Department of Natural Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, China.
Pharmacology. 2010;86(5-6):287-92. doi: 10.1159/000320956. Epub 2010 Oct 29.
The liquorice plant has long been used in both Eastern and Western cultures. Glycyrrhizin is the major triterpenoid saponin in liquorice root, and glycyrrhetinic acid (GA) is its predominant metabolite and a pharmacologically active form of glycyrrhizin. We have assessed the ability of GA to inhibit the enzyme cytochrome P450 3A (CYP3A). A Lineweaver-Burk plot showed that GA was a mixed inhibitor of CYP3A, with an IC₅₀ of 7.25 μmol/l, a K(m) of 4.3 μmol/l and a K(i) of 6.4 μmol/l by non-linear regression analysis. CYP3A activity was also affected by intragastric administration of GA, which resulted in increases in area under the plasma concentration-time curve (AUC)(₀-t) and in apparent elimination half-time (t₁/₂) and significant decreases in body clearance, as well as in the formation of 1-hydroxy-midazolam after intragastric or intravenous administration of midazolam (p < 0.05). An increase in C(max) after intragastric administration (p < 0.05) was also observed. These results suggest the likelihood of an interaction between GA and CYP3A-metabolised drugs in humans and indicate that liquorice root should be used with caution when taken concomitantly with other drugs that interact with CYP3A.
甘草植物在东方和西方文化中都被长期使用。甘草酸是甘草根中的主要三萜皂苷，而甘草次酸（GA）是其主要代谢物和甘草酸的一种药理活性形式。我们评估了 GA 抑制细胞色素 P450 3A（CYP3A）酶的能力。Lineweaver-Burk 图表明，GA 是 CYP3A 的混合抑制剂，通过非线性回归分析，IC₅₀为 7.25 μmol/l，K(m)为 4.3 μmol/l，K(i)为 6.4 μmol/l。GA 的胃内给药也会影响 CYP3A 活性，导致血浆浓度-时间曲线下面积（AUC）（₀-t）和表观消除半衰期（t₁/₂）增加，以及身体清除率显著降低，同时在咪达唑仑的胃内或静脉给药后，1-羟基-咪达唑仑的形成也显著减少（p < 0.05）。胃内给药后 C(max)增加（p < 0.05）也观察到。这些结果表明 GA 和 CYP3A 代谢药物之间在人类中可能存在相互作用，并表明当与其他与 CYP3A 相互作用的药物同时服用时，应谨慎使用甘草根。
