丹参中11个活性成分对人肝微粒体细胞色素酶活性的作用研究

徐文,王泽霞,刘涛,曹志红,马敏,马霖*

中国药学杂志 ›› 2015, Vol. 50 ›› Issue (7) : 619-622.

PDF(678 KB)
PDF(678 KB)
中国药学杂志 ›› 2015, Vol. 50 ›› Issue (7) : 619-622. DOI: 10.11669/cpj.2015.07.012
论著

丹参中11个活性成分对人肝微粒体细胞色素酶活性的作用研究

  • 徐文1,王泽霞2,刘涛1,曹志红1,马敏1,马霖1*
作者信息 +

Inhibitory Effects of Eleven Active Components of Salvia miltiorrhiza Bge. Extract on Catalytic Activity of Cytochrome P450 Enzymes in Human Liver Microsomes

  • XU Wen1,WANG Ze-xia2,LIU Tao1,CAO Zhi-hong1,MA Min1,MA Lin1*
Author information +
文章历史 +

摘要

目的 为了更好的预测丹参制剂导致药物相互作用的可能性,考察了丹参中11个活性成分对5种主要药物代谢酶CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4活性的影响。方法 采用人肝微粒体外孵育方法,以非那西丁、甲苯磺丁脲、美芬妥因、氢溴酸右美沙芬和咪达唑仑作为CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4的探针药物,采用液相色谱-质谱联用检测探针药物代谢产物生成速率,通过与空白组探针药物代谢产物生成速率比较,计算各个成分对这5种酶活性是否产生影响。结果 丹参中多个成分对药物代谢酶有抑制作用,尤其是二氢丹参酮Ⅰ对CYP3A4有强抑制作用,IC50值为0.367 μmol·L-1结论 二氢丹参酮Ⅰ含量较高的丹参制剂有可能导致药物相互作用,为精准的预测这种作用,有必要对其含量和体内过程进行进一步研究。

Abstract

OBJECTIVE To predict the potential for drug-drug interactions of Salvia miltiorrhiza Bge. preparations with other drugs, the effects of 11 active components of Salvia miltiorrhiza Bge. on the catalytic activities of 5 drug-metabolizing enzymes were assessed.METHODS Human liver microsome incubation experiment was carried out to assay these components on the catalytic activities of these enzymes. Phenacetin, tolbutamide, S-mephenytoin, dextromethorphane and midazolam were used as the substrates of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, respectively. After the incubation, the metabolite of each substrate was quantified by LC-MS/MS method. The inhibitions of five main drug metabolism enzymes were calculated by comparing the formation velocities of metabolites with or without Salvia miltiorrhiza Bge. component.RESULTS Some components of Salvia miltiorrhiza Bge. showed obvious inhibiton on the catalytic activities of CYPs, especially dihydrotanshinone Ⅰ showed strong inhibiton on CYP3A4 with IC50 value of 0.367 μmol·L-1.CONCLUSION Salvia miltiorrhiza Bge. preparation with high content of dihydrotanshinone Ⅰ may cause drug-drug interactions. To predict the interaction precisely, the content of dihydrotanshinone Ⅰ as well as its in vivo process need a further study.

关键词

丹参 / 细胞色素P450 / 抑制 / 二氢丹参酮Ⅰ / 肝微粒体

Key words

Salvia miltiorrhiza Bge. / cytochrome P450 / inhibition / dihydrotanshinone Ⅰ / liver microsome

引用本文

导出引用
徐文,王泽霞,刘涛,曹志红,马敏,马霖*. 丹参中11个活性成分对人肝微粒体细胞色素酶活性的作用研究[J]. 中国药学杂志, 2015, 50(7): 619-622 https://doi.org/10.11669/cpj.2015.07.012
XU Wen,WANG Ze-xia,LIU Tao,CAO Zhi-hong,MA Min,MA Lin*. Inhibitory Effects of Eleven Active Components of Salvia miltiorrhiza Bge. Extract on Catalytic Activity of Cytochrome P450 Enzymes in Human Liver Microsomes[J]. Chinese Pharmaceutical Journal, 2015, 50(7): 619-622 https://doi.org/10.11669/cpj.2015.07.012
中图分类号: R969.1   

参考文献

[1] GUENGENRICH F P. Cytochrome P450 and chemical toxicology. Chem Res Toxicol,2008,21(1):70-83. [2] FOTI R S,WAHLSTROM J L,WIENKERS L C. The in vitro drug interaction potential of dietary supplements containing multiple herbal components. Drug Metab Dispos,2007,35(2):185-188. [3] LEE L S,ANDRADE A S,FLEXNER C. Interactions between natural health products and antiretroviral drugs:pharmacokinetic and pharmacodynamic effects. Clin Infect Dis,2006,43(8):1052-1059. [4] QIU F,ZHANG R,SUN J,et al. Inhibitory effects of seven components of danshen extract on catalytic activity of cytochrome P450 enzyme in human liver microsomes. Drug Metab Dispos,2008,36(7):1308-1314. [5] WANG X,CHEUNG C M,LEE W Y,et al. Major tanshinones of Danshen (Salvia miltiorrhiza) exhibit different modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro. Phytomedicine,2010,17(11):868-875. [6] WANG X,YEUNG J H. Investigation of cytochrome P4501A2 and 3A inhibitory properties of Danshen tincture. Phytomedicine,2012,19(3-4):348-354. [7] LEE J H,SHIN Y J,KIM H J,et al. Danshen extract does not alter pharmacokinetics of docetaxel and clopidogrel, reflecting its negligible potential in P-glycoprotein and cytochrome P4503A-mediated herb-drug interactions. Int J Pharm,2011,410(1-2):68-74. [8] WANG J,MA C Y,QIU L L,et al. The accelerated stability and Platelet-aggregation function of Salvia miltiorrhiza powder for injection (SMPI) and its solution for injection (SMLI):Comparative studies. Chin Pharm J (中国药学杂志),1996,31(12):730-732. [9] XU B,ZHAO G,WEI H,et al. Effects of 20 Chinese patent medicines on the catalytic activities of five main cytochrome P450s of human liver microsome. J Pharm Prac(药学实践杂志),2009,27(5):353-356. [10] ZHOU G J,LI Y,QIN M J, et al. Fast determination of 5 constituents in Radix et Rhizoma Salviae miltiorrhizae by HPLC. Chin J Pharm Anal(药物分析杂志),2012,32(8):1357-1361. [11] WU W B,TANG J. UPLC Simultaneous determination of 5 lipophilic components in Salvia miltiorrhiza Bge. Chin J Pharm Anal (药物分析杂志), 2009, 29(5):827-829. [12] SUN G X,SONG Y J. Digitized HPLC fingerprints of compound Danshen Dropping Pills. Chin Tradit Pat Med(中成药),2009,31(8):1152-1155.

基金

青岛市民生计划资助项目(13-1-3-32-nsh)
PDF(678 KB)

Accesses

Citation

Detail

段落导航
相关文章

/