甘草次酸在人细胞色素CYP450中体外代谢研究(英)

甘草根是中医临床常用解毒草药, 其活性成分甘草次酸主要是通过肝脏代谢。本文研究了人肝微粒体以及人源性CYP450s对甘草次酸的体外代谢影响, 以及甘草次酸对几种CYP450酶活性的影响。实验结果表明, 甘草次酸体外主要代谢酶为CYP3A4。体外药代动力学参数K_m, V_max和CL_int分别为18.6 μmol·L⁻¹, 4.4 nmol·mg⁻¹(protein)·min⁻¹和0.237 mL·mg⁻¹(protein)·min⁻¹。体外抑制试验显示, 50 μmol·L⁻¹甘草次酸可以抑制CYP2C19、CYP2C9、CYP3A4酶的活性, 其抑制率可高达50%以上。

In vitro metabolism of glycyrrhetic acid by human cytochrome P450

Licorice root has been frequently used as antitode in traditional Chinese medicine.  As the main active component of Licorice root, glycyrrhetic acid (GA) is mainly metabolized in liver.  This study was designed to investigate the in vitro metabolism of GA by human liver microsomes (HLM) and human recombinant cytochrome P450 (CYP) isoforms.  The results indicated that GA was metabolized mainly by CYP3A4.  The K_m, V_max and CL_int of GA in HLM were 18.6 μmol·L⁻¹, 4.4 nmol·mg⁻¹(protein)·min⁻¹ and 0.237 mL·mg⁻¹(protein)·min⁻¹, respectively.  At concentration up to 50 μmol·L⁻¹, GA inhibited CYP2C19, CYP2C9 and CYP3A4 enzyme activities with the inhibitory potencies up to 50%.