Affiliation:
1. Department of Oncology Affiliated Hospital of Yangzhou University Yangzhou University Yangzhou 225000 China
2. Institute of Digestive Diseases Affiliated Hospital of Yangzhou University Yangzhou University Yangzhou 225000 China
3. Department of Pathology Affiliated Hospital of Yangzhou University Yangzhou University Yangzhou 225000 China
4. Department of Gastroenterology Yangzhou Key Laboratory for Precision Treatment of Refractory Bowel Diseases The Affiliated Hospital of Yangzhou University Yangzhou University Yangzhou 225000 China
5. Department of Neurosurgery Affiliated Hospital of Yangzhou University Yangzhou University Yangzhou 225000 China
Abstract
ScopeNaringenin (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 resultsC57BL/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.ConclusionNAR inhibits the apoptosis pathway by downregulating TRPV6 and reducing calcium ion level, thereby alleviating RIII. Therefore, NAR is a promising therapeutic drug for RIII.
Funder
Natural Science Foundation of Jiangsu Province
YangZhou Municipal Science and Technology Bureau