{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:09:10Z","timestamp":1787314150126,"version":"build-2736575974"},"reference-count":28,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Shanghai","award":["22ZR1461600"],"award-info":[{"award-number":["22ZR1461600"]}]},{"name":"Natural Science Foundation of Shanghai","award":["23ZR1460800"],"award-info":[{"award-number":["23ZR1460800"]}]},{"name":"Natural Science Foundation of Shanghai","award":["82373908"],"award-info":[{"award-number":["82373908"]}]},{"name":"Natural Science Foundation of Shanghai","award":["82404918"],"award-info":[{"award-number":["82404918"]}]},{"name":"Natural Science Foundation of Shanghai","award":["2022YFE0203600"],"award-info":[{"award-number":["2022YFE0203600"]}]},{"name":"National Natural Science Foundation of China","award":["22ZR1461600"],"award-info":[{"award-number":["22ZR1461600"]}]},{"name":"National Natural Science Foundation of China","award":["23ZR1460800"],"award-info":[{"award-number":["23ZR1460800"]}]},{"name":"National Natural Science Foundation of China","award":["82373908"],"award-info":[{"award-number":["82373908"]}]},{"name":"National Natural Science Foundation of China","award":["82404918"],"award-info":[{"award-number":["82404918"]}]},{"name":"National Natural Science Foundation of China","award":["2022YFE0203600"],"award-info":[{"award-number":["2022YFE0203600"]}]},{"name":"National Key R&amp;D Program \u201cStrategic Scientific and Technological Innovation Cooperation\u201d Key Project","award":["22ZR1461600"],"award-info":[{"award-number":["22ZR1461600"]}]},{"name":"National Key R&amp;D Program \u201cStrategic Scientific and Technological Innovation Cooperation\u201d Key Project","award":["23ZR1460800"],"award-info":[{"award-number":["23ZR1460800"]}]},{"name":"National Key R&amp;D Program \u201cStrategic Scientific and Technological Innovation Cooperation\u201d Key Project","award":["82373908"],"award-info":[{"award-number":["82373908"]}]},{"name":"National Key R&amp;D Program \u201cStrategic Scientific and Technological Innovation Cooperation\u201d Key Project","award":["82404918"],"award-info":[{"award-number":["82404918"]}]},{"name":"National Key R&amp;D Program \u201cStrategic Scientific and Technological Innovation Cooperation\u201d Key Project","award":["2022YFE0203600"],"award-info":[{"award-number":["2022YFE0203600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms26031385","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T09:54:38Z","timestamp":1738835678000},"page":"1385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rubiadin Mediates the Upregulation of Hepatic Hepcidin and Alleviates Iron Overload via BMP6\/SMAD1\/5\/9-Signaling Pathway"],"prefix":"10.3390","volume":"26","author":[{"given":"Xueting","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Immunology and Pathogenic Biology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyue","family":"Chang","sequence":"additional","affiliation":[{"name":"Natural Product Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"},{"name":"University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, 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