Chrysanthemum ‘Honglian’ extract (CM-HLE) alleviates colitis by inhibiting ferroptosis in intestinal epithelial cells

Chrysanthemum, a traditional Chinese medicinal herb, exhibits various biological activities, including anti-inflammatory, anti-tumor, and antiviral effects. However, its potential role in preventing inflammatory bowel disease (IBD) and the underlying mechanisms remain unclear. In this study, we cultivated and identified a chrysanthemum variety, Hong Lian, with a high content of flavonoid. We extracted components from the plant and applied Chrysanthemum ‘Honglian’ extract (CM-HLE) to DSS-induced colitis C57BL6 mice. We found that CM-HLE pretreatment could significantly alleviate symptoms of intestinal inflammation in mice, including weight loss, colon shortening, intestinal epithelial injury, and immune cell infiltration. Further, we found that CM-HLE treatment effectively prevented intestinal epithelial CCD841 cells from DSS-induced ferroptosis, a programmed cell death triggered by iron accumulation and lipid peroxidation in cells. Mechanistically, we validated the enrichment of ferroptosis-related signaling pathways in intestinal epithelial cells of mice treated with CM-HLE in the RNA-seq analysis and demonstrated that CM-HLE inhibited ferroptosis in intestinal epithelial cells by upregulating SLC7A11. The untargeted metabolomics analysis of CM-HLE revealed that its main components, apigenin-7-glucuronide and apigenin-7-glucoside, both inhibit ferroptosis via the ATF3/SLC7A11 axis. In conclusion, our study reveals a novel medicinal value of chrysanthemum, offering a new strategy for the prevention and treatment of IBD.