Work

Huangqi decoction ameliorated intestinal barrier dysfunction via regulating NF-κB signaling pathway in slow transit constipation model mice

Year: 2025

Type: article

Abstract: BACKGROUND: The development of slow transit constipation (STC) is associated with intestinal barrier damage. Huangqi decoction (HQD) is effective in treating STC, but mechanisms are unclear. AIM: To investigate whether HQD alleviates STC by downregulating the nuclear factor κB (NF-κB) signaling pathway and restoring intestinal barrier function. METHODS: experiments evaluated the effects of HQD on the LS174T cell line. RESULTS: HQD improved intestinal motility, restored mucosal epithelium function and morphology. Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells, decreased mucin 2 secretion, and activated apoptotic pathways in STC mice. The population of intestinal stem cells was reduced, and proliferation along with Wnt/β-catenin pathways were inhibited. STC also altered the distribution of intestinal cell states, increasing immune-associated Enterocyte_C3. Aberrant NF-κB pathway activation was noted across various cell types. After HQD treatment, NF-κB pathway activity was down-regulated, while cell proliferation pathways were up-regulated, alongside an increase in Enterocyte_C1 related to material transport. Immunocytochemical, Western blot, and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice, with HQD inhibiting this aberrant activation. CONCLUSION: STC involves intestinal mucosal barrier damage. HQD may treat STC by suppressing NF-κB signaling in epithelial cells, restoring intestinal epithelial cell function, and promoting mucosal barrier repair.

Source: World Journal of Gastrointestinal Surgery

DOI: 10.4240/wjgs.v17.i5.106000