In vitro inhibition of Huanglianjiedu Decoction on 6 cytochrome P450 isoforms in human liver microsomes

Abstract

Abstract: AIM: To predict the herb-drug interactions in clinical application, Huanglianjiedu Decoction was evaluated for its in vitro inhibition effect on 6 cytochrome P450 isoforms (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in human liver microsomes.METHODS: Seven metabolites of cytochrome P450 probe substrate (including Paracetamol for CYP1A2, 6α- Hydroxypaclitaxel for CYP2C8, 4-Hydroxydiclofenac for CYP2C9, 4-Hydroxymephenytoin for CYP2C19, Dextrorphan for CYP2D6, 6β-Hydroxytestosterone and 1-Hydroxymidazolam for CYP3A4) were simultaneously measured by LC-MS/MS. Huanglianjiedu Decoction was incubated with human liver microsomes in the presence of seven probe substrates of CYP450 isforms, and the inhibitory effect were evaluated with IC₅₀ values.RESULTS: IC₅₀ value of Huanglianjiedu Decoction on CYP2D6 and CYP1A2 were 3.54 and 10.8 μg/mL, and the other IC₅₀ values were 67.7, 299, 530, 199 and 607 μg/mL with respect to CYP2C8, CYP2C9, CYP2C19, CYP3A4_T and CYP3A4_M isoforms.CONCLUSION: Huanglianjiedu Decoction shows inhibitory effect on CYP2D6 and CYP1A2, but minor inhibitory effects on CYP2C8, CYP2C9, CYP2C19 and CYP3A4.

Key words: Huanglianjiedu Decoction, Cytochrome P450, Inhibition, Drug-drug interactions

CLC Number:

R965.2

LI Dan, HAN Yong-long, YU Tao, Fu Yao, MENG Xiang-le, YU Qi, GUO Cheng. In vitro inhibition of Huanglianjiedu Decoction on 6 cytochrome P450 isoforms in human liver microsomes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(2): 131-136.

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