Therapeutic enhancement and toxicity reduction of total glucosides of paeony combined with conventional therapy in juvenile idiopathic arthritis: a meta-analysis and network pharmacology

Objective This study aimed to evaluate the efficacy and safety of total glucosides of paeony (TGP) combined with conventional therapy in juvenile idiopathic arthritis (JIA) and explore the network regulatory mechanisms underlying TGP's synergistic enhancement and toxicity reduction effects. Method We searched for randomized controlled trials (RCTs) on the efficacy of TGP combined with conventional therapy in JIA until 1 February 2026 (databases: PubMed, Embase, Web of Science, Cochrane Library, SinoMed, Chinese National Knowledge Infrastructure, Wanfang, and VIP). The outcome measures included overall effective rate, adverse reactions, inflammation indicators, autoantibody levels, and clinical symptoms. Subsequently, an integrative pharmacology approach was employed to construct a “drug target–efficacy/toxicity gene” interaction network, elucidating potential molecular mechanisms of TGP's synergistic and toxicity-reducing effects. Result A total of 17 RCTs were included, involving 966 children with JIA. Compared with conventional Western medicine alone, TGP combination therapy significantly improved the overall response rate [risk ratio (RR) = 1.13, 95% confidence interval (CI) 1.07–1.19, P < 0.0001]and reduced the incidence of adverse events (RR = 0.63, 95% CI 0.43–0.91, P = 0.02), markedly ameliorating serum inflammatory indicators [interleukin (IL)-1, IL-17, tumor necrosis factor α , C-reactive protein, and erythrocyte sedimentation rate], autoantibody levels, and clinical symptoms in JIA patients. The “drug target–efficacy/toxicity gene” interaction network revealed that TGP exerts synergistic effects primarily by regulating energy metabolism, alleviating oxidative stress and inflammation, and suppressing synovitis and osteoclastogenesis. Its toxicity-reducing effects were mediated through the inhibition of hepatic inflammation, oxidative stress, and angiogenesis, as well as modulation of lipid and amino acid metabolism. Notably, oxidative stress and lipid metabolism emerged as potential common mechanisms for TGP enhancement and toxicity reduction. Conclusion The therapy of TGP combined with conventional Western medicine could enhance clinical efficacy and reduce adverse events in JIA patients. The synergistic and toxicity-reducing mechanisms of TGP might be associated with multi-pathway regulation, particularly involving oxidative stress and lipid metabolism.