Modulation of matrix metalloproteinase and cytokine production by licorice isolates licoricidin and licorisoflavan A: potential therapeutic approach for periodontitis.
BACKGROUND
Inflammatory cytokines and matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in response to periodontopathogens play a major role in the tissue destruction observed in periodontitis, which is a disease that affects tooth-supporting structures. In the present study, we investigate the effects of licorice-derived licoricidin (LC) and licorisoflavan A (LIA) on the secretion of various cytokines and MMPs by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) lipopolysaccharide (LPS).


METHODS
Macrophages were treated with non-toxic concentrations of LC or LIA before being stimulated with A. actinomycetemcomitans LPS. The secretion of cytokines and MMPs and the activation of nuclear factor-kappa B (NF-κB) p65 and activator protein (AP)-1 were assessed by enzyme-linked immunosorbent assays.


RESULTS
LC and LIA inhibited the secretion of interleukin (IL)-6 and chemokine (C-C motif) ligand 5 in a concentration-dependent manner but did not affect the secretion of IL-8 by LPS-stimulated macrophages. LC and LIA also inhibited the secretion of MMP-7, -8, and -9 by macrophages. The suppression of cytokine and MMP secretion by LC and LIA was associated with the reduced activation of NF-κB p65 but not that of AP-1.


CONCLUSIONS
The present study suggests that LC and LIA have potential for the development of novel host-modulating strategies for the treatment of cytokine and/or MMP-mediated disorders such as periodontitis.
La
Vu Dang
VD
Faculty of Dentistry, Laval University, Quebec City, QC, Canada.
Tanabe
Shin-ichi
S
Bergeron
Chantal
C
Gafner
Stefan
S
Grenier
Daniel
D
D016976:Aggregatibacter actinomycetemcomitans; D001578:Benzopyrans / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D006035:Glycyrrhiza; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D016209:Interleukin-8 / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D020783:Matrix Metalloproteinase 7; D020784:Matrix Metalloproteinase 8; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000187:drug effects; D051996:Transcription Factor RelA / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
D001578:Benzopyrans; D018946:Chemokine CCL5; D016207:Cytokines; D004791:Enzyme Inhibitors; D005419:Flavonoids; D018836:Inflammation Mediators; D016209:Interleukin-8; D008070:Lipopolysaccharides; D020783:Matrix Metalloproteinase 7; D020784:Matrix Metalloproteinase 8; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases; D010936:Plant Extracts; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D000093242:Interleukin-6 Inhibitors; C558581:licorisoflavan A; C401293:licoricidin; C060932:MMP7 protein, human; C488762:MMP8 protein, human