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Artemisia dracunculus L. Ethanolic Extract and an Isolated Component, DMC2, Ameliorate Inflammatory Signaling in Pancreatic β-Cells via Inhibition of p38 MAPK

Non-resolving pancreatic islet inflammation is widely viewed as a contributor to decreases in β-cell mass and function that occur in both Type 1 and Type 2 diabetes. Therefore, strategies aimed at reducing or eliminating pathological inflammation would be useful to protect islet β-cells. Herein, we...

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Autores principales: Smoak, Peter, Burke, Susan J., Martin, Thomas M., Batdorf, Heidi M., Floyd, Z. Elizabeth, Collier, J. Jason
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139089/
https://www.ncbi.nlm.nih.gov/pubmed/35625635
http://dx.doi.org/10.3390/biom12050708
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author Smoak, Peter
Burke, Susan J.
Martin, Thomas M.
Batdorf, Heidi M.
Floyd, Z. Elizabeth
Collier, J. Jason
author_facet Smoak, Peter
Burke, Susan J.
Martin, Thomas M.
Batdorf, Heidi M.
Floyd, Z. Elizabeth
Collier, J. Jason
author_sort Smoak, Peter
collection PubMed
description Non-resolving pancreatic islet inflammation is widely viewed as a contributor to decreases in β-cell mass and function that occur in both Type 1 and Type 2 diabetes. Therefore, strategies aimed at reducing or eliminating pathological inflammation would be useful to protect islet β-cells. Herein, we described the use of 2′,4′-dihydroxy-4-methoxydihydrochalcone (DMC2), a bioactive molecule isolated from an ethanolic extract of Artemisia dracunculus L., as a novel anti-inflammatory agent. The ethanolic extract, termed PMI 5011, reduced IL-1β-mediated NF-κB activity. DMC2 retained this ability, indicating this compound as the likely source of anti-inflammatory activity within the overall PMI 5011 extract. We further examined NF-κB activity using promoter-luciferase reporter constructs, Western blots, mRNA abundance, and protein secretion. Specifically, we found that PMI 5011 and DMC2 each reduced the ability of IL-1β to promote increases in the expression of the Ccl2 and Ccl20 genes. These genes encode proteins that promote immune cell recruitment and are secreted by β-cells in response to IL-1β. Phosphorylation of IκBα and the p65 subunit of NF-κB were not reduced by either PMI 5011 or DMC2; however, phosphorylation of p38 MAPK was blunted in the presence of DMC2. Finally, we observed that while PMI 5011 impaired glucose-stimulated insulin secretion, insulin output was preserved in the presence of DMC2. In conclusion, PMI 5011 and DMC2 reduced inflammation, but only DMC2 did so with the preservation of glucose-stimulated insulin secretion.
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spelling pubmed-91390892022-05-28 Artemisia dracunculus L. Ethanolic Extract and an Isolated Component, DMC2, Ameliorate Inflammatory Signaling in Pancreatic β-Cells via Inhibition of p38 MAPK Smoak, Peter Burke, Susan J. Martin, Thomas M. Batdorf, Heidi M. Floyd, Z. Elizabeth Collier, J. Jason Biomolecules Article Non-resolving pancreatic islet inflammation is widely viewed as a contributor to decreases in β-cell mass and function that occur in both Type 1 and Type 2 diabetes. Therefore, strategies aimed at reducing or eliminating pathological inflammation would be useful to protect islet β-cells. Herein, we described the use of 2′,4′-dihydroxy-4-methoxydihydrochalcone (DMC2), a bioactive molecule isolated from an ethanolic extract of Artemisia dracunculus L., as a novel anti-inflammatory agent. The ethanolic extract, termed PMI 5011, reduced IL-1β-mediated NF-κB activity. DMC2 retained this ability, indicating this compound as the likely source of anti-inflammatory activity within the overall PMI 5011 extract. We further examined NF-κB activity using promoter-luciferase reporter constructs, Western blots, mRNA abundance, and protein secretion. Specifically, we found that PMI 5011 and DMC2 each reduced the ability of IL-1β to promote increases in the expression of the Ccl2 and Ccl20 genes. These genes encode proteins that promote immune cell recruitment and are secreted by β-cells in response to IL-1β. Phosphorylation of IκBα and the p65 subunit of NF-κB were not reduced by either PMI 5011 or DMC2; however, phosphorylation of p38 MAPK was blunted in the presence of DMC2. Finally, we observed that while PMI 5011 impaired glucose-stimulated insulin secretion, insulin output was preserved in the presence of DMC2. In conclusion, PMI 5011 and DMC2 reduced inflammation, but only DMC2 did so with the preservation of glucose-stimulated insulin secretion. MDPI 2022-05-15 /pmc/articles/PMC9139089/ /pubmed/35625635 http://dx.doi.org/10.3390/biom12050708 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
Smoak, Peter
Burke, Susan J.
Martin, Thomas M.
Batdorf, Heidi M.
Floyd, Z. Elizabeth
Collier, J. Jason
Artemisia dracunculus L. Ethanolic Extract and an Isolated Component, DMC2, Ameliorate Inflammatory Signaling in Pancreatic β-Cells via Inhibition of p38 MAPK
title Artemisia dracunculus L. Ethanolic Extract and an Isolated Component, DMC2, Ameliorate Inflammatory Signaling in Pancreatic β-Cells via Inhibition of p38 MAPK
title_full Artemisia dracunculus L. Ethanolic Extract and an Isolated Component, DMC2, Ameliorate Inflammatory Signaling in Pancreatic β-Cells via Inhibition of p38 MAPK
title_fullStr Artemisia dracunculus L. Ethanolic Extract and an Isolated Component, DMC2, Ameliorate Inflammatory Signaling in Pancreatic β-Cells via Inhibition of p38 MAPK
title_full_unstemmed Artemisia dracunculus L. Ethanolic Extract and an Isolated Component, DMC2, Ameliorate Inflammatory Signaling in Pancreatic β-Cells via Inhibition of p38 MAPK
title_short Artemisia dracunculus L. Ethanolic Extract and an Isolated Component, DMC2, Ameliorate Inflammatory Signaling in Pancreatic β-Cells via Inhibition of p38 MAPK
title_sort artemisia dracunculus l. ethanolic extract and an isolated component, dmc2, ameliorate inflammatory signaling in pancreatic β-cells via inhibition of p38 mapk
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139089/
https://www.ncbi.nlm.nih.gov/pubmed/35625635
http://dx.doi.org/10.3390/biom12050708
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