Molecular mechanisms of active compounds from Tripterygium wilfordii in prevention and treatment of rheumatoid arthritis

Abstract

BACKGROUND: Currently, traditional Chinese medicine has been proven to play a significant role in combating rheumatoid arthritis. The efficacy and mechanisms of active components of Tripterygium wilfordii against rheumatoid arthritis have gained increasing recognition among researchers. OBJECTIVE: To summarize the research progress on the anti-rheumatoid arthritis effects of active components from Tripterygium wilfordii in vitro and in vivo. METHODS: Relevant literature published from inception to March 2025 was retrieved from CNKI, WanFang, VIP, and PubMed databases. Search terms included “rheumatoid arthritis, synovial cells, bone erosion, osteoclast, Tripterygium wilfordii, signal path” in Chinese and English. Eighty-seven articles were ultimately selected for review. RESULTS AND CONCLUSION: (1) Triptolide effectively alleviates joint inflammation and inhibits the abnormal proliferation and migration of fibroblast-like synoviocytes. Triptolide inhibits the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway mediated by interleukin-6 and soluble interleukin-6 receptor, thereby suppressing downstream pro-inflammatory cytokines (e.g., interleukin-6, interleukin-17), and time-dependently inhibits the expression of circRNA0003353 in rheumatoid arthritis fibroblast-like synoviocytes, while increasing the level of anti-inflammatory cytokine interleukin-4, reducing cell viability and migration, demonstrating dual potential for anti-inflammatory and inhibition of pathological synovial hyperplasia. (2) Celastrol significantly reduces joint swelling, synovial hyperplasia, inflammatory cell infiltration, and bone erosion. Celastrol inhibits the reactive oxygen species/nuclear factor kappa B/NOD-like receptor pyrin domain-containing protein 3 signaling pathway, reducing secretion of pro-inflammatory cytokines interleukin-1β and interleukin-18 in serum and immune cells. In collagen-induced arthritis rat models, celastrol induces autophagy and inhibits the phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin signaling pathway, significantly reducing levels of inflammatory cytokines such as tumor necrosis factor α and interleukin-1β, exerting cytoprotective and anti-inflammatory effects. (3) Wilforine can inhibit the inflammatory response of rheumatoid arthritis and potentially affect bone metabolism. In collagen-induced arthritis rat models, wilforine significantly downregulates levels of interleukin-6, interleukin-1β, and tumor necrosis factor α, and exerts therapeutic effects by inhibiting the abnormally activated Wnt/β-catenin signaling pathway. (4) The active components of Tripterygium wilfordii show good therapeutic effects in rheumatoid arthritis, but the mechanisms are complex, involving interactions of multiple genes, proteins, and signaling pathways. Current research has not fully elucidated the specific mechanisms, limiting their widespread clinical application. Future research should further explore the molecular mechanisms of active components and conduct large-scale clinical trials to verify efficacy and safety, while exploring combination strategies with other drugs to achieve better therapeutic outcomes.

1. Introduction

Rheumatoid arthritis is a systemic autoimmune disease [1] that primarily affects the joints of the hands, knees, and feet. Pathologically, it is characterized by synovial hyperplasia, immune cell infiltration, pannus formation, and destruction of articular cartilage, leading to joint damage. If not treated properly, rheumatoid arthritis can cause cumulative joint damage and permanent disability. The pathogenesis of rheumatoid arthritis remains unclear, but risk factors include genetics, estrogen levels, environment, and disruption of immune cell balance [2]. Early rheumatoid arthritis is characterized by general symptoms such as fatigue, joint swelling, and morning stiffness [3]. In contrast, inadequately treated rheumatoid arthritis presents with complex clinical manifestations, including pleural effusion, pulmonary nodules, interstitial lung disease, joint misalignment, loss of range of motion, bone erosion, and cartilage erosion [4].

Currently, the global incidence of rheumatoid arthritis is 0.5%-1%, with approximately 41 cases per 100,000 population. In China, there are about 5 million patients with rheumatoid arthritis, and the prevalence in women (0.44%) is significantly higher than in men (0.21%) [5-6]. Common drugs for treating rheumatoid arthritis include nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids, biologics, and their combinations [7]. Although these can alleviate disease progression, they are accompanied by many adverse reactions such as gastrointestinal reactions and cardiovascular complications [8]. Most patients have short remission periods and multiple relapses [9]. Therefore, seeking new therapeutic approaches is of great significance for improving the quality of life and survival rate of patients with rheumatoid arthritis.