Glycyrrhizin binds to High Mobility Group Box 1 protein (HMGB1) and inhibits its cytokine activities

High-mobility group box 1 protein (HMGB1) is anuclear component, but extracellularly it servesas a signaling molecule involved in acute andchronic inflammation, for example in sepsisand arthritis. The identification of HMGB1 inhibitorsis therefore of significant experimental andclinical interest. We show that glycyrrhizin, anatural anti-inflammatory and antiviral triterpenein clinical use, inhibits HMGB1 chemoattractantand mitogenic activities, and has aweak inhibitory effect on its intranuclear DNAbindingfunction. NMR and fluorescence studiesindicate that glycyrrhizin binds directly toHMGB1 (Kd 150 mM), interacting with twoshallow concave surfaces formed by the twoarms of both HMG boxes. Our results explainin part the anti-inflammatory properties of glycyrrhizin,and might direct the design of newderivatives with improved HMGB1-bindingproperties.