| Objective This study have evaluated the drug inhibitory effects of the body liver UDP-glucuronosyltransferases(UGTs) by corylin, psoralidin, bavachin, bavachinin, neobavaisoflavone, which are the bioactive ingredients isolated from psoralea. Furthermore, to indicate that the deglycosylation process played an important role in the inhibitory potential towards UGT isoforms.The two inhibition constants we studied are a class of compounds by in vitro for its evaluation of the strength of inhibition.Methods The present study aims to investigate the inhibition of corylin, psoralidin, bavachin, bavachinin,neobavaisoflavone towards important UGTs isoforms in vitro.The study have analyzed and determined the chemical composition of activity in psoralea in phase II metabolic products by UFLC and have studied metabolic stability of the chemical composition of activity.Results The corylin had weak inhibition towards UGTs. The IC50 of psoralidin was 0.38 μmol/L for UGT1A7. The Ki was 0.27 μmol/L for UGT1A7. Psoralidin was demonstrated to noncompetitively inhibit the activity of UGT1A7. The IC50 of bavachin were 20.33 μmol/L, 1.52 μmol/L, 1.35 μmol/L, 26.64 μmol/L, 7.71 μmol/L for UGT1A6, 1A7, 1A9, 2B4, 2B7, respectively.The Ki was 10.61 μmol/ L,1.51 μmol/L,0.612 μmol/L,27.19 μmol/Lfor UGT1A6, 1A7, 1A9, 2B7, respectively. Bavachin was demonstrated to noncompetitively inhibit the activity of UGT1A6, 1A7, 1A9, 2B7. The IC50 of bavachinin were 3.191 μmol/L, 24.87 μmol/L, 0.145 μmol/L, 18.1 μmol/L for UGT1A7, 1A8, 1A9, 2B7. The Ki was 3.2 μmol/L, 0.226 μmol/L,9.38 μmol/L for UGT1A7, UGT1A8, 1A9, 2B7. Bavachinin was demonstrated to noncompetitively inhibit the activity of UGT1A7,1A9, 2B7. The IC50 of neobavaisoflavone were 3.63 μmol/L,21.6 μmol/L, 0.15μmol/L, 11.54 μmol/L,0.022 μmol/L,3.61 μmol/L for UGT1A1,1A6, 1A7, 1A8, 1A9, 2B4. The Ki was 3.32μmol/L,0.167μmol/L,0.0147μmol/L,0.287μmol/L,12.79 μmol/L for UGT1A6, 1A7, 1A8, 1A9, 2B4. Neobavaisoflavone was demonstrated to noncompetitively inhibit the activity of UGT1A6,1A8 and competitively inhibit the activity of UGT1A7, 1A9, 2B4.Conclusions The corylin had weak inhibition towards UGTs. Psoralidin was demon- strated to noncompetitively inhibit the activity of UGT1A7. Bavachin was demonstrated to noncompetitively inhibit the activity of UGT1A6,1A7,1A9, 2B7. Bavachinin was demonstrated to noncompetitively inhibit the activity of UGT1A7,1A9,2B7. Neobavaisoflavone was demonstrated to noncompetitively inhibit the activity of UGT1A6,1A8 and competitively inhibit the activity of UGT1A9,1A7,2B4.Finally through the results infer UGTs possibility of drug enzyme inhibition of the interaction. Through the final determined UGT enzyme on the psoralen active component results inferred from various aspects of drugs inhibit interaction problem in vivo. And results can be used to consider using psoralen clinical on drug safety and validity issues, also provide a theory of demand for the future research in the human body joints. |
