Kaempferol in inflammatory bowel disease: regulating intestinal epithelial-fibroblast crosstalk

Inflammatory bowel disease (IBD) has an intricate pathophysiology that greatly impacts patients' quality of life. Wumei Wan, a traditional Chinese medicinal formulation, exhibits specific therapeutic effects on IBD. Kaempferol (KF), an active ingredient in Wumei Wan, may significantly contribute to IBD.

A 2% DSS-induced chronic colitis mouse model was established, randomly divided into six groups and treated with KF. Relevant indicators of chronic colitis were measured, including body weight, Disease Activity Index (DAI), colon length, histological alterations, as well as indicators of inflammatory factors, fibrosis, intestinal barrier function, hepatic and renal function, and oxidative stress. TNF-α was employed to stimulate colonic epithelial cells in cell studies. After KF intervention, cytotoxicity, transforming growth factor-β1 (TGF-β1), and cell survival were observed to investigate its impact on IBD. The HT29/CCD-18Co medium with TNF-α/TNF-α+KF was co-cultured with CCD-18Co/HT29 cells, and a cell line with heme oxygenase 1 (HMOX1) silencing/overexpression was generated to explore the impact of KF on intestinal epithelial cell-fibroblast crosstalk.

In vivo, KF therapy increased body weight, reduced DAI, and improved colon length as well as histopathology. Furthermore, KF reversed the elevated levels of inflammatory cytokines, intestinal barrier function, and oxidative stress markers observed in the model group. In vitro, KF reversed TNF-α-induced decrease of intestinal epithelial cells, TGF-β1 downregulation, regulated cell function, and reduced inflammation. KF may suppress TNF-α-induced fibroblast activation, and HMOX1 was crucial for regulating cell crosstalk.

Collectively, KF mitigates IBD by modulating intestinal epithelial-fibroblast interaction, suppressing inflammatory responses, reducing intestinal fibrosis, and increasing intestinal mucosal barrier function.