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Molecules 2018, 23(8), 1880; https://doi.org/10.3390/molecules23081880

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

1
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea
2
Department of Biomedical Engineering and Sciences, School of Mechanical and Manufacturing Engineering, National University of Sciences and Technology, Islamabad 44000, Pakistan
3
Division of Biotechnology and Convergence, Daegu Haany University, Daegu 38610, Korea
4
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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Abstract

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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