Next Article in Journal
Insights into Structure-Activity Relationships of 3-Arylhydrazonoindolin-2-One Derivatives for Their Multitarget Activity on β-Amyloid Aggregation and Neurotoxicity
Previous Article in Journal
Design, Synthesis and Biological Evaluation of 6,7-Disubstituted-4-phenoxyquinoline Derivatives Bearing Pyridazinone Moiety as c-Met Inhibitors
Open AccessArticle

Hepatic Metabolism of Sakuranetin and Its Modulating Effects on Cytochrome P450s and UDP-Glucuronosyltransferases

1
Graduate School of Biological Sciences, Sookmyung Women’s University, Seoul 04310, Korea
2
Department of Biological Sciences and Research Institute of Women’s Health, Sookmyung Women’s University, Seoul 04310, Korea
3
Center for Research and Development of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
4
College of Pharmacy, Sookmyung Women’s University, Seoul 04310, Korea
*
Author to whom correspondence should be addressed.
Molecules 2018, 23(7), 1542; https://doi.org/10.3390/molecules23071542
Received: 18 May 2018 / Revised: 19 June 2018 / Accepted: 23 June 2018 / Published: 26 June 2018
Sakuranetin (SKN), found in cherry trees and rice, is a flavanone with various pharmacological activities. It is biosynthesized from naringenin in rice or cherry trees, and the metabolism of SKN has been studied in non-human species. The present study aimed to investigate the metabolic pathways of SKN in human liver microsomes and identify the phase I and phase II metabolites, as well as evaluate the potential for drug–herb interactions through the modulation of drug metabolizing enzymes (DMEs). HPLC-DAD and HPLC-electrospray mass spectrometry were used to study the metabolic stability and identify the metabolites from human liver microsomes incubated with SKN. The potential of SKN to inhibit the DMEs was evaluated by monitoring the formation of a DME-specific product. The cytochrome P450 2B6 and 3A4-inductive effects were studied using promoter reporter assays in human hepatocarcinoma cells. The major pathways for SKN metabolism include B-ring hydroxylation, 5-O-demethylation, and conjugation with glutathione or glucuronic acid. The phase I metabolites were identified as naringenin and eriodictyol. SKN was found to be a UDP-glucuronosyltransferases (UGT) 1A9 inhibitor, whereas it induced transactivation of the human pregnane X receptor-mediated cytochrome P450 (CYP) 3A4 gene. View Full-Text
Keywords: sakuranetin; flavanone; drug metabolism; cytochrome P450; UDP glucuronosyltransferase; drug-herb interaction; metabolic interconversion sakuranetin; flavanone; drug metabolism; cytochrome P450; UDP glucuronosyltransferase; drug-herb interaction; metabolic interconversion
Show Figures

Figure 1

MDPI and ACS Style

Jeong, H.; Lee, J.; Kim, S.; Yeo, Y.Y.; So, H.; Wu, H.; Song, Y.S.; Jang, C.-Y.; Kim, H.-D.; Kim, M.J.; Chang, M. Hepatic Metabolism of Sakuranetin and Its Modulating Effects on Cytochrome P450s and UDP-Glucuronosyltransferases. Molecules 2018, 23, 1542.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop