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

doi:10.5246/jcps.2019.04.023

Journal of Chinese Pharmaceutical Sciences ›› 2019, Vol. 28 ›› Issue (4): 229-237.DOI: 10.5246/jcps.2019.04.023

• Original articles • Previous Articles Next Articles

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

Yan Li, Yuqing Meng, Yingyuan Lu, Kun Chang, Peng Gao, Yong Jiang, Pengfei Tu, Xiaoyu Guo^*

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2018-09-04 Revised:2018-11-13 Online:2019-04-30 Published:2018-12-15
Contact: Tel.: +86-010-82805641, E-mail: guoxiaoyu@bjmu.edu.cn
Supported by:
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) and Beijing Municipal Science and Technology Project (Grant No. Z181100002218028).

Abstract

Abstract:

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 IC₅₀values 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.

Key words: UDP-glucuronosyltransferases, Human liver microsomes, Herb-drug interaction, Notoginseng Radix et Rhizoma, Carthami Flos

CLC Number:

R284

Supporting:

Yan Li, Yuqing Meng, Yingyuan Lu, Kun Chang, Peng Gao, Yong Jiang, Pengfei Tu, Xiaoyu Guo. Inhibitory effect of the combination of notoginseng total saponins and safflower total flavonoids on UDP-glucuronosyltransferases 1A1, 1A4, and 2B7 in human liver microsomes[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(4): 229-237.

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

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