Comparative studies of the stereoisomers of glycyrrhetinic acid on anti-inflammatory activities.
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.
D000311:Adrenal Glands / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D000893:Anti-Inflammatory Agents; D001835:Body Weight / Q000187:drug effects; D004487:Edema / Q000517:prevention & control; D005938:Glucocorticoids / Q000378:metabolism; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006099:Granuloma / Q000517:prevention & control; D006854:Hydrocortisone / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013739:Testosterone / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D013739:Testosterone; D010088:Oxidoreductases; C021936:3-oxo-5 beta-steroid delta 4-dehydrogenase; D006034:Glycyrrhetinic Acid; D006854:Hydrocortisone