Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Glucuronidation of the Red Clover Isoflavone Irilone by Liver Microsomes from Different Species and Human UDP-Glucuronosyltransferases

Ronald Maul, Diana Siegl and Sabine E. Kulling
Drug Metabolism and Disposition April 2011, 39 (4) 610-616; DOI: https://doi.org/10.1124/dmd.110.033076
Ronald Maul
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Diana Siegl
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sabine E. Kulling
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

Red clover (Trifolium pratense L.) is used as a source for isoflavone (IF) dietary supplements. In this study, we focused on the red clover IF irilone (IRI), because of its reported comparatively high bioavailability. Because the conjugative metabolism plays a key role in the elimination of IF, we investigated the species-specific differences and glucuronidation kinetics of IRI using different liver microsomes as well as the recombinant UDP-glucuronosyltransferases (UGTs) 1A1, 1A7, 1A8, 1A9, 1A10, and 2B15. Both possible monoglucuronides, the IRI-O-4′-monoglucuronide (IRI-G4′) and the IRI-O-5-monoglucuronide (IRI-G5), were detected. Human liver microsomes (HLM) as well as rat liver microsomes predominantly formed IRI-G5, whereas for porcine liver microsomes, IRI-G4′ prevailed. HLM showed an apparent Vmax value of 0.43 nmol/min · mg and an apparent Km value of 9.8 μM for the formation of IRI-G5 and a Vmax of 0.35 nmol/min · mg and a Km of 64.7 μM in the case of IRI-G4′. Formation of both glucuronides was best fit using the substrate inhibition equation. The glucuronidation of IRI by UGTs led to values for the intrinsic clearance varying between 4 and 100 ml/min · mg, with UGT1A7 showing the lowest and UGT1A10 the highest IRI conversion rate. The results indicate that IRI undergoes an efficient glucuronidation, presumably in the intestine and liver, following atypical kinetic profiles.

Footnotes

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.110.033076.

  • ↵Embedded Image The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.

  • ABBREVIATIONS:

    IF
    isoflavone
    DAD
    diode array detector
    HLM
    human liver microsomes
    HPLC
    high-performance liquid chromatography
    IRI
    5,4′-dihydroxy-6,7-methylenedioxy-IF
    IRI-G4′
    IRI-O-4′-monoglucuronide
    IRI-G5
    IRI-O-5-monoglucuronide
    HPLC-DAD
    high-performance liquid chromatography-diode array detector
    MUG
    4-(trifluoromethyl) umbelliferone-glucuronide
    PLM
    porcine liver microsomes
    RLM
    rat liver microsomes
    UGT
    UDP glucuronosyltransferase
    UDPGA
    uridine-5′-diphosphate-β,d-glucuronic acid.

  • Received March 2, 2010.
  • Accepted December 21, 2010.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 39 (4)
Drug Metabolism and Disposition
Vol. 39, Issue 4
1 Apr 2011
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Glucuronidation of the Red Clover Isoflavone Irilone by Liver Microsomes from Different Species and Human UDP-Glucuronosyltransferases
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Glucuronidation of the Red Clover Isoflavone Irilone by Liver Microsomes from Different Species and Human UDP-Glucuronosyltransferases

Ronald Maul, Diana Siegl and Sabine E. Kulling
Drug Metabolism and Disposition April 1, 2011, 39 (4) 610-616; DOI: https://doi.org/10.1124/dmd.110.033076

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Glucuronidation of the Red Clover Isoflavone Irilone by Liver Microsomes from Different Species and Human UDP-Glucuronosyltransferases

Ronald Maul, Diana Siegl and Sabine E. Kulling
Drug Metabolism and Disposition April 1, 2011, 39 (4) 610-616; DOI: https://doi.org/10.1124/dmd.110.033076
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Human ADME Properties of Abrocitinib
  • MSCs Pharmacokinetics under liver diseases
  • In Vitro-In Vivo Extrapolation Using Empirical Scaling
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics