Mechanism underlying the action of Duanteng-Yimu Tang in regulating Treg/Th17 imbalance and anti-rheumatoid arthritis

Background:Rheumatoid arthritis (RA) is a chronic immune disease characterised by synovitis and cartilage destruction. Currently, many patients experience poor remission after new antirheumatic drug treatments. Duanteng-Yimu Tang (DTYMT), a traditional Chinese medicine, is effective in the treatment of RA. In this research, we designed to investigate the anti-RA effects of DTYMT and explore its potential mechanisms. Methods:Network pharmacology was adopted to explore the main pathways of DTYMT in patients with RA. Collagen-induced arthritis models of male DBA/1 mice were established, and their histopathological changes were observed by hematoxylin-eosin staining and micro-CT. qRT-PCR was performed to detect the expression of Foxp3 and ROR & gamma;t in the serum and synovial tissue and IL-17, IL-1 & beta;, TNF-& alpha;, and IL-10 mRNA in vivo. The proliferation and invasion of synovial cells were analyzed using Cell Counting Kit-8 and transwell assays, respectively. The ratio of T helper 17 (Th17) to regulatory T (Treg) cells was analyzed by flow cytometry. Results:Network pharmacology analysis revealed that Th17 cell differentiation may be the key pathway of DTYMT in RA. DTYMT ameliorated joint damage, inhibited ROR & gamma;t expression, and increased Foxp3 expression in CIA mice. DTYMT significantly decreased IL-1 & beta;, IL-17, and TNF-& alpha; mRNA levels, and increased IL-10 mRNA levels in IL-6-induced cells. Additionally, DTYMT inhibited Th17 cell differentiation and promoted Treg cell production, thus improving the Treg/ Th17 imbalance. DTYMT also inhibited the proliferation, migration, and invasion of RA fibroblast-like synovial cells. Conclusions:These results indicate that DTYMT could regulate the Treg/Th17 cell balance, which is a possible mechanism of DTYMT in treating RA.