Glycyrrhetinic acid inhibits Porphyromonas gingivalis lipopolysaccharide-induced vascular permeability via the suppression of interleukin-8.

Abstract

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.

• Authors: Su-Ryun Kim, Hwa-Jin Jeon, Hyun-Joo Park, Mi-Kyoung Kim, Woo-Soo Choi, Hye-Ock Jang, Soo-Kyung Bae, Chul-Ho Jeong, Moon-Kyoung Bae
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 62 Issue 2 Pg. 145-54 (Feb 2013) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 23064654 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-8
• Lipopolysaccharides
• NF-kappa B
• Glycyrrhetinic Acid

Topics

• Capillary Permeability (drug effects)
• Cells, Cultured
• Endothelial Cells (drug effects, metabolism)
• Glycyrrhetinic Acid (pharmacology)
• Humans
• Interleukin-8 (metabolism)
• Lipopolysaccharides
• NF-kappa B (metabolism)
• Porphyromonas gingivalis