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生脉注射液成分对 UDP-葡萄糖醛酸转移酶的抑制作用。

The Inhibition of the Components from Shengmai Injection towards UDP-Glucuronosyltransferase.

机构信息

The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, China.

School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.

出版信息

Evid Based Complement Alternat Med. 2014;2014:594354. doi: 10.1155/2014/594354. Epub 2014 Oct 29.

DOI:10.1155/2014/594354
PMID:25530784
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4229968/
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.

摘要

生脉注射液（SMI）相关药物相互作用的机制尚不清楚。评估 SMI 成分对 UDP-葡萄糖醛酸转移酶（UGTs）活性的抑制潜力将为理解 SMI 相关药物相互作用提供新的见解。使用体外孵育系统来模拟 UGT 反应。采用重组 UGT 同工酶催化 4-甲基伞形酮（4-MU）葡萄糖醛酸化和 UGT1A4 催化三氟拉嗪（TFP）葡萄糖醛酸化反应，表型分析麦冬成分对 UGT 同工酶活性的抑制特征。观察到麦冬成分对不同 UGT 同工酶的抑制潜力不同。根据抑制动力学研究结果，麦冬皂苷 D（OD）非竞争性抑制 UGT1A6 和竞争性抑制 UGT1A8，麦冬皂苷 D'（OD'）非竞争性抑制 UGT1A6 和 UGT1A10，而鲁斯可定（RU）对 UGT1A4 表现出竞争性抑制。抑制动力学参数分别计算为 20.6、40.1、5.3、9.0 和 0.02 μM。结合我们之前获得的关于人参皂苷和五味子成分对 UGT 同工酶抑制的结果，突出了显示出对 UGT 同工酶强抑制作用的重要 SMI 成分。本研究中的所有结果提供了一个新的视角来理解 SMI 相关的药物相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/c170d6e11c62/ECAM2014-594354.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/3389a3800057/ECAM2014-594354.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/6298d1573eb0/ECAM2014-594354.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/c4104b86837e/ECAM2014-594354.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/29974699ff6a/ECAM2014-594354.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/197eb2eaee09/ECAM2014-594354.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/f7f2c41ed3d6/ECAM2014-594354.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/c170d6e11c62/ECAM2014-594354.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/3389a3800057/ECAM2014-594354.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/6298d1573eb0/ECAM2014-594354.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/c4104b86837e/ECAM2014-594354.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/29974699ff6a/ECAM2014-594354.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/197eb2eaee09/ECAM2014-594354.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/f7f2c41ed3d6/ECAM2014-594354.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/4229968/c170d6e11c62/ECAM2014-594354.007.jpg

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