Naringenin Alleviates Radiation‐Induced Intestinal Injury by Inhibiting TRPV6 in Mice

Scope Naringenin (NAR) possesses unique anti‐inflammatory, antiapoptosis effects and various bioactivities; however, its role against radiation‐induced intestinal injury (RIII) remains unclear. This study aims to investigate whether NAR has protective effects against radiation‐induced intestinal injury and the underlying mechanisms. Methods and results C57BL/6J mice are exposed to a single dose of 13 Gy X‐ray total abdominal irradiation (TAI), then gavaged with NAR for 7 days. NAR treatment prolongs the survival rate, protects crypts and villi from damage, alleviates the level of radiation‐induced inflammation, and mitigates intestinal barrier damage in the irradiated mice. Additionally, NAR reduces immune cell infiltration and intestinal epithelial cell apoptosis. NAR also shows radioprotective effects in human colon cancer cells (HCT116) and human intestinal epithelial cells (NCM460). It reduces cell damage by reducing intracellular calcium ion levels and reactive oxygen species (ROS) levels. NAR‐mediated radioprotection is associated with the downregulation of transient receptor potential vanilloid 6 (TRPV6), and inhibition of apoptosis pathway. Notably, treatment with NAR fails to further increase the protective effects of the TRPV6 inhibitor 2‐APB, indicating that TRPV6 inhibition is essential for NAR activity. Conclusion NAR inhibits the apoptosis pathway by downregulating TRPV6 and reducing calcium ion level, thereby alleviating RIII. Therefore, NAR is a promising therapeutic drug for RIII.