Inhibitory Effects and Characteristics of Byakangelicol on the Activity of Multiple Cytochrome P450 Isoforms

Abstract

Byakangelicol, a furanocoumarin derived from Angelica dahurica, possesses anti-inflammatory and antitumor activities. Since cytochrome P450 2A6 (CYP2A6) is the major enzyme responsible for coumarin metabolism, it is important to evaluate the effect of byakangelicol on CYP enzyme activity. The purpose was to explore the effects of byakangelicol on CYPs and to provide a reference for its drug development and clinical application. The present study investigated the impact of byakangelicol on CYPs in human liver microsomes (HLMs). Byakangelicol demonstrated the capacity to suppress the activities of CYP1A2, 2A6, and 3A4 in HLMs, with IC₅₀ values of 19.42, 10.11, and 12.80 μM, respectively. Byakangelicol exhibited competitive inhibition of CYP1A2 and 2A6 with K _i values of 9.86 μM and 5.23 μM, whereas the inhibitory effect on CYP3A4 was noncompetitive with a K _i value of 6.55 μM. In addition, the inhibitory effect of byakangelicol on CYP3A4 was found to be time-dependent (K _inact = 0.041 min⁻¹ and K _I = 6.67 μM). This study revealed the inhibitory properties of byakangelicol on CYP1A2, 2A6, and 3A4 activity in HLMs. It suggests the potential for drug–drug interactions when byakangelicol is co-administered with drugs metabolized by these CYPs. These findings offer a foundation for investigating the interaction of byakangelicol with other drugs, which may assist in clinical prescription and drug development.