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梓醇通过靶向Nrf2/NF-κB信号通路改善肾性贫血和肾纤维化。

Catalpol from Targets Nrf2/NF-κB Signaling Pathway to Improve Renal Anemia and Fibrosis.

作者信息

Liu Zhi-Hui, Xu Qing-Yang, Wang Yu, Gao Hong-Xin, Min Ya-Hong, Jiang Xiao-Wen, Yu Wen-Hui

机构信息

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.

出版信息

Am J Chin Med. 2024;52(5):1451-1485. doi: 10.1142/S0192415X24500575. Epub 2024 Jul 30.

Abstract

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.

摘要

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。

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