conducted using RevMan 5.4 software, with evidence quality assessed via the GRADE system. Additionally, network pharmacology, molecular docking, and molecular dynamics simulations (constant pressure for 100 ns) were utilized to further analyze the potential targets and pathways involved in TGP’s therapeutic effects on AS. Results The meta-analysis ultimately included 28 studies involving 2,130 patients, with results indicating that the TGP combination therapy group significantly improved spinal function in AS patients, reduced inflammatory responses, enhanced quality of life, and played a crucial role in anti-inflammatory and immune modulation with favorable safety profiles. The therapeutic targets of TGP in AS include TLR4, NFKB1, HSP90AA1, HIF1A, MTOR, ITGB1, and CXCR4, with its mechanism of action linked to TLR and NF-κB pathways. Molecular docking and MD simulations revealed benzoylpaeoniflorin exhibits the strongest binding affinity, suggesting TGP may regulate AS pathogenesis by interacting with TLR4. Conclusion TGP demonstrates favorable clinical efficacy in treating AS, with a multi-targeted intervention mechanism that holds therapeutic promise. Systematic review registration The study was prospectively registered in PROSPERO (Registration No. CRD: 420251111863, URL: https://www.crd.york.ac.uk/PROSPERO/ ).