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 Gambogic Acid in Rats: A Rare Intestinal Metabolic Pathway Responsible for Its Final Disposition

Jing Yang, Li Ding, Linlin Hu, Wenjuan Qian, Shaohong Jin, Xiaoping Sun, Zhenzhong Wang and Wei Xiao
Drug Metabolism and Disposition April 2011, 39 (4) 617-626; DOI: https://doi.org/10.1124/dmd.110.037044
Jing Yang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Li Ding
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Linlin Hu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wenjuan Qian
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shaohong Jin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaoping Sun
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhenzhong Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wei Xiao
  • 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

Gambogic acid (GA) is a promising natural anticancer candidate. Although the anticancer activity of GA has been well demonstrated, information regarding the metabolic fate of GA is limited. Previous studies suggested that GA is mainly excreted into intestinal tract in rats through bile after intravenous administration, whereas only traces appeared in the feces, suggesting that GA is metabolized extensively in the intestine. However, there has been no report about the intestinal metabolism of GA either in animals or humans. In this study, large amounts of two sulfonic acid metabolites of GA were found in the feces samples of rats after intravenous administration, and their structures were identified as 10-α sulfonic acid GA and 10-β sulfonic acid GA by comparison of the retention times and spectral data with those of synthesized reference substances using liquid chromatography-diode array detector-tandem mass spectrometry. This rare intestinal metabolic pathway mainly involves Michael addition of the sulfite ion to the 9,10 carbon–carbon double bond of α,β-unsaturated ketone. In addition, a more detailed metabolic profile in rats is proposed, according to the results of in vitro and in vivo studies. It was found that GA can be metabolized by a variety of routes, including monooxidation, hydration, glutathionylation, glucuronidation, and glucosidation in the liver of rats. These findings provide information on the major metabolic soft spot of GA in the intestine and liver of rats, which is not only useful in the future human metabolic study of this compound but also of value in the metabolic studies of GA analogs.

Footnotes

  • This work was supported by the National Natural Science Foundation of China [Grant 81072609].

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

    doi:10.1124/dmd.110.037044.

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

  • ABBREVIATIONS:

    GA
    gambogic acid
    UDPGA
    UDP-glucuronic acid
    RLM
    rat liver microsome
    HPLC
    high-performance liquid chromatography
    10-α SGA
    10-α sulfonic acid GA
    10-β SGA
    10-β sulfonic acid GA
    MS
    mass spectrometry
    10-GGA
    10-glutathionyl GA
    P450
    cytochrome P450
    GST
    glutathione transferase
    LC
    liquid chromatography
    MS/MS
    tandem mass spectrometry
    DAD
    diode array detector
    ESI
    electrospray ionization
    CID
    collision-induced dissociation
    NOESY
    nuclear Overhauser effect spectroscopy
    SULT
    sulfotransferase
    S-23121
    N-[4-chloro-2-fluoro-5-[(1-methyl-2-propynyl)oxy]phenyl]-3,4,5,6-tetrahydrophthalimide.

  • Received November 5, 2010.
  • Accepted December 29, 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.
Metabolism of Gambogic Acid in Rats: A Rare Intestinal Metabolic Pathway Responsible for Its Final Disposition
(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 Gambogic Acid in Rats: A Rare Intestinal Metabolic Pathway Responsible for Its Final Disposition

Jing Yang, Li Ding, Linlin Hu, Wenjuan Qian, Shaohong Jin, Xiaoping Sun, Zhenzhong Wang and Wei Xiao
Drug Metabolism and Disposition April 1, 2011, 39 (4) 617-626; DOI: https://doi.org/10.1124/dmd.110.037044

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 Gambogic Acid in Rats: A Rare Intestinal Metabolic Pathway Responsible for Its Final Disposition

Jing Yang, Li Ding, Linlin Hu, Wenjuan Qian, Shaohong Jin, Xiaoping Sun, Zhenzhong Wang and Wei Xiao
Drug Metabolism and Disposition April 1, 2011, 39 (4) 617-626; DOI: https://doi.org/10.1124/dmd.110.037044
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

  • Warfarin PBPK Model with TMDD Mechanism
  • Identification of payload-containing catabolites of ADCs
  • PK Interactions of Licorice with Cytochrome P450s
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