RESUMO
Rheumatoid arthritis (RA) is a chronic disease characterized by persistent synovitis and angiogenesis. Its clinical manifestations are synovial hyperplasia and progressive destruction of bone and cartilage, eventually leading to joint deformation and even disability. The healing effect of monomer stigmasterol, the main active ingredient of the Jinwujiangu recipe the Chinese Herbal Compound, on RA has been confirmed in several studies. Fibroblast-like synoviocytes (FLS) are related to the occurrence and development of RA. This study aims to investigate the effects of stigmasterol on FLS cell proliferation and apoptosis, as well as its impact on FLS cell cycle proteins and key genes in the Phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway, providing insights into the development of stigmasterol as an alternative therapeutic drug for RA. We administered 20 g/kg stigmasterol to rats continuously for 5 d to obtain stigmasterol-containing serum, and established rat models of osteoarthritis induced by ossein to obtain FLS. To explore the effects of stigmasterol on the viability, migration, proliferation and apoptosis of collagen-induced arthritis (CIA)-FLS cells, we selected 0% (control), 5% (low concentration), 10% (medium concentration) and 20% (high concentration) drug-containing serum to intervene cells and conducted Cell Counting Kit-8 (CCK-8), Transwell, 5-ethynyl-2' -deoxyuridine (EdU) staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) experiments, respectively. The results showed that compared with the control group, low, medium, and high serum significantly inhibited the activity, migration, and proliferation of FLS cells, and promoted their apoptosis, and high serum had the best effect. In addition, we investigated the mechanism of stigmasterol inhibiting FLS proliferation and promoting its apoptosis by qPCR, Western blot, and immunofluorescence assays. The results showed that stigmasterol significantly inhibited the expression of Cyclin D1, cyclin-dependent kinase 4 (CDK4), and Retinoblastoma (Rb), and decreased the expression of key genes kinase insert domain-containing receptor (KDR), PI3K, AKT, phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) in the KDR-mediated PI3K/AKT signaling pathway, thus inhibiting the proliferation of FLS and promoting the apoptosis of FLS. It was suggested that stigmasterol may be a potential alternative drug for RA treatment.
RESUMO
Objective: This study aims to evaluate the efficacy of various conventional synthetic DMARDs, including Tripterygium wilfordii Hook F (TwHF) for treating rheumatoid arthritis (RA) by network meta-analysis. Methods: We retrieved the related literature from online databases and supplemented it by using a manual retrieval method. Data was extracted from the literature and analyzed with STATA software. Results: A total of 21 trials (5,039 participants) were identified. Assessment of ACR20 response found that TwHF combined with methotrexate (MTX) had the greatest probability for being the best treatment option among the treatments involved, while TwHF used singly was second only to TwHF combined with MTX. Assessment of ACR50 response found that TwHF combined with MTX ranked second in all treatment options after cyclosporine A (CsA) combined with leflunomide (LEF) and TwHF alone, followed by TwHF combined with MTX. Assessment of ACR70 response found that CsA combined with LEF ranked first, TwHF combined with LEF ranked second, TwHF combined with MTX ranked third, and TwHF used singly ranked fourth. In the safety analysis, TwHF had the least probability of adverse event occurrence, followed by TwHF combined with MTX, which ranked first and second, respectively. Conclusion: Compared with the current csDMARDs for treating RA, the efficacy of TwHF was clear, and TwHF combined with MTX performed well under various endpoints. In the future, large, rigorous, and high-quality RCTs are still needed to confirm the benefits of TwHF therapy on RA.
RESUMO
To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.