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

HUMAN CYTOCHROME P450 INHIBITION AND METABOLIC-INTERMEDIATE COMPLEX FORMATION BY GOLDENSEAL EXTRACT AND ITS METHYLENEDIOXYPHENYL COMPONENTS

Parnali Chatterjee and Michael R. Franklin
Drug Metabolism and Disposition November 2003, 31 (11) 1391-1397; DOI: https://doi.org/10.1124/dmd.31.11.1391
Parnali Chatterjee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael R. Franklin
  • 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
Loading

Abstract

The concurrent use of herbal medicinals with prescription and over-the-counter drugs carries a risk for unanticipated adverse drug-botanical pharmacokinetic interactions, particularly as a result of cytochrome P450 (P450) inhibition. Extracts of goldenseal (Hydrastis canadensis) containing approximately equal concentrations (∼17 mM) of two methylenedioxyphenyl alkaloids, berberine and hydrastine, inhibited with increasing potency (CYP2C9) diclofenac 4′-hydroxylation, (CYP2D6) bufuralol 1′-hydroxylation, and (CYP3A4) testosterone 6β-hydroxylation activities in human hepatic microsomes. The inhibition of testosterone 6β-hydroxylation activity was noncompetitive with an apparent Ki of 0.11% extract. Of the methylenedioxyphenyl alkaloids, berberine (IC50 = 45 μM) was the more inhibitory toward bufuralol 1′-hydroxylation and hydrastine (IC50 ∼350 μM for both isomers), toward diclofenac 4′-hydroxylation. For testosterone 6β-hydroxylation, berberine was the least inhibitory component (IC50 ∼400 μM). Hydrastine inhibited testosterone 6β-hydroxylation with IC50 values for the (+)- and (-)-isomers of 25 and 30 μM, respectively. For (-)-hydrastine, an apparent Ki value of 18 μM without preincubation and an NADPH-dependent mechanism-based inhibition with a kinactivation of 0.23 min-1 and a KI of ∼110 μM were determined. Cytochrome P450 metabolic-intermediate (MI) complex formation could be demonstrated for both hydrastine isomers. With expressed P450 isoforms, hydrastine formed a P450 MI complex with CYP2C9, CYP2D6, and CYP3A4. Coexpression of cytochrome b5 with the P450 isoforms enhanced the rate but not the extent of P450 MI complex formation.

Footnotes

  • ↵1 Abbreviations used are: MDP, methylenedioxyphenyl; MI, metabolic-intermediate; P450, cytochrome P450; HPLC, high-performance liquid chromatography; TFA, trifluoroacetic acid.

    • Received April 3, 2003.
    • Accepted August 18, 2003.
  • 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: 31 (11)
Drug Metabolism and Disposition
Vol. 31, Issue 11
1 Nov 2003
  • Table of Contents
  • About the Cover
  • Index by author
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.
HUMAN CYTOCHROME P450 INHIBITION AND METABOLIC-INTERMEDIATE COMPLEX FORMATION BY GOLDENSEAL EXTRACT AND ITS METHYLENEDIOXYPHENYL COMPONENTS
(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

HUMAN CYTOCHROME P450 INHIBITION AND METABOLIC-INTERMEDIATE COMPLEX FORMATION BY GOLDENSEAL EXTRACT AND ITS METHYLENEDIOXYPHENYL COMPONENTS

Parnali Chatterjee and Michael R. Franklin
Drug Metabolism and Disposition November 1, 2003, 31 (11) 1391-1397; DOI: https://doi.org/10.1124/dmd.31.11.1391

Citation Manager Formats

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

Share
Research ArticleArticle

HUMAN CYTOCHROME P450 INHIBITION AND METABOLIC-INTERMEDIATE COMPLEX FORMATION BY GOLDENSEAL EXTRACT AND ITS METHYLENEDIOXYPHENYL COMPONENTS

Parnali Chatterjee and Michael R. Franklin
Drug Metabolism and Disposition November 1, 2003, 31 (11) 1391-1397; DOI: https://doi.org/10.1124/dmd.31.11.1391
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Metabolic enzymes in nintedanib metabolism
  • Mechanism of AO Inactivation by Hydralazine
  • Warfarin PBPK modeling with target binding
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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics