File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: 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

TitleEffects 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
Authors
KeywordsCYP1A2
CYP2C9
CYP2D6
CYP2E1
CYP3A4
Human liver microsomes
Radix Astragali
Radix Rehmanniae
Issue Date2012
Citation
Phytomedicine, 2012, v. 19, n. 6, p. 535-544 How to Cite?
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 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.
Persistent Identifierhttp://hdl.handle.net/10722/343092
ISSN
2023 Impact Factor: 6.7
2023 SCImago Journal Rankings: 1.267

 

DC FieldValueLanguage
dc.contributor.authorOr, Penelope M.Y.-
dc.contributor.authorLam, Francis F.Y.-
dc.contributor.authorKwan, Y. W.-
dc.contributor.authorCho, C. H.-
dc.contributor.authorLau, C. P.-
dc.contributor.authorYu, H.-
dc.contributor.authorLin, G.-
dc.contributor.authorLau, Clara B.S.-
dc.contributor.authorFung, K. P.-
dc.contributor.authorLeung, P. C.-
dc.contributor.authorYeung, John H.K.-
dc.date.accessioned2024-05-10T09:05:22Z-
dc.date.available2024-05-10T09:05:22Z-
dc.date.issued2012-
dc.identifier.citationPhytomedicine, 2012, v. 19, n. 6, p. 535-544-
dc.identifier.issn0944-7113-
dc.identifier.urihttp://hdl.handle.net/10722/343092-
dc.description.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 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.-
dc.languageeng-
dc.relation.ispartofPhytomedicine-
dc.subjectCYP1A2-
dc.subjectCYP2C9-
dc.subjectCYP2D6-
dc.subjectCYP2E1-
dc.subjectCYP3A4-
dc.subjectHuman liver microsomes-
dc.subjectRadix Astragali-
dc.subjectRadix Rehmanniae-
dc.titleEffects 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-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.phymed.2011.12.005-
dc.identifier.pmid22261394-
dc.identifier.scopuseid_2-s2.0-84859213705-
dc.identifier.volume19-
dc.identifier.issue6-
dc.identifier.spage535-
dc.identifier.epage544-
dc.identifier.eissn1618-095X-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats