Licorice, the root extract of Glycyrrhiza glabra L., is used as a medicine for various diseases. Antiinflammatory as well as anti-allergic activities have been attributed to one of its main constituents, glycyrrhizin. These activities are mainly ascribed to the action of the aglycone, b-glycyrrhetinic acid. b-Glycyrrhetinic acid has a steroid-like structure and is believed to have immunomodulatory properties. To determine whether interference with complement functions may contribute to the immunomodulatory activity of b-glycyrrhetinic acid, its effects on the classical and alternative activation pathways of human complement were investigated. We found that b-glycyrrhetinic acid is a potent inhibitor of the classical complement pathway (IC50=35 mM), whereas no inhibitory activity was observed towards the alternative pathway (IC50>2500 mM). The anticomplementary activity of b-glycyrrhetinic acid was dependent on its conformation, since the a-form was not active. It was also established that naturally occurring steroids, e.g. hydrocortisone and cortisone, did not inhibit human complement activity under similar conditions. Detailed mechanistic studies revealed that b-glycyrrhetinic acid acts at the level of complement component C2.
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