In vitro characterization of the glucuronidation pathways of licochalcone A mediated by human UDP-glucuronosyltransferases.
This study aimed to characterize the glucuronidation pathway of licochalcone A (LCA) in human liver microsomes (HLM). HLM incubation systems were employed to catalyze the formation of LCA glucuronide. The glucuronidation activity of commercially recombinant UDP-glucuronosyltransferase (UGT) isoforms toward LCA was screened. Kinetic analysis was used to identify the UGT isoforms involved in the glucuronidation of LCA in HLM. LCA could be metabolized to two monoglucuronides in HLM, including a major monoglucuronide, namely, 4-O-glucuronide, and a minor monoglucuronide, namely, 4'-O-glucuronide. Species-dependent differences were observed among the glucuronidation profiles of LCA in liver microsomes from different species. UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, UGT1A10 and UGT2B7 participated in the formation of 4-O-glucuronide, with UGT1A9 exhibiting the highest catalytic activity in this biotransformation. Only UGT1A1 and UGT1A3 were involved in the formation of 4'-O-glucuronide, exhibiting similar reaction rates. Kinetic analysis demonstrated that UGT1A9 was the major contributor to LCA-4-O-glucuronidation, while UGT1A1 played important roles in the formation of both LCA-4-O- and 4'-O-glucuronide. UGT1A9 was the major contributor to the formation of LCA-4-O-glucuronide, while UGT1A1 played important roles in both LCA-4-O- and 4'-O-glucuronidation.
['Xia|Yang-Liu|YL|', 'Dou|Tong-Yi|TY|', 'Lv|Xia|X|', 'Ge|Guang-Bo|GB|']
D000818:Animals D047188:Chalcones D004285:Dogs D014453:Glucuronosyltransferase D006168:Guinea Pigs D006801:Humans D007700:Kinetics D008252:Macaca fascicularis D008297:Male D053858:Metabolic Networks and Pathways D051379:Mice D008862:Microsomes, Liver D020033:Protein Isoforms D011817:Rabbits D017207:Rats, Sprague-Dawley D013552:Swine D013556:Swine, Miniature
glucuronidation Licochalcone A human liver microsomes (HLM) UDP-glucuronosyltransferases (UGTs)