Glycyrrhetinic acid inhibits Porphyromonas gingivalis lipopolysaccharide-induced vascular permeability via the suppression of interleukin-8
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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.
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.
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.
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.
KeywordsInterleukin-8 Nuclear factor-κB Porphyromonas gingivalis lipopolysaccharide 18alpha-glycyrrhetinic acid Vascular permeability Vascular endothelial cells
This research was supported by College of Pharmacy-specialized Research Fund (from institute for new drug development) of Keimyung University in 2011 (to C.-H. Jeong) and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0003750) (to M.-K. Bae).
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