Shi Jianan, Peng Xiufang, Huang Junyi, Zhang Mengyi, Wang Yuqin
Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226019, China.
Int J Mol Sci. 2025 Mar 6;26(5):2365. doi: 10.3390/ijms26052365.
Acute kidney injury (AKI) is a common side effect of acetaminophen (APAP) overdose. Dihydromyricetin (DHM) is the most abundant flavonoid in rattan tea, which has a wide range of pharmacological effects. In the current study, APAP-induced AKI models were established both in vivo and in vitro. The results showed that DHM pretreatment remarkably alleviated APAP-induced AKI by promoting antioxidant capacity through the nuclear factor erythroid-related factor 2 (Nrf2) signaling pathway in vivo. In addition, DHM reduced ROS production and mitochondrial dysfunction, thereby alleviating APAP-induced cytotoxicity in HK-2 cells. The way in which DHM improved the antioxidant capacity of HK-2 cells was through promoting the activation of the Nrf2-mediated pathway and inhibiting the expression levels of inflammation-related proteins. Furthermore, Nrf2 siRNA partially canceled out the protective effect of DHM against the cytotoxicity caused by APAP in HK-2 cells. Altogether, the protective effect of DHM on APAP-induced nephrotoxicity was related to Nrf2-dependent antioxidant and anti-inflammatory effects.
急性肾损伤（AKI）是对乙酰氨基酚（APAP）过量服用的常见副作用。二氢杨梅素（DHM）是藤茶中含量最丰富的黄酮类化合物，具有广泛的药理作用。在本研究中，在体内和体外均建立了APAP诱导的AKI模型。结果表明，在体内，DHM预处理通过核因子红细胞相关因子2（Nrf2）信号通路促进抗氧化能力，显著减轻了APAP诱导的AKI。此外，DHM减少了活性氧（ROS）的产生和线粒体功能障碍，从而减轻了APAP对HK-2细胞的细胞毒性。DHM提高HK-2细胞抗氧化能力的方式是通过促进Nrf2介导的信号通路的激活并抑制炎症相关蛋白的表达水平。此外，Nrf2小干扰RNA（siRNA）部分抵消了DHM对HK-2细胞中APAP所致细胞毒性的保护作用。总之，DHM对APAP诱导的肾毒性的保护作用与Nrf2依赖性抗氧化和抗炎作用有关。
