title: The Inhibition of the Components from Shengmai Injection towards UDP-Glucuronosyltransferase.
abstract: The mechanism of shengmai injection- (SMI-) related drug-drug interaction remains unclear. Evaluation of the inhibition potential of SMI's ingredients towards UDP-glucuronosyltransferases (UGTs) activity will provide a new insight to understand SMI-related drug-drug interaction. In vitro incubation system to model UGT reaction was used. Recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation reactions were employed to phenotype the inhibition profile of maidong's components towards the activity of UGT isoforms. Different inhibition potential of maidong's components towards various UGT isoforms was observed. Based on the inhibition kinetic investigation results, ophiopogonin D (OD) noncompetitively inhibited UGT1A6 and competitively inhibited UGT1A8, ophiopogonin D' (OD') noncompetitively inhibited UGT1A6 and UGT1A10, and ruscorectal (RU) exhibited competitive inhibition towards UGT1A4. The inhibition kinetic parameters were calculated to be 20.6, 40.1, 5.3, 9.0, and 0.02 μM, respectively. In combination with our previous results obtained for the inhibition of UGT isoforms by ginsenosides and wuweizi components, the important SMI ingredients exhibiting strong inhibition towards UGT isoforms were highlighted. All the results obtained in the present study provide a new insight to understand SMI-related drug-drug interaction.
authors.affiliation: The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, China.
authors.forename: Li-Peng
authors.initials: LP
authors.lastname: Jiang
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Contraceptives and Devices Research (NPFPC), Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Cao
authors.affiliation: Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and The First Affiliated Hospital of Liaoning Medical University, No. 457, Zhongshan Road, Dalian 116023, China ; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and The Affiliated Zhongshan Hospital of Dalian University, No. 6, Jiefang Street, Zhongshan District, Dalian 116001, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Hong
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Dong-Xue
authors.initials: DX
authors.lastname: Sun
authors.affiliation: Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and The First Affiliated Hospital of Liaoning Medical University, No. 457, Zhongshan Road, Dalian 116023, China ; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and The Affiliated Zhongshan Hospital of Dalian University, No. 6, Jiefang Street, Zhongshan District, Dalian 116001, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Sun
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.affiliation: The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, China.
authors.forename: Zhi-Tu
authors.initials: ZT
authors.lastname: Zhu
authors.affiliation: Department of Toxicology, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China.
authors.forename: Zhong-Ze
authors.initials: ZZ
authors.lastname: Fang