Polysaccharide peptides from Coriolus versicolor competitively inhibit model cytochrome P450 enzyme probe substrates metabolism in human liver microsomes
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AbstractPolysaccharide peptide (PSP), isolated from COV-1 strain of Coriolus versicolor, is commonly used as an adjunct in cancer chemotherapy or health supplement in China. Previous studies have shown that PSP decreased antipyrine clearance and inhibited rat CYP2C11-mediated tolbutamide 4-hydroxylation and in human CYP2C9. In this study, the effects of the water extractable fraction of PSP on the metabolism of model CYP1A2, CYP2D6, CYP2E1 and CYP3A4 probe substrates were investigated in pooled human liver microsomes. PSP (1.25-20 mu M) dose-dependently decreased CYP1A2-mediated metabolism of phenacetin to paracetamol (IC50 19.7 mu M) and CYP3A4-mediated metabolism of testosterone to 6 beta-hydroxytestosterone (IC20 7.06 mu M). Enzyme kinetics studies showed the inhibition of CYP1A2 activity was competitive and concentration-dependent (K-i = 18.4 mu M). Inhibition of testosterone to 6 beta-hydroxytestosterone was also competitive and concentration-dependent (K-i = 31.8 mu M). Metabolism of dextromethorphan to dextrorphan (CYP2D6-mediated) and chlorzoxazone to 6-hydroxychlorzoxazone (CYP2E1-mediated) was only minimally inhibited by PSP, with IC20 values at 15.6 mu M and 11.9 mu M, respectively. This study demonstrated that PSP competitively inhibited the CYP1A2- and CYP3A4-mediated metabolism of model probe substrates in human liver microsomes in vitro. The relatively high K-i values for CYP1A2 and CYP3A4 would suggest a low potential for PSP to cause herb-drug interaction related to these CYP isoforms. (C) 2011 Elsevier GmbH. All rights reserved.
All Author(s) ListYeung JHK, Or PMY
Journal namePhytomedicine
Detailed descriptionTo ORKTS: doi: 10.1016/j.phymed.2011.09.077
Year2012
Month3
Day15
Volume Number19
Issue Number5
PublisherElsevier
Pages457 - 463
ISSN0944-7113
eISSN1618-095X
LanguagesEnglish-United Kingdom
KeywordsCoriolus versicolor; CYP2D6 CYP2E1; CYP3A4; Human CYP1A2; Polysaccharide peptide (PSP)
Web of Science Subject CategoriesChemistry, Medicinal; CHEMISTRY, MEDICINAL; Integrative & Complementary Medicine; INTEGRATIVE & COMPLEMENTARY MEDICINE; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY; Plant Sciences; PLANT SCIENCES

Last updated on 2020-17-11 at 00:54