title: Comparison of inhibition capability of scutellarein and scutellarin towards important liver UDP-glucuronosyltransferase (UGT) isoforms.
abstract: Scutellarin is an important bioactive flavonoid extracted from Erigeron breviscapus (Vant.) Hand-Mazz, and scutellarein is the corresponding aglycone of scutellarin. The present study aims to compare the inhibition potential of scutellarin and scutellarein towards several important UDP-glucuronosyltransferase (UGT) isoforms, including UGT1A1, UGT1A6, UGT1A9 and UGT2B7. It was demonstrated that scutellarein exerted stronger inhibition towards the tested UGT isoforms than scutellarin. Furthermore, the inhibition kinetic type and parameters (Ki ) were determined for the scutellarein's inhibition towards these UGT isoforms. Competitive inhibition of scutellarein towards all these UGT isoforms was demonstrated, and the Ki values were calculated to be 0.02, 5.0, 5.8 and 35.9 μM for UGT1A1, 1A6, 1A9 and 2B7, respectively. Using in vivo maximum plasma concentration of scutellarein in rat, the in vitro-in vivo extrapolation was performed to predict in vivo situation, indicating the most possible in vivo adverse effects due to the inhibition of scutellarein towards UGT1A1. All these results remind us to monitor the utilization of scutellarin and scutellarein, and the herbs containing these two components.
authors.affiliation: The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Guang-You
authors.initials: GY
authors.lastname: Ma
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Cao
authors.forename: Cui-Min
authors.initials: CM
authors.lastname: Hu
authors.forename: Zhong-Ze
authors.initials: ZZ
authors.lastname: Fang
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Sun
authors.forename: Mo
authors.initials: M
authors.lastname: Hong
authors.forename: Zhi-Tu
authors.initials: ZT
authors.lastname: Zhu
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids; D005965:Glucuronates / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D000090264:UDP-Glucuronosyltransferase 1A9; D000099148:UGT1A1 Enzyme
chemical_list: D047310:Apigenin; D004791:Enzyme Inhibitors; D005419:Flavonoids; D005965:Glucuronates; D014453:Glucuronosyltransferase; D007527:Isoenzymes; D000090264:UDP-Glucuronosyltransferase 1A9; C499946:Ugt1a1 protein, rat; D000099148:UGT1A1 Enzyme; C484876:scutellarin; C107611:UDP-glucuronosyltransferase, UGT1A7; C458179:scutellarein; C041477:3-hydroxyflavone
keywords: UDP-glucuronosyltransferase (UGT); enzyme inhibition; scutellarein; scutellarin