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Scopoletin Suppresses Activation of Dendritic Cells and Pathogenesis of Experimental Autoimmune Encephalomyelitis by Inhibiting NF-κB Signaling
Scopoletin, a phenolic coumarin derived from many medical or edible plants, is involved in various pharmacological functions. In the present study, we showed that Scopoletin effectively ameliorated experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through n...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688631/ https://www.ncbi.nlm.nih.gov/pubmed/31427972 http://dx.doi.org/10.3389/fphar.2019.00863 |
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author | Zhang, Fei Zhang, Yuan Yang, Ting Ye, Ze-Qing Tian, Jing Fang, Hai-Rong Han, Juan-Juan Wang, Zhe-Zhi Li, Xing |
author_facet | Zhang, Fei Zhang, Yuan Yang, Ting Ye, Ze-Qing Tian, Jing Fang, Hai-Rong Han, Juan-Juan Wang, Zhe-Zhi Li, Xing |
author_sort | Zhang, Fei |
collection | PubMed |
description | Scopoletin, a phenolic coumarin derived from many medical or edible plants, is involved in various pharmacological functions. In the present study, we showed that Scopoletin effectively ameliorated experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through novel regulatory mechanisms involving inhibition of NF-κB activity in dendritic cells (DCs). Scopoletin treatment significantly improved the severity of the disease and prominently decreased inflammation and demyelination of central nervous system (CNS) in EAE mice. Disease alleviation correlated with the downregulation of major histocompatibility complex (MHC) class II, CD80 and CD86, expressed on DCs of CNS or spleens, and the infiltration and polarization of encephalitogenic Th1/Th17 cells. Consistent with the in vivo data, Scopoletin-treated, bone marrow-derived dendritic cells (BM-DCs) exhibited reduced expression of MHC class II and costimulatory molecules (e.g., CD80 and CD86) and reduced NF-κB phosphorylation. These findings, for the first time, demonstrated the ability of Scopoletin to impair DC activation, downregulating pathogenic Th1/Th17 inflammatory cell responses and, eventually, reducing EAE severity. Our study demonstrates new evidence that natural products derived from medical or edible plants, such as Scopoletin, will be valuable in developing a novel therapeutic agent for MS in the future. |
format | Online Article Text |
id | pubmed-6688631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66886312019-08-19 Scopoletin Suppresses Activation of Dendritic Cells and Pathogenesis of Experimental Autoimmune Encephalomyelitis by Inhibiting NF-κB Signaling Zhang, Fei Zhang, Yuan Yang, Ting Ye, Ze-Qing Tian, Jing Fang, Hai-Rong Han, Juan-Juan Wang, Zhe-Zhi Li, Xing Front Pharmacol Pharmacology Scopoletin, a phenolic coumarin derived from many medical or edible plants, is involved in various pharmacological functions. In the present study, we showed that Scopoletin effectively ameliorated experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through novel regulatory mechanisms involving inhibition of NF-κB activity in dendritic cells (DCs). Scopoletin treatment significantly improved the severity of the disease and prominently decreased inflammation and demyelination of central nervous system (CNS) in EAE mice. Disease alleviation correlated with the downregulation of major histocompatibility complex (MHC) class II, CD80 and CD86, expressed on DCs of CNS or spleens, and the infiltration and polarization of encephalitogenic Th1/Th17 cells. Consistent with the in vivo data, Scopoletin-treated, bone marrow-derived dendritic cells (BM-DCs) exhibited reduced expression of MHC class II and costimulatory molecules (e.g., CD80 and CD86) and reduced NF-κB phosphorylation. These findings, for the first time, demonstrated the ability of Scopoletin to impair DC activation, downregulating pathogenic Th1/Th17 inflammatory cell responses and, eventually, reducing EAE severity. Our study demonstrates new evidence that natural products derived from medical or edible plants, such as Scopoletin, will be valuable in developing a novel therapeutic agent for MS in the future. Frontiers Media S.A. 2019-08-02 /pmc/articles/PMC6688631/ /pubmed/31427972 http://dx.doi.org/10.3389/fphar.2019.00863 Text en Copyright © 2019 Zhang, Zhang, Yang, Ye, Tian, Fang, Han, Wang and Li http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Zhang, Fei Zhang, Yuan Yang, Ting Ye, Ze-Qing Tian, Jing Fang, Hai-Rong Han, Juan-Juan Wang, Zhe-Zhi Li, Xing Scopoletin Suppresses Activation of Dendritic Cells and Pathogenesis of Experimental Autoimmune Encephalomyelitis by Inhibiting NF-κB Signaling |
title | Scopoletin Suppresses Activation of Dendritic Cells and Pathogenesis of Experimental Autoimmune Encephalomyelitis by Inhibiting NF-κB Signaling |
title_full | Scopoletin Suppresses Activation of Dendritic Cells and Pathogenesis of Experimental Autoimmune Encephalomyelitis by Inhibiting NF-κB Signaling |
title_fullStr | Scopoletin Suppresses Activation of Dendritic Cells and Pathogenesis of Experimental Autoimmune Encephalomyelitis by Inhibiting NF-κB Signaling |
title_full_unstemmed | Scopoletin Suppresses Activation of Dendritic Cells and Pathogenesis of Experimental Autoimmune Encephalomyelitis by Inhibiting NF-κB Signaling |
title_short | Scopoletin Suppresses Activation of Dendritic Cells and Pathogenesis of Experimental Autoimmune Encephalomyelitis by Inhibiting NF-κB Signaling |
title_sort | scopoletin suppresses activation of dendritic cells and pathogenesis of experimental autoimmune encephalomyelitis by inhibiting nf-κb signaling |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688631/ https://www.ncbi.nlm.nih.gov/pubmed/31427972 http://dx.doi.org/10.3389/fphar.2019.00863 |
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