Paeoniflorin protects against radiation enteritis by suppressing YY1/ACSL4 axis to attenuate murine intestinal epithelial injury and ferroptosis

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunobiology Pub Date : 2026-03-01 Epub Date: 2026-02-21 DOI:10.1016/j.imbio.2026.153167

Jiao Yu , Yang Zhang , Qing Wang , Lei An , Yuyan Guo , Hongtao Ren

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引用次数: 0

Abstract

Background

Radiation enteritis (RE), an intestinal complication due to abdominal or pelvic radiotherapy, severely impacts patients' life and health. Paeoniflorin (PF), a water-soluble monoterpene glycoside, is reported to relieve RE, but its molecular mechanism needs further exploration. Thus, this study aims to clarify the molecular mechanism underlying PF's effect on RE.

Methods

An in vitro ionizing radiation (IR)-induced cell model was constructed. Subsequently, CCK-8, EdU, flow cytometry and relevant kits were applied to examine cellular behaviors and ferroptosis. Protein and mRNA expression levels were assessed via Western blot and qRT-PCR. Bioinformatics tools, ChIP, and dual-luciferase reporter assays were employed to ascertain the regulatory relationship between YY1 and ACSL4. Furthermore, the RE mouse model was established for in vivo experiments.

Results

PF inhibited ionizing radiation (IR)-induced injury and ferroptosis in mouse intestinal epithelial cells (IEC-6). The inhibitory effect of PF was mediated by inhibiting ACSL4. YY1 activated the transcription of ACSL4 to promote its expression. Moreover, ACSL4 upregulation abrogated the protective effect of silencing YY1 on cell damage induced by IR. PF curbed YY1 expression, thereby suppressing the damage to IEC-6 cells induced by IR. Besides, PF constrained ACSL4 and the progression of radiation enteritis in vivo.

Conclusion

PF alleviated IR-induced damage and ferroptosis of IEC-6 cells by targeting the YY1/ACSL4 axis, providing a novel mechanistic basis for its application in RE treatment.

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芍药苷通过抑制YY1/ACSL4轴减轻小鼠肠上皮损伤和铁下垂来预防放射性肠炎

背景放射性肠炎是腹部或盆腔放射治疗引起的一种肠道并发症，严重影响患者的生活和健康。芍药苷（Paeoniflorin， PF）是一种水溶性单萜苷类化合物，有缓解RE的作用，但其分子机制有待进一步探讨。为此，本研究旨在阐明PF对re影响的分子机制。方法建立离体电离辐射（IR）诱导的细胞模型。随后采用CCK-8、EdU、流式细胞术及相关试剂盒检测细胞行为及铁下垂。Western blot和qRT-PCR检测蛋白和mRNA表达水平。采用生物信息学工具、ChIP和双荧光素酶报告基因检测来确定YY1和ACSL4之间的调控关系。并建立小鼠模型进行体内实验。结果spf对电离辐射（IR）诱导的小鼠肠上皮细胞（IEC-6）损伤和铁下垂有抑制作用。PF的抑制作用是通过抑制ACSL4介导的。YY1激活ACSL4的转录，促进其表达。此外，ACSL4的上调消除了沉默YY1对IR诱导的细胞损伤的保护作用。PF抑制YY1的表达，从而抑制IR对IEC-6细胞的损伤。此外，PF在体内抑制ACSL4和放射性肠炎的进展。结论pf通过靶向YY1/ACSL4轴减轻ir诱导的IEC-6细胞损伤和铁凋亡，为其在RE治疗中的应用提供了新的机制基础。

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

Immunobiology 医学-免疫学

CiteScore

5.00

自引率

3.60%

发文量

108

审稿时长

55 days

期刊介绍： Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.