Identification of major human UDP-glucuronosyltransferases responsible for the glucuronidation of is

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  A canthopanax senticosus (AS) Harms is distributed widely in regions such as the Heilongjiang, Jilin Province of the Peoples Republic of China, the northern regions of Japan and Korea.A.senticosus injection has been used in clinic for forty years.Isofraxidin, the main active constituent in the AS root, has been found with antifatigue, antistress, and immuneaccomondating effects.However, the metabolic pathways and involved enzymes in human have not been reported yet.The aim of this study is to investigate the UDP-glucuronosyltransferases (UGTs) metabolism of isofraxidin in human liver.UGTs involved in isofraxidin metabolism were identified by using twelve human recombinant UGTs (UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B4, UGT2B7, UGT2B15 and UGT2B17).Our study found that isofraxidin could be metabolized to one glucuronide in human liver microsomes.The metabolite was biosynthesized and characterized as 7-O-glucuronide.
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