TY - JOUR
T1 - 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
AU - Or, Penelope M.Y.
AU - Lam, Francis F.Y.
AU - Kwan, Y. W.
AU - Cho, C. H.
AU - Lau, C. P.
AU - Yu, H.
AU - Lin, G.
AU - Lau, Clara B.S.
AU - Fung, K. P.
AU - Leung, P. C.
AU - Yeung, John H.K.
N1 - Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].
PY - 2012/4/15
Y1 - 2012/4/15
N2 - The 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 6β-hydroxylase) activities were investigated using pooled human liver microsomes. NF3 competitively inhibited activities of CYP2C9 (IC 50 = 0.98 mg/ml) and CYP3A4 (IC 50 = 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 (IC 50 = 0.86 mg/ml) and CYP3A4 (IC 50 = 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 6β-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. © 2011 Elsevier GmbH.
AB - The 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 6β-hydroxylase) activities were investigated using pooled human liver microsomes. NF3 competitively inhibited activities of CYP2C9 (IC 50 = 0.98 mg/ml) and CYP3A4 (IC 50 = 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 (IC 50 = 0.86 mg/ml) and CYP3A4 (IC 50 = 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 6β-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. © 2011 Elsevier GmbH.
KW - CYP1A2
KW - CYP2C9
KW - CYP2D6
KW - CYP2E1
KW - CYP3A4
KW - Human liver microsomes
KW - Radix Astragali
KW - Radix Rehmanniae
UR - http://www.scopus.com/inward/record.url?scp=84859213705&partnerID=8YFLogxK
UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-84859213705&origin=recordpage
U2 - 10.1016/j.phymed.2011.12.005
DO - 10.1016/j.phymed.2011.12.005
M3 - RGC 21 - Publication in refereed journal
C2 - 22261394
SN - 0944-7113
VL - 19
SP - 535
EP - 544
JO - Phytomedicine
JF - Phytomedicine
IS - 6
ER -