Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China; Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No.2, Haidian District, Beijing 100193, China.
Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No.2, Haidian District, Beijing 100193, China.
Sci Total Environ. 2023 Dec 15;904:166885. doi: 10.1016/j.scitotenv.2023.166885. Epub 2023 Sep 8.
The risks of Zinc oxide nanoparticles (ZnO NPs) applications in biological medicine, food processing industry, agricultural production and the biotoxicity brought by environmental invasion of ZnO NPs both gradually troubled the public due to the lack of research on detoxification strategies. TFEB-regulated autophagy-pyroptosis pathways were found as the crux of the hepatotoxicity induced by ZnO NPs in our latest study. Here, our study served as a connecting link between preceding toxic target and the following protection mechanism of Paeoniflorin (PF). According to a combined analysis of network pharmacology/molecular docking-intestinal microbiota-metabolomics first developed in our study, PF alleviated the hepatotoxicity of ZnO NPs from multiple aspects. The hepatic inflammatory injury and hepatocyte pyroptosis in mice liver exposed to ZnO NPs was significantly inhibited by PF. And the intestinal microbiota disorder and liver metabolic disturbance were rescued. The targets predicted by bioinformatics and the signal trend in subacute toxicological model exhibited the protectiveness of PF related to the SIRT1-mTOR-TFEB pathway. These evidences clarified multiple protective mechanisms of PF which provided a novel detoxification approach against ZnO NPs, and further provided a strategy for the medicinal value development of PF.
氧化锌纳米粒子（ZnO NPs）在生物医学、食品加工业、农业生产中的应用风险以及 ZnO NPs 对环境的入侵所带来的生物毒性，由于缺乏解毒策略的研究，逐渐引起了公众的关注。在我们最近的研究中，发现 TFEB 调控的自噬-细胞焦亡途径是 ZnO NPs 诱导肝毒性的关键。在本研究中，我们首次结合网络药理学/分子对接-肠道微生物群-代谢组学进行了综合分析，发现白芍总苷（PF）可从多个方面减轻 ZnO NPs 的肝毒性。PF 显著抑制了 ZnO NPs 暴露小鼠肝脏的肝炎症损伤和肝细胞焦亡，并挽救了肠道微生物群紊乱和肝代谢紊乱。通过生物信息学预测的靶点和亚急性毒理学模型中的信号趋势表明，PF 的保护作用与 SIRT1-mTOR-TFEB 通路有关。这些证据阐明了 PF 的多种保护机制，为 ZnO NPs 的解毒提供了一种新方法，并进一步为 PF 的药用价值开发提供了一种策略。
