放射性肺损伤（RILI）是胸部肿瘤患者接受放射治疗后常见的副作用。目前，在RILI治疗中广泛使用的理想放射保护剂尚不存在。黄杨素（AST）是一种活性黄酮类化合物，具有抗炎、抗氧化和抗纤维化的多种生物学效应，部分原因是在各种病理情况下减少氧化应激和炎症反应。然而，AST在缓解RILI方面的保护效果尚未报道。本研究采用网络药理学、RNA测序和实验评估的方法，揭示了AST治疗体内外RILI的效果和药理机制。我们观察到，AST可以减少辐射引起的人正常肺上皮细胞BEAS-2B的凋亡、DNA损伤、炎症反应和活性氧（ROS）水平。进一步研究表明，在C57BL/6J小鼠中，AST治疗显著改善了辐射引起的肺组织病理变化和炎症反应。机制上，AST治疗减轻了上皮-间质转化（EMT）标志物的表达和辐射引发的p53蛋白乙酰化。此外，在经过曲安西坦A（TSA）干预后，AST还减轻了p53的乙酰化。我们的数据表明，AST通过抑制炎症反应和EMT过程，降低p53乙酰化的表达，可以缓解RILI。总之，本研究提示AST在缓解RILI方面具有潜力，可作为一种新的保护性和治疗性化合物。© 2023 Wiley Periodicals LLC.

Radiation-induced lung injury (RILI) is a common side effect in thoracic tumor patients undergoing radiotherapy. At present, there is no ideal radio-protective agent which is widely used in RILI treatment. Astilbin (AST), a bioactive flavonoid, exhibits various biological effects, including anti-inflammatory, antioxidant, and anti-fibrotic 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-induced apoptosis, DNA damage, inflammatory reactions, and the reactive oxygen species (ROS) level in human normal lung epithelial cells BEAS-2B. Further study showed that AST treatment significantly ameliorated RILI by reducing the radiation-induced pathology changes and inflammatory reaction of lung tissue in C57BL/6J mice. Mechanistically, the expression of epithelial-mesenchymal transition (EMT) markers and radiation-triggered 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.© 2023 Wiley Periodicals LLC.