A licorice extract reduces lipopolysaccharide-induced proinflammatory cytokine secretion by macrophages and whole blood.
BACKGROUND
Periodontal diseases are a group of inflammatory disorders initiated by specific Gram-negative periodontopathogenic bacteria that lead to the destruction of tooth-supporting tissues. In this study, we tested whether a carbon dioxide-supercritical extract of Glycyrrhiza uralensis (licorice) can reduce the periodontopathogen-induced inflammatory response.


METHODS
Monocyte-derived macrophages were treated with various concentrations of the licorice extract prior to being stimulated with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) and Porphyromonas gingivalis lipopolysaccharide (LPS). The capacity of the licorice extract to mediate the inflammatory response was also tested in an ex vivo whole blood model stimulated with P. gingivalis LPS. The secretion of interleukin (IL)-1beta, -6, and -8 and tumor necrosis factor-alpha (TNF-alpha) in both models was assessed by enzyme-linked immunosorbent assays. Changes in the phosphorylation state of macrophage intracellular kinases induced by A. actinomycetemcomitans LPS and the licorice extract in the macrophage model were characterized by immunoblotting.


RESULTS
The licorice extract exhibited potent anti-inflammatory properties, inhibiting the periodontopathogen LPS-induced IL-1beta, -6, and -8 and TNF-alpha responses of macrophages. The licorice extract inhibited the phosphorylation of important macrophage intracellular signaling proteins, including nuclear factor-kappa B p65 nuclear transcription factor and Jun proto-oncogene-encoded activator protein (AP) 1 transcription factor, which are involved in inflammatory signaling pathways. The licorice extract was also a potent inhibitor of the proinflammatory cytokine response in the ex vivo human whole blood model.


CONCLUSIONS
This CO(2)-supercritical licorice extract is a potential candidate for the development of a new therapy to prevent and/or treat periodontitis-associated tissue destruction.
Bodet
Charles
C
Research Group in Oral Ecology, Faculty of Dentistry, Laval University, Quebec City, Quebec, Canada.
La
Vu Dang
VD
Gafner
Stefan
S
Bergeron
Chantal
C
Grenier
Daniel
D
D016976:Aggregatibacter actinomycetemcomitans; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood / Q000187:drug effects*; D006035:Glycyrrhiza; D006801:Humans; D015151:Immunoblotting; D018836:Inflammation Mediators / Q000032:analysis*; D053583:Interleukin-1beta / Q000097:blood / Q000187:drug effects; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood; D016209:Interleukin-8 / Q000097:blood / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D048054:Mitogen-Activated Protein Kinase 7 / Q000187:drug effects; D010510:Periodontal Diseases / Q000097:blood / Q000382:microbiology; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D016966:Porphyromonas gingivalis; D000090063:Proto-Oncogene Mas; D018808:Transcription Factor AP-1 / Q000187:drug effects; D051996:Transcription Factor RelA / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C000715470:MAS1 protein, human; D010936:Plant Extracts; D000090063:Proto-Oncogene Mas; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D048054:Mitogen-Activated Protein Kinase 7