Exploring the mechanism of action of tripterygium glycosides tablets in the treatment of rheumatoid arthritis based on the Lnc-ENST00000602558/IGF1 signaling pathway

Exploring the Therapeutic Potential and Safety Profile of Tripterygium wilfordii Hook.f. in Osteoarthritis: Mechanisms, Toxicity, and Clinical Perspectives.

INTRODUCTION Tripterygium wilfordii Hook.f. (TwHF), A traditional Chinese medicine has been historically used for treating inflammatory conditions such as osteoarthritis (OA) and rheumatoid arthritis (RA), owing to its potent anti-inflammatory and immunomodulatory properties. Notably, OA is now recognized as a whole-joint disorder driven not merely by mechanical wear and tear, but by complex pathophysiological processes involving immune response dysregulation and localized metabolic disturbances. Despite its therapeutic potential, the clinical application of TwHF remains constrained by significant multi-organ toxicity and a narrow therapeutic window. This review aims to summarize the therapeutic mechanisms, toxicity profile, and clinical evidence of TwHF and its active components in OA treatment, and to discuss strategies for mitigating toxicity and future research directions. METHODS A systematic search was performed across multiple electronic databases, including PubMed and Web of Science, up to February 2026, to identify studies on TwHF and its components in OA. The process followed PRISMA guidelines using keywords including "Tripterygium wilfordii," "osteoarthritis," and "toxicity." Included studies focused on TwHF and OA pharmacology, toxicity, or clinical outcomes; those with insufficient data were excluded. Data on authors, year, findings, and conclusions were extracted and synthesized narratively by themes. RESULTS TwHF active components demonstrate potent anti-inflammatory and chondroprotective effects in cellular and animal OA models. However, they also cause dose-dependent hepatotoxicity, nephrotoxicity, and immunosuppression. Strategies like drug combination, targeted delivery, and metabolic modulation can reduce toxicity. Clinical evidence in OA remains limited and lowquality, whereas more robust data support its use in rheumatoid arthritis. DISCUSSION TwHF presents a compelling therapeutic profile for OA due to its multi-faceted anti- inflammatory and immunomodulatory actions, primarily mediated by its active constituents through a multi-targeted approach. However, its promise is tempered by significant safety concerns, particularly hepatotoxicity and nephrotoxicity, and a lack of conclusive efficacy data from robust clinical trials in OA.Future research should prioritize high-quality RCTs, deeper investigation into toxicity mechanisms, development of safer derivatives, and establishment of predictive biomarkers. CONCLUSION While TwHF holds promise for OA treatment due to its multimodal anti-inflammatory mechanisms, its toxicity and insufficient clinical evidence necessitate further high-quality trials, precise therapeutic targeting, and safer formulation development for safe clinical integration.

Therapeutic Properties and Underlying Mechanisms of Traditional Chinese Medicine in Managing Rheumatoid Arthritis: An Integrative Review of Clinical and Molecular Findings.

Traditional Chinese medicine (TCM) has a long-standing history in the treatment of rheumatoid arthritis (RA), known as "Bi Zheng," and offers a comprehensive therapeutic approach characterized by multi-target and multi-pathway mechanisms. Modern pharmacological research has demonstrated that bioactive compounds and herbal formulas derived from TCM (e.g., triptolide [TPL] from Tripterygium wilfordii and the Xinfeng Capsule [XFC]) effectively interfere with the complex pathogenesis of RA. These interventions modulate diverse pathological processes, including the suppression of pro-inflammatory cytokines (e.g., TNF-α, IL-6, and IL-1β), induction of apoptosis in hyperplastic synovial cells, and regulation of novel cell death pathways (such as ferroptosis and pyroptosis). Furthermore, TCM components exhibit potent antioxidant properties, inhibit pathological angiogenesis, ameliorate hypercoagulable states, and restore gut microbiota dysbiosis, which is increasingly recognized as a key environmental factor in RA development. Notably, emerging evidence highlights the critical role of non-coding RNAs (ncRNAs) as mediators of these therapeutic effects. Concurrently, a growing body of clinical evidence from randomized controlled trials (RCTs), cohort studies, and real-world data mining consistently confirms the significant efficacy and safety of TCM interventions in relieving RA symptoms, improving joint function, and reducing disease activity. By integrating preclinical and clinical findings, a robust evidence chain emerges, validating traditional TCM concepts through modern scientific rigor. Therefore, TCM represents a valuable resource for RA drug discovery and integrative treatment strategies. Further in-depth investigation is needed into its specific molecular targets, optimal formulations, and long-term clinical outcomes to facilitate its global translation and application.

Anti-Inflammatory Effects of Chrysin (5,7-Dihydroxyflavone) in Freund's Complete Adjuvant-Induced Arthritis in Rats

Background: Inflammation is a key pathological process underlying arthritis and contributes to progressive damage to the joints, cartilage, and surrounding tissues. Persistent inflammatory responses are associated with infiltration of inflamma-tory cells, pannus formation, cartilage degradation, and bone erosion, ultimately leading to impaired joint function. Chrysin (5,7-dihydroxyflavone) is a naturally occurring flavonoid found in various plants, honey, and propolis. It possesses several pharmacological properties, particularly anti-inflammatory and antioxidant activities, which may help attenuate inflamma-tory tissue damage. Therefore, the present study was designed to evaluate the anti-inflammatory effects of chrysin in an experimentally induced arthritic rat model using histopathological assessment of joint tissues.Methodology: This study determined the healing effect of Chrysin in a FCA-induced arthritic rat model. Chrysin was inject-ed intraperitoneally on the 8th post-administration day of FCA, and treatment continued for the next three consecutive weeks. GraphPad Prism was used to analyse the results, considering p-values ≤ 0.05 statistically significant. Results: Anti-inflammatory effect of Chrysin upon bones and cartilage was determined by Ankle joint histopathology. Upon histopathology, Chrysin reduced the severity of arthritis in the joint, infiltration of inflammatory cells, subcutaneous in-flammation, cartilage erosion, bone erosion and pannus formation. Piroxicam was used as a reference drug to compare the anti-arthritic effect of Chrysin.Conclusion: Results showed that Chrysin possesses anti-arthritic effects and may be a potential drug for the treatment of arthritis. 

Mechanistic Study of Yibi Decoction in Treating Rheumatoid Arthritis via Modulating the JAK2/STAT3 Signaling Pathway.

OBJECTIVE To investigate the therapeutic effects of Yibi Decoction (YBD) in rheumatoid arthritis (RA) and to elucidate the underlying mechanisms, with a particular focus on the JAK/STAT signaling pathway. METHODS Network pharmacology analysis was employed to predict the bioactive compounds and potential therapeutic targets of Yibi Decoction. A collagen-induced arthritis (CIA) rat model was established to validate the predicted effects in vivo. Western blotting, enzyme-linked immunosorbent assay (ELISA), and histopathological analyses were conducted to evaluate alterations in joint tissues and serum inflammatory biomarkers. RESULTS Network pharmacology analysis identified 128 bioactive components in YBD, among which quercetin and luteolin were predicted to be key active compounds. In CIA rats, YBD treatment significantly downregulated the expression of IL-6, IL-17, IL-23, JAK2, and STAT3 in ankle joint tissues (P < 0.05), and markedly reduced serum levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (P < 0.05). In parallel, the arthritis index was significantly decreased, and histopathological examination revealed substantial attenuation of synovial hyperplasia and cartilage destruction. DISCUSSION These findings suggest that YBD exerts anti-rheumatoid arthritis effects through a multi-component, multi-target regulatory mechanism involving inhibition of the JAK/STAT signaling pathway. Quercetin and luteolin may contribute to these effects by suppressing pro-inflammatory cytokine production and ameliorating joint pathological changes. CONCLUSION YBD ameliorates rheumatoid arthritis by suppressing the JAK/STAT signaling pathway and associated inflammatory responses, thereby providing a mechanistic basis for its potential therapeutic application in rheumatoid arthritis.

The Anti-Inflammatory Effects and Mechanisms of Baicalin on Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common chronic autoimmune disease clinically, with persistent synovial inflammation as its core pathological feature. However, current treatment strategies often face limitations in efficacy and significant side effects. Baicalin, the main active flavonoid component of the traditional Chinese medicine Scutellaria baicalensis, possesses various pharmacological activities, including but not limited to anti-inflammatory, antioxidant, and immunomodulatory effects. This article focuses on exploring how the anti-inflammatory effect of baicalin plays a role in the treatment of RA, systematically discussing the molecular mechanism of baicalin from the perspectives of NF-κB and TLR signaling pathways and their synergistic regulatory effects, and showcasing the research progress of baicalin in current treatment. Studies have shown that baicalin can significantly downregulate the expression and release of pro-inflammatory cytokines such as TNF-α and IL-1β by inhibiting the activation of TLR2 and TLR4 receptors and blocking the TLR and NF-κB signaling pathways. Furthermore, baicalin can inhibit the abnormal proliferation of synovial fibroblasts, induce their apoptosis, alleviate synovial inflammation and pannus formation, and delay the pathological progression of rheumatoid arthritis. Currently, the main problem facing baicalin is its low bioavailability. In the future, priority should be given to researching its drug delivery system and conducting high-quality clinical trials to facilitate the clinical translation and application of baicalin in the treatment of RA.

Tetrandrine nanocrystals for rheumatoid arthritis: enhanced therapeutic efficacy associated with reduced JAK1 and STAT3 expression.