Cynaroside alleviates radiation-induced intestinal injury by inhibiting dynamin 2.

Cynaroside (Cyn) exhibits unique anti-inflammatory, anti-apoptotic properties and diverse bioactivities; however, its role in mitigating radiation-induced intestinal injury (RIII) remains unclear. This study aimed to investigate the protective effects of Cyn against RIII and explore the underlying mechanisms. C57BL/6 mice were subjected to a single 12 Gy X-ray total abdominal irradiation (TAI) followed by Cyn gavage. Cyn exhibited dose-dependent protection against RIII. Treatment with Cyn improved survival rates, attenuated body weight loss, preserved colon length and intestinal architecture (crypts and villi), reduced radiation-induced inflammatory markers, increased Ki67+ expression, and restore gut microbiota dysbiosis in irradiated mice. Proteomic analysis revealed dynamin 2 as a potential mediator of Cyn's anti-RIII effects. Consistently, dynamin 2 expression was significantly upregulated in colon mucosa specimens from patients who received neoadjuvant radiotherapy. In human intestinal epithelial cells (NCM460), Cyn conferred radioprotection while downregulating dynamin 2 expression. Importantly, treatment with Cyn failed to further increase the protective effects of the dynamin 2 inhibitor dynasore similarly, indicating that dynamin 2 inhibition is essential for Cyn activity. Our findings suggested that Cyn alleviated RIII by suppressing dynamin 2, highlighting its potential as a therapeutic agent for RIII.