Lespedeza bicolor Turcz. Honey Prevents Inflammation Response and Inhibits Ferroptosis by Nrf2 / HO-1 Pathway in DSS-Induced Human Caco-2 Cells

Turcz. ( ) honey, a monofloral honey, has garnered increased attention due to its origin in the plant. A previous study has shown that honey can ameliorate inflammation. In this study, we aimed to investigate the effects of honey extract and its biomarker (Trifolin) on DSS-induced ulcerative colitis (UC). Our results demonstrated that honey extract and Trifolin significantly increased the expression levels of the tight junction cytokines and . Additionally, they decreased the pro-inflammatory factors and and enhanced the antioxidant factors and . Based on metabolomic analyses, honey extract and Trifolin regulated the progression of UC by inhibiting ferroptosis. Mechanistically, they improved the levels of SOD and iron load, increased the GSH/GSSG ratio, reduced MDA content and ROS release, and upregulated the / pathway, thereby inhibiting DSS-induced UC. Moreover, the expression levels of ferroptosis-related genes indicated that they decreased , , and while increasing expression to resist ferroptosis. In conclusion, our study found that honey improves DSS-induced UC by inhibiting ferroptosis by activating the / pathway. These findings further elucidate the understanding of anti-inflammatory and antioxidant activities of honey.