Deglycosylation of liquiritin strongly enhances its inhibitory potential towards UDP-glucuronosyltransferase (UGT) isoforms. 2013

Bin Guo, and Xu-Ran Fan, and Zhong-Ze Fang, and Yun-Feng Cao, and Cui-Min Hu, and Julin Yang, and Yan-Yan Zhang, and Rong-Rong He, and Xu Zhu, and Zhen-Wen Yu, and Xiao-Yu Sun, and Mo Hong, and Lu Yang
The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China. Guobin@163.com

The detailed mechanisms on licorice-drug interaction remain to be unclear. The aim of the present study is to investigate the inhibition of important UGT isoforms by two important ingredients of licorice, liquiritin, and liquiritigenin. The results showed that liquiritigenin exhibited stronger inhibition towards all the tested UGT isoforms than liquiritin. Data fitting using Dixon and Lineweaver-Burk plots demonstrated the competitive inhibition of liquiritigenin towards UGT1A1 and UGT1A9-mediated 4-MU glucuronidation reaction. The inhibition kinetic parameters (Ki ) were calculated to be 9.1 and 3.2 μM for UGT1A1 and UGT1A9, respectively. Substrate-dependent inhibition behaviour was also observed for UGT1A1 in the present study. All these results will be helpful for understanding the deep mechanism of licorice-drug interaction. However, when translating these in vitro parameters into in vivo situations, more complex factors should be considered, such as substrate-dependent inhibition of UGT isoforms, the contribution of UGT1A1 and UGT1A9 towards the metabolism of drugs, and many factors affecting the abundance of ingredients in the licorice.

UI MeSH Term Description Entries
D007527 Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D007700 Kinetics The rate dynamics in chemical or physical systems.
D005960 Glucosides A GLYCOSIDE that is derived from GLUCOSE. Glucoside
D006035 Glycyrrhiza A genus of leguminous herbs or shrubs whose roots yield GLYCYRRHETINIC ACID and its derivative, CARBENOXOLONE. Licorice,Glycyrrhiza glabra,Liquorice,Licorices,Liquorices
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006923 Hymecromone A coumarin derivative possessing properties as a spasmolytic, choleretic and light-protective agent. It is also used in ANALYTICAL CHEMISTRY TECHNIQUES for the determination of NITRIC ACID. Imecromone,Methylumbelliferone,Resocyanine,4-Methylumbelliferone,7-Hydroxy-4-methyl-coumarin,Cholestil,Mendiaxon,4 Methylumbelliferone,7 Hydroxy 4 methyl coumarin
D000090264 UDP-Glucuronosyltransferase 1A9 A PPAR alpha and PPAR gamma target gene. The enzyme plays an important role in elimination and DETOXIFICATION of drugs, XENOBIOTICS, and metabolizing endogenous compounds, including CATECHOLESTROGENS and FIBRATES. UDP-Glucuronosyltransferase, UGT1A9,UGT1A9 Protein,Uridine Diphosphate-Glucuronosyltransferase 1A9,1A9, UDP-Glucuronosyltransferase,1A9, Uridine Diphosphate-Glucuronosyltransferase,Protein, UGT1A9,UDP Glucuronosyltransferase, UGT1A9,UGT1A9 UDP-Glucuronosyltransferase
D014453 Glucuronosyltransferase A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17. Glucuronyltransferase,UDP Glucuronosyltransferase,17 beta-Hydroxysteroid UDP-Glucuronosyltransferase,4-Nitrophenol-UDP-Glucuronosyltransferase,7-Hydroxycoumarin UDP Glucuronyltransferase,Androsterone UDP-Glucuronosyltransferase,Bilirubin UDP-Glucuronyltransferase,Estrogen UDP-Glucuronosyltransferase,Estrone Glucuronyltransferase,Glucuronic Transferase,Morphine Glucuronyltransferase,UDP Glucuronyl Transferase,UDP-Glucuronic Acid 3-O-beta-D-Galactosyl-D-Galactose Glucuronosyltransferase,p-Nitrophenyl UDP-Glucuronosyltransferase,17 beta Hydroxysteroid UDP Glucuronosyltransferase,4 Nitrophenol UDP Glucuronosyltransferase,7 Hydroxycoumarin UDP Glucuronyltransferase,Androsterone UDP Glucuronosyltransferase,Bilirubin UDP Glucuronyltransferase,Estrogen UDP Glucuronosyltransferase,Glucuronosyltransferase, UDP,Glucuronyl Transferase, UDP,Glucuronyltransferase, 7-Hydroxycoumarin UDP,Glucuronyltransferase, Estrone,Glucuronyltransferase, Morphine,Transferase, Glucuronic,Transferase, UDP Glucuronyl,UDP Glucuronic Acid 3 O beta D Galactosyl D Galactose Glucuronosyltransferase,UDP Glucuronyltransferase, 7-Hydroxycoumarin,UDP-Glucuronosyltransferase, 17 beta-Hydroxysteroid,UDP-Glucuronosyltransferase, Androsterone,UDP-Glucuronosyltransferase, Estrogen,UDP-Glucuronosyltransferase, p-Nitrophenyl,UDP-Glucuronyltransferase, Bilirubin,p Nitrophenyl UDP Glucuronosyltransferase
D044950 Flavanones A group of FLAVONOIDS characterized with a 4-ketone. 2-Phenyl-Benzopyran-4-Ones,2 Phenyl Benzopyran 4 Ones
D018565 Food-Drug Interactions The pharmacological result, either desirable or undesirable, of drugs interacting with components of the diet. (From Stedman, 25th ed) Drug-Food Interactions,Food Interactions,Drug Food Interactions,Drug-Food Interaction,Food Drug Interactions,Food Interaction,Food-Drug Interaction,Interaction, Drug-Food,Interaction, Food,Interaction, Food-Drug,Interactions, Drug-Food,Interactions, Food,Interactions, Food-Drug

Related Publications

Bin Guo, and Xu-Ran Fan, and Zhong-Ze Fang, and Yun-Feng Cao, and Cui-Min Hu, and Julin Yang, and Yan-Yan Zhang, and Rong-Rong He, and Xu Zhu, and Zhen-Wen Yu, and Xiao-Yu Sun, and Mo Hong, and Lu Yang
September 2012, Die Pharmazie,
Bin Guo, and Xu-Ran Fan, and Zhong-Ze Fang, and Yun-Feng Cao, and Cui-Min Hu, and Julin Yang, and Yan-Yan Zhang, and Rong-Rong He, and Xu Zhu, and Zhen-Wen Yu, and Xiao-Yu Sun, and Mo Hong, and Lu Yang
December 2015, Chirality,
Bin Guo, and Xu-Ran Fan, and Zhong-Ze Fang, and Yun-Feng Cao, and Cui-Min Hu, and Julin Yang, and Yan-Yan Zhang, and Rong-Rong He, and Xu Zhu, and Zhen-Wen Yu, and Xiao-Yu Sun, and Mo Hong, and Lu Yang
August 2012, Die Pharmazie,
Bin Guo, and Xu-Ran Fan, and Zhong-Ze Fang, and Yun-Feng Cao, and Cui-Min Hu, and Julin Yang, and Yan-Yan Zhang, and Rong-Rong He, and Xu Zhu, and Zhen-Wen Yu, and Xiao-Yu Sun, and Mo Hong, and Lu Yang
April 2015, Die Pharmazie,
Bin Guo, and Xu-Ran Fan, and Zhong-Ze Fang, and Yun-Feng Cao, and Cui-Min Hu, and Julin Yang, and Yan-Yan Zhang, and Rong-Rong He, and Xu Zhu, and Zhen-Wen Yu, and Xiao-Yu Sun, and Mo Hong, and Lu Yang
September 2013, Phytotherapy research : PTR,
Bin Guo, and Xu-Ran Fan, and Zhong-Ze Fang, and Yun-Feng Cao, and Cui-Min Hu, and Julin Yang, and Yan-Yan Zhang, and Rong-Rong He, and Xu Zhu, and Zhen-Wen Yu, and Xiao-Yu Sun, and Mo Hong, and Lu Yang
July 2016, Phytotherapy research : PTR,
Bin Guo, and Xu-Ran Fan, and Zhong-Ze Fang, and Yun-Feng Cao, and Cui-Min Hu, and Julin Yang, and Yan-Yan Zhang, and Rong-Rong He, and Xu Zhu, and Zhen-Wen Yu, and Xiao-Yu Sun, and Mo Hong, and Lu Yang
March 2015, Chirality,
Bin Guo, and Xu-Ran Fan, and Zhong-Ze Fang, and Yun-Feng Cao, and Cui-Min Hu, and Julin Yang, and Yan-Yan Zhang, and Rong-Rong He, and Xu Zhu, and Zhen-Wen Yu, and Xiao-Yu Sun, and Mo Hong, and Lu Yang
March 2014, Phytotherapy research : PTR,
Bin Guo, and Xu-Ran Fan, and Zhong-Ze Fang, and Yun-Feng Cao, and Cui-Min Hu, and Julin Yang, and Yan-Yan Zhang, and Rong-Rong He, and Xu Zhu, and Zhen-Wen Yu, and Xiao-Yu Sun, and Mo Hong, and Lu Yang
February 2008, Drug metabolism and disposition: the biological fate of chemicals,
Bin Guo, and Xu-Ran Fan, and Zhong-Ze Fang, and Yun-Feng Cao, and Cui-Min Hu, and Julin Yang, and Yan-Yan Zhang, and Rong-Rong He, and Xu Zhu, and Zhen-Wen Yu, and Xiao-Yu Sun, and Mo Hong, and Lu Yang
September 2016, Toxicology letters,
Copied contents to your clipboard!