Probe substrate and enzyme source-dependent inhibition of UDP-glucuronosyltransferase (UGT) 1A9 by wogonin
Abstract
Background: Drug-metabolizing enzymes (DMEs) inhibition based drug-drug interaction and herb-drug interaction severely challenge the R&D process of drugs or herbal ingredients.
Objective: To evaluate the inhibition potential of wogonin (an important flavonoid isolated from the root of Scutellaria baicalensis) towards one of the most important phase II DMEs, UDP-glucuronosyltransferase (UGT) 1A9.
Methods: Both recombinant UGT1A9-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and human liver microsomes (HLMs)-catalyzed propofol glucuronidation reaction were used as two different probe reactions.
Results: Wogonin noncompetitively inhibited recombinant UGT1A9-catalyzed 4-MU glucuronidation, and exerted competitive inhibition towards HLMs-catalyzed propofol glucuronidation. The inhibition kinetic parameters (Ki) were calculated to be 3.2 ìM and 52.0ìM, respectively.
Conclusion: Necessary monitoring was needed when wogonin was co-administered with the clinical drugs mainly undergoing UGT1A9-mediated glucuronidation elimination. Additionally, probe reactions-dependent inhibition of wogonin towards the activity of UGT1A9 should be paid attention when translating these in vitro data into in vivo situation.
Keywords: wogonin, drug-drug interaction (DDI), UDP-glucuronosyltransferases (UGTs)
While African Health Sciences has been freely accessible online there have been questions on whether it is Open Access or not. We wish to clearly state that indeed African Health Sciences is Open Access. There are key issues regarding Open Access needing clarification for avoidance of doubt:
- 1. Henceforth, papers in African Health Sciences will be published under the CC BY (Creative Commons Attribution License) 4.0 International. See details on https://creativecomons.org/)
- 2. The copyright owners or the authors grant the 3rd party (perpetually and in advance) the right to disseminate, reproduce, or use the research papers in part or in full, format/medium as long as:
- No substantive errors are introduced in the process
- Attribution of authorship and correct citation details are given
- The referencing details are not changed.
Should the papers be reproduced in part, this must be clearly stated.
- 3. The papers will be freely and universally accessible online in an easily readable format such as XML in at least one widely recognized open access repository such as PUBMED CENTRAL.
B. ABRIDGED LICENCE AGREEMENT BETWEEN AUTHORS AND African Health Sciences
I submitted my manuscript to African Health Sciences and would like to affirm that:
1.0 I am authorized by my co-authors to enter into these arrangements.
2.0 I guarantee, on behalf of self and co-authors:
- That the paper is original, and has not been published in any other peer-reviewed journal; nor is it under consideration by other journal (s). It does not infringe existing copyright or any other person’s rights
- That we are/I am the sole author(s) of the paper and with authority to enter into this agreement. My granting rights to African Health Sciences is not in breach of any other obligation
- That the paper contains nothing unlawful, or libelous. Nor anything that would constitute a breach of contract, confidence or commitment given to secrecy, if published
- That I/we have taken care to ensure the integrity of the article.
3.0 I and all co-authors, agree that the paper, if accepted for publication, shall be licensed under the Creative Commons Attribution License 4.0. (see https://creativecommons.org/)
