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Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities.
- Source :
-
Chemistry & biology [Chem Biol] 2007 Apr; Vol. 14 (4), pp. 431-41. - Publication Year :
- 2007
-
Abstract
- High-mobility group box 1 protein (HMGB1) is a nuclear component, but extracellularly it serves as a signaling molecule involved in acute and chronic inflammation, for example in sepsis and arthritis. The identification of HMGB1 inhibitors is therefore of significant experimental and clinical interest. We show that glycyrrhizin, a natural anti-inflammatory and antiviral triterpene in clinical use, inhibits HMGB1 chemoattractant and mitogenic activities, and has a weak inhibitory effect on its intranuclear DNA-binding function. NMR and fluorescence studies indicate that glycyrrhizin binds directly to HMGB1 (K(d) approximately 150 microM), interacting with two shallow concave surfaces formed by the two arms of both HMG boxes. Our results explain in part the anti-inflammatory properties of glycyrrhizin, and might direct the design of new derivatives with improved HMGB1-binding properties.
- Subjects :
- 3T3 Cells
Animals
Anti-Inflammatory Agents, Non-Steroidal chemistry
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Binding Sites
Cytokines metabolism
DNA metabolism
Fluorescence
Glycyrrhizic Acid chemistry
Glycyrrhizic Acid pharmacology
HMGB1 Protein chemistry
Humans
Magnetic Resonance Spectroscopy
Mice
Mitogens antagonists & inhibitors
Mitogens pharmacology
Models, Molecular
Protein Binding
Anti-Inflammatory Agents, Non-Steroidal metabolism
Cytokines antagonists & inhibitors
Glycyrrhizic Acid metabolism
HMGB1 Protein antagonists & inhibitors
HMGB1 Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1074-5521
- Volume :
- 14
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Chemistry & biology
- Publication Type :
- Academic Journal
- Accession number :
- 17462578
- Full Text :
- https://doi.org/10.1016/j.chembiol.2007.03.007