In Vitro Inhibitory Potential of Decursin and Decursinol Angelate on the Catalytic Activity of Cytochrome P-450 1A1/2, 2D15, and 3A12 Isoforms in Canine Hepatic Microsomes

Danggui is one of the most popular herbal medicines consumed by patients in different clinical settings in Asian countries. In this study, the two major pyranocoumarin compounds extracted from the Korean Angelica gigas root decursin (DC) and decursinol angelate (DA) were examined in vitro with regard to their abilities to inhibit hepatic CYP1A1/2, CYP2D15, and CYP3A12 catalytic activities in canine liver microsomes. The two components were capable of inhibiting CYP1A1/2, CYP2D15, and CYP3A12 catalytic activities, but the potencies varied. DC and DA selectively and noncompetitively inhibited CYP1A1/2 activity, with K-i values of 90.176 and 67.560 mu M, respectively. On the other hand, they exhibited slight inhibitory effects on CYP2D15 and CYP3A12 with Ki values of 666.180 and 872.502 mu M, 990.500 and 909.120 mu M (1'hydroxymidazolam, MDZ1'H), and 802.800 and 853.920 mu M (4-hydroxymidazolam, MDZ4H), respectively. Additionally, they showed increased inhibition after preincubation, which suggests the involvement of a mechanism-based inhibition. In sum, this in vitro data should be heeded as a signal of possible in vivo interactions. The use of human liver preparations would considerably strengthen the practical impact of the data generated from this study.