title: Astragalus polysaccharide upregulates hepcidin and reduces iron overload in mice via activation of p38 mitogen-activated protein kinase.
abstract: Thalassemia is a genetic disease characterized by iron overload which is a major detrimental factor contributing to mortality and organ damage. The hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. Lowering iron load in thalassemia patients by means of increasing hepcidin might be a therapeutic strategy. In this study, we first found that astragalus polysaccharide (APS) significantly increased hepcidin expression in HepG2 and L-02 cell lines originating from hepatocytes and mice liver, respectively. Following treatment with APS, the iron concentrations in serum, liver, spleen, and heart were significantly reduced in comparison to saline treated control mice. In further experiments, upregulation of interleukin-6 (IL-6) and enhanced p38 MAPK phosphorylation were detected in APS treated cells and mice, and as documented in previous studies, IL-6 and P38 MAPK phosphorylation are involved in the regulation of hepcidin expression. We also found that the effects of APS on upregulating hepcidin and IL-6 expressions could be antagonized by pretreatment with SB203580, an inhibitor of p38 MAPK signaling. These findings suggest that activation of p38 MAPK and release of IL-6 might mediate induction of hepcidin by APS. It is concluded that APS might have therapeutic implications in patients with iron overload, especially for thalassemia patients.
authors.affiliation: Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ren
authors.affiliation: Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: qxh_nfyy@sina.com.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Qian
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China. Electronic address: qxlrfv@sina.com.
authors.forename: Xin-Lai
authors.initials: XL
authors.lastname: Qian
mesh_terms: D000818:Animals; D027885:Astragalus propinquus / Q000737:chemistry; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006485:Hemosiderin / Q000378:metabolism; D056945:Hep G2 Cells; D064451:Hepcidins / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008517:Phytotherapy; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D013789:Thalassemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004365:Drugs, Chinese Herbal; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D011134:Polysaccharides; D006485:Hemosiderin; D007501:Iron; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Astragalus polysaccharide; Hepcidin; Interleukin-6; Iron load; Thalassemia; p38MAPK signaling pathway