Anti-angiogenic effect of tripterygium glycosides tablets in animal models of rheumatoid arthritis: A systematic review and meta-analysis

To explore and summarize the beneficial effects of a traditional Chinese medicine preparation, Tripterygium glycosides tablets (TGT), in rheumatoid arthritis (RA) animal models of neovascularization, and to provide a reference for future clinical applications and research on its pharmacologic mechanism. We searched the databases PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, VIP, Wan Fang and SinoMed (China Biomedical Document Service System) to identify studies of TGT with outcome indicators of angiogenesis-related factors that were published before April 2020. Subgroup analysis and meta-regression were performed for dosage and duration of TGT. Statistical tests and subgroup analysis were conducted using RevMan 5.3, and meta-regression and sensitivity analysis were conducted using STATA/SE 15.0. Fourteen studies of TGT in RA rats were included in this analysis. Treatment with TGT significantly reduces synovial microvessel density and the expression of vascular endothelial growth factor (VEGF), VEGF receptor 2, hypoxia inducible factor α, c-Fos, c-Jun, angiopoietin-1 and angiopoietin-2 compared with control groups (P < .05). Subgroup analysis did not show a significant association of the mRNA levels of VEGF in synovium, assessed using quantitative real-time PCR, with duration or dosage of TGT. Meta-regression analysis also indicated that the effects of dosage and duration were not significantly associated with differences in VEGF mRNA levels. Sensitivity analysis on VEGF mRNA levels did not fundamentally change the results. TGT can reduce synovial neovascularization by decreasing synovial microvessel density and expression of VEGF, VEGF receptor 2, hypoxia-inducible factor α, c-Fos, c-Jun, Ang-1 and Ang-2, thereby suppressing pannus formation and bone destruction in rat models of RA. Additional well-designed studies are required to confirm these findings.