COMPARATIVE STUDIES OF THE STEREOISOMERS OF GLYCYRRHETINIC ACID ON ANTI-INFLAMMATORY ACTIVITIES

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Anti-inflammatory of the stereoisomers, 18α and 18β-glycyrrhetinic acid (18α and 18β-GA), obtained from Glycyrrhizae Radix, was investigated by using carrageenan-induced edema in mice and 18α-GA was found to be more active than 18β-GA. Therefore, to clarify the difference of action of 18α and 18β-GA, the inhibitory effects of both stereoisomers on the cotton pellet granuloma formation in adrenalectomized rats and on the reduction of steroidal compounds by Δ⁴-5β-reductase in the microsome fraction of rat liver were investigated. 18α-GA, 30 mg/kg p.o., showed the similar antigranulomatous action in normal and adrenalectomized rats. On the other hand, 18β-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 18α and 18β-GA on the 5β-reduction of testosterone and cortisol were recognized by an equimolar ratio of steroids to 18α or 18β-GA. From these results, the activity of 18α-GA is similar to that of glucocorticoid and the difference of action between 18α and 18β-GA could be explained by its stereochemical structure of D/E trans conformation. In addition to the glucocorticoid action, 18α-GA inhibited the inactivation of endogenous glucocorticoid in liver, which is also recognized by the application of 18β-GA.