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%.