Abstract
Ulcerative colitis (UC) is characterized by recurrent inflammation of the gastrointestinal tract, and currently available treatment drugs are limited. Plant-derived polysaccharides hold promise for UC prevention. A water-soluble α-D-glucan (CLP80-1) with a molecular weight of 8.17 × 10[5] Da was isolated and characterized from the roots of traditional Chinese medicinal plant Crepis lignea. Structural analysis revealed that its repeating units comprise →6)-α-D-Glcp-(1 → and →3,6)-α-D-Glcp-(1 → residues as the backbone, with α-D-Glcp-(1 → as side chains substituted at C-3. The protective effects of CLP80-1 on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in Drosophila melanogaster were investigated. Our results demonstrated that treatment with 1% CLP80-1 significantly improved survival rates, attenuated gut atrophy, reduced intestinal permeability, enhanced intestinal barrier function, suppressed excessive proliferation of intestinal stem cells (ISCs) and enteroblasts (EBs), and inhibited the death of intestinal epithelial cells (IECs). Metabolomic and transcriptomic analyses revealed that CLP80-1 mainly affected amino acid metabolism, TCA cycle, oxidative phosphorylation and JAK/STAT signaling pathway. Furthermore, CLP80-1 reduced reactive oxygen species (ROS) levels, suppressed the expression of pro-inflammatory factors, and downregulated the JAK-STAT signaling pathway, thereby mitigating oxidative stress and inflammatory responses. These findings suggest that CLP80-1 is effective in alleviating intestinal inflammation and may serve as a promising therapeutic candidate for addressing gut inflammatory conditions.
