In vitro glucuronidation of methyl gallate and pentagalloyl glucopyranose by liver microsomes.
Methyl gallate (MG) and pentagalloyl glucopyranose (PGG) are bioactive phenolic compounds that possess various pharmacological activities. However, the knowledge of hepatic metabolism of MG and PGG is limited. The purpose of this study was to investigate the in vitro glucuronidation of MG and PGG using liver microsomes from human (HLMs) and rats (Sprague-Dawley, SDRLMs; Wistar, WRLMs; and Gunn, GRLMs), and recombinant human uridine 5'-diphospho-glucuronosyltransferases (UGT) 1A1 and 1A9. The results demonstrated that liver microsomes catalyzed two mono-glucuronided MG (M1 and M2) formations but that UGT1A1 and 1A9 catalyzed only M1 formation. For PGG, a mono-glucuronided metabolite was mediated by liver microsomes or UGT1A9. However, a PGG glucuronide was absent in the UGT1A1 system. Additionally, all metabolites showed susceptibility to β-glucuronidases. Furthermore, the glucuronidation activities of PGG were lower than those of MG. The kinetic parameters of MG glucuronidation demonstrated that the SDRLMs and GRLMs were more similar to the HLMs than the WRLMs for the formations of M1 and M2, respectively and that the SDRLMs and HLMs preferentially contributed to M1, whereas the WRLMs and GRLMs showed the favored formation of M2. In conclusion, MG and PGG were subjectively glucuronided by liver microsomes to demonstrate species- and strain-dependent metabolism.
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, TX 77030, USA.
Pimsumon
P
Jiamboonsri
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand. Electronic address: pimolpan.pit@mahidol.ac.th.
Pimolpan
P
Pithayanukul
Department of Pharmaceutical Botany and Pharmacognosy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Rapepol
R
Bavovada
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
Jiraporn
J
Leanpolchareanchai
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, TX 77030, USA.
Song
S
Gao
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, TX 77030, USA.
Ming
M
Hu
D000818:Animals; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology*; D011911:Rats, Gunn; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D000090264:UDP-Glucuronosyltransferase 1A9; D000099148:UGT1A1 Enzyme
D005707:Gallic Acid; D005966:Glucuronidase; D014453:Glucuronosyltransferase; D047348:Hydrolyzable Tannins; D000090264:UDP-Glucuronosyltransferase 1A9; D000099148:UGT1A1 Enzyme; C000715591:UGT1A9 protein, human; C000616074:pentagalloyl glucopyranose; C052082:methyl gallate
Glucuronidation; Liver microsomes; Methyl gallate; Methyl gallate (PubChem CID: 7428); Pentagalloyl glucopyranose; Pentagalloyl glucopyranose (PubChem CID: 65238); β-glucuronidases