A tea catechin, epigallocatechin-3-gallate, is a unique modulator of the farnesoid X receptor
dc.contributor.author | Li, Guodong | |
dc.contributor.author | Lin, Wenwei | |
dc.contributor.author | Araya, Juan Jose | |
dc.contributor.author | Chen, Taosheng | |
dc.contributor.author | Timmermann, Barbara N. | |
dc.contributor.author | Guo, Grace L. | |
dc.date.accessioned | 2017-04-17T20:36:49Z | |
dc.date.available | 2017-04-17T20:36:49Z | |
dc.date.issued | 2012-12-04 | |
dc.identifier.citation | Li, Guodong et al. “A Tea Catechin, Epigallocatechin-3-Gallate, Is a Unique Modulator of the Farnesoid X Receptor.” Toxicology and Applied Pharmacology 258.2 (2012): 268–274. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23718 | |
dc.description.abstract | Farnesoid X receptor (FXR) is a ligand-activated nuclear receptor and serves as a key regulator to maintain health of the liver and intestine. Bile acids are endogenous ligands of FXR, and there are increasing efforts to identify FXR modulators to serve as biological probes and/or pharmaceutical agents. Natural FXR ligands isolated from plants may serve as models to synthesize novel FXR modulators. In this study, we demonstrated that epigallocatechin-3-gallate (EGCG), a major tea catechin, specifically and dose-dependently activates FXR. In addition, EGCG induced FXR target gene expression in vitro. Surprisingly, in a co-activator (SRC2) recruitment assay, we found that EGCG does not recruit SRC2 to FXR, but it dose-dependently inhibits recruitment of SRC2 to FXR (IC50, 1 μM) by GW6064, which is a potent FXR synthetic ligand. In addition, EGCG suppressed FXR target gene expression induced by either GW4064 or chenodeoxycholic acid in vitro. Furthermore, wild-type and FXR knockout mice treated with an acute dose of EGCG had induced mRNA expression in a subset of FXR target genes in the intestine but not in the liver. In conclusion, EGCG is a unique modulator of FXR in the intestine and may serve as an important model for future development of FXR modulators. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
dc.subject | Farnesoid x receptor | en_US |
dc.subject | Epigallocatechin-3-gallate | en_US |
dc.subject | Nuclear receptor | en_US |
dc.subject | Tea catechin | en_US |
dc.subject | Modulator | en_US |
dc.subject | Mice | en_US |
dc.title | A tea catechin, epigallocatechin-3-gallate, is a unique modulator of the farnesoid X receptor | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Timmerman, Barbara N. | |
kusw.kudepartment | Medicinal Chemistry | en_US |
dc.identifier.doi | 10.1016/j.taap.2011.11.006 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0003-4525-7291 | |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess |
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Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.