Application of Plant Metabonomics in Quality Assessment for
                    Large-Scale Production of Traditional Chinese Medicine

Zhangchi Ning; Cheng Lu; Yuxin Zhang; Siyu Zhao; Baoqin Liu; Xuegong Xu; Yuanyan Liu

doi:10.1055/s-0032-1328656

Planta Medica, Inhaltsverzeichnis

Planta Med 2013; 79(11): 897-908
DOI: 10.1055/s-0032-1328656

Reviews

Georg Thieme Verlag KG Stuttgart · New York

Application of Plant Metabonomics in Quality Assessment for Large-Scale Production of Traditional Chinese Medicine

Zhangchi Ning

¹School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China

,

Cheng Lu

²Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China

,

Yuxin Zhang

¹School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China

,

Siyu Zhao

¹School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China

,

Baoqin Liu

³Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou, China

,

Xuegong Xu

³Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou, China

,

Yuanyan Liu

¹School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China

› Institutsangaben

Abstract

The curative effects of traditional Chinese medicines are principally based on the synergic effect of their multi-targeting, multi-ingredient preparations, in contrast to modern pharmacology and drug development that often focus on a single chemical entity. Therefore, the method employing a few markers or pharmacologically active constituents to assess the quality and authenticity of the complex preparations has a number of severe challenges. Metabonomics can provide an effective platform for complex sample analysis. It is also reported to be applied to the quality analysis of the traditional Chinese medicine. Metabonomics enables comprehensive assessment of complex traditional Chinese medicines or herbal remedies and sample classification of diverse biological statuses, origins, or qualities in samples, by means of chemometrics. Identification, processing, and pharmaceutical preparation are the main procedures in the large-scale production of Chinese medicinal preparations. Through complete scans, plants metabonomics addresses some of the shortfalls of single analyses and presents a considerable potential to become a sharp tool for traditional Chinese medicine quality assessment.

Key words

plant metabonomics - large-scale production - discrimination - processing - pharmaceutics

Volltext

Referenzen

References
1 Nicholson JK, Wilson ID. Opinion: understanding ʼglobalʼ systems biology: metabonomics and the continuum of metabolism. Nat Rev Drug Discov 2003; 2: 668-676
2 Hui-Ru T, Yu-Lan W. Metabonomics: a revolution in progress. Prog Biochem Biophys 2006; 33: 401-417
3 Dong J, Xu L, Cao H, Dai X, Li X, Yang S, Chen Z. A new data processing method for metabonomic and its application in a study of diabetes. Chin J Magn Reson 2007; 24: 393
4 Lu YH, Hao HP, Wang GJ, Chen XH, Zhu XX, Xiang BR, Huang Q. A JY. Metabolomics approach to the biochemical differentiation of Traditional Chinese Medicine syndrome types of hypertension. Chin J Clin Pharmacol Ther 2007; 12: 1144-1150
5 Cheng LL, Chang IW, Louis DN, Gonzalez RG. Correlation of high-resolution magic angle spinning proton magnetic resonance spectroscopy with histopathology of intact human brain tumor specimens. Cancer Res 1998; 58: 1825-1832
6 Cheng L, Ma M, Becerra L, Ptak T, Tracey I, Lackner A, Gonzalez R. Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy. Proc Natl Acad Sci U S A 1997; 94: 6408-6413
7 Lao YM, Jiang JG, Yan L. Application of metabonomic analytical techniques in the modernization and toxicology research of traditional Chinese medicine. Br J Pharmacol 2009; 157: 1128-1141
8 Kim N, Kim K, Choi BY, Lee DH, Shin YS, Bang KH, Cha SW, Lee JW, Choi HK, Jang DS. Metabolomic approach for age discrimination of Panax ginseng using UPLC-Q-Tof MS. J Agric Food Chem 2011; 59: 10435-10441
9 Holmes E, Wilson ID, Nicholson JK. Metabolic phenotyping in health and disease. Cell 2008; 134: 714-717
10 Yuliana ND, Khatib A, Choi YH, Verpoorte R. Metabolomics for bioactivity assessment of natural products. Phytother Res 2010; 25: 157-169
11 Nobeli I, Thornton JM. A bioinformaticianʼs view of the metabolome. Bioessays 2006; 28: 534-545
12 Wold S, Sjöström M, Eriksson L. PLS-regression: a basic tool of chemometrics. Chemom Intell Lab Syst 2001; 58: 109-130
13 Gabrielsson J, Jonsson H, Airiau C, Schmidt B, Escott R, Trygg J. OPLS methodology for analysis of pre-processing effects on spectroscopic data. Chemom Intell Lab Syst 2006; 84: 153-158
14 Wold S, Trygg J, Berglund A, Antti H. Some recent developments in PLS modeling. Chemom Intell Lab Syst 2001; 58: 131-150
15 Ceglarek U, Leichtle A, Brügel M, Kortz L, Brauer R, Bresler K, Thiery J, Fiedler GM. Challenges and developments in tandem mass spectrometry based clinical metabolomics. Mol Cell Endocrinol 2009; 301: 266-271
16 Hastings CA, Norton SM, Roy S. New algorithms for processing and peak detection in liquid chromatography/mass spectrometry data. Rapid Commun Mass Spectrom 2002; 16: 462-467
17 Danielsson R, Bylund D, Markides KE. Matched filtering with background suppression for improved quality of base peak chromatograms and mass spectra in liquid chromatography–mass spectrometry. Anal Chim Acta 2002; 454: 167-184
18 Andreev VP, Rejtar T, Chen HS, Moskovets EV, Ivanov AR, Karger BL. A universal denoising and peak picking algorithm for LC-MS based on matched filtration in the chromatographic time domain. Anal Chem 2003; 75: 6314-6326
19 Bueschl C, Kluger B, Berthiller F, Lirk G, Winkler S, Krska R, Schuhmacher R. MetExtract: a new software tool for the automated comprehensive extraction of metabolite-derived LC/MS signals in metabolomics research. Bioinformatics 2012; 28: 736-738
20 Mok DKW, Chau FT. Chemical information of Chinese medicines: A challenge to chemist. Chemom Intell Lab Syst 2006; 82: 210-217
21 Xie P, Chen S, Liang YZ, Wang X, Tian R, Upton R. Chromatographic fingerprint analysis–a rational approach for quality assessment of traditional Chinese herbal medicine. J Chromatogr A 2006; 1112: 171-180
22 Li L, Sun B, Zhang Q, Fang J, Ma K, Li Y, Chen H, Dong F, Gao Y, Li F, Yan X. Metabonomic study on the toxicity of Hei-Shun-Pian, the processed lateral root of Aconitum carmichaelii Debx. (Ranunculaceae). J Ethnopharmacol 2008; 116: 561-568
23 Zhang A, Sun H, Wang P, Han Y, Wang X. Recent and potential developments of biofluid analyses in metabolomics. J Proteom 2012; 75: 1079-1088
24 Duan LX, Chen TL, Li M, Chen M, Zhou YQ, Cui GH, Zhao AH, Jia W, Huang LQ, Qi X. Use of the metabolomics approach to characterize Chinese medicinal material Huangqi. Mol Plant 2012; 5: 376-386
25 Xie G, Plumb R, Su M, Xu Z, Zhao A, Qiu M, Long X, Liu Z, Jia W. Ultra-performance LC/TOF MS analysis of medicinal Panax herbs for metabolomic research. J Sep Sci 2008; 31: 1015-1026
26 Yi L, Yuan D, Liang Y, Xie P, Zhao Y. Fingerprinting alterations of secondary metabolites of tangerine peels during growth by HPLC–DAD and chemometric methods. Anal Chim Acta 2009; 649: 43-51
27 Wang L, Wang X, Kong L. Automatic authentication and distinction of Epimedium koreanum and Epimedium wushanense with HPLC fingerprint analysis assisted by pattern recognition techniques. Biochem Syst Ecol 2012; 40: 138-145
28 Francisco CS, Messiano GB, Lopes LM, Tininis AG, de Oliveira JE, Capellari Jr. L. Classification of Aristolochia species based on GC-MS and chemometric analyses of essential oils. Phytochemistry 2008; 69: 168-175
29 Sun H, Wang M, Zhang A, Ni B, Dong H, Wang X. UPLC-Q-TOF-HDMS analysis of constituents in the root of two kinds of Aconitum using a metabolomics approach. Phytochem Anal 2013; 24: 263-276
30 Liu NQ, Cao M, Frederich M, Choi YH, Verpoorte R, van der Kooy F. Metabolomic investigation of the ethnopharmacological use of Artemisia afra with NMR spectroscopy and multivariate data analysis. J Ethnopharmacol 2010; 128: 230-235
31 Lucio-Gutiérrez JR, Coello J, Maspoch S. Application of near infrared spectral fingerprinting and pattern recognition techniques for fast identification of Eleutherococcus senticosus . Food Res Int 2011; 44: 557-565
32 Lu GH, Chan K, Liang YZ, Leung K, Chan CL, Jiang ZH, Zhao ZZ. Development of high performance liquid chromatographic fingerprints for distinguishing Chinese Angelica from related Umbelliferae herbs. J Chromatogr A 2005; 1073: 383-392
33 Tistaert C, Dejaegher B, Chataigne G, Van Minh C, Quetin-Leclercq J, Vander Heyden Y. Dissimilar chromatographic systems to indicate and identify antioxidants from Mallotus species. Talanta 2011; 83: 1198-1208
34 Qin X, Dai Y, Liu NQ, Li Z, Liu X, Hu J, Choi YH, Verpoorte R. Metabolic fingerprinting by (1)H-NMR for discrimination of the two species used as Radix Bupleuri. Planta Med 2012; 78: 926-933
35 Tian RT, Xie PS, Liu HP. Evaluation of traditional Chinese herbal medicine: Chaihu (Bupleuri Radix) by both high-performance liquid chromatographic and high-performance thin-layer chromatographic fingerprint and chemometric analysis. J Chromatogr A 2009; 1216: 2150-2155
36 Fukuda E, Baba M, Iwasaki N, Uesawa Y, Arifuku K, Kamoe O, Tsubono K, Okada Y. Identification of Glycyrrhiza species by direct analysis in real time mass spectrometry. Nat Prod Commun 2010; 5: 1755-1758
37 Pan R, Guo F, Lu H, Feng WW, Liang YZ. Development of the chromatographic fingerprint of Scutellaria barbatan D. Don by GC-MS combined with chemometrics methods. J Pharm Biomed Anal 2011; 55: 391-396
38 Zhao YY, Zhang Y, Lin RC, Sun WJ. An expeditious HPLC method to distinguish Aconitum kusnezoffii from related species. Fitoterapia 2009; 80: 333-338
39 Xiang Z, Wang XQ, Cai XJ, Zeng S. Metabolomics study on quality control and discrimination of three Curcuma species based on gas chromatograph-mass spectrometry. Phytochem Anal 2011; 22: 411-418
40 Wu HW. Studies on warm and cold nature of JiangHuang and YuJin based on metabonomics [dissertation]. Beijing: Chinese Academy of Chinese Medical Sciences; 2011
41 Grubesić RJ, Vukovic J, Kremer D, Vladimir-Knezevic S. Spectrophotometric method for polyphenols analysis: prevalidation and application on Plantago L. species. J Pharm Biomed Anal 2005; 39: 837-842
42 Dan M, Su M, Gao X, Zhao T, Zhao A, Xie G, Qiu Y, Zhou M, Liu Z, Jia W. Metabolite profiling of Panax notoginseng using UPLC-ESI-MS. Phytochemistry 2008; 69: 2237-2244
43 Fukuda E, Yoshida M, Baba M, Uesawa Y, Suzuki R, Kamo O, Tsubono K, Arifuku K, Yatsunami K, Okada Y. Application to classification of mulberry leaves using multivariate analysis of proton NMR metabolomic data. Nat Prod Commun 2011; 6: 1621-1625
44 Kong WJ, Zhao YL, Xiao XH, Jin C, Li ZL. Quantitative and chemical fingerprint analysis for quality control of rhizoma Coptidischinensis based on UPLC-PAD combined with chemometrics methods. Phytomedicine 2009; 16: 950-959
45 Lai Y, Ni Y, Kokot S. Discrimination of Rhizoma Corydalis from two sources by near-infrared spectroscopy supported by the wavelet transform and least-squares support vector machine methods. Vib Spectrosc 2011; 56: 154-160
46 Zou P, Hong Y, Koh HL. Chemical fingerprinting of Isatis indigotica root by RP-HPLC and hierarchical clustering analysis. J Pharm Biomed Anal 2005; 38: 514-520
47 Chen Y, Xie MY, Yan Y, Zhu SB, Nie SP, Li C, Wang YX, Gong XF. Discrimination of Ganoderma lucidum according to geographical origin with near infrared diffuse reflectance spectroscopy and pattern recognition techniques. Anal Chim Acta 2008; 618: 121-130
48 Gong F, Liang YZ, Xu QS, Chau FT. Gas chromatography-mass spectrometry and chemometric resolution applied to the determination of essential oils in Cortex cinnamomi. J Chromatogr A 2001; 905: 193-205
49 Guo FQ, Liang YZ, Xu CJ, Li XN, Huang LF. Analyzing of the volatile chemical constituents in Artemisia capillaris herba by GC-MS and correlative chemometric resolution methods. J Pharm Biomed Anal 2004; 35: 469-478
50 Jung JH, Hong J. GC/MS combined with chemometrics methods for quality control of Schizonepeta tenuifolia Briq: Determination of essential oils. Microchem J 2011; 97: 274-281
51 Li W, Xing L, Cai Y, Qu H. Classification and quantification analysis of Radix scutellariae from different origins with near infrared diffuse reflection spectroscopy. Vib Spectrosc 2011; 55: 58-64
52 Ioset KN, Nyberg NT, Van Diermen D, Malnoe P, Hostettmann K, Shikov AN, Jaroszewski JW. Metabolic profiling of Rhodiola rosea rhizomes by (1)H-NMR spectroscopy. Phytochem Anal 2011; 22: 158-165
53 Zhao C, Chan HY, Yuan D, Liang Y, Lau TY, Chau FT. Rapid simultaneous determination of major isoflavones of Pueraria lobata and discriminative analysis of its geographical origins by principal component analysis. Phytochem Anal 2011; 22: 503-508
54 Tianniam S, Bamba T, Fukusaki E. Pyrolysis GC-MS-based metabolite fingerprinting for quality evaluation of commercial Angelica acutiloba roots. J Biosci Bioeng 2010; 109: 89-93
55 Wang HL, Yao WF, Zhu DN, Hu YZ. Chemical fingerprinting by HPLC-DAD-ELSD and principal component analysis of Polygala japonica from different locations in China. Chin J Nat Med 2010; 8: 343-348
56 Suzuki R, Ikeda Y, Yamamoto A, Saima T, Fujita T, Fukuda T, Fukuda E, Baba M, Okada Y, Shirataki Y. Classification using NMR-based metabolomics of Sophora flavescens grown in Japan and China. Nat Prod Commun 2012; 7: 1453-1455
57 Kim N, Kim K, Choi BY, Lee D, Shin YS, Bang KH, Cha SW, Lee JW, Choi HK, Jang DS. Metabolomic approach for age discrimination of Panax ginseng using UPLC-Q-Tof MS. J Agric Food Chem 2011; 59: 10435-10441
58 Yang SO, Shin YS, Hyun SH, Cho S, Bang KH, Lee D, Choi SP, Choi HK. NMR-based metabolic profiling and differentiation of ginseng roots according to cultivation ages. J Pharm Biomed Anal 2012; 58: 19-26
59 Xue SY, Wang XJ, Sun HF, Zhang LZ, Qin XM, Li ZY. Metabolomic study of flower buds of Tussilago farfara in different development stages by GC-MS. Zhongguo Zhong Yao Za Zhi 2012; 37: 2863-2869
60 Wang JH, Wang ZH. Studies on enhancing therapeutic action of processing Chinese crude drugs. Lishizhen J Tradit Chin Med Res 1997; 8: 67-68
61 Sun H, Ni B, Zhang A, Wang M, Dong H, Wang X. Metabolomics study on Fuzi and its processed products using ultra-performance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry coupled with pattern recognition analysis. Analyst 2012; 137: 170-185
62 Kim SH, Hyun SH, Yang SO, Choi HK, Lee BY. (1)H-NMR-based discrimination of thermal and vinegar treated ginseng roots. J Food Sci 2010; 75: C577-C581
63 Angelova N, Kong HW, van der Heijden R, Yang SY, Choi YH, Kim HK, Wang M, Hankemeier T, van der Greef J, Xu G, Verpoorte R. Recent methodology in the phytochemical analysis of ginseng. Phytochem Anal 2008; 19: 2-16
64 Zhang HM, Li SL, Zhang H, Wang Y, Zhao ZL, Chen SL, Xu HX. Holistic quality evaluation of commercial white and red ginseng using a UPLC-QTOF-MS/MS-based metabolomics approach. J Pharm Biomed Anal 2012; 62: 258-273
65 Lee JI, Ha YW, Choi TW, Kim HJ, Kim SM, Jang HJ, Choi JH, Choi MH, Chung BC, Sethi G, Kim SH, Ahn KS, Choi SH, Shim BS. Cellular uptake of ginsenosides in Korean white ginseng and red ginseng and their apoptotic activities in human breast cancer cells. Planta Med 2011; 77: 133-140
66 Kim SN, Ha YW, Shin H, Son SH, Wu SJ, Kim YS. Simultaneous quantification of 14 ginsenosides in Panax ginseng C.A. Meyer (Korean red ginseng) by HPLC-ELSD and its application to quality control. J Pharm Biomed Anal 2007; 45: 164-170
67 Leung KW, Wong AST. Pharmacology of ginsenosides: a literature review. Chin Med 2010; 5: 20
68 Yun TK, Lee YS, Lee YH, Kim SI, Yun HY. Anticarcinogenic effect of Panax ginseng CA Meyer and identification of active compounds. J Korean Med Sci 2001; 16: 6-18
69 Shibata S. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Korean Med Sci 2001; 16: S28-S37
70 Kim WY, Kim JM, Han SB, Lee SK, Kim ND, Park MK, Kim CK, Park JH. Steaming of ginseng at high temperature enhances biological activity. J Nat Prod 2000; 63: 1702-1704
71 Kwon SW, Han SB, Park IH, Kim JM, Park MK, Park JH. Liquid chromatographic determination of less polar ginsenosides in processed ginseng. J Chromatogr A 2001; 921: 335-339
72 Park IH, Kim NY, Han SB, Kim JM, Kwon SW, Kim HJ, Park MK, Park JH. Three new dammarane glycosides from heat processed ginseng. Arch Pharm Res 2002; 25: 428-432
73 Lee SM, Shon HJ, Choi CS, Hung TM, Min BS, Bae KH. Ginsenosides from heat processed ginseng. Chem Pharm Bull 2009; 57: 92-94
74 Park IH, Han SB, Kim JM, Piao L, Kwon SW, Kim NY, Kang TL, Park MK, Park JH. Four new acetylated ginsenosides from processed ginseng (sun ginseng). Arch Pharm Res 2002; 25: 837-841
75 Chan EC, Yap SL, Lau AJ, Leow PC, Toh DF, Koh HL. Ultra-performance liquid chromatography/time-of-flight mass spectrometry based metabolomics of raw and steamed Panax notoginseng . Rapid Commun Mass Spectrom 2007; 21: 519-528
76 Toh DF, New LS, Koh HL, Chan EC. Ultra-high performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOFMS) for time-dependent profiling of raw and steamed Panax notoginseng . J Pharm Biomed Anal 2010; 52: 43-50
77 Li SL, Song JZ, Qiao CF, Zhou Y, Qian K, Lee KH, Xu HX. A novel strategy to rapidly explore potential chemical markers for the discrimination between raw and processed Radix Rehmanniae by UHPLC-TOFMS with multivariate statistical analysis. J Pharm Biomed Anal 2010; 51: 812-823
78 Guo N, Fan B, Peng J, Yan H, Ma F, Yu Y. Ultra-performance LC/TOF MS analysis of fruits of Ligustrum lucidum for metabolomic research. Chin J Exp Tradit Med F 2010; 10: 131-133
79 Wang XJ. Based on NMR/UPLC plant metabonomics study on quality control of Polygala tenuifolia Willd [dissertation]. Shanxi: Shanxi University; 2012
80 Ruan GH, Li GK. The study on the chromatographic fingerprint of Fructus xanthii by microwave assisted extraction coupled with GC-MS. J Chromatogr B Analyt Technol Biomed Life Sci 2007; 850: 241-248
81 Ni Y, Peng Y, Kokot S. Fingerprinting of complex mixtures with the use of high performance liquid chromatography, inductively coupled plasma atomic emission spectroscopy and chemometrics. Anal Chim Acta 2008; 616: 19-27
82 Tanaka K, Tamura T, Fukuda S, Batkhuu J, Sanchir C, Komatsu K. Quality evaluation of Astragali Radix using a multivariate statistical approach. Phytochemistry 2008; 69: 2081-2087
83 Okada T, Afendi FM, Altaf-Ul-Amin M, Takahashi H, Nakamura K, Kanaya S. Metabolomics of medicinal plants: the importance of multivariate analysis of analytical chemistry data. Curr Comput Aided Drug Des 2010; 6: 179-196
84 Tang JC, Zhang JN, Wu YT, Li ZX. Effect of the water extract and ethanol extract from traditional Chinese medicines Angelica sinensis (Oliv.) Diels, Ligusticum chuanxiong Hort. and Rheum palmatum L. on rat liver cytochrome P450 activity. Phytother Res 2006; 20: 1046-1051
85 Li HB, Jiang Y, Wong CC, Cheng KW, Chen F. Evaluation of two methods for the extraction of antioxidants from medicinal plants. Anal Bioanal Chem 2007; 388: 483-488
86 Martin J, Stöger EA, Wiebrecht A. Praxisleitfaden TCM-Drogen–Vorbehandlung–Zubereitung–Sondervorschriften. Dtsch Zeitschrift Akupunktur (DZA) 2009; 52: 72-74
87 Ding Y, Wu EQ, Liang C, Chen J, Tran MN, Hong CH, Jang Y, Park KL, Bae K, Kim YH, Kang JS. Discrimination of cinnamon bark and cinnamon twig samples sourced from various countries using HPLC-based fingerprint analysis. Food Chem 2011; 127: 755-760
88 Ni Y, Zhang L, Churchill J, Kokot S. Application of high performance liquid chromatography for the profiling of complex chemical mixtures with the aid of chemometrics. Talanta 2007; 72: 1533-1539
89 Li Y, Wu T, Zhu J, Wan L, Yu Q, Li X, Cheng Z, Guo C. Combinative method using HPLC fingerprint and quantitative analyses for quality consistency evaluation of an herbal medicinal preparation produced by different manufacturers. Pharm Biomed Anal 2010; 52: 597-602
90 Peng JB, Jia HM, Liu YT, Zhang HW, Dong S, Zou ZM. Qualitative and quantitative characterization of chemical constituents in Xin-Ke-Shu preparations by liquid chromatography coupled with a LTQ Orbitrap mass spectrometer. J Pharm Biomed Anal 2011; 55: 984-995
91 Yang CF. Application of UPLC/RRLC/UFLC in study on Chinese materia medica and its preparation. Chin Tradit Herb Drugs 2009; 39: 1259-1263
92 Zhang LJ. The development of NMR. J Hebei Morm Univ 2000; 24: 224-227
93 Daolio C, Beltrame FL, Ferreira AG, Cass QB, Cortez DA, Ferreira MM. Classification of commercial Catuaba samples by NMR, HPLC and chemometrics. Phytochem Anal 2008; 19: 218-228
94 Lin Y, Schiavo S, Orjala J, Vouros P, Kautz R. Microscale LC-MS-NMR platform applied to the identification of active cyanobacterial metabolites. Anal Chem 2008; 80: 8045-8054
95 Ali K, Iqbal M, Korthout HA, Maltese F, Fortes AM, Pais MS, Verpoorte R, Choi YH. NMR spectroscopy and chemometrics as a tool for anti-TNFalpha activity screening in crude extracts of grapes and other berries. Metabolomics 2012; 8: 1148-1161
96 Yang J, Xu G, Kong H, Zheng Y, Pang T, Yang Q. Artificial neural network classification based on high-performance liquid chromatography of urinary and serum nucleosides for the clinical diagnosis of cancer. J Chromatogr B Analyt Technol Biomed Life Sci 2002; 780: 27-33
97 Yang J, Xu G, Zheng Y, Kong H, Pang T, Lv S, Yang Q. Diagnosis of liver cancer using HPLC-based metabonomics avoiding false-positive result from hepatitis and hepatocirrhosis diseases. J Chromatogr B Analyt Technol Biomed Life Sci 2004; 813: 59-65
98 Yang J, Xu G, Zheng Y, Kong H, Wang C, Zhao X, Pang T. Strategy for metabonomics research based on high-performance liquid chromatography and liquid chromatography coupled with tandem mass spectrometry. J Chromatogr A 2005; 1084: 214-221
99 Pham-Tuan H, Kaskavelis L, Daykin CA, Janssen HG. Method development in high-performance liquid chromatography for high-throughput profiling and metabonomic studies of biofluid samples. J Chromatogr B Analyt Technol Biomed Life Sci 2003; 789: 283-301
100 Lenz EM, Wilson ID. Analytical strategies in metabonomics. J Proteome Res 2007; 6: 443-458
101 Chace DH, Kalas TA. A biochemical perspective on the use of tandem mass spectrometry for newborn screening and clinical testing. Clin Biochem 2005; 38: 296-309
102 Fan TW, Lorkiewicz PK, Sellers K, Moseley HN, Higashi RM, Lane AN. Stable isotope-resolved metabolomics and applications for drug development. Pharmacol Ther 2012; 133: 366-391
103 Gad HA, El-Ahmady SH, Abou-Shoer MI, Al-Azizi MM. Application of chemometrics in authentication of herbal medicines: a review. Phytochem Anal 2013; 24: 1-24
104 Dharmaraj S, Jamaludin AS, Razak HM, Valliappan R, Ahmad NA, Harn GL, Ismail Z. The classification of Phyllanthus niruri Linn. according to location by infrared spectroscopy. Vib Spectrosc 2006; 41: 68-72
105 Vlachos N, Skopelitis Y, Psaroudaki M, Konstantinidou V, Chatzilazarou A, Tegou E. Applications of Fourier transform-infrared spectroscopy to edible oils. Anal Chim Acta 2006; 573–574: 459-465
106 Kokalj M, Kolar J, Trafela T, Kreft S. Differences among Epilobium and Hypericum species revealed by four IR spectroscopy modes: transmission, KBr tablet, diffuse reflectance and ATR. Phytochem Anal 2011; 22: 541-546
107 Debonneville C, Thome MA, Chaintreau A. Hyphenation of quadrupole MS to GC and comprehensive two-dimensional GC for the analysis of suspected allergens: review and improvement. J Chromatogr Sci 2004; 42: 450-455
108 Ronda F, Rodríguez-Nogales JM, Sancho D. Multivariate optimisation of a capillary electrophoretic method for the separation of glutenins. Application to quantitative analysis of the endosperm storage proteins in wheat. Food Chem 2008; 108: 287-296
109 Ou LJ, Sun XP, Liu QD, Mi SQ, Wang NS. Effects of Rhizoma Zingiberis and Pericarpium Citri reticulatae extracts on myocardial ischemia in rats. Zhong Yao Cai 2009; 32: 1723-1726
110 Ooi LS, Li Y, Kam SL, Wang H, Wong EY, Ooi VE. Antimicrobial activities of cinnamon oil and cinnamaldehyde from the Chinese medicinal herb Cinnamomum cassia Blume. Am J Chin Med 2006; 34: 511-522
111 de Sousa DP, Nobrega FF, de Lima MR, de Almeida RN. Pharmacological activity of (R)-(+)-pulegone, a chemical constituent of essential oils. Z Naturforsch C 2011; 66: 353-359
112 Zhang GC, Fang SM. Antioxidation of Pueraria lobata iIsoflavones. Zhong Yao Cai 1997; 26: 340-343
113 Qi CF, Song SW, Liu DF, Du XF, Wan XC, Song LH. Effects of total isoflavones of Pueraria DC. on bone mineral density and Ca in ovariectomized rats. J Biol 2007; 24: 22-24
114 Gao D, Li Q, Li Y, Liu Z, Fan Y, Zhao H, Li J, Han Z. Antidiabetic and antioxidant effects of oleanolic acid from Ligustrum lucidum Ait in alloxan-induced diabetic rats. Phytother Res 2009; 23: 1257-1262