Kaempferol relieves the DSS-induced chronic colitis in C57BL/6J mice, alleviates intestinal angiogenesis, and regulates colonic microflora structure

Purpose: The progression of chronic colitis is accompanied by an increase in inflammation and intestinal angiogenesis. Kaempferol, a dietary flavonoid, has been shown to exhibit anti-inflammatory and anti-angiogenic properties. However, the anti-angiogenic effect of kaempferol in chronic colitis has not been elucidated. The present study aimed to investigate the effects of kaempferol on intestinal angiogenesis and microflora of mice with chronic colitis. Methods: The dextran sulfate sodium (DSS)-induced chronic colitis mouse model was used in this study. The effects of kaempferol and 5-aminosalicylic acid (5-ASA) were evaluated by histopathology, ELISA, western blot, and immunohistochemistry. The integrity of the gut-vascular barrier (GVB) was studied using FITC-dextran and D-Lactate. The colonic flora of mice was analyzed using 16S rDNA sequencing. Results: Kaempferol supplementation could relieve the symptoms (weight loss, colonic pathological injury, hemogram index, etc.) of chronic colitis in mice, down-regulate the secretion of inflammatory factors (IL-1β, IL-6, TNF-α, and CRP), and modulate the expression of inflammatory regulatory proteins (COX-2, TRAF6, and IL-22BP) in colonic tissues. Moreover, kaempferol decreased the secretion of colonic VEGF and NO, high intestinal microvascular density (MVD), and abnormal expression of VEGFR2 caused by DSS. Our finding also indicated that kaempferol alleviates chronic colitis by maintaining GVB, suppressing pro-inflammatory flora (Verrucomicrobiota, Campilobacterota, and Desulfobacterota), and enhancing the abundance of beneficial flora (Actinobacteria, and Odoribacter). Conclusion: Kaempferol exerted its therapeutic effect on chronic colitis by alleviating the inflammation of the colon and intestinal angiogenesis, maintaining the integrity of GVB, and regulating colonic microflora. Our study demonstrated similar pharmacological effects of kaempferol to 5-ASA (drug of clinical application for intestinal inflammatory diseases), and revealed the potential of kaempferol treatment as a preventive strategy for chronic colitis.