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Molecules. 2018 Jul 27;23(8). pii: E1880. doi: 10.3390/molecules23081880.

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

Author information

1
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea. salman2013@knu.ac.kr.
2
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea. quiet93@knu.ac.kr.
3
Department of Biomedical Engineering and Sciences, School of Mechanical and Manufacturing Engineering, National University of Sciences and Technology, Islamabad 44000, Pakistan. adeeb.shehzad@smme.nust.edu.pk.
4
Division of Biotechnology and Convergence, Daegu 38610, Korea. ahnEM@dhu.ac.kr.
5
College of Pharmacy, National Basic Research Laboratory of Vascular Homeostasis Regulation, Kyungpook National University, Daegu 41566, Korea. lym@knu.ac.kr.
6
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea. yselee@knu.ac.kr.

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.

KEYWORDS:

MAP kinase; NFκB; cytokines; decursinol angelate; inflammation

PMID:
30060484
PMCID:
PMC6222640
DOI:
10.3390/molecules23081880
[Indexed for MEDLINE]
Free PMC Article

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