Simple jQuery Dropdowns
Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/31231
Title: Identification of three novel natural product compounds that activate PXR and CAR and inhibit inflammation
Authors: Suticha Kittayaruksakul
Wenchen Zhao
Meishu Xu
Songrong Ren
Jing Lu
Ju Wang
Michael Downes
Ronald M. Evans
Raman Venkataramanan
Varanuj Chatsudthipong
Wen Xie
Mahidol University
University of Pittsburgh
Capital Medical University China
Salk Institute for Biological Studies
Keywords: Biochemistry, Genetics and Molecular Biology;Chemistry;Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Sep-2013
Citation: Pharmaceutical Research. Vol.30, No.9 (2013), 2199-2208
Abstract: Purpose: To investigate the effects of three natural product compounds, carapin, santonin and isokobusone, on the activity of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in induction of drug-metabolizing enzymes and inhibition of inflammation. Methods: The monkey kidney-derived fibroblast (CV-1) cells and human embryonic kidney HEK293 cells were used for transient transfection and luciferase reporter gene assays. Human primary hepatocytes and primary hepatocytes from wild type, PXR-/-, and hPXR transgenic mice were used to study the induction of drug-metabolizing enzymes and the implication of these compounds in inflammation. Results: Carapin, santonin and isokobusone activated both PXR and CAR in transient transfection and luciferase reporter gene assays. Mutagenesis studies showed that two amino acid residues, Phe305 of the rodent PXR and Leu308 of the human PXR, are critical for the recognition of these compounds by PXR. Importantly, the activation of PXR and CAR by these compounds induced the expression of drug-metabolizing enzymes in primary human and mouse hepatocytes. Furthermore, activation of PXR by these compounds inhibited the expression of inflammatory mediators in response to lipopolysaccharide (LPS). The effects of these natural compounds on drug metabolism and inflammation were abolished in PXR-/- hepatocytes. Conclusions: Our results show that carapin, santonin and isokobusone activate PXR and CAR and induce drug-metabolizing enzymes. In addition, these compounds inhibited the expression of inflammatory mediators in response to LPS through the activation of PXR. © 2013 Springer Science+Business Media New York.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84883278321&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/31231
ISSN: 1573904X
07248741
Appears in Collections:Scopus 2011-2015

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.