Introduction: Ulcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract in which mucosal healing is a crucial measure of therapeutic efficacy. Quercetin, a flavonoid prevalent in various foods and traditional Chinese medicines, exhibits notable pharmacological properties, including antioxidant and anti-inflammatory activities. Consequently, it warrants investigation to determine its potential therapeutic effects on UC. The objective of this study was to investigate the effects and underlying mechanisms of quercetin in a murine model of UC.Methods: A comprehensive approach integrating network predictions with transcriptomic analyses was employed to identify the potential targets and enriched pathways associated with quercetin in UC. Subsequently, the effects of quercetin on pathological morphology, inflammatory mediators, and mucosal barrier-associated proteins, as well as the identified potential targets and enriched pathways, were systematically investigated in a murine model of dextran sulfate sodium (DSS)-induced UC.Results: Network analyses identified CXCL8 and its receptors, CXCR1 and CXCR2, as primary target genes for therapeutic intervention in UC. Further validation through transcriptomic analysis and immunofluorescence staining demonstrated significant upregulation of the CXCL8-CXCR1/2 axis in the intestinal tissues of patients with UC. Experimental investigations in animal models have shown that quercetin markedly alleviates DSS-induced symptoms in mice. This effect includes the restoration of colonic crypt architecture, normalization of goblet cell structure and density, reduction of inflammatory cell infiltration, and decreased concentrations of inflammatory mediators. Quercetin enhanced the expression of tight junction (TJ) proteins, including ZO-1, MUC2 (Mucin 2), and occludin, thereby preserving the integrity of the intestinal mucosal barrier. Additionally, it significantly diminished the levels of IL-17A, NF-κB, CXCL8, CXCR1, and CXCR2 in the colonic tissues of mice with UC.Discussion: The ameliorative effects of quercetin on colon tissue damage in DSS-induced UC mice were significant, possibly due to its ability to inhibit the CXCL8-CXCR1/2 signaling axis. These findings provide a solid foundation for the clinical application and pharmaceutical advancement of quercetin.

Background: Colorectal cancer (CRC) is a malignancy that arises within the gastrointestinal tract. Despite ongoing research, the etiology and pathogenesis of CRC remain elusive; particularly, the distribution and characteristics of tumor‐associated macrophages is currently an active area of investigation in understanding the pathological progression and prevention of CRC.Methods: This study utilized CRC patient surgical samples, mouse models of colitis‐associated cancer, colonic organoid, and co‐culture cell line to examine the changes in CD11b/CD86 at different pathological region and detect the Wnt signaling pathway activity.Results: Our findings revealed a sensitive and increased expression of CD11b from the early to the advanced CRC tissues and correlated with poor prognosis, while CD86 expression was reduced in advanced CRC tissues. CD133 expression was also elevated in advanced CRC tissues and mainly co‐localized with CD11b, suggesting a positive regulatory effect of CD11b and CD133 expression that may contribute to CRC progression. In AOM/DSS mouse models, activation of the Wnt signaling pathway was associated with increased CD133 and CD11b expression. In vitro, THP‐1 cell was induced to high expression of CD11b, and the above conditional cultural medium enhanced HCT116 cell colony number and CD133 protein expression. Furthermore, colonic crypts from AOM/DSS mouse models were isolated to culture, and the colonic organoids exhibited dilation and significant increases expression of CD133 and β‐Catenin/N‐P‐B‐Catenin.Conclusions: CD11b might be an important factor to participate the progress of CRC. And the high CD11b of CRC microenviroment might potentially promote CD133 expression and associate with Wnt signal activation.

Background: Colorectal intraepithelial neoplasia (CR-EN) is a precursor lesion of colitis-associated colorectal cancer (CAC). This study investigated the interventional effects and molecular mechanisms of Rhapontici Radix extract on CR-EN. Methods: An azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mouse model of colonic intraepithelial neoplasia, bioinformatics analysis, organoid models, and HCT116 cell experiments were employed, coupled with histopathological examination, inflammatory cytokine detection, Western blot, immunofluorescence, and HPLC-MS/MS. Results: The results showed that the YAP/AKT-PI3K signaling pathway is aberrantly activated in CRC. Rhapontici Radix extract ameliorated colonic pathology, suppressed inflammatory responses, and remodeled gut microbiota composition in model mice. The extract selectively inhibited the proliferation of CR-EN organoids by downregulating Ki67 and β-catenin while upregulating p53, and suppressed the proliferation, colony formation, and migration of HCT116 cells. Mechanistically, the extract modulated the YAP/PI3K/AKT pathway by upregulating phosphorylated YAP (p-YAP) and downregulating phosphorylated AKT (p-AKT), phosphorylated PI3K (p-PI3K), and their downstream targets p-SRC and c-MYC. Conclusions: This study suggests that Rhapontici Radix extract intervenes in inflammation-associated carcinogenesis through a multi-pathway, multi-target strategy, offering potential therapeutic targets for CAC prevention and treatment.