Identification of UDP-glucuronosyltransferase isoforms responsible for leonurine glucuronidation in human liver and intestinal microsomes

Xenobiotica ◽  
2014 ◽  
Vol 44 (9) ◽  
pp. 775-784 ◽  
Author(s):  
Bo Tan ◽  
Weimin Cai ◽  
Jinlian Zhang ◽  
Ning Zhou ◽  
Guo Ma ◽  
...  
Keyword(s):  
Human Liver ◽  
Intestinal Microsomes ◽  
Udp Glucuronosyltransferase

scholarly journals Glucuronidation of hyodeoxycholic acid in human liver. Evidence for a selective role of UDP-glucuronosyltransferase 2B4.

1993 ◽  
Vol 268 (34) ◽  
pp. 25636-25642
Author(s):  
T Pillot ◽  
M Ouzzine ◽  
S Fournel-Gigleux ◽  
C Lafaurie ◽  
A Radominska ◽  
...  
Keyword(s):  
Human Liver ◽  
Hyodeoxycholic Acid ◽  
Udp Glucuronosyltransferase

scholarly journals Identification of Catalposide Metabolites in Human Liver and Intestinal Preparations and Characterization of the Relevant Sulfotransferase, UDP-glucuronosyltransferase, and Carboxylesterase Enzymes

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 355 ◽  
Author(s):  
Deok-Kyu Hwang ◽  
Ju-Hyun Kim ◽  
Yongho Shin ◽  
Won-Gu Choi ◽  
Sunjoo Kim ◽  
...  
Keyword(s):  
Human Liver ◽  
Individual Variability ◽  
Hydroxybenzoic Acid ◽  
Catalpa Ovata ◽  
Anti Oxidant ◽  
Extrahepatic Tissues ◽  
Udp Glucuronosyltransferase ◽  
Hydrolysis Of

Catalposide, an active component of Veronica species such as Catalpa ovata and Pseudolysimachion lingifolium, exhibits anti-inflammatory, antinociceptic, anti-oxidant, hepatoprotective, and cytostatic activities. We characterized the in vitro metabolic pathways of catalposide to predict its pharmacokinetics. Catalposide was metabolized to catalposide sulfate (M1), 4-hydroxybenzoic acid (M2), 4-hydroxybenzoic acid glucuronide (M3), and catalposide glucuronide (M4) by human hepatocytes, liver S9 fractions, and intestinal microsomes. M1 formation from catalposide was catalyzed by sulfotransferases (SULTs) 1C4, SULT1A1*1, SULT1A1*2, and SULT1E1. Catalposide glucuronidation to M4 was catalyzed by gastrointestine-specific UDP-glucuronosyltransferases (UGTs) 1A8 and UGT1A10; M4 was not detected after incubation of catalposide with human liver preparations. Hydrolysis of catalposide to M2 was catalyzed by carboxylesterases (CESs) 1 and 2, and M2 was further metabolized to M3 by UGT1A6 and UGT1A9 enzymes. Catalposide was also metabolized in extrahepatic tissues; genetic polymorphisms of the carboxylesterase (CES), UDP-glucuronosyltransferase (UGT), and sulfotransferase (SULT) enzymes responsible for catalposide metabolism may cause inter-individual variability in terms of catalposide pharmacokinetics.

UDP-glucuronosyltransferase activity in human liver and colon

1999 ◽  
Vol 116 (1) ◽  
pp. 149-160 ◽  
Author(s):  
Christian P. Strassburg ◽  
Nghia Nguyen ◽  
Michael P. Manns ◽  
Robert H. Tukey
Keyword(s):  
Human Liver ◽  
Udp Glucuronosyltransferase

scholarly journals Effect of a New Prokinetic Agent DA-9701 Formulated with Corydalis Tuber and Pharbitidis Semen on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Hye Young Ji ◽  
Kwang Hyeon Liu ◽  
Ji Hyeon Jeong ◽  
Dae-Young Lee ◽  
Hyun Joo Shim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Udp Glucuronosyltransferase ◽  
Index Value ◽  
Tuber Extract ◽  
Corydalis Tuber

DA-9701 is a new botanical drug composed of the extracts of Corydalis tuber and Pharbitidis semen, and it is used as an oral therapy for the treatment of functional dyspepsia in Korea. The inhibitory potentials of DA-9701 and its component herbs, Corydalis tuber and Pharbitidis semen, on the activities of seven major human cytochrome P450 (CYP) enzymes and four UDP-glucuronosyltransferase (UGT) enzymes in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. DA-9701 and Corydalis tuber extract slightly inhibited UGT1A1-mediated etoposide glucuronidation, with 50% inhibitory concentration (IC50) values of 188 and 290 μg/mL, respectively. DA-9701 inhibited CYP2D6-catalyzed bufuralol1′-hydroxylation with an inhibition constant (Ki) value of 6.3 μg/mL in a noncompetitive manner. Corydalis tuber extract competitively inhibited CYP2D6-mediated bufuralol1′-hydroxylation, with aKivalue of 3.7 μg/mL, whereas Pharbitidis semen extract showed no inhibition. The volume in which the dose could be diluted to generate an IC50equivalent concentration (volume per dose index) value of DA-9701 for inhibition of CYP2D6 activity was 1.16 L/dose, indicating that DA-9701 may not be a potent CYP2D6 inhibitor. Further clinical studies are warranted to evaluate thein vivoextent of the observedin vitrointeractions.

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