<i>Tripterygium wilfordii</i> Hook. f. and Xinfeng capsule in rheumatoid arthritis: a review of clinical evidence, molecular mechanisms, and translational perspectives.

Abstract

<i>Tripterygium wilfordii</i> Hook. f. (TWHf) has long been used in traditional medicine to treat rheumatoid arthritis (RA); however, but its clinical application needsrequires a balanced understanding of its efficacy, mechanismsms, and safety. This review aimed to summarize the efficacy, mechanisms, clinical evidence, and translational challenges of TWHf-derived monomers, Tripterygium Glycosides Tablets (TGT), and Xinfeng Capsule (XFC) in RA. We searched relevant studies in PubMed, Web of Science, Scopus, Embase, and CNKI from database inception to [insert search date] for eligible studies. These include clinical trials, preclinical studies, pharmacological investigations, and mechanistic studies on TWHf/XFC in RA. Preclinical evidence indicates that TWHf-derived compounds regulate multiple RA-related processes, including the NF-&#x3ba;B and PI3K/AKT/mTOR signaling pathways, ROS-NLRP3 inflammasome activation, synovial hyperplasia, angiogenesis, and immune cell dysfunction. Compared with isolated monomers, XFC exhibits broader multi-component and multi-target regulation, involving epigenetic modulation, NETosis, cuproptosis, pyroptosis, oxidative stress, and coagulation homeostasis, which may enhance efficacy and reduce toxicity via compound compatibility. Clinical studies suggest that TWHf-related preparations may improve disease activity, joint symptoms, and inflammatory markers, whether used alone or in combination with conventional DMARDs or biologics. However, several major challenges remain, such as toxicity, insufficient high-quality multicenter RCTs, limited standardization, and a lack of personalized dosing. Future studies should focus on standardized formulations, rigorous clinical evaluation, safety monitoring, and toxicity-attenuating delivery systems, as well as biomarker-guided precision application of TWHf and XFC in RA.