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Molecules 2018, 23(8), 1880;

Decursinol Angelate Inhibits LPS-Induced Macrophage Polarization through Modulation of the NFκB and MAPK Signaling Pathways

School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea
Department of Biomedical Engineering and Sciences, School of Mechanical and Manufacturing Engineering, National University of Sciences and Technology, Islamabad 44000, Pakistan
Division of Biotechnology and Convergence, Daegu Haany University, Daegu 38610, Korea
College of Pharmacy, National Basic Research Laboratory of Vascular Homeostasis Regulation, Kyungpook National University, Daegu 41566, Korea
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 4 July 2018 / Revised: 24 July 2018 / Accepted: 26 July 2018 / Published: 27 July 2018
(This article belongs to the Special Issue Anti-Inflammatory Activity of Natural Products)
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Inflammation is considered the root cause of various inflammatory diseases, including cancers. Decursinol angelate (DA), a pyranocoumarin compound obtained from the roots of Angelica gigas, has been reported to exhibit potent anti-inflammatory effects. In this study, the anti-inflammatory effects of DA on the MAP kinase and NFκB signaling pathways and the expression of pro-inflammatory cytokines were investigated in phorbol 12-myristate 13-acetate (PMA)-activated human promyelocytic leukemia (HL-60) and lipopolysaccharide (LPS)-stimulated macrophage (Raw 264.7) cell lines. PMA induced the activation of the MAP kinase-NFκB pathway and the production of pro-inflammatory cytokines in differentiated monocytes. Treatment with DA inhibited the activation of MAP kinases and the translocation of NFκB, and decreased the expression and exogenous secretion of IL-1β and IL-6. Furthermore, LPS-stimulated Raw 264.7 cells were found to have increased expression of M1 macrophage-associated markers, such as NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS), and the M2 macrophage-associated marker CD11b. LPS also activated pro-inflammatory cytokines and Erk-NFκB. Treatment with DA suppressed LPS-induced macrophage polarization and the inflammatory response by blocking Raf-ERK and the translocation of NFκB in Raw 264.7 cells. Treatment with DA also inhibited the expression of pro-inflammatory cytokines, such as IL-1β and IL-6, NOX, and iNOS in Raw 264.7 cells. These results suggest that DA has the potential to inhibit macrophage polarization and inflammation by blocking the activation of pro-inflammatory signals. These anti-inflammatory effects of DA may contribute to its potential use as a therapeutic strategy against various inflammation-induced cancers. View Full-Text
Keywords: inflammation; cytokines; MAP kinase; NFκB; decursinol angelate inflammation; cytokines; MAP kinase; NFκB; decursinol angelate

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Islam, S.U.; Lee, J.H.; Shehzad, A.; Ahn, E.-M.; Lee, Y.M.; Lee, Y.S. Decursinol Angelate Inhibits LPS-Induced Macrophage Polarization through Modulation of the NFκB and MAPK Signaling Pathways. Molecules 2018, 23, 1880.

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