Inhibition of human cytochrome P450 enzymes by licochalcone A, a naturally occurring constituent of licorice

Abstract

Licochalcone A (LCA) is a major bioactive compound in traditional Chinese herbal liquorice that possesses multiple pharmacological activities. However, the effects of the potential herb–drug interactions (HDIs) between LCA and therapeutic drugs on the inhibition of human cytochrome P450 (CYP) enzymes remain unclear. In the present study, the inhibitory effects of LCA on seven major human CYP isoforms, including CYP1A2, 2D6, 2E1, 2C19, 2C8, 2C9 and 3A4, were investigated in human liver microsomes (HLMs). The results demonstrated that LCA significantly inhibited the activities of CYP1A2, 2C19, 2C8, 2C9 and 3A4 and exhibited weak inhibitory effects on CYP2E1 and CYP2D6. Dixon and Lineweaver–Burk plots revealed that the inhibition types of LCA against CYP1A2, 2C9, 2C19 and 2C8 were best fit as mixed-type inhibitions, while LCA was a competitive inhibitor towards CYP3A4. The inhibition kinetic parameters (Ki) were calculated to be 1.02μM, 0.17μM, 3.89μM 0.89μM, and 2.29μM, for CYP1A2, 2C9, 2C19, 2C8, and 3A4, respectively. Furthermore, the areas under the plasma concentration–time curves (AUCs) of several drugs that are primarily metabolized by CYPs were estimated to increase by 2–398% in the presence of LCA, which suggested that LCA exhibited high HDI potentials via CYP inhibition. These data are significant for the clinical applications of LCA-containing herbs.