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Objective <p>To elucidate the molecular mechanisms by which astilbin (AST) prevents and mitigates radiation-induced lung injury (RILI) both <i>in vivo</i> and <i>in vitro</i>.</p> Methods <p><i>In vitro</i>, murine-derived lung epithelial cells (TC-1) were transfected with either wild-type (WT) or mutant (Mut) p53 overexpression plasmid, and exposed to 6 Gy of radiation and subsequently treated with 50 µ g/mL AST or DMSO. Cellular assays, including Western blot, immunofluorescence, TUNEL and flow cytometry, were employed to assess expressions of acetylation p53 (Ap53), phosphorylated histone H2AX (<i>γ</i>-H2AX), Bax and Bcl-2, as well as apoptosis and reactive oxygen species (ROS) levels, respectively. For <i>in vivo</i> experiment, 12 female p53-WT and 12 female p53-homozygous knockout (KO) mice were randomly assigned to 4 groups per genotype (<i>n</i>=3 per group) using block randomization. p53-WT and p53-KO mice received either normal saline or AST [50 mg/(kg·d)], followed by 15 Gy whole-thorax irradiation or not. Lung injury was assessed at 6 weeks post-irradiation via hematoxylin and eosin staining and immunohistochemical (IHC) detection of p53 and Ap53.</p> Results <p><i>In vitro</i>, AST markedly reduced Ap53, ROS levels, <i>γ</i>-H2AX expression, and apoptosis in WT-p53 cells, whereas no noticeable protective effects were observed in Mut-p53 cells (<i>P</i>&lt;0.05 or <i>P</i>&lt;0.01). <i>In vivo</i> studies showed AST effectively mitigated RILI in p53-WT mice while exhibiting no significant effects in p53-KO mice. Additionally, IHC analysis revealed that AST decreased p53 protein and Ap53 levels in the lung tissue of p53-WT mice, but had no impact on p53-KO mice.</p> Conclusion <p>AST alleviates radiation-induced oxidative stress, DNA damage, and apoptosis by inhibiting Ap53.</p>

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Astilbin Confers Radioprotection in Lung Injury via p53-Mediated Suppression of Oxidative Damage and Apoptosis

  • 期刊论文

  • 发表日期：

    2026年3月11日

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  • Qian-xin Hu,
  • Xue Ou,
  • Ya-qin Huang,
  • Jing Qin,
  • Jing Liu,
  • Ting-ting Zhang,
  • Xue-ting Yan,
  • Xian Liang,
  • Wei-mei Huang,
  • Kai Hu

摘要

Objective

To elucidate the molecular mechanisms by which astilbin (AST) prevents and mitigates radiation-induced lung injury (RILI) both in vivo and in vitro.

Methods

In vitro, murine-derived lung epithelial cells (TC-1) were transfected with either wild-type (WT) or mutant (Mut) p53 overexpression plasmid, and exposed to 6 Gy of radiation and subsequently treated with 50 µ g/mL AST or DMSO. Cellular assays, including Western blot, immunofluorescence, TUNEL and flow cytometry, were employed to assess expressions of acetylation p53 (Ap53), phosphorylated histone H2AX (γ-H2AX), Bax and Bcl-2, as well as apoptosis and reactive oxygen species (ROS) levels, respectively. For in vivo experiment, 12 female p53-WT and 12 female p53-homozygous knockout (KO) mice were randomly assigned to 4 groups per genotype (n=3 per group) using block randomization. p53-WT and p53-KO mice received either normal saline or AST [50 mg/(kg·d)], followed by 15 Gy whole-thorax irradiation or not. Lung injury was assessed at 6 weeks post-irradiation via hematoxylin and eosin staining and immunohistochemical (IHC) detection of p53 and Ap53.

Results

In vitro, AST markedly reduced Ap53, ROS levels, γ-H2AX expression, and apoptosis in WT-p53 cells, whereas no noticeable protective effects were observed in Mut-p53 cells (P<0.05 or P<0.01). In vivo studies showed AST effectively mitigated RILI in p53-WT mice while exhibiting no significant effects in p53-KO mice. Additionally, IHC analysis revealed that AST decreased p53 protein and Ap53 levels in the lung tissue of p53-WT mice, but had no impact on p53-KO mice.

Conclusion

AST alleviates radiation-induced oxidative stress, DNA damage, and apoptosis by inhibiting Ap53.