1. Rubiadin Mediates the Upregulation of Hepatic Hepcidin and Alleviates Iron Overload via BMP6/SMAD1/5/9-Signaling Pathway.
- Author
-
Xie X, Chang L, Zhu X, Gong F, Che L, Zhang R, Wang L, Gong C, Fang C, Yao C, Hu D, Zhao W, Zhou Y, and Zhu S
- Subjects
- Animals, Humans, Mice, Hep G2 Cells, Iron metabolism, Up-Regulation drug effects, Male, Smad Proteins metabolism, Mice, Inbred C57BL, Lignans pharmacology, Pyrazoles, Pyrimidines, Hepcidins metabolism, Hepcidins genetics, Iron Overload metabolism, Iron Overload drug therapy, Bone Morphogenetic Protein 6 metabolism, Bone Morphogenetic Protein 6 genetics, Signal Transduction drug effects, Liver metabolism, Liver drug effects
- Abstract
Iron overload disease is characterized by the excessive accumulation of iron in the body. To better alleviate iron overload, there is an urgent need for safe and effective small molecule compounds. Rubiadin, the active ingredient derived from the Chinese herb Prismatomeris tetrandra, possesses notable anti-inflammatory and hepatoprotective properties. Nevertheless, its impact on iron metabolism remains largely unexplored. To determine the role of rubiadin on iron metabolism, Western blot analysis, real-time PCR analysis, and the measurement of serum iron were performed. Herein, we discovered that rubiadin significantly downregulated the expression of transferrin receptor 1, ferroportin 1, and ferritin light chain in ferric-ammonium-citrate-treated or -untreated HepG2 cells. Moreover, intraperitoneal administration of rubiadin remarkably decreased serum iron and duodenal iron content and upregulated expression of hepcidin mRNA in the livers of high-iron-fed mice. Mechanistically, bone morphogenetic protein 6 (BMP6) inhibitor LDN-193189 completely reversed the hepcidin upregulation and suppressor of mother against decapentaplegic 1/5/9 (SMAD1/5/9) phosphorylation induced by rubiadin. These results suggested that rubiadin increased hepcidin expression through the BMP6/SMAD1/5/9-signaling pathway. Collectively, our findings uncover a crucial mechanism through which rubiadin modulates iron metabolism and highlight it as a potential natural compound for alleviating iron-overload-related diseases.
- Published
- 2025
- Full Text
- View/download PDF