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

Mechanistic Studies on the Absorption and Disposition of Scutellarin in Humans: Selective OATP2B1-Mediated Hepatic Uptake Is a Likely Key Determinant for Its Unique Pharmacokinetic Characteristics

Chunying Gao, Hongjian Zhang, Zitao Guo, Tiangeng You, Xiaoyan Chen and Dafang Zhong
Drug Metabolism and Disposition October 2012, 40 (10) 2009-2020; DOI: https://doi.org/10.1124/dmd.112.047183
Chunying Gao
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (C.G., X.C., Z.G., D.Z.); College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China (H.Z.); and Shanghai East Hospital, Shanghai, China (T.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hongjian Zhang
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (C.G., X.C., Z.G., D.Z.); College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China (H.Z.); and Shanghai East Hospital, Shanghai, China (T.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zitao Guo
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (C.G., X.C., Z.G., D.Z.); College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China (H.Z.); and Shanghai East Hospital, Shanghai, China (T.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tiangeng You
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (C.G., X.C., Z.G., D.Z.); College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China (H.Z.); and Shanghai East Hospital, Shanghai, China (T.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaoyan Chen
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (C.G., X.C., Z.G., D.Z.); College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China (H.Z.); and Shanghai East Hospital, Shanghai, China (T.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dafang Zhong
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (C.G., X.C., Z.G., D.Z.); College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China (H.Z.); and Shanghai East Hospital, Shanghai, China (T.Y.)
  • 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

Scutellarin [scutellarein-7-O-glucuronide (S-7-G)] displayed a unique pharmacokinetic profile in humans after oral administration: the original compound was hardly detected, whereas its isomeric metabolite isoscutellarin [scutellarein-6-O-glucuronide (S-6-G)] had a markedly high exposure. Previous rat study revealed that S-7-G and S-6-G in the blood mainly originated from their aglycone in enterocytes, and that the S-7-G/S-6-G ratio declined dramatically because of a higher hepatic elimination of S-7-G. In the present study, metabolite profiling in human excreta demonstrated that the major metabolic pathway for S-6-G and S-7-G was through further glucuronidation. To further understand the cause for the exposure difference between S-7-G and S-6-G in humans, studies were conducted to uncover mechanisms underlying their formation and elimination. In vitro metabolism study suggested that S-7-G was formed more easily but metabolized more slowly in human intestinal and hepatic microsomes. Efflux transporter study showed that S-6-G and S-7-G were good substrates of breast cancer resistance protein and multidrug resistance-associated protein (MRP) 2 and possible substrates of MRP3; however, there was no preference great enough to alter the S-7-G/S-6-G ratio in the blood. Among the major hepatic anion uptake transporters, organic anion-transporting polypeptide (OATP) 2B1 played a predominant role in the hepatic uptake of S-6-G and S-7-G and showed greater preference for S-7-G with higher affinity than S-6-G (Km values were 1.77 and 43.9 μM, respectively). Considering the low intrinsic permeability of S-6-G and S-7-G and the role of OATP2B1 in the hepatic clearance of such compounds, the selective hepatic uptake of S-7-G mediated by OATP2B1 is likely a key determinant for the much lower systemic exposure of S-7-G than S-6-G in humans.

Footnotes

  • This work was supported by the National Natural Science Foundation of China [Grants 30271525, 81173117].

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

    http://dx.doi.org/10.1124/dmd.112.047183.

  • ABBREVIATIONS:

    S-7-G
    scutellarin, scutellarein-7-O-glucuronide
    S-6-G
    isoscutellarin, scutellarein-6-O-glucuronide
    HPLC
    high-performance liquid chromatography
    HLM
    human liver microsomes
    HIM
    human intestinal microsomes
    RLM
    rat liver microsomes
    UGT
    UDP-glucuronosyltransferase
    MRP
    multidrug resistance-associated protein
    BCRP
    breast cancer resistance protein
    HBSS
    Hanks' balanced salt solution
    HEK
    human embryonic kidney
    OATP
    organic anion-transporting polypeptide
    OAT
    organic anion transporter
    RIM
    rat intestinal microsomes
    MDR
    multidrug resistance protein
    UPLC
    ultraperformance liquid chromatography
    TOF
    time of flight
    MS
    mass spectrometry
    LC-MS/MS
    liquid chromatography/tandem mass spectrometry
    E2-17β-G
    estradiol-17β-d-glucuronide
    CE
    collision energy
    S-6,7-diG
    scutellarein-6,7-diglucuronide
    GlcUA
    glucuronic acid.

  • Received June 11, 2012.
  • Accepted July 20, 2012.
  • Copyright © 2012 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: 40 (10)
Drug Metabolism and Disposition
Vol. 40, Issue 10
1 Oct 2012
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • 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.
Mechanistic Studies on the Absorption and Disposition of Scutellarin in Humans: Selective OATP2B1-Mediated Hepatic Uptake Is a Likely Key Determinant for Its Unique Pharmacokinetic Characteristics
(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

ABSORPTION AND DISPOSITION OF SCUTELLARIN IN HUMANS

Chunying Gao, Hongjian Zhang, Zitao Guo, Tiangeng You, Xiaoyan Chen and Dafang Zhong
Drug Metabolism and Disposition October 1, 2012, 40 (10) 2009-2020; DOI: https://doi.org/10.1124/dmd.112.047183

Citation Manager Formats

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

Share
Research ArticleArticle

ABSORPTION AND DISPOSITION OF SCUTELLARIN IN HUMANS

Chunying Gao, Hongjian Zhang, Zitao Guo, Tiangeng You, Xiaoyan Chen and Dafang Zhong
Drug Metabolism and Disposition October 1, 2012, 40 (10) 2009-2020; DOI: https://doi.org/10.1124/dmd.112.047183
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
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • PK Interactions of Licorice with Cytochrome P450s
  • Biotransformation of Trastuzumab and Pertuzumab
  • Humanized CYP3A Mice Without Endogenous Mouse CYP2C Enzymes
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