甘草酸及其苷元甘草次酸的糖皮质激素样作用

Glucocorticoid-like effect of glycyrrhizic acid and its aglycone glycyrrhetic acid

甘草酸在体内水解成甘草次酸,因此甘草酸是甘草次酸的前体药物,而甘草次酸的药理作用强于甘草酸。甘草次酸的化学结构类似于甾体激素。甘草次酸和甘草酸是甾体激素代谢失活酶抑制剂,可提高内源性和外源性糖皮质激素的活性。甘草次酸和甘草酸又可作为配体,与糖皮质激素受体结合,由于甘草次酸和甘草酸的糖皮质激素受体激动活性远低于糖皮质激素,因此是糖皮质激素受体的部分激动拮抗剂。临床上可将甘草酸作为弱糖皮质激素样药物应用,不仅增强糖皮质激素的作用,而且拮抗大剂量糖皮质激素的不良反应。

Glycyrrhizic acid is hydrolyzed to glycyrrhetic acid in vivo. Pharmacological action of glycyrrhetic acid is higher than that of glycyrrhizic acid, so glycyrrhizic acid is a prodrug of glycyrrhetic acid. Chemical structure of glycyrrhetic acid is similar to steroid hormone. Glycyrrhetic acid and glycyrrhizic acid are the inhibitors of enzymes in steroid hormone metabolism, therefore they can enhance effects of endogenic and exogenic glucocorticoids. Glycyrrhetic acid and glycyrrhizic acid, as ligands, can combine with glucocorticoid receptor, but receptor activation is far inferior to glucocorticoid. For this reason, glycyrrhetic acid and glycyrrhizic acid are partial agonists of glucocorticoid receptor. In clinic, glycyrrhizic acid may be used as weak glucocorticoid-like drug, not only enhances glucocorticoid effects but also antagonizes adverse reactions of large dose glucocorticoids.