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首页> 外文期刊>Journal of Ethnopharmacology: An Interdisciplinary Journal Devoted to Bioscientific Research on Indigenous Drugs >Study to establish the role of JAK2 and SMAD1/5/8 pathways in the inhibition of hepcidin by polysaccharides from Angelica sinensis
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Study to establish the role of JAK2 and SMAD1/5/8 pathways in the inhibition of hepcidin by polysaccharides from Angelica sinensis

机译：建立JAK2和SMAD1 / 5/8途径在当归多糖抑制铁调素中的作用的研究

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Ethnopharmacological relevance: Angelica sinensis polysaccharide (ASP) is one of the major active ingredients in Angelica sinensis (Oliv.) Diels. This traditional Chinese medicine has been used for thousands of years for treating gynecological diseases. Aim of the study: Previous studies have suggested that ASP from the roots of Angelica sinensis (Oliv.) Diels suppresses hepcidin expression, but the underlying molecular mechanisms are not known. The present study was designed to establish the role of the janus-kinases 2 (JAK2) and son of mothers against decapentaplegic 1/5/8 (SMAD1/5/8) pathways in the inhibition of hepcidin by polysaccharides from Angelica sinensis in normal rats. Materials and methods: ASP was administered orally (0.3, 0.6 and 1.2 g/kg body weight) to male Sprague-Dawley rats every day for 20 days. Intraperitoneal injections of recombinant human erythropoietin (rhEPO; 800 and 2000 U/kg body weight) were given to the positive control group every day for 3 days. After administration, hepcidin levels, blood parameters, serum iron status and non-heme iron concentrations in the liver were examined. Western blot analyses were used to investigate the expression of five relevant signaling proteins in the liver. Results: RhEPO injection significantly stimulated erythropoiesis and expression of the serum transferrin receptor (sTfR), and decreased serum iron status and non-heme iron concentrations in the liver. However, blood parameters barely changed in the ASP groups. sTfR, serum iron, and liver iron levels altered only in the ASP high-dose group (1.2 g/kg body weight). rhEPO and ASP significantly reduced hepcidin expression by inhibiting the expression of phospho-SMAD1/5/8 and JAK2 in the liver, but not through transmembrane protease serine 6 (TMPRSS6) and extracellular signal-regulated kinase 1/2 (ERK1/2). Conclusions: These data suggested that ASP can interrupt the JAK2 and SMAD1/5/8 pathways, which eventually results in lower expression of hepcidin.
机译：民族药理意义：当归多糖（ASP）是当归Diels中的主要活性成分之一。这种中药已被用于治疗妇科疾病数千年。研究的目的：先前的研究表明，当归根中的ASP能抑制hepcidin的表达，但其潜在的分子机制尚不清楚。本研究旨在确定janus激酶2（JAK2）和母亲的儿子对抗去Cappleplegic 1/5/8（SMAD1 / 5/8）途径在正常大鼠中当归多糖抑制铁调素中的作用。材料和方法：每天对雄性Sprague-Dawley大鼠口服ASP（0.3、0.6和1.2 g / kg体重），持续20天。每天向阳性对照组进行腹膜内注射重组人促红细胞生成素（rhEPO; 800和2000 U / kg体重）。给药后，检查肝中的铁调素水平，血液参数，血清铁状态和非血红素铁浓度。 Western印迹分析用于研究肝脏中五种相关信号蛋白的表达。结果：RhEPO注射显着刺激红细胞生成和血清转铁蛋白受体（sTfR）的表达，并降低肝脏中的血清铁状态和非血红素浓度。但是，ASP组的血液参数几乎没有变化。 sTfR，血清铁和肝铁水平仅在ASP大剂量组（1.2 g / kg体重）中改变。 rhEPO和ASP通过抑制肝脏中的磷酸-SMAD1 / 5/8和JAK2的表达来显着降低hepcidin的表达，但不能通过跨膜蛋白酶丝氨酸6（TMPRSS6）和细胞外信号调节激酶1/2（ERK1 / 2）来降低。结论：这些数据表明ASP可以中断JAK2和SMAD1 / 5/8途径，最终导致铁调素的较低表达。

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