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At present, there is no ideal radio\u2010protective agent which is widely used in RILI treatment. Astilbin (AST), a bioactive flavonoid, exhibits various biological effects, including anti\u2010inflammatory, antioxidant, and anti\u2010fibrotic activities, which partly result from reducing oxidative stress and inflammation in various pathogenic conditions. However, the protective efficacy of AST to ameliorate RILI has not been reported. In this study, we employed network pharmacology, RNA sequencing, and experimental evaluation to reveal the effects and pharmacological mechanism of AST to treat RILI in vivo and in vitro. We observed that AST reduced radiation\u2010induced apoptosis, DNA damage, inflammatory reactions, and the reactive oxygen species (ROS) level in human normal lung epithelial cells BEAS\u20102B. Further study showed that AST treatment significantly ameliorated RILI by reducing the radiation\u2010induced pathology changes and inflammatory reaction of lung tissue in C57BL\/6J mice. Mechanistically, the expression of epithelial\u2010mesenchymal transition (EMT) markers and radiation\u2010triggered acetylation of the p53 protein were alleviated by AST treatment. Furthermore, AST alleviated the acetylation of p53 after intervention of Trichostatin A (TSA). Our data indicate that AST can alleviate RILI by inhibiting inflammatory reactions and the EMT process through decreasing the expression of p53 acetylation. In conclusion, our study suggests that AST has great potential to be a new protective and therapeutic compound for RILI.<\/jats:p>","DOI":"10.1002\/tox.23931","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T09:09:36Z","timestamp":1692695376000},"page":"2967-2980","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Radioprotective efficacy of Astilbin in mitigating radiation\u2010induced lung injury through inhibition of p53 acetylation"],"prefix":"10.1002","volume":"38","author":[{"given":"Lixing","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology The First Affiliated Hospital of Guangxi Medical University  Nanning China"},{"name":"Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University) Ministry of Education  Nanning China"},{"name":"Guangxi Key Laboratory of Immunology and Metabolism 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