Research Center for Medicine and Biology, Zunyi Medical University, Zunyi, Guizhou, China.
Institute of Translational and Precision Medicine, Nantong University, Nantong, Jiangsu, China.
Nat Prod Res. 2024 Feb-Mar;38(4):673-678. doi: 10.1080/14786419.2023.2185236. Epub 2023 Feb 28.
Norcantharidin (NCTD) is a demethylated analogue of cantharidin. It was recently demonstrated that NCTD reduces iron contents in the liver and spleen of mice , indicating that NCTD can affect iron metabolism hepcidin. Here, we investigated the effects of NCTD on expression of iron storage protein ferritin-light chain (Ft-L), transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), ferroportin 1 (Fpn1), hepcidin, iron regulatory protein 1 (IRP1), IL-6, p-JAK2 and p-STAT3 in lipopolysaccharides (LPS)-treated RAW264.7 cells Real-time PCR and Western blotting analysis. We demonstrate that NCTD down-regulates Ft-L, hepcidin, IL-6, pJAK2, pSTAT3 and up-regulates TfR1, DMT1, Fpn1 and IRP1 expression in LPS treated cells, showing that NCTD can inhibit hepcidin the IL-6/JAK2/STAT3 signalling pathway and also increase TfR1, DMT1 and Fpn1 expression down-regulating hepcidin and up-regulating IRP1. Our findings provide further evidence for the role of NCTD in iron metabolism.
去甲基斑蝥素（NCTD）是斑蝥素的去甲基类似物。最近的研究表明，NCTD 可降低小鼠肝脏和脾脏中的铁含量，这表明 NCTD 可能会影响铁代谢和铁调素。在这里，我们研究了 NCTD 对 LPS 处理的 RAW264.7 细胞中铁储存蛋白铁蛋白轻链（Ft-L）、转铁蛋白受体 1（TfR1）、二价金属转运蛋白 1（DMT1）、亚铁转运蛋白 1（Fpn1）、铁调素、铁调节蛋白 1（IRP1）、白细胞介素 6（IL-6）、磷酸化 JAK2（p-JAK2）和磷酸化 STAT3 表达的影响。实时 PCR 和 Western blot 分析显示，NCTD 可下调 LPS 处理细胞中的 Ft-L、hepcidin、IL-6、p-JAK2、p-STAT3，并上调 TfR1、DMT1、Fpn1 和 IRP1 的表达，表明 NCTD 可抑制 hepcidin 的表达，通过 IL-6/JAK2/STAT3 信号通路，同时增加 TfR1、DMT1 和 Fpn1 的表达，下调 hepcidin 并上调 IRP1。我们的研究结果为 NCTD 在铁代谢中的作用提供了进一步的证据。
