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Anti-Inflammatory Potential of Fucoidan for Atherosclerosis: In Silico and In Vitro Studies in THP-1 Cells
Several diseases, including atherosclerosis, are characterized by inflammation, which is initiated by leukocyte migration to the inflamed lesion. Hence, genes implicated in the early stages of inflammation are potential therapeutic targets to effectively reduce atherogenesis. Algal-derived polysacch...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146328/ https://www.ncbi.nlm.nih.gov/pubmed/35630678 http://dx.doi.org/10.3390/molecules27103197 |
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author | Huwait, Etimad Al-Saedi, Dalal A. Mirza, Zeenat |
author_facet | Huwait, Etimad Al-Saedi, Dalal A. Mirza, Zeenat |
author_sort | Huwait, Etimad |
collection | PubMed |
description | Several diseases, including atherosclerosis, are characterized by inflammation, which is initiated by leukocyte migration to the inflamed lesion. Hence, genes implicated in the early stages of inflammation are potential therapeutic targets to effectively reduce atherogenesis. Algal-derived polysaccharides are one of the most promising sources for pharmaceutical application, although their mechanism of action is still poorly understood. The present study uses a computational method to anticipate the effect of fucoidan and alginate on interactions with adhesion molecules and chemokine, followed by an assessment of the cytotoxicity of the best-predicted bioactive compound for human monocytic THP-1 macrophages by lactate dehydrogenase and crystal violet assay. Moreover, an in vitro pharmacodynamics evaluation was performed. Molecular docking results indicate that fucoidan has a greater affinity for L-and E-selectin, monocyte chemoattractant protein 1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) as compared to alginate. Interestingly, there was no fucoidan cytotoxicity on THP-1 macrophages, even at 200 µg/mL for 24 h. The strong interaction between fucoidan and L-selectin in silico explained its ability to inhibit the THP-1 monocytes migration in vitro. MCP-1 and ICAM-1 expression levels in THP-1 macrophages treated with 50 µg/mL fucoidan for 24 h, followed by induction by IFN-γ, were shown to be significantly suppressed as eight- and four-fold changes, respectively, relative to cells treated only with IFN-γ. These results indicate that the electrostatic interaction of fucoidan improves its binding affinity to inflammatory markers in silico and reduces their expression in THP-1 cells in vitro, thus making fucoidan a good candidate to prevent inflammation. |
format | Online Article Text |
id | pubmed-9146328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91463282022-05-29 Anti-Inflammatory Potential of Fucoidan for Atherosclerosis: In Silico and In Vitro Studies in THP-1 Cells Huwait, Etimad Al-Saedi, Dalal A. Mirza, Zeenat Molecules Article Several diseases, including atherosclerosis, are characterized by inflammation, which is initiated by leukocyte migration to the inflamed lesion. Hence, genes implicated in the early stages of inflammation are potential therapeutic targets to effectively reduce atherogenesis. Algal-derived polysaccharides are one of the most promising sources for pharmaceutical application, although their mechanism of action is still poorly understood. The present study uses a computational method to anticipate the effect of fucoidan and alginate on interactions with adhesion molecules and chemokine, followed by an assessment of the cytotoxicity of the best-predicted bioactive compound for human monocytic THP-1 macrophages by lactate dehydrogenase and crystal violet assay. Moreover, an in vitro pharmacodynamics evaluation was performed. Molecular docking results indicate that fucoidan has a greater affinity for L-and E-selectin, monocyte chemoattractant protein 1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) as compared to alginate. Interestingly, there was no fucoidan cytotoxicity on THP-1 macrophages, even at 200 µg/mL for 24 h. The strong interaction between fucoidan and L-selectin in silico explained its ability to inhibit the THP-1 monocytes migration in vitro. MCP-1 and ICAM-1 expression levels in THP-1 macrophages treated with 50 µg/mL fucoidan for 24 h, followed by induction by IFN-γ, were shown to be significantly suppressed as eight- and four-fold changes, respectively, relative to cells treated only with IFN-γ. These results indicate that the electrostatic interaction of fucoidan improves its binding affinity to inflammatory markers in silico and reduces their expression in THP-1 cells in vitro, thus making fucoidan a good candidate to prevent inflammation. MDPI 2022-05-17 /pmc/articles/PMC9146328/ /pubmed/35630678 http://dx.doi.org/10.3390/molecules27103197 Text en © 2022 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 Huwait, Etimad Al-Saedi, Dalal A. Mirza, Zeenat Anti-Inflammatory Potential of Fucoidan for Atherosclerosis: In Silico and In Vitro Studies in THP-1 Cells |
title | Anti-Inflammatory Potential of Fucoidan for Atherosclerosis: In Silico and In Vitro Studies in THP-1 Cells |
title_full | Anti-Inflammatory Potential of Fucoidan for Atherosclerosis: In Silico and In Vitro Studies in THP-1 Cells |
title_fullStr | Anti-Inflammatory Potential of Fucoidan for Atherosclerosis: In Silico and In Vitro Studies in THP-1 Cells |
title_full_unstemmed | Anti-Inflammatory Potential of Fucoidan for Atherosclerosis: In Silico and In Vitro Studies in THP-1 Cells |
title_short | Anti-Inflammatory Potential of Fucoidan for Atherosclerosis: In Silico and In Vitro Studies in THP-1 Cells |
title_sort | anti-inflammatory potential of fucoidan for atherosclerosis: in silico and in vitro studies in thp-1 cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146328/ https://www.ncbi.nlm.nih.gov/pubmed/35630678 http://dx.doi.org/10.3390/molecules27103197 |
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