Honokiol suppresses formyl peptide-induced human neutrophil activation by blocking formyl peptide receptor 1

Fu-Chao Liu; Huang-Ping Yu; Yu-Ting Syu; Jia-You Fang; Chwan-Fwu Lin; Shih-Hsin Chang; Yen-Tung Lee; Tsong-Long Hwang

doi:10.1038/s41598-017-07131-w

Honokiol suppresses formyl peptide-induced human neutrophil activation by blocking formyl peptide receptor 1

Sci Rep. 2017 Jul 27;7(1):6718. doi: 10.1038/s41598-017-07131-w.

Authors

Fu-Chao Liu^{1

2}, Huang-Ping Yu^{1

2}, Yu-Ting Syu^{3

4}, Jia-You Fang^{1

3

4

5}, Chwan-Fwu Lin⁶, Shih-Hsin Chang^{3

5}, Yen-Tung Lee^{3

6

7}, Tsong-Long Hwang^{8

9

10

11

12}

Affiliations

¹ Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.
² School of Medicine, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
³ Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
⁴ Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, 333, Taiwan.
⁵ Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 333, Taiwan.
⁶ Department of Cosmetic Science, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 333, Taiwan.
⁷ Division of Natural Products, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
⁸ Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan. [email protected].
⁹ Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan. [email protected].
¹⁰ Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, 333, Taiwan. [email protected].
¹¹ Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 333, Taiwan. [email protected].
¹² Division of Natural Products, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan. [email protected].

Abstract

Formyl peptide receptor 1 (FPR1) mediates bacterial and mitochondrial N-formyl peptides-induced neutrophil activation. Therefore, FPR1 is an important therapeutic target for drugs to treat septic or sterile inflammatory diseases. Honokiol, a major bioactive compound of Magnoliaceae plants, possesses several anti-inflammatory activities. Here, we show that honokiol exhibits an inhibitory effect on FPR1 binding in human neutrophils. Honokiol inhibited superoxide anion generation, reactive oxygen species formation, and elastase release in bacterial or mitochondrial N-formyl peptides (FPR1 agonists)-activated human neutrophils. Adhesion of FPR1-induced human neutrophils to cerebral endothelial cells was also reduced by honokiol. The receptor-binding results revealed that honokiol repressed FPR1-specific ligand N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein binding to FPR1 in human neutrophils, neutrophil-like THP-1 cells, and hFPR1-transfected HEK293 cells. However, honokiol did not inhibit FPR2-specific ligand binding to FPR2 in human neutrophils. Furthermore, honokiol inhibited FPR1 agonist-induced calcium mobilization as well as phosphorylation of p38 MAPK, ERK, and JNK in human neutrophils. In conclusion, our data demonstrate that honokiol may have therapeutic potential for treating FPR1-mediated inflammatory diseases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / isolation & purification
Anti-Inflammatory Agents / pharmacology*
Biphenyl Compounds / isolation & purification
Biphenyl Compounds / pharmacology*
Brain / cytology
Brain / metabolism
Cell Adhesion / drug effects
Coculture Techniques
Endothelial Cells / cytology
Endothelial Cells / drug effects*
Endothelial Cells / metabolism
Gene Expression Regulation
HEK293 Cells
Humans
Lignans / isolation & purification
Lignans / pharmacology*
MAP Kinase Kinase 4 / genetics
MAP Kinase Kinase 4 / immunology
Magnolia / chemistry
Mice
Mitogen-Activated Protein Kinase 1 / genetics
Mitogen-Activated Protein Kinase 1 / immunology
Mitogen-Activated Protein Kinase 3 / genetics
Mitogen-Activated Protein Kinase 3 / immunology
Neutrophil Activation / drug effects
Neutrophils / cytology
Neutrophils / drug effects*
Neutrophils / immunology
Oligopeptides / antagonists & inhibitors*
Oligopeptides / pharmacology
Plant Extracts / chemistry
Receptors, Formyl Peptide / antagonists & inhibitors
Receptors, Formyl Peptide / genetics*
Receptors, Formyl Peptide / immunology
Receptors, Lipoxin / genetics
Receptors, Lipoxin / immunology
THP-1 Cells
p38 Mitogen-Activated Protein Kinases / genetics
p38 Mitogen-Activated Protein Kinases / immunology

Substances

Anti-Inflammatory Agents
Biphenyl Compounds
FPR1 protein, human
FPR2 protein, human
Lignans
Oligopeptides
Plant Extracts
Receptors, Formyl Peptide
Receptors, Lipoxin
honokiol
F-chemotactic peptide
MAPK1 protein, human
MAPK3 protein, human
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
p38 Mitogen-Activated Protein Kinases
MAP Kinase Kinase 4