Black soyabean seed coat extract regulates iron metabolism by inhibiting the expression of hepcidin

Abstract

Hepcidin, a key regulator of Fe homeostasis, is an ideal drug target for treating patients with Fe disorders such as haemochromatosis, anaemia of chronic inflammation and Fe-deficiency anaemia. However, whether (and how) traditional Chinese black foods (e.g., black soyabeans) target hepcidin and improve Fe-deficiency anaemia remains unclear. Herein, we report that black soyabean seed coat extract (BSSCE) can potently inhibit the in vitro and in vivo expression of hepcidin. In the present study, in cells treated with 200 μg/ml BSSCE, hepcidin expression was found to be reduced to only 6% of the control levels (P<0.01). An AIN-76A diet containing 2% BSSCE was fed to 8-week-old male C57BL/6 mice for 0, 1, 7, 15 or 30 d; importantly, compared with the day 0 group, the day 7 group exhibited nearly a 50% decrease in hepatic hepcidin expression (P<0.01), a 35% decrease in splenic Fe concentrations (P<0.05) and a 135% increase in serum Fe concentrations (P<0.05). Mechanistically, the effect of BSSCE on hepcidin expression was mediated via a reduction in the phosphorylation levels of mothers against decapentaplegic homolog proteins (Smad)1/5/8. Consequently, the mice in the day 30 group exhibited large increases in erythrocyte counts (111% v. day 0, P<0.01), Hb concentrations (109%, P<0.01) and haematocrit values (108%, P<0.01). In conclusion, these results indicate that black soyabean extract regulates Fe metabolism by inhibiting the expression of hepcidin. This finding can be used to optimise the intervention of patients with hepcidin-related diseases, including Fe-deficiency anaemia.

Tucum-Do-Cerrado (Bactris setosa Mart.) Consumption Modulates Iron Homeostasis and Prevents Iron-Induced Oxidative Stress in the Rat Liver

“…The authors demonstrated that the reduction in HAMP expression is mainly due to reducing the levels of phosphorylated SMAD 1/5/8 levels by CS extract, independently of BMP6 content. Similar results were also observed in rats treated with a polysaccharide from Angelica sinensis [ 41 ] or black soybean seed coat extract [ 42 ], the phytochemicals of these plants decreased hepcidin and phosphorylated SMAD 1/5/8 in a dose dependent manner. Therefore, it is possible that tucum-do-cerrado interferes in iron-dependent pathways at phosphorylation level of SMAD 1/5/8 or in iron-independent pathways triggered by IL-6 or erythropoietin.…”

Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms

“…Using functional screening, we previously identified several hepcidin expression antagonists and agonists present in Chinese herbs, 30 black soybeans, 31 and a library of small compounds. However, none of these compounds has been approved for clinical applications.…”

“…Given that both hepcidin and the synthetic peptide minihepcidin 29 drastically reduce serum iron levels in animal models, several strategies have been used to identify novel compounds that might regulate hepcidin expression, thereby treating ironrelated diseases. Although herbal extracts, [30][31][32] epigenetic inhibitors, 33 and sex hormones 34,35 have all been reported to affect hepcidin expression and iron metabolism, none of these products are currently available for clinical use. Here, we found that the FDA-approved anti-rheumatoid arthritis (anti-RA) drug auranofin (AUR) 36 potently upregulates hepcidin expression and induces ferroptosis both in vitro and in vivo.…”

Iron status and dietary iron intake in vegetarians

“…Hepcidin-25 is a direct inhibitor of ferroportin, a protein that transports iron out of the cells that store it. 26,27 The production of hepcidin-25, depending the content of iron in the body, is carried out by high Fe human hemochromatosis protein (HFE), transferrin receptor 1 and 2 (TfR1 and TfR2), bone morphogenetic protein 6 (BMP6), hemojuvelin, and transferrin. In response to the expanding resources of iron, the liver produces hepcidin-25, which inhibits the intestinal absorption and prevents further excessive accumulation.…”