Imanishi N, Kawai H, Hayashi Y, Yatsunami K, Ichikawa A
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Biochem Pharmacol. 1989 Aug 1;38(15):2521-6. doi: 10.1016/0006-2952(89)90097-x.
The effects of glycyrrhizin and its aglycone, glycyrrhetinic acid, on dexamethasone-induced changes in the histamine synthesis of mastocytoma P-815 cells and in the histamine release from antigen-stimulated rat peritoneal mast cells were investigated. Glycyrrhetinic acid but not glycyrrhizin, at concentrations from 20 to 35 microM, almost completely inhibited the dexamethasone-induced increases in both the histamine content and histidine decarboxylase activity of cultured mastocytoma P-815 cells. Glycyrrhetinic acid, however, showed practically no inhibition of [3H]dexamethasone binding to the cytoplasmic receptor. On the other hand, glycyrrhetinic acid but not glycyrrhizin markedly inhibited the release of histamine from antigen-stimulated rat mast cells, and intensified the inhibitory activity induced by dexamethasone. Glycyrrhetinic acid inhibited the antigen-induced release and incorporation of [3H]arachidonic acid in immunized rat mast cells. The administration of glycyrrhizin into rats, in contrast to the in vitro treatment of the cells with glycyrrhizin, markedly inhibited histamine release from antigen-stimulated rat mast cells. These results suggest that glycyrrhetinic acid inhibited dexamethasone-induced changes in the histamine synthesis of mastocytoma P-815 cells, and in the histamine release from rat mast cells. On the other hand, glycyrrhizin may exert its effect after conversion to glycyrrhetinic acid in vivo.
研究了甘草酸及其苷元甘草次酸对地塞米松诱导的肥大细胞瘤P - 815细胞组胺合成变化以及抗原刺激的大鼠腹腔肥大细胞组胺释放的影响。在20至35 microM的浓度范围内，甘草次酸而非甘草酸几乎完全抑制了地塞米松诱导的培养肥大细胞瘤P - 815细胞组胺含量和组氨酸脱羧酶活性的增加。然而，甘草次酸对[3H]地塞米松与细胞质受体的结合几乎没有抑制作用。另一方面，甘草次酸而非甘草酸显著抑制了抗原刺激的大鼠肥大细胞组胺的释放，并增强了地塞米松诱导的抑制活性。甘草次酸抑制了免疫大鼠肥大细胞中抗原诱导的[3H]花生四烯酸的释放和掺入。与用甘草酸对细胞进行体外处理相反，给大鼠注射甘草酸显著抑制了抗原刺激的大鼠肥大细胞组胺的释放。这些结果表明，甘草次酸抑制了地塞米松诱导的肥大细胞瘤P - 815细胞组胺合成变化以及大鼠肥大细胞组胺释放。另一方面，甘草酸可能在体内转化为甘草次酸后发挥其作用。
