Cheng, Anqi
(2023)
Novel Insights into Licorice-Induced Side Effects.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Background and aims: The herbal supplement licorice, also known as Gancao, belongs to the genus Glycyrrhiza and has been used worldwide for its hepatoprotective effect. Recent studies have raised concerns about potential herb-drug interactions associated with licorice via pregnane X receptor (PXR)-mediated induction of hepatic cytochrome P450 3A4 (CYP3A4). The current work aimed to determine the phytochemicals in licorice that activate PXR and induce CYP3A4.
Methods: DPX2 cells were used for cell-based PXR reporter assays. The phytochemicals in licorice extract were identified using a metabolomics approach. The effects of PXR activators identified from in vitro studies were further investigated in PXR- and CYP3A4-humanized mouse models.
Results: Licorice was verified to be a PXR-activating herb. Two major phytochemicals in licorice, glycyrrhizin (GZ) and glycyrrhetinic acid (GA), did not activate PXR in the cell-based reporter assays. However, glabridin was shown to activate PXR in a dose-dependent manner. In vivo studies confirmed that GZ is not a PXR activator and glabridin is a weak PXR activator. Although GA did not active PXR in vitro, it induced CYP3A4 expression in a PXR-dependent manner in the PXR- and CYP3A4-humanized mice.
Conclusions: GZ is not a PXR activator. GA could not activate PXR in cell-based reporter assays but it could activate PXR in vivo. Glabridin is a weak PXR activator. This work provides novel insights into the underlying mechanisms of licorice-related herb-drug interactions via PXR.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
3 May 2023 |
| Date Type: |
Publication |
| Defense Date: |
12 April 2023 |
| Approval Date: |
3 May 2023 |
| Submission Date: |
14 April 2023 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
33 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Licorice, glycyrrhizin, glycyrrhetinic acid (GA), glabridin, Pregnane X receptor (PXR), Cytochrome P450 3A4 (CYP3A4), Herb-drug interactions. |
| Date Deposited: |
03 May 2023 13:45 |
| Last Modified: |
03 May 2023 13:45 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/44555 |
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