Metabonomics study on the effects of the ginsenoside Rg3 in a β-cyclodextrin-based formulation on tumor-bearing rats by a fully automatic hydrophilic interaction/reversed-phase column-switching HPLC-ESI-MS approach

被引:76
作者
Wang, Yuan [2 ]
Wang, Jiangshan [2 ]
Yao, Ming [3 ]
Zhao, Xinjie [2 ]
Fritsche, Jens [4 ]
Schmitt-Kopplin, Philippe [5 ]
Cai, Zongwei [6 ]
Wan, Dafang [3 ]
Lu, Xin [2 ]
Yang, Shengli [2 ,3 ,7 ]
Gu, Jianren [3 ]
Haering, Hans Ulrich [1 ]
Schleicher, Erwin D. [1 ]
Lehmann, Rainer [1 ]
Xu, Guowang [2 ]
机构
[1] Univ Hosp Tuebingen, Div Clin Chem & Pathobiochem, Cent Lab, Dept Internal Med 4, D-72076 Tubingen, Germany
[2] Chinese Acad Sci, Dalian Inst Chem Phys, Natl Chromatog Res & Anal Ctr, Dalian 16023, Peoples R China
[3] Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst, Shanghai 200032, Peoples R China
[4] Immat Biotechnol GmbH, D-72076 Tubingen, Germany
[5] Inst Ecol Chem, German Res Ctr Environm Hlth, Helmholtz Zentrum Muenchen, D-85764 Neuherberg, Germany
[6] Hong Kong Baptist Univ, Dept Chem, Kowloon, Hong Kong, Peoples R China
[7] Chinese Acad Sci, Shanghai Res Ctr Biotechnol, Shanghai 200032, Peoples R China
关键词
D O I
10.1021/ac8002402
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
The goal of this study was the application of a novel, fully automatic column-switching approach in a metabonomics study combining the orthogonal selectivities of hydrophilic interaction chromatography (HILIC) and reversed-phase chromatography. The temporal, pharmacodynamic effects of the ginsenoside Rg3 on the metabonome in urine of healthy and liver-tumor-bearing rats have been investigated. Within a total analysis time of 52 min we detected 5686 polar, and on the second column an additional 1808 apolar, urinary metabolite ions. The administration of a single, high dose of Rg3 in a beta-cyclodextrin-based formulation led to a considerable change of the metabolic pattern in cancer rats during 3 days studied. Seventeen biomarker candidates including three apolar metabolites, which were not retained on the HILIC column, were detected. Overall, the results suggest that the developed liquid chromatography-mass spectrometry strategy is a promising tool in metabonomics studies for global analysis of highly complex biosamples. It may not only increase the number of discovered biomarkers but consequently improve the comprehensive information on metabolic changes in a fully automatic manner.
引用
收藏
页码:4680 / 4688
页数:9
相关论文
共 53 条
[1]   Transformation of ginseng saponins to ginsenoside Rh2 by acids and human intestinal bacteria and biological activities of their transformants [J].
Bae, EA ;
Han, MJ ;
Kim, EJ ;
Kim, DH .
ARCHIVES OF PHARMACAL RESEARCH, 2004, 27 (01) :61-67
[2]   Separation and quantitation of water soluble cellular metabolites by hydrophilic interaction chromatography-tandem mass spectrometry [J].
Bajad, Sunil U. ;
Lu, Wenyun ;
Kimball, Elizabeth H. ;
Yuan, Jie ;
Peterson, Celeste ;
Rabinowitz, Joshua D. .
JOURNAL OF CHROMATOGRAPHY A, 2006, 1125 (01) :76-88
[3]   Large-scale human metabolomics studies: A strategy for data (pre-) processing and validation [J].
Bijlsma, S ;
Bobeldijk, L ;
Verheij, ER ;
Ramaker, R ;
Kochhar, S ;
Macdonald, IA ;
van Ommen, B ;
Smilde, AK .
ANALYTICAL CHEMISTRY, 2006, 78 (02) :567-574
[4]   Liquid chromatography-electrospray ionization mass spectrometry for metabolism and pharmacokinetic studies of ginsenoside Rg3 [J].
Cai, ZW ;
Qian, TX ;
Wong, RNS ;
Jiang, ZH .
ANALYTICA CHIMICA ACTA, 2003, 492 (1-2) :283-293
[5]   The utility of cyclodextrins for enhancing oral bioavailability [J].
Carrier, Rebecca L. ;
Miller, Lee A. ;
Ahmed, Mran .
JOURNAL OF CONTROLLED RELEASE, 2007, 123 (02) :78-99
[6]   Practical approach for the identification and isomer elucidation of biomarkers detected in a metabonomic study for the discovery of individuals at risk for diabetes by integrating the chromatographic and mass spectrometric information [J].
Chen, Jing ;
Zhao, Xinjie ;
Fritsche, Jens ;
Yin, Peiyuan ;
Schmitt-Kopplin, Philippe ;
Wang, Wenzhao ;
Lu, Xin ;
Haring, Hans Ulrich ;
Schleicher, Erwin D. ;
Lehmann, Rainer ;
Xu, Guowang .
ANALYTICAL CHEMISTRY, 2008, 80 (04) :1280-1289
[7]   Virtual chromatographic resolution enhancement in cryoflow LC-NMR experiments via statistical total correlation spectroscopy [J].
Cloarec, Olivier ;
Campbell, Alison ;
Tseng, Li-hong ;
Braumann, Ulrich ;
Spraul, Manfred ;
Scarfe, Graeme ;
Weaver, Richard ;
Nicholson, Jeremy K. .
ANALYTICAL CHEMISTRY, 2007, 79 (09) :3304-3311
[8]   Statistical search space reduction and two-dimensional data display approaches for UPLC-MS in biomarker discovery and pathway analysis [J].
Crockford, Derek J. ;
Lindon, John C. ;
Cloarec, Olivier ;
Plumb, Robert S. ;
Bruce, Stephen J. ;
Zirah, Severine ;
Rainville, Paul ;
Stumpf, Chris L. ;
Johnson, Kelly ;
Holmes, Elaine ;
Nicholson, Jeremy K. .
ANALYTICAL CHEMISTRY, 2006, 78 (13) :4398-4408
[9]   Hydrophilic interaction chromatography for mass spectrometric metabonomic studies of urine [J].
Cubbon, Simon ;
Bradbury, Timothy ;
Wilson, Julie ;
Thomas-Oates, Jane .
ANALYTICAL CHEMISTRY, 2007, 79 (23) :8911-8918
[10]   Prediction and classification of drug toxicity using probabilistic modeling of temporal metabolic data: The Consortium on Metabonomic Toxicology screening approach [J].
Ebbels, Timothy M. D. ;
Keun, Hector C. ;
Beckonert, Olaf P. ;
Bollard, Mary E. ;
Lindon, John C. ;
Holmes, Elaine ;
Nicholson, Jeremy K. .
JOURNAL OF PROTEOME RESEARCH, 2007, 6 (11) :4407-4422