木香中主要活性成分的药代动力学研究
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摘要
目的建立高效液相色谱测定大鼠血样中木香烃内酯及去氢木香内酯药物浓度的分析方法。方法以穿心莲内酯为内标物,血样采用甲醇沉淀蛋白,色谱条件采用反相色谱柱Agilent C18,流动相体系0.1%甲酸水(A)-甲醇(B)(35∶65),检测波长设置为225 nm,对大鼠口服给予木香提取物后木香烃内酯、去氢木香内酯血药浓度进行测定。结果血浆样品中2种倍半萜内酯类成分在0.05～10.00μg/mL浓度范围内线性关系良好,且精密度、稳定性及提取回收率实验结果表明该类成分血药浓度的测定方法稳定可靠。结论高效液相色谱法测定木香提取物口服给药后倍半萜内酯类成分木香烃内酯及去氢木香内酯的药代动力学过程简便、可靠,为揭示中药木香中主要成分的体内代谢过程提供了依据。
Objective It is to develop and validate a selective and sensitive high-performance liquid chromatography method for simultaneous quantification of costunolide and dehydrocostuslactone in rat plasma. Methods Using andrographolide as the internal standard, the blood sample was precipitated with methanol. The chromatographic conditions were reversed column Agilent C18, mobile phase system 0.1% formic acid(A)-methanol(B)(35∶65), and the detection wavelength was set to at 225 nm, the blood concentration of costunolide and dehydrocostuslactone was determined after oral administration of Radix Aucklandiae extraction to rats. Results Calibration curves were linear over the concentration range of 0.05-10.00 μg/mL for sesquiterpene lactones costunolide and dehydrocostuslactone, and the experimental results of precision, stability and extraction recovery showed that the determination method of the blood concentration of the components was stable and reliable. Conclusion Determination of the pharmacokinetics of the sesquiterpene lactones acostunolide and dehydrocostuslactone after oral administration of Radix Aucklandiae extraction by liquid chromatography was simple and reliable, which an evidence basis for revealing metabolic process in vivo of the main components of Chinese medicine Radix Aucklandiae.
Objective It is to develop and validate a selective and sensitive high-performance liquid chromatography method for simultaneous quantification of costunolide and dehydrocostuslactone in rat plasma. Methods Using andrographolide as the internal standard, the blood sample was precipitated with methanol. The chromatographic conditions were reversed column Agilent C18, mobile phase system 0.1% formic acid(A)-methanol(B)(35∶65), and the detection wavelength was set to at 225 nm, the blood concentration of costunolide and dehydrocostuslactone was determined after oral administration of Radix Aucklandiae extraction to rats. Results Calibration curves were linear over the concentration range of 0.05-10.00 μg/mL for sesquiterpene lactones costunolide and dehydrocostuslactone, and the experimental results of precision, stability and extraction recovery showed that the determination method of the blood concentration of the components was stable and reliable. Conclusion Determination of the pharmacokinetics of the sesquiterpene lactones acostunolide and dehydrocostuslactone after oral administration of Radix Aucklandiae extraction by liquid chromatography was simple and reliable, which an evidence basis for revealing metabolic process in vivo of the main components of Chinese medicine Radix Aucklandiae.
引文
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[8] Peng Z,Wang Y,Fan J,et al. Costunolide and dehydrocostuslactone combination treatment inhibit breast cancer by inducing cell cycle arrest and apoptosis through c-Myc/p53 and AKT/14-3-3 pathway[J]. Sci Rep,2017,7:41254
[9] Park E,Song JH,Kim MS,et al. Costunolide, a sesquiterpene lactone, inhibits the differentiation of pro-inflammatory CD4+ T cells through the modulation of mitogen-activated protein kinases[J]. Int immunopharmacol,2016,40:508-516
[10] 刘韵,黄文菁,吴孟华,等. 去氢木香内酯调控肺癌干细胞干性分子的研究[J]. 中药材,2018,41(6):1472-1475
[11] Veeramuthu D,Naif AAH,Savarimuthu I,et al. Antimicrobial activity of sesquiterpene lactones isolated from traditional medicinal plant, Costus speciosus (Koen ex.Retz.) Sm[J]. BMC Complement Altern Med,2012,7(12):13
[12] Zhang JZ,Hu X,Gao WY,et al. Pharmacokinetic study on costunolide and dehydrocostuslactone after oral administration of traditional medicine Aucklandia lappa Decne. by LC-MS/MS[J]. J Ethnopharmacol,2014,151(1):191-197
[13] Zhang JZ,Gao WY,Liu Z,et al. Identification and simultaneous determination of twelve active components in the methanol extract of traditional medicine Weichang'an pill by HPLC-DAD-ESI-MS/MS[J]. Iran J Pharm Res,2013,12(1):15-24
[14] Hu FD,Feng SL,Wu YQ,et al. Quantitative analysis of costunolide and dehydrocostuslactone in rat plasma by ultraperformance liquid chromatography-electrospray ionization-mass spectrometry[J]. Biomed Chromatogr,2011,25(5):547-554
[15] Zhang JZ,Gao WY,Ma CY,et al. The influence of the Seeds of Croton tiglium on the pharmacokinetics of anthraquinones in Radix et Rhizoma Rhei[J]. Lat Am J Pharm,2011,30(4):708-714
[16] Zhang JZ,Gao WY,Hu X,et al. The influence of compatibility of traditional Chinese medicine on the pharmacokinetic of main components in Fructus Aurantii[J]. J Ethnopharmacol,2012,144(2):277-283
[2] Lee MG,Lee KT,Chi SG,et al. Costunolide induces apoptosis by ROS-mediated mitochondrial permeability transition and cytochrome C release[J]. Biol Pharm Bull,2001,24(3):303-306
[3] Zhang S,Won YK,Ong CN,et al. Anti-cancer potential of sesquiterpene lactones:bioactivity and molecular mechanisms[J]. Cur Med Chem Anticancer Agents,2005,5(3):239-249
[4] Shum KC,Chen F,Li SL,et al. Authentication of Radix Aucklandiae and its substitutes by GC-MS and hierarchical clustering analysis[J]. J Sep Sci,2007,30(18):3233-3239
[5] 赵小民,殷高彬. 不同产地木香中木香烃内酯和去氢木香内酯的HPLC测定[J]. 安徽医药, 2009,13(6):617-618
[6] 夏丽珍,李春娇,赖增发. “一测多评”测定木香中木香烃内酯和去氢木香内酯的含量[J]. 福建中医药,2013,44(3):52-54
[7] 中华人民共和国药典委员会. 中华人民共和国药典:2015年版(一部)[S]. 北京:中国医药科技出版社,2015
[8] Peng Z,Wang Y,Fan J,et al. Costunolide and dehydrocostuslactone combination treatment inhibit breast cancer by inducing cell cycle arrest and apoptosis through c-Myc/p53 and AKT/14-3-3 pathway[J]. Sci Rep,2017,7:41254
[9] Park E,Song JH,Kim MS,et al. Costunolide, a sesquiterpene lactone, inhibits the differentiation of pro-inflammatory CD4+ T cells through the modulation of mitogen-activated protein kinases[J]. Int immunopharmacol,2016,40:508-516
[10] 刘韵,黄文菁,吴孟华,等. 去氢木香内酯调控肺癌干细胞干性分子的研究[J]. 中药材,2018,41(6):1472-1475
[11] Veeramuthu D,Naif AAH,Savarimuthu I,et al. Antimicrobial activity of sesquiterpene lactones isolated from traditional medicinal plant, Costus speciosus (Koen ex.Retz.) Sm[J]. BMC Complement Altern Med,2012,7(12):13
[12] Zhang JZ,Hu X,Gao WY,et al. Pharmacokinetic study on costunolide and dehydrocostuslactone after oral administration of traditional medicine Aucklandia lappa Decne. by LC-MS/MS[J]. J Ethnopharmacol,2014,151(1):191-197
[13] Zhang JZ,Gao WY,Liu Z,et al. Identification and simultaneous determination of twelve active components in the methanol extract of traditional medicine Weichang'an pill by HPLC-DAD-ESI-MS/MS[J]. Iran J Pharm Res,2013,12(1):15-24
[14] Hu FD,Feng SL,Wu YQ,et al. Quantitative analysis of costunolide and dehydrocostuslactone in rat plasma by ultraperformance liquid chromatography-electrospray ionization-mass spectrometry[J]. Biomed Chromatogr,2011,25(5):547-554
[15] Zhang JZ,Gao WY,Ma CY,et al. The influence of the Seeds of Croton tiglium on the pharmacokinetics of anthraquinones in Radix et Rhizoma Rhei[J]. Lat Am J Pharm,2011,30(4):708-714
[16] Zhang JZ,Gao WY,Hu X,et al. The influence of compatibility of traditional Chinese medicine on the pharmacokinetic of main components in Fructus Aurantii[J]. J Ethnopharmacol,2012,144(2):277-283