Antithrombotic effect of Glycyrrhizin, a plant-derived thrombin inhibitor

Glycyrrhizin (GL), an anti-inflammatory compound isolated from licorice (Glycyrrhiza glabra), has been previously identified as a thrombin inhibitor (Francischetti et al., Biochem Biophys Res Commun 1997;235:259-63). Here we report the in vivo effects of GL upon two experimental models of induced thrombosis in rats. Intravenous administration of GL caused a dose-dependent reduction in thrombus size on a venous thrombosis model that combines stasis and hypercoagulability. It was observed that GL doses of 180 mg/kg body weight produced 93% decrease on thrombus weight. This effect showed a time-dependent pattern being significantly reduced when the thrombogenic stimulus was applied 60 min after drug administration. GL was also able to prevent thrombosis using an arteriovenous shunt model. GL doses of 180 and 360 mg/kg decreased the thrombus weight by 35 and 90%, respectively. Accordingly, the APTT ex vivo was enhanced by 1.5- and 4.3-fold at GL doses of 180 and 360 mg/kg, respectively. In addition, GL doses above 90 mg/kg caused significant hemorrhagic effect. In contrast with heparin, GL did not potentiate the inhibitory activity of antithrombin III or heparin cofactor II towards thrombin. Altogether, data indicate that GL is an effective thrombin inhibitor in vivo, which may account for its other known pharmacological properties.