Ursolic acid suppresses ferroptosis by modulating Th17/Treg balance and gut dysbiosis in experimental autoimmune thyroiditis rats.

Ursolic acid (UA), a natural pentacyclic triterpenoid, exhibits anti-inflammatory and antioxidant properties. UA treatment modifies gut microbiota composition, and attenuates ROS and TNF-α production, while controlling Th17/Treg balance. However, UA's role in Hashimoto's thyroiditis (HT) remains unexplored, here, we employed experimental autoimmune thyroiditis (EAT) rat to explore its therapeutic potential in HT. Our studies indicated UA suppressed HT inflammation, as reflected by reduced baseline levels of IL-17 A, TNF-α, and ROS. These alterations correlated with decreased frequencies of CD4+ IL-17 A+ Th17 cells, and elevated frequencies of CD4+ CD25+ FoxP3+ Treg cells in peripheral blood and spleen. Additionally, UA improved gut microbiota composition, increasing Lactobacillus and Bifidobacterium. Moreover, UA upregulated FoxP3 and ferroptosis inhibitors HO-1, FTH1, GPX4, and SLC7A11 expression, and downregulated ferroptosis inducer ROS and ACSL4 expression. These findings suggest that UA can alleviates EAT symptoms by modulating immune balance, gut dysbiosis, and ferroptosis, providing insights into its potential as a therapeutic agent for HT.