Effects of tanshinones from Salvia miltiorrhiza on CYP2C19 activity in human liver microsomes: Enzyme kinetic and molecular docking studies

被引：22

作者：

Hu, Tao ^{[1
]}

Zhou, Xuelin ^{[1
]}

Wang, Lin ^{[1
]}

Or, Penelope M. Y. ^{[1
]}

Yeung, John H. K. ^{[1
]}

Kwan, Yiu Wa ^{[1
]}

Cho, Chi Hin ^{[1
]}

机构：

[1] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Shatin, Hong Kong, Peoples R China

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 2015年 / 230卷

关键词：

Tanshinones; CYP2C19; Omeprazole; Human liver microsomes; Molecular docking; CYTOCHROME-P450; 2C19; DRUG-INTERACTIONS; HEALTHY-SUBJECTS; IN-VITRO; INHIBITOR; WARFARIN; RAT; HYDROXYLATION; OMEPRAZOLE; INCREASES;

D O I：

10.1016/j.cbi.2015.02.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Objectives: This study aimed to investigate the effects of five tanshinones, the lipophilic components from Danshen (Salvia miltiorrhiza), on CYP2C19 activity in pooled human liver microsomes (HLMs). Methods: The effects of tanshinones on CYP2C19 activity were compared by enzyme inhibition study using omeprazole 5-hydroxylation in pooled HLMs. The inhibition constant (Ki) values and inhibition modes of effective tanshinones were evaluated by enzyme kinetic study. Molecular docking analysis was used to simulate the binding conformations of tanshinones to the active cavity of human CYP2C19. Results: Dihydrotanshinone and miltirone showed potent inhibitory effects on CYP2C19 activity in a concentration-dependent manner. Tanshinone I showed weaker inhibitory effect, whereas tanshinone IIA and cryptotanshinone had no inhibitory effect. Further enzyme kinetic study showed that the inhibition by dihydrotanshinone and miltirone was a mixed type. The effects of tanshinones were also confirmed by a molecular docking study. Besides, the ethanol extract of Danshen also showed a mixed type of inhibition, whereas the water extract had no inhibitory effect. Conclusions: The current findings demonstrate the inhibition of CYP2C19 activity by the ethanol extract of Danshen and its components tanshinones, implicating the potential herb-drug interactions between Danshen and therapeutic agents metabolized by CYP2C19 in clinical practice. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：1 / 8

页数：8

共 30 条

[1] Conserved water mediated H-bonding dynamics of Ser117 and Thr119 residues in human transthyretin-thyroxin complexation: Inhibitor modeling study through docking and molecular dynamics simulation [J].

Banerjee, Avik ;

Bairagya, Hridoy R. ;

Mukhopadhyay, Bishnu P. ;

Nandi, Tapas K. ;

Mishra, Deepak K. .

JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2013, 44 :70-80

[2] Study of tanshinone IIA tissue distribution in rat by liquid chromatography-tandem mass spectrometry method [J].

Bi, Hui-chang ;

Law, Francis C. P. ;

Zhong, Guo-ping ;

Xu, Chen-shu ;

Pan, Ying ;

Ding, Liang ;

Chen, Xiao ;

Zhao, Li-zi ;

Xu, Qiong ;

Huang, Min .

BIOMEDICAL CHROMATOGRAPHY, 2007, 21 (05) :473-479

[3] Validation of (-)-N-3-benzyl-phenobarbital as a selective inhibitor of CYP2C19 in human liver microsomes [J].

Cai, XX ;

Wang, RW ;

Edom, RW ;

Evans, DC ;

Shou, MG ;

Rodrigues, AD ;

Liu, WS ;

Dean, DC ;

Baillie, TA .

DRUG METABOLISM AND DISPOSITION, 2004, 32 (06) :584-586

[4] Interaction between warfarin and danshen (Salvia miltiorrhiza) [J].

Chan, TYK .

ANNALS OF PHARMACOTHERAPY, 2001, 35 (04) :501-504

[5]

Chan TYK, 1998, INT J CLIN PHARM TH, V36, P403

[6] Further Assessment of 17α-Ethinyl Estradiol as an Inhibitor of Different Human Cytochrome P450 Forms in Vitro [J].

Chang, Shu-Ying ;

Chen, Cliff ;

Yang, Zheng ;

Rodrigues, A. David .

DRUG METABOLISM AND DISPOSITION, 2009, 37 (08) :1667-1675

[7] Clopidogrel Inhibits CYP2C19-Dependent Hydroxylation of Omeprazole Related to CYP2C19 Genetic Polymorphisms [J].

Chen, B. L. ;

Chen, Y. ;

Tu, J. H. ;

Li, Y. L. ;

Zhang, W. ;

Li, Q. ;

Fan, L. ;

Tan, Z. R. ;

Hu, D. L. ;

Wang, D. ;

Wang, L. S. ;

OuYang, D. S. ;

Zhou, H. H. .

JOURNAL OF CLINICAL PHARMACOLOGY, 2009, 49 (05) :574-581

[8]

CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099

[9] Biosynthesis, total syntheses, and antitumor activity of tanshinones and their analogs as potential therapeutic agents [J].

Dong, Yizhou ;

Morris-Natschke, Susan L. ;

Lee, Kuo-Hsiung .

NATURAL PRODUCT REPORTS, 2011, 28 (03) :529-542

[10] Membrane transporters in drug development [J].

Giacomini, Kathleen M. ;

Huang, Shiew-Mei ;

Tweedie, Donald J. ;

Benet, Leslie Z. ;

Brouwer, Kim L. R. ;

Chu, Xiaoyan ;

Dahlin, Amber ;

Evers, Raymond ;

Fischer, Volker ;

Hillgren, Kathleen M. ;

Hoffmaster, Keith A. ;

Ishikawa, Toshihisa ;

Keppler, Dietrich ;

Kim, Richard B. ;

Lee, Caroline A. ;

Niemi, Mikko ;

Polli, Joseph W. ;

Sugiyama, Yuicchi ;

Swaan, Peter W. ;

Ware, Joseph A. ;

Wright, Stephen H. ;

Yee, Sook Wah ;

Zamek-Gliszczynski, Maciej J. ;

Zhang, Lei .

NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (03) :215-236

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