Tea Polyphenols Mitigate Radiation-Induced Ferroptosis and Intestinal Injury by Targeting the Nrf2/HO-1/GPX4 Signaling Pathway
Radiation-induced intestinal injury (RIII) is a significant concern for cancer patients receiving radiation therapy, as it can lead to complications such as radiation enteropathy. Presently, there are limited options for preventing or treating RIII. Tea polyphenols (TP), found in tea, provide variou...
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MDPI AG
2025-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/5/580 |
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| author | Runtian Li Lintao Li Haiyang Wu Hui Gan Zhuona Wu Ruolan Gu Xiaoxia Zhu Shuchen Liu Zhiyun Meng Guifang Dou |
| author_facet | Runtian Li Lintao Li Haiyang Wu Hui Gan Zhuona Wu Ruolan Gu Xiaoxia Zhu Shuchen Liu Zhiyun Meng Guifang Dou |
| author_sort | Runtian Li |
| collection | DOAJ |
| description | Radiation-induced intestinal injury (RIII) is a significant concern for cancer patients receiving radiation therapy, as it can lead to complications such as radiation enteropathy. Presently, there are limited options for preventing or treating RIII. Tea polyphenols (TP), found in tea, provide various health benefits, but their antiradiation mechanisms are not fully understood. C57BL/6 mice pre-treated with TP for five days showed a significant improvement in survival rates after being exposed to 10 Gy of <sup>60</sup>Co radiation. In the same way, abdominal exposure to 15 Gy of <sup>60</sup>Co radiation effectively mitigated radiation-induced colon shortening, damage to intestinal tissues, oxidative stress, the release of inflammatory factors, and disruptions in intestinal microbial balance. In addition, TP treatment lowered the elevation of reactive oxygen species (ROS), iron imbalance, mitochondrial damage, and ferroptosis in IEC-6 cells post-irradiation. Utilizing network pharmacology, molecular docking, and affinity testing, we identified that TP has the capability to target the Nrf2/HO-1/GPX4 signaling pathway, while EGCG, a principal constituent of TP, interacts with HSP90 and mitigates radiation-induced ferroptosis. These findings suggest that TP may serve as a promising therapeutic agent to alleviate radiation-induced intestinal injury (RII). |
| format | Article |
| id | doaj-art-fbf938eb5d4b4c6faab8bc3edd3d9c82 |
| institution | DOAJ |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-fbf938eb5d4b4c6faab8bc3edd3d9c822025-08-20T03:14:39ZengMDPI AGAntioxidants2076-39212025-05-0114558010.3390/antiox14050580Tea Polyphenols Mitigate Radiation-Induced Ferroptosis and Intestinal Injury by Targeting the Nrf2/HO-1/GPX4 Signaling PathwayRuntian Li0Lintao Li1Haiyang Wu2Hui Gan3Zhuona Wu4Ruolan Gu5Xiaoxia Zhu6Shuchen Liu7Zhiyun Meng8Guifang Dou9Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, ChinaSchool of Public Health, University of South China, Hengyang 421001, ChinaBeijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, ChinaRadiation-induced intestinal injury (RIII) is a significant concern for cancer patients receiving radiation therapy, as it can lead to complications such as radiation enteropathy. Presently, there are limited options for preventing or treating RIII. Tea polyphenols (TP), found in tea, provide various health benefits, but their antiradiation mechanisms are not fully understood. C57BL/6 mice pre-treated with TP for five days showed a significant improvement in survival rates after being exposed to 10 Gy of <sup>60</sup>Co radiation. In the same way, abdominal exposure to 15 Gy of <sup>60</sup>Co radiation effectively mitigated radiation-induced colon shortening, damage to intestinal tissues, oxidative stress, the release of inflammatory factors, and disruptions in intestinal microbial balance. In addition, TP treatment lowered the elevation of reactive oxygen species (ROS), iron imbalance, mitochondrial damage, and ferroptosis in IEC-6 cells post-irradiation. Utilizing network pharmacology, molecular docking, and affinity testing, we identified that TP has the capability to target the Nrf2/HO-1/GPX4 signaling pathway, while EGCG, a principal constituent of TP, interacts with HSP90 and mitigates radiation-induced ferroptosis. These findings suggest that TP may serve as a promising therapeutic agent to alleviate radiation-induced intestinal injury (RII).https://www.mdpi.com/2076-3921/14/5/580radiation-induced intestinal injurytea polyphenolferroptosisHSP90gut microbiotametabolites |
| spellingShingle | Runtian Li Lintao Li Haiyang Wu Hui Gan Zhuona Wu Ruolan Gu Xiaoxia Zhu Shuchen Liu Zhiyun Meng Guifang Dou Tea Polyphenols Mitigate Radiation-Induced Ferroptosis and Intestinal Injury by Targeting the Nrf2/HO-1/GPX4 Signaling Pathway Antioxidants radiation-induced intestinal injury tea polyphenol ferroptosis HSP90 gut microbiota metabolites |
| title | Tea Polyphenols Mitigate Radiation-Induced Ferroptosis and Intestinal Injury by Targeting the Nrf2/HO-1/GPX4 Signaling Pathway |
| title_full | Tea Polyphenols Mitigate Radiation-Induced Ferroptosis and Intestinal Injury by Targeting the Nrf2/HO-1/GPX4 Signaling Pathway |
| title_fullStr | Tea Polyphenols Mitigate Radiation-Induced Ferroptosis and Intestinal Injury by Targeting the Nrf2/HO-1/GPX4 Signaling Pathway |
| title_full_unstemmed | Tea Polyphenols Mitigate Radiation-Induced Ferroptosis and Intestinal Injury by Targeting the Nrf2/HO-1/GPX4 Signaling Pathway |
| title_short | Tea Polyphenols Mitigate Radiation-Induced Ferroptosis and Intestinal Injury by Targeting the Nrf2/HO-1/GPX4 Signaling Pathway |
| title_sort | tea polyphenols mitigate radiation induced ferroptosis and intestinal injury by targeting the nrf2 ho 1 gpx4 signaling pathway |
| topic | radiation-induced intestinal injury tea polyphenol ferroptosis HSP90 gut microbiota metabolites |
| url | https://www.mdpi.com/2076-3921/14/5/580 |
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