Inhibition of CYP450 activity by honokiol and other four components of Chinese traditionalmedicine in vitro

Abstract

Abstract:

AIM: To explore the inhibition of honokiol and other four components of Chinese traditional medicine on four kinds of cytochrome P450 activity in human liver microsomes (HLM) and rat liver microsomes (RLM) in vitro, and to provide foundation for further research of clinical combination of Chinese medicine with western medicine. METHODS: Paclitaxel, tolbutamide, chlorzoxazone and coumarin were incubated in vitro as probe drugs of CYP2C8, CYP2C9/CYP2C11, CYP2E1 and CYP2A6/CYP2A1/2 respectively. HPLC was used to detect the amounts of metabolites of the probe drug. The inhibition ratio and the IC50 of the five kinds of effective components of Chinese traditional medicine were calculated and analyzed to find out whether they can affect the enzyme activity. RESULTS:IC50 of honokiol and magnolol on CYP2C9 in HLM were 7.7 μmol/L and 7.6 μmol/L, while IC50 of honokiol and magnolol on CYP2C11 in RLM were 13.0 μmol/L and 3.8 μmol/L separately. IC50 of honokiol and magnolol on CYP2C8 in HLM were 19.2 μmol/L and 84.5 μmol/L, while IC50 of honokiol and magnolol on CYP2C8, CYP2E1, CYP2A1/2 in RLM and CYP2E1, CYP2A6 in HLM were all above 100 μmol/L. IC50 of geniposide, chlorogenic acid and astragaloside on four kinds of CYP enzymes were all above 100 μmol/L. CONCLUSION: Honokiol has obvious inhibition on CYP2C9/CYP2C11 in both HLM and RLM and CYP2C8 in HLM. Magnolol has obvious inhibition on CYP2C9/CYP2C11 in both HLM and RLM and has slightly inhibition on CYP2C8 in HLM.

Key words: effective components of Chinese traditional medicine, cytochrome P450, liver microsomes, inhibition

CLC Number:

R969

ZHANG Peiyu, REN Jing, ZHI Wenqian, LIU Chengming, GAO Na. Inhibition of CYP450 activity by honokiol and other four components of Chinese traditionalmedicine in vitro[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(8): 922-926.

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