Glycyrrhetinic acid inhibits Porphyromonas gingivalis lipopolysaccharide-induced vascular permeability via the suppression of interleukin-8.
OBJECTIVE
Porphyromonas gingivalis is a major periodontopathogen that plays a role in the pathogenesis of periodontal disease. In this study, we investigated the effect of 18alpha-glycyrrhetinic acid (18α-GA), a natural triterpenoid compound derived from licorice root extract, on P. gingivalis lipopolysaccharide (LPS)-induced vascular permeability, which is a hallmark of inflammatory diseases such as periodontitis.


METHODS
The inhibitory effects of 18α-GA on endothelial permeability were determined by measuring in vivo and in vitro endothelial permeability. Endothelial cells were pretreated with 18α-GA before exposure to P. gingivalis LPS, and total RNA or proteins were extracted and analyzed by reverse transcription polymerase chain reaction or western blotting.


RESULTS
Porphyromonas gingivalis LPS-induced endothelial permeability was significantly inhibited by 18α-GA both in vivo and in vitro. 18α-GA reduces P. gingivalis LPS-induced gap formation of endothelial cells. Importantly, 18α-GA modulated the expression and secretion of interleukin-8 (IL-8), a key inducer of vascular permeability, by downregulating nuclear factor-κB (NF-κB). 18α-GA suppressed P. gingivalis LPS-stimulated inhibitor of kappa B (IκB) kinase activation, IκBα phosphorylation, and nuclear translocation of NF-κB.


CONCLUSIONS
Overall, these findings suggest that 18α-GA significantly reduces P.                   gingivalis LPS-induced vascular permeability by repressing NF-κB-dependent endothelial IL-8 production, suggesting its therapeutic potential in P.                   gingivalis-related vascular diseases.
School of Dentistry, Pusan National University, Yangsan 626-770, South Korea.
Su-Ryun
SR
Kim
Hwa-Jin
HJ
Jeon
Hyun-Joo
HJ
Park
Mi-Kyoung
MK
Kim
Woo-Soo
WS
Choi
Hye-Ock
HO
Jang
Soo-Kyung
SK
Bae
Chul-Ho
CH
Jeong
Moon-Kyoung
MK
Bae
D002199:Capillary Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000378:metabolism; D016966:Porphyromonas gingivalis
D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D006034:Glycyrrhetinic Acid