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
[11]   Metabolomic evaluation of rat liver and testis to characterize the toxicity of triazole fungicides [J].
Ekman, Drew R. ;
Keun, Hector C. ;
Eads, Charles D. ;
Furnish, Carrie M. ;
Rockett, John C. ;
Dix, David J. .
METABOLOMICS, 2006, 2 (02) :63-73
[12]   Using chemometrics for navigating in the large data sets of genomics, proteomics, and metabonomics (gpm) [J].
Eriksson, L ;
Antti, H ;
Gottfries, J ;
Holmes, E ;
Johansson, E ;
Lindgren, F ;
Long, I ;
Lundstedt, T ;
Trygg, J ;
Wold, S .
ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 2004, 380 (03) :419-429
[13]  
Eriksson L., 2006, MULTI MEGAVARIATE DA, DOI [10.1002/cem.713, DOI 10.1002/CEM.713]
[14]   Evaluation of different techniques for data fusion of LC/MS and 1H-NMR [J].
Forshed, Jenny ;
Idborg, Helena ;
Jacobsson, Sven P. .
CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS, 2007, 85 (01) :102-109
[15]  
GEHRKE CW, 1979, CANCER RES, V39, P1150
[16]  
Grosse PY, 1998, ANTICANCER RES, V18, P379
[17]   Antiproliferative effect of methyl-β-cyclodextrin in vitro and in human tumour xenografted athymic nude mice [J].
Grosse, PY ;
Bressolle, F ;
Pinguet, F .
BRITISH JOURNAL OF CANCER, 1998, 78 (09) :1165-1169
[18]   A gender-specific discriminator in Sprague-Dawley rat urine: The deployment of a metabolic profiling strategy for biomarker discovery and identification [J].
Hodson, Mark P. ;
Dear, Gordon J. ;
Roberts, Andy D. ;
Haylock, Claire L. ;
Ball, Rachel J. ;
Plumb, Robert S. ;
Stumpf, Chris L. ;
Griffin, Julian L. ;
Haselden, John N. .
ANALYTICAL BIOCHEMISTRY, 2007, 362 (02) :182-192
[19]   Probing latent biomarker signatures and in vivo pathway activity in experimental disease states via statistical total correlation spectroscopy (STOCSY) of biofluids:: Application to HgCl2 toxicity [J].
Holmes, E. ;
Cloarec, O. ;
Nicholson, J. K. .
JOURNAL OF PROTEOME RESEARCH, 2006, 5 (06) :1313-1320
[20]   Metabolic fingerprinting of rat urine by LC/MS Part 1. Analysis by hydrophilic interaction liquid chromatography-electrospray ionization mass spectrometry [J].
Idborg, H ;
Zamani, L ;
Edlund, PO ;
Schuppe-Koistinen, I ;
Jacobsson, SP .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2005, 828 (1-2) :9-13