In vitro study on the effect of leonurine hydrochloride on the enzyme activity of cytochrome P450 enzymes in human liver microsomes

Abstract

1. Leonurine hydrochloride (LH) is derived from an ingredient of Leonurus japonicus Houtt which is widely used for diseases in women.

2. The influence of LH on the activity of cytochrome P450 (CYPs) enzymes was investigated in this study.

3. The effect of LH on CYPs enzyme activities were studied using the enzyme-selective substrates phenacetin (1A2), coumarin (2A6), diclofenac (2C9), S-mephenytoin (2C19), paclitaxel (2C8), dextromethorphan (2D6), chlorzoxazone (2E1) and testosterone (3A4). The IC₅₀ value was calculated to express the strength of inhibition. The inhibition of CYPs was fitted with competitive or non-competitive inhibition models and corresponding parameters were also obtained.

4. LH exerted inhibitory effects on the activity of CYP1A2, 2D6, and 3A4 with the IC₅₀ values of 18.05, 15.13, and 20.09 μM, respectively. The obtained results showed that LH inhibited the activity of CYP1A2 and CYP2D6 via competitive manners (K_i = 8.667 μM and K_i = 7.805 μM, respectively), while LH attenuated the CYP3A4 activity via a non-competitive manner (K_i = 9.507 μM). Moreover, LH showed time-dependent inhibition on CYP3A4 with the K_I/K_inact value of 4.31/0.044 min⁻¹·μM⁻¹.

5. The inhibition of CYP1A2, CYP2D6, and CYP3A4 by LH, demonstrated in vitro, indicated the potential herb–drug interaction. Therefore, pharmacokinetic interactions involving LH and CYP1A2 or CYP2D6 or CYP1A2 substrates are likely to occur.

Keywords:

• CYP1A2
• CYP2D6
• CYP3A4
• herb–drug interaction
• inhibition

Disclosure statement

No potential conflict of interest was reported by the author(s).