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Schröfelbauer, B; Raffetseder, J; Hauner, M; Wolkerstorfer, A; Ernst, W; Szolar, OH.
(2009): Glycyrrhizin, the main active compound in liquorice, attenuates pro-inflammatory responses by interfering with membrane-dependent receptor signalling.
Biochem J. 2009; 421(3):473-482 FullText FullText_BOKU

Abstract:
The triterpene glycoside glycyrrhizin is the main active compound in liquorice. It is used as it herbal medicine owing to its anticancer, antiviral and anti-inflammatory properties. Its mode of action, however, remains widely Unknown. In the present study, we aimed to elucidate the molecular mechanism of glycyrrhizin in attenuating inflammatory responses in macrophages. Using microarray analysis, we found that glycyrrhizin caused a broad block in the induction of pro-inflammatory mediators induced by the TLR (Toll-like receptor) 9 agonist CpG-DNA in RAW 264.7 cells. Furthermore, we found that glycyrrhizin also strongly attenuated inflammatory responses induced by TLR3 and TLR4 ligands. The inhibition was accompanied by decreased activation not only of the NF-kappa B (nuclear factor kappa B) pathway but also Of the parallel MAPK (mitogen-activated protein kinase) signalling cascade upon stimulation with TLR9 and TLR4 agonists. Further analysis of upstream events revealed that glycyrrhizin treatment decreased cellular attachment and/or uptake of CpG-DNA and strongly impaired TLR4 internalization. Moreover. we found that the anti-inflammatory effects were specific for membrane-dependent receptor-mediated stimuli, as glycyrrhizin was ineffective ill blocking Tnfa (tumour necrosis factor a alpha gene) induction upon stimulation with PMA, it receptor- and membrane-independent stimulus. These observations suggest that the broad anti-inflammatory activity of glycyrrhizin is mediated by the interaction with the lipid bilayer, thereby attenuating receptor-mediated signalling.
Authors BOKU Wien:
Ernst Wolfgang
BOKU Gendermonitor:

Find related publications in this database (using NML MeSH Indexing)
Animals -
Anti-Inflammatory Agents - metabolism
Cell Line -
Cell Membrane - drug effects
Glycyrrhiza - chemistry
Glycyrrhizic Acid - metabolism
Macrophages - drug effects
Mice -
Mitogen-Activated Protein Kinases - genetics
NF-kappa B - genetics
Receptors, Cell Surface - immunology
Signal Transduction - drug effects
Toll-Like Receptors - genetics

Find related publications in this database (Keywords)
cell membrane
cytokine
glycyrrhizin
inflammation
signalling
Toll-like receptor (TLR)


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