ObjectiveRheumatoid arthritis (RA) is a chronic inflammatory joint disease and the leading cause of joint-related limb disability. Traditional Chinese Medicine (TCM) offers certain advantages in RA treatment, and Tripterygium preparations are widely used due to their significant clinical efficacy. This study aimed to investigate the mechanism of action of Tripterygium Glycosides Tablets (TG) in the treatment of RA through in vivo and ex vivo experiments, providing a theoretical basis for clinical application.MethodsA collagen-induced arthritis (CIA) rat model was established, and the rats received oral administration of the corresponding drugs or distilled water for 4 weeks. The therapeutic effect and mechanism of TG on CIA rats were evaluated by comparing joint swelling severity, radiographic changes in the synovium, and alterations in the JAK/STAT signaling pathway and related inflammatory factors. Further ex vivo experiments were performed using fibroblast-like synoviocytes (FLS) as the research subject. Lentiviral infection technology was used to overexpress IGF1 or interfere with the expression of Lnc-ENST00000602558. Drug-containing serum was used for intervention. The mechanism of TG in treating RA was further elucidated by detecting changes in cell migration ability, the expression of IGF1 and Lnc-ENST00000602558, JAK/STAT pathway-related targets, and inflammatory factors.ResultsTG significantly improved joint swelling, bone and cartilage destruction in CIA rats, reduced synovial tissue hyperplasia, inhibited the JAK/STAT pathway and IGF1 in the rat joint synovium, lowered serum levels of the inflammatory factors TNF-α and IL-1β, alleviated joint damage, and delayed disease progression. Ex vivo experiments showed that the Lnc-ENST00000602558/IGF1 axis could activate the JAK/STAT pathway in FLS. When Lnc-ENST00000602558 was expressed at low levels, the regulatory capacity of TG on the Lnc-ENST00000602558/IGF1 axis and the JAK/STAT pathway was diminished.ConclusionTG may regulate the JAK/STAT pathway via the Lnc-ENST00000602558/IGF1 axis, thereby inhibiting the inflammatory response, mitigating bone and cartilage destruction, and delaying disease progression.