title: Screening identifies the Chinese medicinal plant Caulis Spatholobi as an effective HAMP expression inhibitor.
abstract: Hepcidin, the pivotal regulator of iron metabolism, plays a critical role in multiple diseases including anemia of chronic disease and hemochromatosis. Recent studies have focused on identifying antagonists of hepcidin. We hypothesized that bioactive extracts from Chinese medicinal plants may be efficacious in the inhibition of expression of the hepcidin-encoding gene (HAMP) product, hepcidin. To test this, we measured the level of hepcidin expression in cultured cells treated with 16 different medicinal plant extracts, all of which are used to treat anemia-related disorders in traditional Chinese medicine. Among the extracts tested, that of Caulis Spatholobi (CS; also called Jixueteng, the stem of Spatholobus suberectus Dunn) showed the most potent inhibitory effect on HAMP expression in the Huh7 cell line and was therefore selected for further mechanistic study. In cells treated with 400 μg/mL of extract, phosphorylated mothers against decapentaplegic homolog proteins 1/5/8 levels were 80% less than those of controls (P < 0.001), and the inhibitory effect on interleukin-6-induced HAMP expression (65% inhibition) was weaker than the strong inhibition on bone morphogenetic protein 6-induced HAMP expression (97% inhibition). Seven-week-old C57BL/6 female mice were fed an AIN-76A diet containing 10.8% dried CS and then analyzed on d 0, 5, 10, or 15. On d 5, there was a 60% decrease in hepatic HAMP expression (P < 0.05), an 18% decrease in hepatic iron concentration, and a 100% increase in serum iron concentration (P < 0.05) compared with the d 0 group. In conclusion, we identify the extract of CS as a novel, potent HAMP expression inhibitor, which may be further modified and optimized to become a dietary supplement or a therapeutic option for the amelioration of hepcidin-overexpression-related diseases, including iron deficiency anemia.
authors.affiliation: Department of Nutrition, Institute of Nutrition and Food Safety, School of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Guan
authors.forename: Peng
authors.initials: P
authors.lastname: An
authors.forename: Zhuzhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Yu
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Shi
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Tao
authors.forename: Fudi
authors.initials: F
authors.lastname: Wang
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000188:drug therapy / Q000235:genetics; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D055418:Bone Morphogenetic Protein 6 / Q000494:pharmacology; D045744:Cell Line, Tumor; D007887:Fabaceae / Q000737:chemistry*; D005260:Female; D056945:Hep G2 Cells; D064451:Hepcidins; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007501:Iron / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: D023181:Antimicrobial Cationic Peptides; C525816:BMP6 protein, human; D055418:Bone Morphogenetic Protein 6; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D015850:Interleukin-6; D010936:Plant Extracts; D012333:RNA, Messenger; D007501:Iron