TY - JOUR
T1 - 18β-Glycyrrhetinic acid inhibits periodontitis via glucocorticoid-independent nuclear factor-ΚB inactivation in interleukin-10-deficient mice
AU - Sasaki, H.
AU - Suzuki, N.
AU - AlShwaimi, E.
AU - Xu, Y.
AU - Battaglino, R.
AU - Morse, L.
AU - Stashenko, P.
PY - 2010/12/1
Y1 - 2010/12/1
N2 - Background and Objective: 18β-Glycyrrhetinic acid (GA) is a natural anti-inflammatory compound derived from licorice root extract (Glycyrrhiza glabra). The effect of GA on experimental periodontitis and its mechanism of action were determined in the present study.Material and Methods: Periodontitis was induced by oral infection with Porphyromonas gingivalis W83 in interleukin-10-deficient mice. The effect of GA, which was delivered by subcutaneous injections in either prophylactic or therapeutic regimens, on alveolar bone loss and gingival gene expressions was determined on day 42 after initial infection. The effect of GA on lipopolysaccharide (LPS)-stimulated macrophages, T cell proliferation and osteoclastogenesis was also examined in vitro.Results: 18β-Glycyrrhetinic acid administered either prophylactically or therapeutically resulted in a dramatic reduction of infection-induced bone loss in interleukin-10-deficient mice, which are highly disease susceptible. Although GA has been reported to exert its anti-inflammatory activity via downregulation of 11β-hydroxysteroid dehydrogenase-2 (HSD2), which converts active glucocorticoids to their inactive forms, GA did not reduce HSD2 gene expression in gingival tissue. Rather, in glucocorticoid-free conditions, GA potently inhibited LPS-stimulated proinflammatory cytokine production and RANKL-stimulated osteoclastogenesis, both of which are dependent on nuclear factor-κB. Furthermore, GA suppressed LPS- and RANKL-stimulated phosphorylation of nuclear factor-κB p105 in vitro.Conclusion: These findings indicate that GA inhibits periodontitis by inactivation of nuclear factor-κB in an interleukin-10- and glucocorticoid-independent fashion.
AB - Background and Objective: 18β-Glycyrrhetinic acid (GA) is a natural anti-inflammatory compound derived from licorice root extract (Glycyrrhiza glabra). The effect of GA on experimental periodontitis and its mechanism of action were determined in the present study.Material and Methods: Periodontitis was induced by oral infection with Porphyromonas gingivalis W83 in interleukin-10-deficient mice. The effect of GA, which was delivered by subcutaneous injections in either prophylactic or therapeutic regimens, on alveolar bone loss and gingival gene expressions was determined on day 42 after initial infection. The effect of GA on lipopolysaccharide (LPS)-stimulated macrophages, T cell proliferation and osteoclastogenesis was also examined in vitro.Results: 18β-Glycyrrhetinic acid administered either prophylactically or therapeutically resulted in a dramatic reduction of infection-induced bone loss in interleukin-10-deficient mice, which are highly disease susceptible. Although GA has been reported to exert its anti-inflammatory activity via downregulation of 11β-hydroxysteroid dehydrogenase-2 (HSD2), which converts active glucocorticoids to their inactive forms, GA did not reduce HSD2 gene expression in gingival tissue. Rather, in glucocorticoid-free conditions, GA potently inhibited LPS-stimulated proinflammatory cytokine production and RANKL-stimulated osteoclastogenesis, both of which are dependent on nuclear factor-κB. Furthermore, GA suppressed LPS- and RANKL-stimulated phosphorylation of nuclear factor-κB p105 in vitro.Conclusion: These findings indicate that GA inhibits periodontitis by inactivation of nuclear factor-κB in an interleukin-10- and glucocorticoid-independent fashion.
KW - 18β-glycyrrhetinic acid
KW - Interleukin-10-deficient mouse
KW - Nuclear factor-κB
KW - Periodontal disease
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U2 - 10.1111/j.1600-0765.2010.01296.x
DO - 10.1111/j.1600-0765.2010.01296.x
M3 - Article
C2 - 20682015
AN - SCOPUS:77958568362
SN - 0022-3484
VL - 45
SP - 757
EP - 763
JO - Journal of Periodontal Research
JF - Journal of Periodontal Research
IS - 6
ER -