Catalpol from Rehmannia glutinosa Targets Nrf2/NF-[Formula: see text]B Signaling Pathway to Improve Renal Anemia and Fibrosis.

ABSTRACT

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.