Angmo, Stanzin and Tripathi, Neha and Abbat,, Sheenu and Sharma, Shailesh and Sardul Singh , Shelley and Halder, Avishek and Yadav, Kamalendra and Shukla, Geeta and Sandhir, Rajat and Rishi, Vikas and Bharatam, Prasad V. and Yadav, Hariom and Singhal, Singhal (2017) Identification of Guanosine 5′-diphosphate as Potential Iron Mobilizer: Preventing the Hepcidin-Ferroportin Interaction and Modulating the Interleukin-6/Stat-3 Pathway. Scientific Reports (40097 ). ISSN 2045-2322

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Abstract

Hepcidin, a peptide hormone, is a key regulator in mammalian iron homeostasis. Increased level of hepcidin due to inflammatory conditions stimulates the ferroportin (FPN) transporter internalization, impairing the iron absorption; clinically manifested as anemia of inflammation (AI). Inhibiting hepcidin-mediated FPN degradation is proposed as an important strategy to combat AI. A systematic approach involving in silico, in vitro, ex vivo and in vivo studies is employed to identify hepcidin-binding agents. The virtual screening of 68,752 natural compounds via molecular docking resulted into identification of guanosine 5′-diphosphate (GDP) as a promising hepcidin-binding agent. The molecular dynamics simulations helped to identify the important hepcidin residues involved in stabilization of hepcidin-GDP complex. The results gave a preliminary indication that GDP may possibly inhibit the hepcidin-FPN interactions. The in vitro studies revealed that GDP caused FPN stabilization (FPN-GFP cell lines) and increased the FPN-mediated cellular iron efflux (HepG2 and Caco-2 cells). Interestingly, the co-administration of GDP and ferrous sulphate (FeSO4) ameliorated the turpentine-induced AI in mice (indicated by increased haemoglobin level, serum iron, FPN expression and decreased ferritin level). These results suggest that GDP a promising natural small-molecule inhibitor that targets Hepcidin-FPN complex may be incorporated with iron supplement regimens to ameliorate AI.

Item Type:	Article
Subjects:	Food Science and Technology Nutrition Science and Technology
Depositing User:	Dr. Author @NABI
Date Deposited:	12 Mar 2021 05:03
Last Modified:	12 Mar 2021 05:03
URI:	http://nabi.sciencecentral.in/id/eprint/56

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