Anti‐Inflammatory Effects of Immature Pomelo Fruit Polysaccharides on Experimental Ulcerative Colitis Via Modulation of Gut Microbiota and the ERK1/2 Signaling Pathway

The immature pomelo fruit (IPF) of Citrus maxima (Burm.) Merr. is an agricultural by‐product rich in bioactive compounds, particularly the lipophilic flavonoid naringin. However, research on water‐soluble polysaccharides, another critical component of IPF, including their fundamental structural characteristics and biological activities, remains limited. In this study, a crude polysaccharide named immature pomelo fruit polysaccharides (IPFP), with a polysaccharide content of 81.10%, was extracted from the IPF using the water extraction‐alcohol precipitation method. High‐performance gel permeation chromatography with refractive index detection (HPGPC‐RID) revealed that IPFP consists of two components: IPFP‐1 with a molecular weight of 9187 Da and IPFP‐2 with a molecular weight exceeding 100 kDa. Analysis via 1‐phenyl‐3‐methyl‐5‐pyrazolone‐high performance liquid chromatography (PMP‐HPLC) indicated that IPFP primarily comprises galactose, glucose, and xylose, with glucose being the predominant monosaccharide. To investigate the biological activity of IPFP, a mouse model of acute ulcerative colitis was established using 2.5% dextran sulfate sodium (DSS). Fifty BALB/c mice were randomly assigned to five groups: a control group, a DSS‐induced model group, and three IPFP treatment groups with low, medium, and high doses. Molecular biological techniques, including quantitative polymerase chain reaction (qPCR), Western blotting, and 16S ribosomal RNA (16S rRNA) sequencing, were employed to evaluate the expression of inflammatory genes in colon tissues, activation of the extracellular signal‐regulated kinase (ERK) signaling pathway, and composition of fecal microbiota. The animal experiments demonstrated that IPFP significantly alleviated DSS‐induced symptoms, such as body weight loss and colon shortening. Additionally, it mitigated colonic histopathological damage, suppressed the expression of proinflammatory cytokines tumor necrosis factor‐alpha (TNF‐ α ), interleukin‐1 beta (IL‐1β), and interleukin‐6 (IL‐6), while promoting the expression of the anti‐inflammatory cytokine interleukin‐10 (IL‐10). Notably, the high‐dose IPFP group exhibited the most pronounced effects. Following IPFP treatment, there was a significant reduction in the phosphorylation levels of ERK1/2 protein and restoration of intestinal microbiota diversity and abundance. These findings suggest that IPFP may alleviate DSS‐induced inflammatory damage by modulating gut microbiota, particularly bacteroidetes, and inhibiting the ERK1/2 pathway. Our study provides initial insights into the structure and pharmacological mechanisms of IPFP against ulcerative colitis, highlighting its potential as an anti‐inflammatory agent for promoting intestinal health in inflammatory diseases.