Inhibitory effect of the combination of notoginseng total saponins and safflower total flavonoids on UDP-glucuronosyltransferases 1A1, 1A4, and 2B7 in human liver microsomes  

三七-红花有效组分复方对人肝微粒体中UGT1A1、1A4和2B7活性抑制作用的研究（英文）

作　　者：李岩 孟雨晴 逯颖媛 常坤 高鹏 姜勇 屠鹏飞[1] 郭晓宇[1] 

机构地区：[1]北京大学医学部药学院天然药物及仿生药物国家重点实验室,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2019年第4期229-237,共9页中国药学（英文版）

基　　金：National Natural Science Foundation of China(Grant No.81573684);National Key Technology R&D Program "New Drug Innovation" of China(Grant No.2018ZX09711001-008-003);Beijing Municipal Science and Technology Project(Grant No.Z181100002218028)

摘　　要：In the present study, the potential inhibition behaviors of notoginseng total saponins(NS), safflower total flavonoids(SF), and their combination(CNS) towards three major isoforms of UDP-glucuronosyltransferases(UGTs) in human liver microsomes(HLMs) were investigated to study the mechanism of the synergistic effect of CNS.Etoposide, trifluoperazine and azidothymidine were selected as the probe drugs to elucidate the activities of UGT1A1, 1A4 and 2B7 by UPLC-MS/MS method, respectively.The results showed that CNS, NS and SF significantly inhibited the activities of UGT1A1, 1A4 and 2B7(P<0.05) with the IC_(50) values less than 30 mg/mL.Furthermore, the inhibitory effects of CNS towards UGT1A1, 1A4 and 2B7 were stronger than those of NS and SF(P<0.05).In conclusion, the combination of NS and SF could increase their inhibitory effects on UGT1A1, 1A4 and 2B7 activities in HLMs and might be conducive to reduce the phase II metabolism of the effective constituents in CNS.The potential herb-drug interactions of CNS based on UGT enzymes provided a useful experimental basis for its further research and development.为探讨三七-红花有效组分复方(CNS)的配伍作用机制,本研究考察了CNS、三七总皂苷(NS)和红花总黄酮(SF)对人肝微粒体中三种主要尿苷二磷酸葡萄糖醛酸转移酶(UGT)亚型活性的影响。采用人肝微粒体作为体外孵育模型,分别以依托泊苷、三氟拉嗪和叠氮胸苷作为UGT1A1、1A4及2B7的特异性探针底物,利用LC-MS/MS检测技术测定底物代谢产物的含量。研究结果表明, CNS、NS和SF对UGT1A1、1A4和2B7具有显著的抑制作用(P<0.05),其IC_(50)值均小于30mg/mL。与NS和SF相比较,CNS对UGT1A1、1A4和2B7具有更强的抑制作用(P<0.05)。综上,在人肝微粒体中CNS配伍给药可显著提高对UGT1A1、1A4和2B7的抑制能力,可能有利于减少CNS中主要活性成分在体内的II相代谢。基于UGT酶的CNS潜在草药-药物相互作用研究将为CNS的合理开发和利用提供有力的实验依据。

关 键 词：UDP-GLUCURONOSYLTRANSFERASES Human liver MICROSOMES Herb-drug interaction Notoginseng RADIX et Rhizoma Carthami Flos 

分 类 号：R284[医药卫生—中药学]