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

Why It Matters

TGP offers a multi‑targeted, potentially safer adjunct for AS, addressing unmet needs in inflammation control and functional preservation, and could broaden therapeutic options beyond NSAIDs and biologics.

Key Takeaways

• TGP improves spinal function and inflammatory markers in AS patients
• Meta‑analysis of 28 RCTs shows higher clinical efficacy rates
• Benzoylpaeoniflorin binds TLR4 with strongest affinity
• Safety profile indicates fewer gastrointestinal and liver adverse events
• Targets include TLR4, NF‑κB, mTOR, HIF1A, CXCR4

Pulse Analysis

Ankylosing spondylitis remains a therapeutic challenge, with NSAIDs, DMARDs, and biologics offering limited long‑term efficacy and notable side‑effects. In this context, total glucosides of paeony—a purified extract from the traditional Chinese herb white peony root—has emerged from recent Asian clinical data as a promising adjunct. The meta‑analysis of 28 randomized studies demonstrates consistent improvements in disease activity indices such as BASDAI and BASFI, alongside measurable reductions in ESR and CRP, suggesting that TGP can meaningfully modulate the inflammatory cascade driving spinal fusion.

Beyond clinical outcomes, the study leverages network pharmacology to map TGP’s molecular footprint. Seven hub proteins—TLR4, NFKB1, HSP90AA1, MTOR, HIF1A, ITGB1, and CXCR4—were identified, converging on Toll‑like receptor and NF‑κB signaling pathways that are pivotal in AS pathogenesis. Molecular docking highlighted benzoylpaeoniflorin as the lead ligand, exhibiting a binding energy of ‑9.2 kcal/mol to TLR4, while 100‑nanosecond dynamics simulations confirmed a stable ligand‑receptor complex. These mechanistic insights provide a biologically plausible explanation for the observed clinical benefits and open avenues for targeted drug development.

For clinicians and investors, the implications are twofold. First, integrating TGP into existing treatment regimens could reduce reliance on high‑cost biologics and mitigate adverse gastrointestinal or hepatic events. Second, the multi‑targeted nature of TGP aligns with precision‑medicine trends, encouraging further high‑quality, multicenter trials across diverse populations to validate efficacy and safety. As the global market for biologic‑sparing therapies expands, TGP stands poised to become a valuable component of an integrated AS management strategy.