Rutin Enhances Intestinal Barrier Function and Protects Against X‐Ray Radiation‐Induced Barrier Dysfunction in Human Epithelial Caco‐2 Cells

The small intestinal epithelium plays a critical role in nutrient absorption but is highly sensitive to radiation-induced injury. Despite this vulnerability, therapeutic strategies to prevent or restore radiation-induced intestinal barrier dysfunction remain limited. Polyphenols are known to protect the intestinal barrier by mitigating and repairing damage. Rutin, a quercetin-3-O-rhamnosylglucoside with antioxidant, anticancer, antidiabetic, and antihypertensive activities, may help preserve intestinal epithelial integrity under radiation-induced stress. This study investigated whether rutin could enhance intestinal barrier integrity and protect against X-ray irradiation-induced impairment in human epithelial Caco-2 cell monolayers. Rutin pretreatment improved cell viability and barrier function, as shown by elevated transepithelial electrical resistance (TEER) and lowered fluorescein permeability. Additionally, rutin upregulated the mRNA and protein expression levels of key tight junction (TJ) markers, including ZO-2, occludin, and claudin-3. Notably, rutin pretreatment significantly attenuated X-ray-induced barrier dysfunction by restoring TEER, reducing paracellular permeability, and preventing the downregulation of TJ-related genes and proteins. Rutin enhances intestinal barrier function and mitigates X-ray-induced barrier disruption by preventing the downregulation of ZO-2, occludin, and claudin-3 at both the mRNA and protein levels, thereby reinforcing epithelial integrity. Rutin may serve as a natural radioprotective agent, preserving gut barrier function during radiation exposure.