Artemisia dracunculus L. Ethanolic Extract and an Isolated Component, DMC2, Ameliorate Inflammatory Signaling in Pancreatic β-Cells via Inhibition of p38 MAPK
Year: 2022
Type: article
Abstract: 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.
Source: Biomolecules
DOI: 10.3390/biom12050708
Institution: Pennington Biomedical Research Center
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,199
Funders: National Institutes of Health, Nutrition Obesity Research Center, University of North Carolina, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Complementary and Integrative Health
Awards: SGK1 is a regulator of islet beta cell mass and secretory function, Botanicals and Metabolic Resiliency , G305254594, G3334739079, Mentoring Obesity and Diabetes Research in Louisiana, Mentoring Obesity and Diabetes Research in Louisiana, Development of Mice with Conditional ICAM-1 Deletion, Botanical Approaches to Combat Metabolic Syndrome, Metabolic Basis of Disease - Phase 2, Pennington/Louisiana NORC
OpenAlex ID: W4280508580