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

Cynaroside alleviates radiation-induced intestinal injury by inhibiting dynamin 2

  • Int Immunopharmacol. 2025 Sep 23:162:115167. doi: 10.1016/j.intimp.2025.115167.
Jing Xu 1,  Xueting Yang 2,  Kefeng Pu 3,  Qingyi Zhang 2,  Qichun Wei 1,  Xiaochuan Ma 4,  Zhixing He 5
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, The Second Affiliated Hospital and Cancer Institute, Zhejiang University School of Medicine, Hangzhou 310009, China.
  • 2 Research Institute of Chinese Medical Clinical Foundation and Immunology, School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
  • 3 Nano-Bio-Chem Centre, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
  • 4 State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China. Electronic address: xcma@suda.edu.cn.
  • 5 Research Institute of Chinese Medical Clinical Foundation and Immunology, School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: hzx2015@zcmu.edu.cn.
PMID: 40614595 DOI: 10.1016/j.intimp.2025.115167
Abstract

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.

Keywords

Cynaroside; Dynamin 2; Proteomics; Radiation-induced intestinal injury; Small intestine.

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