地黄中的梓醇靶向 Nrf2/NF-[式中:见正文]B 信号通路,改善肾脏贫血和纤维化。

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

地黄被公认为是一种著名的药材,历代医家都将其用于滋补肾阴。在地黄中,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,包括对慢性肾脏疾病(最突出的是肾性贫血和肾脏纤维化)的改善作用,尚未得到明确界定。本研究通过马兜铃酸 I(AA-I)暴露制备了 NRK-52E 细胞和 C57BL/6N 雄性小鼠肾损伤模型,发现 CAT 在体内和体外均能改善氧化应激损伤、炎症损伤、细胞凋亡、肾性贫血、肾纤维化和其他肾损伤。用 Nrf2 抑制剂(ML385)和激活剂(ML334)以及 NF-[式中:见正文]B 抑制剂(PDTC)进一步处理 NRK-52E 细胞,验证了 CAT 靶向激活 Nrf2 的能力。此外,磷酸化 NF-[式中:见正文]B p65、IL-6 和裂解-Caspase3 蛋白的表达也受到了抑制。CAT 还能抑制 NF-[式:见正文]B,进而抑制 IL-6、p-STAS3 和 TGF-[式:见正文]1 蛋白的表达。因此,CAT能调节Nrf2/NF-[式:见正文]B信号通路,显著纠正肾性贫血和肾纤维化,有利于保护肾脏结构和功能,从而达到保护肾脏的作用。
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Catalpol from Rehmannia glutinosa Targets Nrf2/NF-[Formula: see text]B Signaling Pathway to Improve Renal Anemia and Fibrosis.

Rehmannia glutinosa is widely recognized as a prominent medicinal herb employed by practitioners across various generations for the purpose of fortifying kidney yin. Within Rehmannia glutinosa, 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 in vivo and in vitro. Further treatment of NRK-52E cells with Nrf2 inhibitors (ML385) and activators (ML334), as well as NF-[Formula: see text]B inhibitors (PDTC), validated CAT's ability to target Nrf2 activation. Furthermore, the expression of phosphorylated NF-[Formula: see text]B p65, IL-6, and Cleaved-Caspase3 protein was inhibited. CAT also inhibited NF-[Formula: see text]B, and then inhibited the expression of IL-6, p-STAS3, TGF-[Formula: see text]1 protein. Therefore, CAT can regulate Nrf2/NF-[Formula: see text]B 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.

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