Exploring the multi-barrier repair effects of Codonopsis pilosula water extract in improving rhubarb-induced intestinal dysfunction in mice based on the tryptophan metabolism-AhR pathway.

内容摘要

The intestine is the core digestive and absorptive organ and the largest immune barrier. Intestinal dysfunction impairs physiological function, but current treatments remain suboptimal because of its complex etiologies. This study investigated whether Codonopsis pilosula water extract (CPWE) repairs intestinal mucosal barrier damage in mice and elucidated the underlying mechanisms. Intestinal dysfunction was induced in male ICR mice by continuous gavage with rhubarb water extract to establish a diarrhea model. The efficacy of CPWE was evaluated by measuring body weight, fecal water content, and the small intestinal propulsion rate. Histopathological changes in intestinal tissues were examined using H&E and AB-PAS staining. Intestinal barrier damage was assessed by immunofluorescence and Western blotting. Furthermore, transcriptomic and microbiome sequencing were employed to explore the specific mechanisms by which CPWE repairs intestinal mucosal barrier damage. CPWE effectively alleviated rhubarb-induced diarrhea and restored the intestinal mucosal barrier in mice. It increased onula occludens-1 (ZO-1) and occludin (OCLN) expression, promoted mucin 2 (MUC2) secretion, reduced the proportions of Th1 and Th17 cells in the colonic lamina propria, and modulated gut microbial composition. These changes were associated with regulation of tryptophan metabolism and aryl hydrocarbon receptor (AhR) signaling, consistent with a role in maintaining the integrity of the mechanical, chemical, immune, and biological barriers. These findings suggest that CPWE ameliorates rhubarb-induced intestinal barrier dysfunction through multi-barrier repair associated with tryptophan metabolism and AhR signaling. This study provides a theoretical basis for multi-component strategies in diarrhea-related intestinal injury and supports the application of traditional Chinese medicine in precision treatment of intestinal diseases.