Liu Zhi-Hui, Xu Qing-Yang, Wang Yu, Gao Hong-Xin, Min Ya-Hong, Jiang Xiao-Wen, Yu Wen-Hui
College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, 150030, P. R. China.
Chinese Veterinary Research Institute, Northeast Agricultural University, Harbin, Heilongjiang Province, 150030, P. R. China.
Am J Chin Med. 2024;52(5):1451-1485. doi: 10.1142/S0192415X24500575. Epub 2024 Jul 30.
is widely recognized as a prominent medicinal herb employed by practitioners across various generations for the purpose of fortifying kidney yin. Within , the compound known as catalpol (CAT) holds significant importance as a bioactive constituent. However, the protective effects of CAT on kidneys, including ameliorative effects on chronic kidney disease - most prominently renal anemia and renal fibrosis - have not been clearly defined. In this study, the kidney injury model of NRK-52E cells and C57BL/6N male mice was prepared by exposure to aristolochic acid I (AA-I), and it was discovered that CAT could ameliorate oxidative stress injury, inflammatory injury, apoptosis, renal anemia, renal fibrosis, and other renal injuries both and . Further treatment of NRK-52E cells with Nrf2 inhibitors (ML385) and activators (ML334), as well as NF-κB inhibitors (PDTC), validated CAT's ability to target Nrf2 activation. Furthermore, the expression of phosphorylated NF-κB p65, IL-6, and Cleaved-Caspase3 protein was inhibited. CAT also inhibited NF-κB, and then inhibited the expression of IL-6, p-STAS3, TGF-β1 protein. Therefore, CAT can regulate Nrf2/NF-κB signaling pathway, significantly correct renal anemia and renal fibrosis, and is conducive to the preservation of renal structure and function, thus achieving a protective effect on the kidneys.
被广泛认为是历代从业者用于滋补肾阴的一种著名草药。在其内部,被称为梓醇(CAT)的化合物作为一种生物活性成分具有重要意义。然而,CAT对肾脏的保护作用,包括对慢性肾脏病的改善作用——最显著的是肾性贫血和肾纤维化——尚未明确界定。在本研究中,通过暴露于马兜铃酸I(AA-I)制备了NRK-52E细胞和C57BL/6N雄性小鼠的肾损伤模型,并且发现CAT在体内和体外均可改善氧化应激损伤、炎症损伤、细胞凋亡、肾性贫血、肾纤维化及其他肾损伤。用Nrf2抑制剂(ML385)和激活剂(ML334)以及NF-κB抑制剂(PDTC)对NRK-52E细胞进行进一步处理,验证了CAT靶向激活Nrf2的能力。此外,磷酸化NF-κB p65、IL-6和裂解的Caspase3蛋白的表达受到抑制。CAT还抑制NF-κB,进而抑制IL-6、p-STAT3、TGF-β1蛋白的表达。因此,CAT可调节Nrf2/NF-κB信号通路,显著纠正肾性贫血和肾纤维化,有利于维持肾脏结构和功能,从而对肾脏起到保护作用。