Effects of Radix Astragali and Radix Rehmanniae, the components of an anti-diabetic foot ulcer herbal formula, on metabolism of model CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 probe substrates in pooled human liver microsomes and specific CYP isoforms
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AbstractThe present study investigated the effects of Radix Astragali (RA) and Radix Rehmanniae (RR), the major components of an anti-diabetic foot ulcer herbal formula (NF3), on the metabolism of model probe substrates of human CYP isoforms, CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4, which are important in the metabolism of a variety of xenobiotics. The effects of RA or RR on human CYP1A2 (phenacetin O-deethylase), CYP2C9 (tolbutamide 4-hydroxylase), CYP2D6 (dextromethorphan O-demethylase), CYP2E1 (chlorzoxazone 6-hydroxylase) and CYP3A4 (testosterone 6 beta-hydroxylase) activities were investigated using pooled human liver microsomes. NF3 competitively inhibited activities of CYP2C9 (IC50 = 0.98 mg/ml) and CYP3A4 (IC50 = 0.76 mg/ml), with K-i of 0.67 and 1.0 mg/ml, respectively. With specific human CYP2C9 and CYP3A4 isoforms, NF3 competitively inhibited activities of CYP2C9 (IC50 = 0.86 mg/ml) and CYP3A4 (IC50 = 0.88 mg/ml), with K-i of 0.57 and 1.6 mg/ml, respectively. Studies on RA or RR individually showed that RR was more important in the metabolic interaction with the model CYP probe substrates. RR dose-dependently inhibited the testosterone 6 beta-hydroxylation (K-i = 0.33 mg/ml) while RA showed only minimal metabolic interaction potential with the model CYP probe substrates studied. This study showed that RR and the NF3 formula are metabolized mainly by CYP2C9 and/or CYP3A4, but weakly by CYP1A2, CYP2D6 and CYP2E1. The relatively high K-i values of NF3 (for CYP2C9 and CYP3A4 metabolism) and RR (for CYP3A4 metabolism) would suggest a low potential for NF3 to cause herb-drug interaction involving these CYP isoforms. (C) 2011 Elsevier GmbH. All rights reserved.
All Author(s) ListOr PMY, Lam FFY, Kwan YW, Cho CH, Lau CP, Yu H, Lin G, Lau CBS, Fung KP, Leung PC, Yeung JHK
Journal namePhytomedicine
Detailed descriptionTo ORKTS: doi: 10.1016/j.phymed.2011.12.005
Volume Number19
Issue Number6
Pages535 - 544
LanguagesEnglish-United Kingdom
KeywordsCYP1A2; CYP2C9; CYP2D6; CYP2E1; CYP3A4; Human liver microsomes; Radix Astragali; Radix Rehmanniae
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 2020-28-11 at 00:23