Download PDF
Planta Med 2006; 72(9): 771-785
DOI: 10.1055/s-2006-946682
Review
© Georg Thieme Verlag KG Stuttgart · New York

The Assessment of Plant Metabolite Profiles by NMR-Based Methodologies

Elaine Holmes1 , Huiru Tang2 , Yulan Wang1 , Christoph Seger3
  • 1Biological Chemistry, Biomedical Sciences Division, Faculty of Natural Science, Imperial College, London, U.K.
  • 2State Key Laboratory of Magnetic Resonance and Molecular and Atomic Physics, Wuhan Magnetic Resonance Centre, Wuhan Institute of Physics and Mathematics, The Chinese Academy of Sciences, Wuhan, P.R. China
  • 3Institute of Pharmacy/Pharmacognosy, Centre of Molecular Biosciences, University of Innsbruck, Innsbruck, Austria
Further Information

Publication History

Received: April 13, 2006

Accepted: May 16, 2006

Publication Date:
17 July 2006 (online)

Also available at
   Permissions and Reprints

Abstract

NMR-based metabolic profiling techniques can simultaneously track changes in many plant metabolites and have found a number of applications in both systems biology and biosafety. Together with multivariate statistical analyses, NMR spectroscopy has been successfully applied to the characterisation of various herbs and plant products for quality control, authentication, determining geographical origin and for detecting adulteration of products. Additionally, the metabolic consequences of plant extracts have been demonstrated in experimental animals and in man using NMR-based metabonomics approaches to characterise the response. Here the application of NMR spectroscopy and chemometric tools for analysing plant-based products and their metabolic consequences are considered with particular emphasis on deconvolving biological complexity and minimising confounding biological variability with analytical ‘noise’.

Key words

NMR - metabolic profiling - metabolic fingerprinting - metabolomics - metabonomics - phytomedicines - traditional Chinese medicine - genetically modified plants - toxicology - xenobiotics

References

  • 1 Nakanishi K. In: Barton D, Nakanishi K, editors Comprehensive natural products chemistry. An historical perspective of natural products chemistry. Amsterdam; Elsevier 1999: XXIII-XL
    Search in Google Scholar
  • 2 Cragg G M, Newman D J. Natural product drug discovery in the next millennium.  Pharm Biol. 2001;  39 (Suppl.) 8-17
    PubMedSearch in Google Scholar
  • 3 Cordella C, Moussa I, Martel A C, Sbirrazzuoli N, Lizzani-Cuvelier L. Recent developments in food characterization and adulteration detection: Technique-oriented perspectives.  J Agric Food Chem. 2002;  50 1751-64
    CrossrefPubMedSearch in Google Scholar
  • 4 Hadacek F. Secondary metabolites as plant traits: Current assessment and future perspective.  Crit Rev Plant Sci. 2002;  21 273-322
    PubMedSearch in Google Scholar
  • 5 Wink M. Evolution of secondary metabolites from an ecological and molecular phylogenetic perspective.  Phytochemistry. 2003;  64 2-19
    PubMedSearch in Google Scholar
  • 6 Verpoorte R. Exploration of nature’s chemodiversity: the role of secondary metabolites as leads in drug development.  Drug Discov Today. 1998;  3 232-8
    CrossrefPubMedSearch in Google Scholar
  • 7 Tulp M, Bohlin L. Functional versus chemical diversity: is biodiversity important for drug discovery?.  Trends Pharmacol Sci. 2002;  23 225-31
    CrossrefPubMedSearch in Google Scholar
  • 8 Tulp M, Bohlin L. Rediscovery of known natural compounds: Nuisance or goldmine?.  Bioorg Med Chem. 2005;  13 5274-82
    CrossrefPubMedSearch in Google Scholar
  • 9 Pichersky E, Noel J P, Dudareva N. Biosynthesis of plant volatiles: Nature’s diversity and ingenuity.  Science. 2006;  311 808-11
    CrossrefPubMedSearch in Google Scholar
  • 10 Wolfender J L, Terreaux C, Hostettmann K. The importance of LC-MS and LC-NMR in the discovery of new lead compounds from plants.  Pharm Biol. 2000;  38 (Suppl.) 41-54
    PubMedSearch in Google Scholar
  • 11 Williams D H, Bardsley B. The vancomycin group of antibiotics and the fight against resistant bacteria.  Angew Chem Int Ed Engl. 1999;  38 1173-93
    PubMedSearch in Google Scholar
  • 12 Zhang A J, Burgess K. Total syntheses of vancomycin.  Angew Chem Int Ed Engl. 1999;  38 634-6
    CrossrefPubMedSearch in Google Scholar
  • 13 Stierle A, Strobel G, Stierle D. Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew.  Science. 1993;  260 214-7
    CrossrefPubMedSearch in Google Scholar
  • 14 Kingston D GI. Taxol, a molecule for all seasons. Chem Commun (Camb) 2001: 867-80
    Search in Google Scholar
  • 15 Jaroszewski J W. Hyphenated NMR methods in natural products research, part 1: Direct hyphenation.  Planta Med. 2005;  71 691-700
    Thieme ConnectPubMedSearch in Google Scholar
  • 16 Jaroszewski J W. Hyphenated NMR methods in natural products research, part 2: HPLC-SPE-NMR and other new trends in NMR hyphenation.  Planta Med. 2005;  71 795-802
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Bligny R, Douce R. NMR and plant metabolism.  Curr Opin Plant Biol. 2001;  4 191-6
    CrossrefPubMedSearch in Google Scholar
  • 18 Kruger N J, Ratcliffe R G, Roscher A. Quantitative approaches for analysing fluxes through plant metabolic networks using NMR and stable isotope labelling.  Phytochem Rev. 2003;  2 17-30
    CrossrefPubMedSearch in Google Scholar
  • 19 Krishnan P, Kruger N J, Ratcliffe R G. Metabolite fingerprinting and profiling in plants using NMR.  J Exp Bot. 2005;  56 255-65
    PubMedSearch in Google Scholar
  • 20 Ratcliffe R G, Shachar-Hill Y. Revealing metabolic phenotypes in plants: inputs from NMR analysis.  Biol Rev. 2005;  80 27-43
    CrossrefPubMedSearch in Google Scholar
  • 21 Ratcliffe R G, Shachar-Hill Y. Measuring multiple fluxes through plant metabolic networks.  Plant J. 2006;  45 490-511
    CrossrefPubMedSearch in Google Scholar
  • 22 Wolfender J L, Ndjoko K, Hostettmann K. Liquid chromatography with ultraviolet absorbance-mass spectrometric detection and with nuclear magnetic resonance spectrometry: a powerful combination for the on-line structural investigation of plant metabolites.  J Chromatogr A. 2003;  1000 437-55
    CrossrefPubMedSearch in Google Scholar
  • 23 Seger C, Römpp H, Sturm S, Haslinger E, Schmidt P C, Hadacek F. Characterization of supercritical fluid extracts of St. John’s wort (Hypericum perforatum L.) by HPLC-MS and GC-MS.  Eur J Pharm Sci. 2004;  21 453-63
    PubMedSearch in Google Scholar
  • 24 Shaw A D, diCamillo A, Vlahov G, Jones A, Bianchi G, Rowland J. et al . Discrimination of the variety and region of origin of extra virgin olive oils using C-13 NMR and multivariate calibration with variable reduction.  Anal Chim Acta. 1997;  348 357-74
    CrossrefPubMedSearch in Google Scholar
  • 25 Tapp H S, Defernez M, Kemsley K E. FTIR spectroscopy and multivariate analysis can distinguish the geographic origin of extra virgin olive oils.  J Agric Food Chem. 2003;  51 6110-5
    CrossrefPubMedSearch in Google Scholar
  • 26 Rager I, Roos G, Schmidt P C, Kovar K A. Rapid quantification of constituents in St. John’s wort extracts by NIR spectroscopy.  J Pharm Biomed Anal. 2002;  28 439-46
    CrossrefPubMedSearch in Google Scholar
  • 27 Laasonen M, Harmia-Pulkkinen T, Simard C L, Michiels E, Räsänen M, Vuorela H. Fast identification of Echinacea purpurea dried roots using near infrared spectroscopy.  Anal Chem. 2002;  74 2493-9
    CrossrefPubMedSearch in Google Scholar
  • 28 Salgueiro L, Vila R, Tomas X, Tomi F, Canigueral S, Casanova J. et al . Chemical polymorphism of the essential oil of Thymus carnosus from Portugal.  Phytochemistry. 1995;  38 391-6
    CrossrefPubMedSearch in Google Scholar
  • 29 Nicholson J K, Lindon J C, Holmes E. ”Metabonomics”: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data.  Xenobiotica. 1999;  29 1181-9
    CrossrefPubMedSearch in Google Scholar
  • 30 Fiehn O, Kopka J, Dormann P, Altmann T, Trethewey R N, Willmitzer L. Metabolite profiling for plant functional genomics.  Nat Biotechnol. 2000;  18 1157-61
    PubMedSearch in Google Scholar
  • 31 Fiehn O. Metabolomics - the link between genotype and phenotype.  Plant Mol Biol. 2002;  48 155-71
    CrossrefPubMedSearch in Google Scholar
  • 32 Dunn W B, Ellis D I. Metabolomics: Current analytical platforms and methodologies.  Trends Anal Chem. 2005;  24 285-94
    CrossrefPubMedSearch in Google Scholar
  • 33 Hall R D. Plant metabolomics: from holistic hope, to hype, to hot topic.  New Phytol. 2006;  169 453-68
    CrossrefPubMedSearch in Google Scholar
  • 34 Pauli G F. qNMR - a versatile concept for the validation of natural product reference compounds.  Phytochem Anal. 2001;  12 28-42
    CrossrefPubMedSearch in Google Scholar
  • 35 Pauli G F, Jaki B U, Lankin D C. Quantitative 1H NMR: development and potential of a method for natural products analysis.  J Nat Prod. 2005;  68 133-49
    CrossrefPubMedSearch in Google Scholar
  • 36 Fernie A R, Trethewey R N, Krotzky A J, Willmitzer L. Metabolite profiling: from diagnostics to systems biology.  Nat Rev Mol Cell Biol. 2004;  5 1-7
    PubMedSearch in Google Scholar
  • 37 Rochfort S. Metabolomics reviewed: A new ”omics” platform technology for systems biology and implications for natural products research.  J Nat Prod. 2005;  68 1813-20
    CrossrefPubMedSearch in Google Scholar
  • 38 Roessner U, Wagner C, Kopka J, Trethewey R N, Willmitzer L. Simultaneous analysis of metabolites in potato tuber by gas chromatography-mass spectrometry.  Plant J. 2000;  23 131-42
    CrossrefPubMedSearch in Google Scholar
  • 39 Roessner U, Luedemann A, Brust D, Fiehn O, Linke T, Willmitzer L. et al . Metabolic profiling allows comprehensive phenotyping of genetically or environmentally modified plant systems.  Plant Cell. 2001;  13 11-29
    CrossrefPubMedSearch in Google Scholar
  • 40 Overy S A, Walker H J, Malone S, Howard T P, Baxter C J, Sweetlove L J. et al . Application of metabolite profiling to the identification of traits in a population of tomato introgression lines.  J Exp Bot. 2005;  56 287-96
    PubMedSearch in Google Scholar
  • 41 Schauer N, Zamir D, Fernie A R. Metabolic profiling of leaves and fruit of wild species tomato: a survey of the Solanum lycopersicum complex.  J Exp Bot. 2005;  56 297-307
    PubMedSearch in Google Scholar
  • 42 Crockford D J, Keun H C, Smith L M, Holmes E, Nicholson J K. Curve-fitting method for direct quantitation of compounds in complex biological mixtures using 1H NMR: application in metabonomic toxicology studies.  Anal Chem. 2005;  77 4556-62
    CrossrefPubMedSearch in Google Scholar
  • 43 Noteborn H P, Lommen A, van der Jagt R C, Weseman J M. Chemical fingerprinting for the evaluation of unintended secondary metabolic changes in transgenic food crops.  J Biotechnol. 2000;  77 103-14
    CrossrefPubMedSearch in Google Scholar
  • 44 Choi Y H, Choi H K, Hazekamp A, Bermejo P, Schilder Y, Erkelens C. et al . Quantitative analysis of bilobalide and ginkgolides from Ginkgo biloba leaves and ginkgo products using 1H-NMR.  Chem Pharm Bull. 2003;  51 158-61
    CrossrefPubMedSearch in Google Scholar
  • 45 Keun H C, Ebbels T MD, Antti H, Bollard M E, Beckonert O, Schlotterbeck G. et al . Analytical reproducibility in 1H NMR-based metabonomic urine analysis.  Chem Res Toxicol. 2002;  15 1380-6
    CrossrefPubMedSearch in Google Scholar
  • 46 Belton P S, Delgadillo I, Gil A M, Roma P, Casuscelli F, Colquhoun I J. et al . High-field proton NMR studies of apple juices.  Magn Reson Chem. 1997;  35 S52-60
    CrossrefPubMedSearch in Google Scholar
  • 47 Sacchi R, Addeo F, Paolillo L. 1H and 13C NMR of virgin olive oil. An overview.  Magn Reson Chem. 1997;  35 S133-45
    CrossrefPubMedSearch in Google Scholar
  • 48 Kim H K, Choi Y H, Chang W T, Verpoorte R. Quantitative analysis of ephedrine analogues from Ephedra species using 1H-NMR.  Chem Pharm Bull. 2003;  51 1382-5
    CrossrefPubMedSearch in Google Scholar
  • 49 Bilia A R, Bergonzi M C, Lazari D, Vincieri F F. Characterization of commercial kava-kava herbal drug and herbal drug preparations by means of nuclear magnetic resonance spectroscopy.  J Agric Food Chem. 2002;  50 5016-25
    CrossrefPubMedSearch in Google Scholar
  • 50 Frederich M, Choi Y H, Verpoorte R. Quantitative analysis of strychnine and brucine in Strychnos nux-vomica using 1H-NMR.  Planta Med. 2003;  69 1169-71
    Thieme ConnectPubMedSearch in Google Scholar
  • 51 Li C Y, Lin C H, Wu C C, Lee K H, Wu T S. Efficient 1H nuclear magnetic resonance method for improved quality control analyses of ginkgo constituents.  J Agric Food Chem. 2004;  52 3721-5
    CrossrefPubMedSearch in Google Scholar
  • 52 Villas-Boas S G, Rasmussen S, Lane G A. Metabolomics or metabolite profiles?.  Trends Biotechnol. 2005;  23 385-6
    CrossrefPubMedSearch in Google Scholar
  • 53 Lindon J C, Holmes E, Nicholson J K. Toxicological applications of magnetic resonance.  Prog Nucl Magn Reson Spectrosc. 2004;  45 109-43
    PubMedSearch in Google Scholar
  • 54 Bollard M E, Stanley E G, Lindon J C, Nicholson J K, Holmes E. NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition.  NMR Biomed. 2005;  18 143-62
    CrossrefPubMedSearch in Google Scholar
  • 55 Bailey N JC, Sampson J, Hylands P J, Nicholson J K, Holmes E. Multi-component metabolic classification of commercial feverfew preparations via high-field 1H-NMR spectroscopy and chemometrics.  Planta Med. 2002;  68 734-8
    Thieme ConnectPubMedSearch in Google Scholar
  • 56 Frederich M, Choi Y H, Angenot L, Harnischfeger G, Lefeber A WM, Verpoorte R. Metabolomic analysis of Strychnos nux-vomica, Strychnos icaja and Strychnos ignatii extracts by 1H nuclear magnetic resonance spectrometry and multivariate analysis techniques.  Phytochemistry. 2004;  65 993-2001
    PubMedSearch in Google Scholar
  • 57 Moing A, Maucourt M, Renaud C, Gaudillere M, Brouquisse R, Lebouteiller B. et al . Quantitative metabolic profiling by 1-dimensional 1H-NMR analyses: application to plant genetics and functional genomics.  Funct Plant Biol. 2004;  31 889-902
    CrossrefPubMedSearch in Google Scholar
  • 58 Kirk H, Choi Y H, Kim H K, Verpoorte R, van der Meijden E. Comparing metabolomes: The chemical consequences of hybridization in plants.  New Phytol. 2005;  167 613-22
    CrossrefPubMedSearch in Google Scholar
  • 59 Pereira G E, Gaudillere J P, Van Leeuwen C, Hilbert G, Lavialle O, Maucourt M. et al . 1H NMR and chemometrics to characterize mature grape berries in four wine-growing areas in Bordeaux, France.  J Agric Food Chem. 2005;  53 6382-9
    CrossrefPubMedSearch in Google Scholar
  • 60 Lindon J C, Nicholson J K, Holmes E, Everett J R. Metabonomics: metabolic processes studied by NMR spectroscopy of biofluids.  Concepts Magn Reson. 2000;  12 289-320
    PubMedSearch in Google Scholar
  • 61 Le Gall G, Colquhoun I J, Davis A L, Collins G J, Verhoeyen M E. Metabolite profiling of tomato (Lycopersicon esculentum) using 1H NMR spectroscopy as a tool to detect potential unintended effects following a genetic modification.  J Agric Food Chem. 2003;  51 2447-56
    CrossrefPubMedSearch in Google Scholar
  • 62 Holmes E, Foxall P JD, Spraul M, Farrant D, Nicholson J K, Lindon J C. 750 MHz 1H NMR spectroscopy characterisation of the complex metabolic pattern of urine from patients with inborn errors in metabolism: 2-hydroxyglutaric aciduria and maple syrup urine disease.  J Pharm Biomed Anal. 1997;  15 1647-59
    CrossrefPubMedSearch in Google Scholar
  • 63 Lindon J C, Nicholson J K. Recent advances in high-resolution NMR spectroscopic methods in bioanalytical chemistry.  Trends Anal Chem. 1997;  16 190-200
    CrossrefPubMedSearch in Google Scholar
  • 64 Phalaraksh C, Lenz E M, Lindon J C, Nicholson J K, Farrant R D, Reynolds S E. et al . NMR spectroscopic studies on the hemolymph of the tobacco hornworm, Manduca sexta: assignment of 1H and 13C NMR spectra.  Insect Biochem Mol Biol. 1999;  29 795-805
    CrossrefPubMedSearch in Google Scholar
  • 65 Viant M R. Improved methods for the acquisition and interpretation of NMR metabolomic data.  Biochem Biophys Res Commun. 2003;  310 943-8
    CrossrefPubMedSearch in Google Scholar
  • 66 Scheidt H A, Pampel A, Nissler L, Gebhardt R, Huster D. Investigation of the membrane localization and distribution of flavonoids by high-resolution magic angle spinning NMR spectroscopy.  Biochim Biophys Acta. 2004;  1663 7-107
    PubMedSearch in Google Scholar
  • 67 Terskikh V V, Feurtado J A, Borchardt S, Giblin M, Abrams S R, Kermode A R. In vivo 13C NMR metabolite profiling: potential for understanding and assessing conifer seed quality.  J Exp Bot. 2005;  56 2253-65
    CrossrefPubMedSearch in Google Scholar
  • 68 Bilia A R, Bergonzi M C, Mazzi G, Vincieri F F. Analysis of plant complex matrixes by use of nuclear magnetic resonance spectroscopy: St. John’s wort extract.  J Agric Food Chem. 2001;  49 2115-24
    CrossrefPubMedSearch in Google Scholar
  • 69 Reynolds W F, Enriquez R G. Choosing the best pulse sequences, acquisition parameters, postacquisition processing strategies, and probes for natural product structure elucidation by NMR spectroscopy.  J Nat Prod. 2002;  65 221-44
    CrossrefPubMedSearch in Google Scholar
  • 70 Khatib A A, Wilson E G, Kim H K, Lefeber A WM, Erkelens C, Choi Y H. et al . Application of two-dimensional J-resolved nuclear magnetic resonance spectroscopy to differentiation of beer.  Anal Chim Acta. 2006;  559 264-70
    CrossrefPubMedSearch in Google Scholar
  • 71 Seger C, Godejohann M, Spraul M, Girtler A, Sturm S, Stuppner H. The LC-DAD-MS/SPE-NMR hyphenation. A tool for the analysis of pharmaceutically used plant extracts: Identification of isobaric iridoid glycoside regioisomers from Harpagophytum procumbens .  Anal Chem. 2005;  77 878-85
    CrossrefPubMedSearch in Google Scholar
  • 72 Wold S, Sjostrom M, Eriksson L. PLS-regression: a basic tool of chemometrics.  Chemometr Intell Lab Syst. 2001;  58 109-30
    CrossrefPubMedSearch in Google Scholar
  • 73 Holmes E, Antti H. Chemometric contributions to the evolution of metabonomics.  Analyst. 2002;  127 1549-57
    CrossrefPubMedSearch in Google Scholar
  • 74 Defernez M, Colquhoun I J. Factors affecting the robustness of metabolite fingerprinting using 1H NMR spectra.  Phytochemistry. 2003;  62 1009-17
    CrossrefPubMedSearch in Google Scholar
  • 75 Trygg J. O2-PLS for qualitative and quantitative analysis in multivariate calibration.  J Chemometr. 2002;  16 283-93
    CrossrefPubMedSearch in Google Scholar
  • 76 Cloarec O, Dumas M E, Craig A, Barton R H, Trygg J, Hudson J. et al . Statistical total correlation spectroscopy: An exploratory approach for latent biomarker identification from metabolic 1H NMR data sets.  Anal Chem. 2005;  77 1282-9
    CrossrefPubMedSearch in Google Scholar
  • 77 Wang Y, Tang H, Nicholson J K, Hylands P J, Sampson J, Whitcombe S. et al . Metabolomic strategy for the classification and quality control of phytomedicine: a case study of chamomile flower (Matricaria recutita L.)  Planta Med. 2004;  70 250-5
    Thieme ConnectPubMedSearch in Google Scholar
  • 78 Boti J B, Koukoua G, N"Guessan T Y, Muselli A, Bernardini A F, Casanova J. Composition of the leaf, stem bark and root bark oils of Isolona cooperi investigated by GC (retention index), GC-MS and 13C-NMR spectroscopy.  Phytochem Anal. 2005;  16 357-63
    CrossrefPubMedSearch in Google Scholar
  • 79 Ward J L, Harris C, Lewis J, Beale M H. Assessment of 1H NMR spectroscopy and multivariate analysis as a technique for metabolite fingerprinting of Arabidopsis thaliana .  Phytochemistry. 2003;  62 949-57
    CrossrefPubMedSearch in Google Scholar
  • 80 Sobolev A P, Segre A, Lamanna R. Proton high-field NMR study of tomato juice.  Magn Reson Chem. 2003;  41 237-45
    CrossrefPubMedSearch in Google Scholar
  • 81 Gil A M, Duarte I F, Delgadillo I, Colquhoun I J, Casuscelli F, Humpfer E. et al . Study of the compositional changes of mango during ripening by use of nuclear magnetic resonance spectroscopy.  J Agric Food Chem. 2000;  48 524-6
    CrossrefPubMedSearch in Google Scholar
  • 82 Belton P S, Colquhoun I J, Kemsley E K, Delgadillo I, Roma P, Dennis M J. et al . Application of chemometrics to the 1H NMR spectra of apple juices: discrimination between apple varieties.  Food Chem. 1998;  61 207-13
    CrossrefPubMedSearch in Google Scholar
  • 83 Vogels J TWE, Terwel L, Tas A C, van den Berg F, Dukel F, van der Greef J. Detection of adulteration in orange juices by a new screening method using proton NMR spectroscopy in combination with pattern recognition techniques.  J Agric Food Chem. 1996;  44 175-80
    CrossrefPubMedSearch in Google Scholar
  • 84 Le Gall G, Puaud M, Colquhoun I J. Discrimination between orange juice and pulp wash by 1H nuclear magnetic resonance spectroscopy: identification of marker compounds.  J Agric Food Chem. 2001;  49 580-8
    CrossrefPubMedSearch in Google Scholar
  • 85 Sobolev A P, Brosio E, Gianferri R, Segre A L. Metabolic profile of lettuce leaves by high-field NMR spectra.  Magn Reson Chem. 2005;  43 625-38
    CrossrefPubMedSearch in Google Scholar
  • 86 Kosir I J, Kidric J. Identification of amino acids in wines by one- and two-dimensional nuclear magnetic resonance spectroscopy.  J Agric Food Chem. 2001;  49 50-6
    CrossrefPubMedSearch in Google Scholar
  • 87 Kosir I J, Kidric J. Use of modern nuclear magnetic resonance spectroscopy in wine analysis: determination of minor compounds.  Anal Chim Acta. 2002;  458 77-84
    CrossrefPubMedSearch in Google Scholar
  • 88 Vlahov G. Application of NMR to the study of olive oils.  Prog Nucl Magn Reson Spectrosc. 1999;  35 341-57
    PubMedSearch in Google Scholar
  • 89 Duarte I F, Barros A, Belton P S, Righelato R, Spraul M, Humpfer E. et al . High-resolution nuclear magnetic resonance spectroscopy and multivariate analysis for the characterization of beer.  J Agric Food Chem. 2002;  50 2475-81
    CrossrefPubMedSearch in Google Scholar
  • 90 Duarte I F, Barros A, Almeida C, Spraul M, Gil A M. Multivariate Analysis of NMR and FT-IR data as a potential tool for the quality control of beer.  J Agric Food Chem. 2004;  52 1031-8
    PubMedSearch in Google Scholar
  • 91 Lachenmeier D W, Frank W, Humpfer E, Schäfer H, Keller S, Mörtter M. et al . Quality control of beer using high-resolution nuclear magnetic resonance spectroscopy and multivariate analysis.  Eur Food Res Technol. 2005;  220 215-22
    CrossrefPubMedSearch in Google Scholar
  • 92 Nilsson M, Duarte I F, Almeida C, Delgadillo I, Goodfellow B J, Gil A M. et al . High-resolution NMR and diffusion-ordered spectroscopy of port wine.  J Agric Food Chem. 2004;  52 3736-43
    CrossrefPubMedSearch in Google Scholar
  • 93 Le Gall G, Colquhoun I J, Defernez M. Metabolite profiling using 1H NMR spectroscopy for quality assessment of green tea, Camellia sinensis (L.)  J Agric Food Chem. 2004;  52 692-700
    CrossrefPubMedSearch in Google Scholar
  • 94 Charlton A J, Farrington W HH, Brereton P. Application of 1H NMR and multivariate statistics for screening complex mixtures: quality control and authenticity of instant coffee.  J Agric Food Chem. 2002;  50 3098-103
    CrossrefPubMedSearch in Google Scholar
  • 95 Eads T M, Bryant R G. High-resolution proton NMR spectroscopy of milk, orange juice, and apple juice with efficient suppression of the water peak.  J Agric Food Chem. 1986;  34 834-7
    CrossrefPubMedSearch in Google Scholar
  • 96 Martin G J, Guillou C, Martin M L, Cabanis M T, Tep Y, Aerny J. Natural factors of isotope fractionation and the characterization of wines.  J Agric Food Chem. 1988;  36 316-22
    CrossrefPubMedSearch in Google Scholar
  • 97 Brescia M A, Caldarola V, De Giglio A, Benedetti D, Fanizzi F P, Sacco A. Characterization of the geographical origin of Italian red wines based on traditional and nuclear magnetic resonance spectrometric determinations.  Anal Chim Acta. 2002;  458 177-86
    CrossrefPubMedSearch in Google Scholar
  • 98 Brescia M A, Kosir I J, Caldarola V, Kidric J, Sacco A. Chemometric classification of Apulian and Slovenian wines using 1H NMR and ICP-OES together with HPICE data.  J Agric Food Chem. 2003;  51 21-6
    CrossrefPubMedSearch in Google Scholar
  • 99 Forveffle L, Vercauteren J, Rutledge D N. Multivariate statistical analysis of two-dimensional NMR data to differentiate grapevine cultivars and clones.  Food Chem. 1996;  57 441-50
    CrossrefPubMedSearch in Google Scholar
  • 100 Mannina L, Patumi M, Proietti N, Bassi D, Segre A L. Geographical characterization of Italian extra virgin olive oils using high-field H-1 NMR spectroscopy.  J Agric Food Chem. 2001;  49 2687-96
    PubMedSearch in Google Scholar
  • 101 Mannina L, Patumi M, Proietti N, Segre A L. P.D.O. (protected designation of origin): geographical characterization of Tuscan extra virgin olive oils using high-field 1H NMR spectroscopy.  Ital J Food Sci. 2001;  13 53-63
    PubMedSearch in Google Scholar
  • 102 Brescia M A, Alviti G, Liuzzi V, Sacco A. Chemometric classification of olive cultivars based on compositional data of oils.  J Am Oil Chem Soc. 2003;  80 945-50
    PubMedSearch in Google Scholar
  • 103 Vlahov G, Del Re P, Simone N. Determination of geographical origin of olive oils using 13C nuclear magnetic resonance spectroscopy. I-Classification of olive oils of the Puglia region with denomination of protected origin.  J Agric Food Chem. 2003;  51 5612-5
    CrossrefPubMedSearch in Google Scholar
  • 104 Mannina L, Dugo G, Salvo F, Cicero L, Ansanelli G, Calcagni C, Segre A L. Study of the cultivar-composition relationship in Sicilian olive oils by GC, NMR, and statistical methods.  J Agric Food Chem. 2003;  51 120-7
    CrossrefPubMedSearch in Google Scholar
  • 105 Rezzi S, Axelson D E, Heberger K, Reniero F, Mariani C, Guillou C. Classification of olive oils using high throughput flow 1H NMR fingerprinting with principal component analysis, linear discriminant analysis and probabilistic neural networks.  Anal Chim Acta. 2005;  552 13-24
    CrossrefPubMedSearch in Google Scholar
  • 106 Garcia-Gonzalez D L, Mannina L, D"Imperio M, Segre A L, Aparicio R. Using 1H and 13C NMR techniques and artificial neural networks to detect the adulteration of olive oil with hazelnut oil.  Eur Food Res Technol. 2004;  219 545-8
    CrossrefPubMedSearch in Google Scholar
  • 107 Fragaki G, Spyros A, Siragakis G, Salivaras E, Dais P. Detection of extra virgin olive oil adulteration with lampante olive oil and refined olive oil using nuclear magnetic resonance spectroscopy and multivariate statistical analysis.  J Agric Food Chem. 2005;  53 2810-6
    PubMedSearch in Google Scholar
  • 108 Lau A J, Holmes M J, Woo S O, Koh H L. Analysis of adulterants in a traditional herbal medicinal product using liquid chromatography-mass spectrometry-mass spectrometry.  J Pharm Biomed Anal. 2003;  31 401-6
    CrossrefPubMedSearch in Google Scholar
  • 109 Balunas M J, Kinghorn A D. Drug discovery from medicinal plants.  Life Sci. 2005;  78 431-41
    CrossrefPubMedSearch in Google Scholar
  • 110 Bilia A R, Bergonzi M C, Mazzi G, Vincieri F F. NMR spectroscopy: a useful tool for characterization of plant extracts, the case of supercritical CO2 arnica extract.  J Pharm Biomed Anal. 2002;  30 321-30
    CrossrefPubMedSearch in Google Scholar
  • 111 Bailey N JC, Wang Y L, Sampson J, Davis W, Whitcombe I, Hylands P J. et al . Prediction of anti-plasmodial activity of Artemisia annua extracts: application of 1H NMR spectroscopy and chemometrics.  J Pharm Biomed Anal. 2004;  35 117-26
    CrossrefPubMedSearch in Google Scholar
  • 112 Kim H K, Choi Y H, Erkelens C, Lefebre A WM, Verpoorte R. Metabolic fingerprinting of Ephedra species using H-1-NMR spectroscopy and principal component analysis.  Chem Pharm Bull. 2005;  53 105-9
    CrossrefPubMedSearch in Google Scholar
  • 113 Choi Y H, Kim H K, Hazekamp A, Erkelens C, Lefeber A WM, Verpoorte R. Metabolomic differentiation of Cannabis sativa cultivars using 1H NMR spectroscopy and principal component analysis.  J Nat Prod. 2004;  67 953-7
    CrossrefPubMedSearch in Google Scholar
  • 114 Choi Y H, Sertic S, Kim H K, Wilson E G, Michopoulos F, Lefeber A WM. et al . Classification of Ilex species based on metabolomic fingerprinting using nuclear magnetic resonance and multivariate data analysis.  J Agric Food Chem. 2005;  53 1237-45
    CrossrefPubMedSearch in Google Scholar
  • 115 Roos G, Röseler C, Berger-Büter K, Simmen U. Classification and correlation of St. John's wort extracts by nuclear magnetic resonance spectroscopy, multivariate data analysis and pharmacological activity.  Planta Med. 2004;  70 771-7
    Thieme ConnectPubMedSearch in Google Scholar
  • 116 Seger C, Sturm S, Humpfer E, Schäfer H, Spraul M, Stuppner H. Differentiation of Hypericum perforatum (St. John’s wort) lots by NMR based metabonomics. 53rd Congress of the Society for Medicinal Plant Research Florence, Italy; 2005
    Search in Google Scholar
  • 117 Le Gall G, DuPont M S, Mellon F A, Davis A L, Collins G J, Verhoeyen M E. et al . Characterization and content of flavonoid glycosides in genetically modified tomato (Lycopersicon esculentum) fruits.  J Agric Food Chem. 2003;  51 2438-46
    CrossrefPubMedSearch in Google Scholar
  • 118 Wang Y, Xue Y, Li J. Towards molecular breeding and improvement of rice in China.  Trends Plant Sci. 2005;  10 610-4
    CrossrefPubMedSearch in Google Scholar
  • 119 Defernez M, Gunning Y M, Parr A J, Shepherd L VT, Davies H V, Colquhoun I J. NMR and HPLC-UV profiling of potatoes with genetic modifications to metabolic pathways.  J Agric Food Chem. 2004;  52 6075-85
    CrossrefPubMedSearch in Google Scholar
  • 120 Choi H K, Choi Y H, Verberne M, Lefeber A WM, Erkelens C, Verpoorte R. Metabolic fingerprinting of wild type and transgenic tobacco plants by 1H NMR and multivariate analysis technique.  Phytochemistry. 2004;  65 857-64
    CrossrefPubMedSearch in Google Scholar
  • 121 Choi Y H, Tapias E C, Kim H K, Lefeber A WM, Erkelens C, Verhoeven J TJ. et al . Metabolic discrimination of Catharanthus roseus leaves infected by phytoplasma using 1H-NMR spectroscopy and multivariate data analysis.  Plant Physiol. 2004;  135 2398-410
    CrossrefPubMedSearch in Google Scholar
  • 122 Gavaghan C L, Holmes E, Lenz E, Wilson I D, Nicholson J K. An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences: application to the C57BL10J and Alpk:ApfCD mouse.  FEBS Lett. 2000;  484 169-74
    CrossrefPubMedSearch in Google Scholar
  • 123 Griffin J L, Williams H J, Sang E, Clarke K, Rae C, Nicholson J K. Metabolic profiling of genetic disorders: A multi tissue 1H nuclear magnetic resonance spectroscopic and pattern recognition study into dystrophic tissue.  Anal Biochem. 2001;  293 16-21
    CrossrefPubMedSearch in Google Scholar
  • 124 Ebbels T MD, Holmes E, Lindon J C, Nicholson J K. Evaluation of metabolic variation in normal rat strains from a statistical analysis of 1H NMR spectra of urine.  J Pharm Biomed Anal. 2004;  36 823-33
    CrossrefPubMedSearch in Google Scholar
  • 125 Gavaghan McKee C L, Wilson I D, Nicholson J K. Metabolic phenotyping of nude and normal (Alpk:ApfCD, C57BL10J) mice.  J Proteome Res. 2006;  5 378-84
    CrossrefPubMedSearch in Google Scholar
  • 126 Raamsdonk L M, Teusink B, Broadhurst D, Zhang N, Hayes A, Walsh M C. et al . A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations.  Nat Biotechnol. 2001;  19 45-50
    PubMedSearch in Google Scholar
  • 127 Charlton A, Allnutt T, Holmes S, Chisholm J, Bean S, Ellis N. et al . NMR profiling of transgenic peas.  Plant Biotech J. 2004;  2 27-35
    CrossrefPubMedSearch in Google Scholar
  • 128 Manetti C, Bianchetti C, Bizzarri M, Casciani L, Castro C, D’Ascenzo G. et al . NMR-based metabonomic study of transgenic maize.  Phytochemistry. 2004;  65 3187-98
    CrossrefPubMedSearch in Google Scholar
  • 129 Wiklund S, Karlsson M, Antti H, Johnels D, Sjoestroem M, Wingsle G. et al . A new metabonomic strategy for analyzing the growth process of the poplar tree.  Plant Biotechnol J. 2005;  3 353-62
    PubMedSearch in Google Scholar
  • 130 Bailey N JC, Oven M, Holmes E, Nicholson J K, Zenk M H. Metabolomic analysis of the consequences of cadmium exposure in Silene cucubalus cell cultures via 1H NMR spectroscopy and chemometrics.  Phytochemistry. 2003;  62 851-8
    CrossrefPubMedSearch in Google Scholar
  • 131 Ott K H, Aranibar N, Singh B, Stockton G W. Metabonomics classifies pathways affected by bioactive compounds. Artificial neural network classification of NMR spectra of plant extracts.  Phytochemistry. 2003;  62 971-85
    CrossrefPubMedSearch in Google Scholar
  • 132 Solanky K S, Bailey N JC, Holmes E, Lindon J C, Davis A L, Mulder T PJ. et al . NMR-based metabonomic studies on the biochemical effects of epicatechin in the rat.  J Agric Food Chem. 2003;  51 4139-45
    CrossrefPubMedSearch in Google Scholar
  • 133 Solanky K S, Bailey N J, Beckwith-Hall B M, Bingham S, Davis A, Holmes E. et al . Biofluid 1H NMR-based metabonomic techniques in nutrition research - metabolic effects of dietary isoflavones in humans.  J Nutr Biochem. 2005;  16 236-44
    PubMedSearch in Google Scholar
  • 134 Solanky K S, Bailey N JC, Beckwith-Hall B M, Davis A, Bingham S, Holmes E. et al . Application of biofluid 1H nuclear magnetic resonance-based metabonomic techniques for the analysis of the biochemical effects of dietary isoflavones on human plasma profile.  Anal Biochem. 2003;  323 197-204
    CrossrefPubMedSearch in Google Scholar
  • 135 Daykin C A, Van Duynhoven J PM, Groenewegen A, Dachtler M, Van Amelsvoort J MM, Mulder T PJ. Nuclear magnetic resonance spectroscopic based studies of the metabolism of black tea polyphenols in humans.  J Agric Food Chem. 2005;  53 1428-34
    CrossrefPubMedSearch in Google Scholar
  • 136 Wang Y, Tang H, Nicholson J K, Hylands P J, Sampson J, Holmes E. A metabonomic strategy for the detection of the metabolic effects of chamomile (Matricaria recutita L.) ingestion.  J Agric Food Chem. 2005;  53 191-196
    CrossrefPubMedSearch in Google Scholar
  • 137 Fukusaki E, Kobayashi A. Plant metabolomics: potential for practical operation.  J Biosci Bioeng. 2005;  100 347-54
    CrossrefPubMedSearch in Google Scholar
  • 138 Weckwerth W. Metabolomics in systems biology.  Ann Rev Plant Biol. 2003;  54 669-89
    PubMedSearch in Google Scholar
  • 139 Verpoorte R, Choi Y H, Kim H K. Ethnopharmacology and systems biology: a perfect holistic match.  J Ethnopharmacol. 2005;  100 53-6
    CrossrefPubMedSearch in Google Scholar
  • 140 Bino R J, Hall R D, Fiehn O, Kopka J, Saito K, Draper J. et al . Potential of metabolomics as a functional genomics tool.  Trends Plant Sci. 2004;  9 418-25
    CrossrefPubMedSearch in Google Scholar
  • 141 Jenkins H, Hardy N, Beckmann M, Draper J, Smith A R, Taylor J. et al . A proposed framework for the description of plant metabolomics experiments and their results.  Nat Biotechnol. 2004;  22 1601-6
    PubMedSearch in Google Scholar
  • 142 Kell D B. Metabolomics and system biology: making sense of the soup.  Curr Opin Microbiol. 2004;  7 296-307
    CrossrefPubMedSearch in Google Scholar
  • 143 Jenkins H, Johnson H, Kular B, Wang T, Hardy N. Toward supportive data collection tools for plant metabolomics.  Plant Physiol. 2005;  138 67-77
    CrossrefPubMedSearch in Google Scholar
  • 144 Lindon J C, Nicholson J K, Holmes E, Keun H C, Craig A, Pearce J T. et al . Summary recommendations for standardization and reporting of metabolic analyses.  Nat Biotechnol. 2005;  23 833-8
    PubMedSearch in Google Scholar

Dr. Christoph Seger

Institute of Pharmacy/Pharmacognosy

Centre of Molecular Biosciences

University of Innsbruck

Innrain 52

6020 Innsbruck

Austria

Phone: +43-512-507-5344

Fax: +43-512-507-2939

Email: christoph.seger@uibk.ac.at