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Novel Insights into Licorice-Induced Side Effects

Cheng, Anqi (2023) Novel Insights into Licorice-Induced Side Effects. Master's Thesis, University of Pittsburgh. (Unpublished)

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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Status: Unpublished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:
CreatorsEmailPitt UsernameORCID
Cheng, Anqianc315@pitt.eduanc315
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMa, Xiaochaomxiaocha@pitt.edumxiaocha
Committee MemberLi, Songsol4@pitt.edusol4
Committee MemberBrixius-Anderko, Simonesib51@pitt.edusib51
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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