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Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion

The endothelial cell lining creates an interface between circulating blood and adjoining tissue and forms one of the most critical barriers and targets for therapeutical intervention. Recent studies suggest that fucoidans, sulfated and fucose-rich polysaccharides from brown seaweed, show multiple pr...

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Autores principales: Kirsten, Nora, Ohmes, Julia, Mikkelsen, Maria Dalgaard, Nguyen, Thuan Thi, Blümel, Martina, Wang, Fanlu, Tasdemir, Deniz, Seekamp, Andreas, Meyer, Anne S., Fuchs, Sabine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300781/
https://www.ncbi.nlm.nih.gov/pubmed/37367664
http://dx.doi.org/10.3390/md21060339
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author Kirsten, Nora
Ohmes, Julia
Mikkelsen, Maria Dalgaard
Nguyen, Thuan Thi
Blümel, Martina
Wang, Fanlu
Tasdemir, Deniz
Seekamp, Andreas
Meyer, Anne S.
Fuchs, Sabine
author_facet Kirsten, Nora
Ohmes, Julia
Mikkelsen, Maria Dalgaard
Nguyen, Thuan Thi
Blümel, Martina
Wang, Fanlu
Tasdemir, Deniz
Seekamp, Andreas
Meyer, Anne S.
Fuchs, Sabine
author_sort Kirsten, Nora
collection PubMed
description The endothelial cell lining creates an interface between circulating blood and adjoining tissue and forms one of the most critical barriers and targets for therapeutical intervention. Recent studies suggest that fucoidans, sulfated and fucose-rich polysaccharides from brown seaweed, show multiple promising biological effects, including anti-inflammatory properties. However, their biological activity is determined by chemical characteristics such as molecular weight, sulfation degree, and molecular structure, which vary depending on the source, species, and harvesting and isolation method. In this study, we investigated the impact of high molecular weight (HMW) fucoidan extract on endothelial cell activation and interaction with primary monocytes (MNCs) in lipopolysaccharide (LPS)-induced inflammation. Gentle enzyme-assisted extraction combined with fractionation by ion exchange chromatography resulted in well-defined and pure fucoidan fractions. FE_F3, with a molecular weight ranging from 110 to 800 kDa and a sulfate content of 39%, was chosen for further investigation of its anti-inflammatory potential. We observed that along with higher purity of fucoidan fractions, the inflammatory response in endothelial mono- and co-cultures with MNCs was reduced in a dose-dependent manner when testing two different concentrations. This was demonstrated by a decrease in IL-6 and ICAM-1 on gene and protein levels and a reduced gene expression of TLR-4, GSK3β and NF-kB. Expression of selectins and, consequently, the adhesion of monocytes to the endothelial monolayer was reduced after fucoidan treatment. These data indicate that the anti-inflammatory effect of fucoidans increases with their purity and suggest that fucoidans might be useful in limiting the inflammatory response of endothelial cells in cases of LPS-induced bacterial infection.
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spelling pubmed-103007812023-06-29 Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion Kirsten, Nora Ohmes, Julia Mikkelsen, Maria Dalgaard Nguyen, Thuan Thi Blümel, Martina Wang, Fanlu Tasdemir, Deniz Seekamp, Andreas Meyer, Anne S. Fuchs, Sabine Mar Drugs Article The endothelial cell lining creates an interface between circulating blood and adjoining tissue and forms one of the most critical barriers and targets for therapeutical intervention. Recent studies suggest that fucoidans, sulfated and fucose-rich polysaccharides from brown seaweed, show multiple promising biological effects, including anti-inflammatory properties. However, their biological activity is determined by chemical characteristics such as molecular weight, sulfation degree, and molecular structure, which vary depending on the source, species, and harvesting and isolation method. In this study, we investigated the impact of high molecular weight (HMW) fucoidan extract on endothelial cell activation and interaction with primary monocytes (MNCs) in lipopolysaccharide (LPS)-induced inflammation. Gentle enzyme-assisted extraction combined with fractionation by ion exchange chromatography resulted in well-defined and pure fucoidan fractions. FE_F3, with a molecular weight ranging from 110 to 800 kDa and a sulfate content of 39%, was chosen for further investigation of its anti-inflammatory potential. We observed that along with higher purity of fucoidan fractions, the inflammatory response in endothelial mono- and co-cultures with MNCs was reduced in a dose-dependent manner when testing two different concentrations. This was demonstrated by a decrease in IL-6 and ICAM-1 on gene and protein levels and a reduced gene expression of TLR-4, GSK3β and NF-kB. Expression of selectins and, consequently, the adhesion of monocytes to the endothelial monolayer was reduced after fucoidan treatment. These data indicate that the anti-inflammatory effect of fucoidans increases with their purity and suggest that fucoidans might be useful in limiting the inflammatory response of endothelial cells in cases of LPS-induced bacterial infection. MDPI 2023-05-31 /pmc/articles/PMC10300781/ /pubmed/37367664 http://dx.doi.org/10.3390/md21060339 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kirsten, Nora
Ohmes, Julia
Mikkelsen, Maria Dalgaard
Nguyen, Thuan Thi
Blümel, Martina
Wang, Fanlu
Tasdemir, Deniz
Seekamp, Andreas
Meyer, Anne S.
Fuchs, Sabine
Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion
title Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion
title_full Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion
title_fullStr Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion
title_full_unstemmed Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion
title_short Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion
title_sort impact of enzymatically extracted high molecular weight fucoidan on lipopolysaccharide-induced endothelial activation and leukocyte adhesion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300781/
https://www.ncbi.nlm.nih.gov/pubmed/37367664
http://dx.doi.org/10.3390/md21060339
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