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Novel Liposome Eencapsulated Guanosine Di Phosphate based Therapeutic Target against Anemia of Inflammation
Hepcidin, master regulator of iron homeostasis, causes anemia under infectious and inflammatory conditions by reducing intestinal absorption of iron with decreased release of iron from macrophages and liver despite adequate iron stores leading to Anemia of Inflammation (AI). Many therapeutic trials...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283875/ https://www.ncbi.nlm.nih.gov/pubmed/30523271 http://dx.doi.org/10.1038/s41598-018-35992-2 |
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author | Angmo, Stanzin Rana, Shilpa Yadav, Kamalendra Sandhir, Rajat Singhal, Nitin Kumar |
author_facet | Angmo, Stanzin Rana, Shilpa Yadav, Kamalendra Sandhir, Rajat Singhal, Nitin Kumar |
author_sort | Angmo, Stanzin |
collection | PubMed |
description | Hepcidin, master regulator of iron homeostasis, causes anemia under infectious and inflammatory conditions by reducing intestinal absorption of iron with decreased release of iron from macrophages and liver despite adequate iron stores leading to Anemia of Inflammation (AI). Many therapeutic trials have been carried out but none have been effective due to its adverse effects. In present study, we discover that Guanosine 5’-diphosphate (GDP) encapsulated in lipid vesicle (NH+) was found to inhibit NF-ҝB activation by limiting phosphorylation and degradation of IҝBα, thus, attenuating IL-6 secretion from macrophage cells. Moreover, the suppressed IL-6 levels down regulated JAK2/STAT3 pathway with decrease inflammation-mediated Hamp mRNA transcription (HepG2) and increase iron absorption (Caco2) in HepG2/Caco2 co-culture model. Analogous results were obtained in acute and chronic AI mice model thus, correcting haemoglobin level. These results proved NH + GDP as novel therapeutic agent to overcome limitations and suggests it as potential drug to ameliorate AI. |
format | Online Article Text |
id | pubmed-6283875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62838752018-12-07 Novel Liposome Eencapsulated Guanosine Di Phosphate based Therapeutic Target against Anemia of Inflammation Angmo, Stanzin Rana, Shilpa Yadav, Kamalendra Sandhir, Rajat Singhal, Nitin Kumar Sci Rep Article Hepcidin, master regulator of iron homeostasis, causes anemia under infectious and inflammatory conditions by reducing intestinal absorption of iron with decreased release of iron from macrophages and liver despite adequate iron stores leading to Anemia of Inflammation (AI). Many therapeutic trials have been carried out but none have been effective due to its adverse effects. In present study, we discover that Guanosine 5’-diphosphate (GDP) encapsulated in lipid vesicle (NH+) was found to inhibit NF-ҝB activation by limiting phosphorylation and degradation of IҝBα, thus, attenuating IL-6 secretion from macrophage cells. Moreover, the suppressed IL-6 levels down regulated JAK2/STAT3 pathway with decrease inflammation-mediated Hamp mRNA transcription (HepG2) and increase iron absorption (Caco2) in HepG2/Caco2 co-culture model. Analogous results were obtained in acute and chronic AI mice model thus, correcting haemoglobin level. These results proved NH + GDP as novel therapeutic agent to overcome limitations and suggests it as potential drug to ameliorate AI. Nature Publishing Group UK 2018-12-06 /pmc/articles/PMC6283875/ /pubmed/30523271 http://dx.doi.org/10.1038/s41598-018-35992-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Angmo, Stanzin Rana, Shilpa Yadav, Kamalendra Sandhir, Rajat Singhal, Nitin Kumar Novel Liposome Eencapsulated Guanosine Di Phosphate based Therapeutic Target against Anemia of Inflammation |
title | Novel Liposome Eencapsulated Guanosine Di Phosphate based Therapeutic Target against Anemia of Inflammation |
title_full | Novel Liposome Eencapsulated Guanosine Di Phosphate based Therapeutic Target against Anemia of Inflammation |
title_fullStr | Novel Liposome Eencapsulated Guanosine Di Phosphate based Therapeutic Target against Anemia of Inflammation |
title_full_unstemmed | Novel Liposome Eencapsulated Guanosine Di Phosphate based Therapeutic Target against Anemia of Inflammation |
title_short | Novel Liposome Eencapsulated Guanosine Di Phosphate based Therapeutic Target against Anemia of Inflammation |
title_sort | novel liposome eencapsulated guanosine di phosphate based therapeutic target against anemia of inflammation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283875/ https://www.ncbi.nlm.nih.gov/pubmed/30523271 http://dx.doi.org/10.1038/s41598-018-35992-2 |
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