Comparative studies of the stereoisomers of glycyrrhetinic acid on anti-inflammatory activities

Abstract

Anti-inflammatory activity of the stereoisomers, 18 alpha and 18 beta-glycyrrhetinic acid (18 alpha and 18 beta-GA), obtained from Glycyrrhizae Radix, was investigated by using carrageenan-induced edema in mice and 18 alpha-GA was found to be more active than 18 beta-GA. Therefore, to clarify the difference of action of 18 alpha and 18 beta-GA, the inhibitory effects of both stereoisomers on the cotton pellet granuloma formation in adrenalectomized rats and on the reduction of steroidal compounds by delta 4-5 beta-reductase in the microsome fraction of rat liver were investigated. 18 alpha-GA, 30 mg/kg p.o., showed the similar antigranulomatous action in normal and adrenalectomized rats. On the other hand, 18 beta-GA, 30 mg/kg p.o., which exhibited the inhibitory effects in normal rats, showed no action in adrenalectomized rats. More than 50% of inhibitory effects of 18 alpha and 18 beta-GA on the 5 beta-reduction of testosterone and cortisol were recognized by an equimolar ratio of steroids to 18 alpha or 18 beta-GA. From these results, the activity of 18 alpha-GA is similar to that of glucocorticoid and the difference of action between 18 alpha-GA and 18 beta-GA could be explained by its stereochemical structure of D/E trans conformation. In addition to the glucocorticoid action, 18 alpha-GA inhibited the inactivation of endogenous glucocorticoid in liver, which is also recognized by the application of 18 beta-GA.