Wu Yijin, Wang Shaofeng, Huang Hui, Yu Jingling, Liang Jieren, Huang Hai, Guo Jianying, Tang Zhaoxin, Liao Jianzhao
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China.
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China.
Int J Biol Macromol. 2025 Aug;320(Pt 1):145750. doi: 10.1016/j.ijbiomac.2025.145750. Epub 2025 Jul 5.
With the increasing application of copper nanoparticles (CuNPs) across various fields, its toxicity and hazards are gradually being confirmed. Hesperidin (Hes), a flavonoid compound with extensive antioxidant and anti-inflammatory effects, has recently attracted public attention.
Molecular docking was employed to investigate the potential binding sites between Hes and SIRT3. The activation of the SIRT3-FOXO3A signaling pathway by Hes was further validated through a series of experiments in vitro and vivo.
The results indicate that exposure to CuNPs can cause pathological damage to liver. Compared with the control group, exposure to CuNPs induced the accumulation of reactive oxygen species and mitochondrial UPR in broiler liver, specifically manifested as an increase in reactive oxygen species and the gene and protein levels of UPR related proteins. The molecular docking results indicate that Hes and SIRT3 have potential binding sites. However, after treatment with Hes, pathological damage in liver was alleviated. At the same time, we found that the SIRT3-FOXO3A signaling pathway was activated, leading to a significant decrease in the expression levels of proteins and genes related to UPR.
Hes can ameliorate hepatic oxidative damage and UPR induced by exposure to CuNPs by activating the SIRT3-FOXO3A pathway.
随着铜纳米颗粒（CuNPs）在各个领域的应用日益增加，其毒性和危害逐渐得到证实。橙皮苷（Hes）是一种具有广泛抗氧化和抗炎作用的黄酮类化合物，最近受到了公众的关注。
采用分子对接技术研究Hes与SIRT3之间的潜在结合位点。通过一系列体内外实验进一步验证Hes对SIRT3-FOXO3A信号通路的激活作用。
结果表明，暴露于CuNPs会对肝脏造成病理损伤。与对照组相比，暴露于CuNPs会诱导肉鸡肝脏中活性氧的积累和线粒体未折叠蛋白反应（UPR），具体表现为活性氧以及UPR相关蛋白的基因和蛋白水平增加。分子对接结果表明Hes与SIRT3具有潜在结合位点。然而，用Hes处理后，肝脏的病理损伤得到缓解。同时，我们发现SIRT3-FOXO3A信号通路被激活，导致UPR相关蛋白和基因的表达水平显著降低。
Hes可通过激活SIRT3-FOXO3A通路改善暴露于CuNPs所致的肝脏氧化损伤和UPR。
