Tremella aurantialba polysaccharides alleviate ulcerative colitis in mice by improving intestinal barrier via modulating gut microbiota and inhibiting ferroptosis
- Int J Biol Macromol. 2024 Sep 20;281(Pt 4):135835. doi: 10.1016/j.ijbiomac.2024.135835.
- 1. Laboratory of Tumor Immunology, The first Hospital of Jilin University, Changchun 130021, China.
- 2. College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
- 3. Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming 650000, China.
- 4. Department of Laboratory Medicine, Lequn Branch, The First Hospital of Jilin University, Changchun 130031, China.
- 5. Jilin Yatai Biopharmaceutical Co., Ltd., Changchun 130032, China.
- 6. Department of Neonatology, Children's Medical Center, First Hospital of Jilin University, Changchun 130021, China.
- 7. Department of Neonatology, Children's Medical Center, First Hospital of Jilin University, Changchun 130021, China; Laboratory of Tumor Immunology, The first Hospital of Jilin University, Changchun 130021, China. Electronic address: [email protected].
We aimed to investigate the effect of a polysaccharide from Tremella aurantialba on ulcerative colitis (UC), which targets Ferroptosis in epithelial cells. TA 2-1 (127 kDa) was isolated from T. aurantialba and consisted of Man, Xyl, GlcA, Glc, Fuc and Rha with a molar ratio of 59.2: 23.2: 13.9: 1.6: 1.7: 0.4, exhibited a 1, 3-Man structure with branch chains of T-Xylp, 1,3-Xylp, 1,4-GlcAp, and T-Manp at its O-2 position. TA 2-1 (100 μg/mL) inhibited the cell viability of Ferroptosis (19.8 %) in RLS3-induced Caco-2 cells and significantly ameliorated symptoms in the colons of mice with dextran sodium sulfate (DSS)-induced UC. TA 2-1 remarkably repaired the intestinal barrier by upregulating claudin-1 and zonula occludens-1 levels. Further analysis found TA 2-1 significantly suppressed lipid peroxidation by regulating ferroptosis-related proteins in UC mice, suggesting that its protective effects are partially mediated by inhibiting Ferroptosis. Further analysis of the gut microbiota and fecal microbiota transplantation revealed TA 2-1 might relieve UC symptoms or inhibit Ferroptosis by modulating the gut microbiota's composition or metabolites. Results suggest the protective effects of TA 2-1 on the intestinal barrier by inhibiting Ferroptosis of epithelial cells, at least by regulating the gut microbiota, highlighting the potential of TA 2-1 in UC treatment.