In vitro inhibitory effects of dihydromyricetin on human liver cytochrome P450 enzymes

Abstract

Context: Dihydromyricetin (DHM) is the most abundant and active flavonoid component isolated from Ampelopsis grossedentata (Hand-Mazz) W.T. Wang (Vitaceae) and it possesses numerous pharmacological activities. However, whether DHM affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear.

Materials and methods: The inhibitory effects of DHM on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs).

Results: The results showed that DHM could inhibit the activity of CYP3A4, CYP2E1 and CYP2D6, with IC₅₀ values of 14.75, 25.74 and 22.69 μM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that DHM was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2D6, with Ki values of 6.06, 9.24 and 10.52 μM, respectively. In addition, DHM is a time-dependent inhibitor for CYP3A4 with K_I/K_inact value of 12.17/0.057 min⁻¹μM⁻¹.

Discussion and conclusion: The in vitro studies of DHM with CYP isoforms indicate that DHM has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2D6. Further clinical studies are needed to evaluate the significance of this interaction.

Keywords:

• Ampelopsis grossedentata
• CYP3A4
• CYP2E1
• CYP2D6
• herb–drug interaction

Disclosure statement

The authors have declared no conflict of interest.

Additional information

Funding

This study was funded by Talent-Development Project of Pudong Health and Family planning Commission of Shanghai [PWRd 2014-16], Project of Science and Technology Development Foundation of Pudong New Area Science and Technology Commission [PKJ2014-Y18] and Shanghai Municipal Commission of Health and Family Planning [201540126].