Taxifolin alleviates FCA-induced arthritis via regulating the Th1/Th2 balance, and down-regulates NLRP3 inflammasome axis activation in Jurkat T cells

Abstract Rheumatoid arthritis (RA) is a chronic inflammatory joint disease mediated by T cells. In traditional Chinese medicine, Smilacis Glabrae Rhizoma is commonly used to treat deoxidation, dampness and ease joint movement. One of its active components, a flavonoid called taxifolin, has been the focus of several studies in recent years. However, the pharmacological action of taxifolin in the development of RA remains unknown. Here, we investigated the therapeutic effects of taxifolin on Freund's complete adjuvant (FCA)-induced arthritis model, and then verified the underlying immunoregulatory mechanisms of taxifolin on activated Jurkat T cells. Taxifolin ameliorated the physical signs including paw volume (PV), arthritis index (AI) and body weight (BW) and reduced the organ coefficients (spleen and thymus) in FCA-induced rats, as well as the inflammatory responses in the left hind paw and plasma. The results also showed that taxifolin greatly improved the imbalance of T helper (Th)1/Th2 status in the plasma and spleen. Further, the Th1/Th2 imbalance status and NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in the activated Jurkat T cells was inhibited significantly by taxifolin. In conclusion, these results suggested that taxifolin potentially targeted the Th1/Th2 status and NLRP3 inflammasome axis in T cells, contributing valuable insights to elucidating the mechanism of action of taxifolin for future studies on RA therapeutics.