INHIBITION OF HUMAN-COMPLEMENT BY BETA-GLYCYRRHETINIC ACID

Licorice, the root extract of Glycyrrhiza glabra L., is used as a medi cine for various diseases. Antiinflammatory as well as anti-allergic a ctivities have been attributed to one of its main constituents, glycyr rhizin. These activities are mainly ascribed to the action of the agly cone, beta-glycyrrhetinic acid. beta-Glycyrrhetinic acid has a steroid -like structure and is believed to have immunomodulatory properties. T o determine whether interference with complement functions may contrib ute to the immunomodulatory activity of beta-glycyrrhetinic acid, its effects on the classical and alternative activation pathways of human complement were investigated. We found that beta-glycyrrhetinic acid i s a potent inhibitor of the classical complement pathway (IC50=35 mu M ), whereas no inhibitory activity was observed towards the alternative pathway (IC50>2500 mu M). The anticomplementary activity of beta-glyc yrrhetinic acid was dependent on its conformation, since the alpha-for m was not active. It was also established that naturally occurring ste roids, e.g. hydrocortisone and cortisone, did not inhibit human comple ment activity under similar conditions. Detailed mechanistic studies r evealed that beta-glycyrrhetinic acid acts at the level of complement component C2.