Cynaroside alleviates radiation-induced intestinal injury by inhibiting dynamin 2

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-07-04 DOI:10.1016/j.intimp.2025.115167

Jing Xu , Xueting Yang , Kefeng Pu , Qingyi Zhang , Qichun Wei , Xiaochuan Ma , Zhixing He

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引用次数: 0

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.

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Cynaroside通过抑制dynamin 2减轻辐射引起的肠道损伤

Cynaroside （Cyn）具有独特的抗炎、抗凋亡特性和多种生物活性；然而，其在减轻辐射引起的肠道损伤（RIII）中的作用尚不清楚。本研究旨在探讨Cyn对RIII的保护作用，并探讨其机制。C57BL/6小鼠腹腔单次12 Gy x线全腹照射（TAI）后灌胃。Cyn对RIII具有剂量依赖性的保护作用。Cyn治疗提高了受辐射小鼠的存活率，减轻了体重减轻，保留了结肠长度和肠道结构（隐窝和绒毛），减少了辐射诱导的炎症标志物，增加了Ki67+的表达，并恢复了肠道微生物群的失调。蛋白质组学分析显示，动力蛋白2是Cyn抗riii作用的潜在介质。同样，在接受新辅助放疗的患者结肠粘膜标本中，dynamin 2的表达显著上调。在人肠上皮细胞（NCM460）中，Cyn在下调dynamin 2表达的同时具有辐射保护作用。重要的是，Cyn治疗同样未能进一步增加动力蛋白2抑制剂的保护作用，这表明抑制动力蛋白2对Cyn活性至关重要。我们的研究结果表明，Cyn通过抑制动力蛋白2来减轻RIII，突出了其作为RIII治疗剂的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.