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

Metabolism of Ebracteolata Compound B Studied In Vitro with Human Liver Microsomes, HepG2 Cells, and Recombinant Human Enzymes

Xia Zhang, Yan Yao, Yan Lou, Huidi Jiang, Xiaowen Wang, Xiaojuan Chai and Su Zeng
Drug Metabolism and Disposition December 2010, 38 (12) 2157-2165; DOI: https://doi.org/10.1124/dmd.110.034496
Xia Zhang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yan Yao
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yan Lou
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Huidi Jiang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaowen Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaojuan Chai
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Su Zeng
  • 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

Ebracteolata compound B (ECB) is one major active component of both Euphorbia ebracteolata and Euphorbia fischeriana, which have been extensively used as a tuberculocide in the Asian countries. The aim of our present study was to characterize ECB metabolism in human liver microsomes, HepG2 cells, and recombinant human enzymes. One monohydroxylation metabolite, determined by mass spectrometry to be 1-(2,4-dihydroxy-6-methoxy-3-methylphenyl)-2-hydroxyethanone, and one monoglucuronide, isolated and determined by hydrolysis with β-glucuronidase, mass spectrometry, and 1H NMR to be 2-hydroxy-6-methoxy-3-methyl-acetophenone-4-O-β-glucuronide, were observed in human liver microsomal incubates in the presence of NADPH or UDP-glucuronic acid (UDPGA), respectively. However, the mixed incubation of ECB with human liver microsomes in the presence of both NADPH and UDPGA showed the monoglucuronide to be the most major metabolite, indicating that glucuronidation was probably the major clearance pathway of ECB in humans. No glucuronide and only trace monohydroxylation metabolite were observed in HepG2 cells. The cytochrome P450 and UDP-glucuronosyltransferase (UGT) isoenzymes were identified by using selective chemical inhibition and recombinant human enzymes. The results indicated that CYP3A4 was probably involved in ECB oxidative metabolism and UGT1A6 and UGT1A9 were important catalytic enzymes in ECB glucuronidation. The results from enzymatic kinetic analysis showed the oxidative metabolism in human liver microsomes; the glucuronidation in human liver microsomes and recombinant UGT1A6 exhibited a typical Michaelis-Menten pattern, but the glucuronidation in UGT1A9 exhibited a substrate inhibition pattern. UGT1A6 had the highest affinity compared with human liver microsomes and UGT1A9, indicating its important role in ECB glucuronidation.

Footnotes

  • This work was supported by the National Major Special Project for Science and Technology Development of Ministry of Science and Technology of China [2009ZX09304-003]; and the National Science Foundation for Post-doctoral Scientists of China [20090461391].

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

    doi:10.1124/dmd.110.034496.

  • ABBREVIATIONS:

    XDR
    drug-resistant
    TB
    tuberculosis
    ECB
    ebracteolata compound B
    P450
    cytochrome P450
    UGT
    UGP glucuronosyltransferase
    HPLC
    high-performance liquid chromatography
    UPLC
    ultraperformance liquid chromatography
    MS
    mass spectrometry
    ESI
    electrospray ionization
    PCR
    polymerase chain reaction
    UDPGA
    UCP-glucuronic acid
    MTT
    3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide
    PBS
    phosphate-buffered saline
    DMSO
    dimethyl sulfoxide
    SIR
    selected ion recording
    MS/MS
    tandem mass spectrometry.

  • Received May 14, 2010.
  • Accepted September 13, 2010.
  • Copyright © 2010 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: 38 (12)
Drug Metabolism and Disposition
Vol. 38, Issue 12
1 Dec 2010
  • 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.
Metabolism of Ebracteolata Compound B Studied In Vitro with Human Liver Microsomes, HepG2 Cells, and Recombinant Human Enzymes
(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

Metabolism of Ebracteolata Compound B Studied In Vitro with Human Liver Microsomes, HepG2 Cells, and Recombinant Human Enzymes

Xia Zhang, Yan Yao, Yan Lou, Huidi Jiang, Xiaowen Wang, Xiaojuan Chai and Su Zeng
Drug Metabolism and Disposition December 1, 2010, 38 (12) 2157-2165; DOI: https://doi.org/10.1124/dmd.110.034496

Citation Manager Formats

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

Share
Research ArticleArticle

Metabolism of Ebracteolata Compound B Studied In Vitro with Human Liver Microsomes, HepG2 Cells, and Recombinant Human Enzymes

Xia Zhang, Yan Yao, Yan Lou, Huidi Jiang, Xiaowen Wang, Xiaojuan Chai and Su Zeng
Drug Metabolism and Disposition December 1, 2010, 38 (12) 2157-2165; DOI: https://doi.org/10.1124/dmd.110.034496
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • Mass Balance Recovery and Disposition of AZD4831 in Humans
  • Biotransformation of AZD4831 in Animals and Humans
  • AKRs and GUSs in Testosterone Disposition
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