绿茶儿茶素类生物标记物的检测及应用

摘要/Abstract

摘要： 绿茶被认为具有多种生理功效,但临床实验和流行病学研究仍存有争议。绿茶儿茶素类生物标记物检测方法的建立是为了从代谢物水平研究绿茶及其提取物对人体的生理效用,有助于阐释绿茶生理功效的作用机理,并避免或减轻由于摄入样品化学组成差异和生物个体差异对实验结果的影响。儿茶素类化合物EGCG、EGC、EC和ECG及其派生物是常用的绿茶儿茶素类生物标记物,主要检测方法有高效液相色谱-电化学检测法、液相色谱-串联质谱法等。本文综述了绿茶儿茶素类生物标记物的种类、备样方法和检测手段,分析、讨论了基于绿茶儿茶素类生物标记物开展的绿茶生物利用率研究,以及临床实验和流行病学研究结果,提出在后续研究中应进一步完善和规范人体中儿茶素类生物标记物的备样和检测方法,并可尝试寻找在生物体内比较稳定的、更能反映绿茶及其提取物摄入水平的新型生物标记物。

关键词: 绿茶儿茶素类生物标记物, HPLC-EC, 儿茶素化合物, EGCG, 代谢产物, 流行病学, 综述

Abstract: Green tea has been considered to have many health benefits, but there is still controversy about the clinical and epidemiological results. Development of green tea catechin biomarkers was to evaluate the physiological effects of green tea from a metabolic point of view, which will be helpful to interpret the functional mechanism of green tea in vivo and also avoid or reduce the influences of chemical compositions of samples intake or individual differences in human studies. Catechin compounds EGCG, EGC, EC, C, ECG and their derivatives are common green tea catechin biomarkers that have many determination methods including HPLC-EC, LC-MS and so on. This paper reviewed the types of green tea catechin biomarkers and their preparation and determination methods, discussed the results of biomarker-level based bioavailability studies, clinical trials and epidemiological studies, proposed suggestions for future research, such as further improvement and standardization of the preparation and determination methods of catechin biomarkers as well as development of new green tea biomarkers with higher stability in human body and sensitivity in reflecting their intake levels.

Key words: green tea catechin biomarker, HPLC-EC, catechin compounds, EGCG, metabolites, epidemiology, review

中图分类号:

孙丽丽, 曾祥泉, NileshWGaikwad, 王欢, 须海荣, 叶俭慧. 绿茶儿茶素类生物标记物的检测及应用[J]. 茶叶科学, 2017, 37(5): 429-441.

SUN Lili, ZENG Xiangquan, Nilesh W Gaikwad, WANG Huan, XU Hairong, YE Jianhui. Determination of Green Tea Catechin Biomarkers and It′s Relative Application[J]. Journal of Tea Science, 2017, 37(5): 429-441.

参考文献 85

[1]	Chan D K, Woo J, Ho S C, et al.Genetic and environmental risk factors for Parkinson's disease in a Chinese population[J]. Journal of Neurology, Neurosurgery and Psychiatry, 1998, 65(5): 781-784.
[2]	刘岗. 茶多酚对脂代谢基因的调控作用及对人群血压影响的荟萃分析[D]. 北京: 北京协和医学院, 2015: 5-76.
[3]	刘智伟, 曾本华, 张晓婧, 等. 茶多酚饮食对HFA小鼠肠道菌群和脂肪代谢的影响[J]. 中国食品学报, 2015, 15(6): 26-31.
[4]	王玮, 曾本华, 李桂花, 等. 茶多酚对apoE-/-小鼠脂类代谢和肠道双歧杆菌的影响[J]. 食品与机械, 2012, 28(4): 106-109.
[5]	王泽穆. 饮食与心血管病风险的Meta分析及绿茶多酚EGCG的抗炎机制实验研究[D]. 南京: 南京医科大学, 2014: 8-59.
[6]	Di Lorenzo A, Nabavi S F, Sureda A, et al.Antidepressive-like effects and antioxidant activity of green tea and GABA green tea in a mouse model of post-stroke depression[J]. Molecular Nutrition & Food Research, 2016, 60(3): 566-579.
[7]	Hu G, Bidel S, Jousilahti P, et al.Coffee and tea consumption and the risk of Parkinson's disease[J]. Movement Disorders, 2007, 22(15): 2242-2248.
[8]	Ogunleye A A, Xue F, Michels K B.Green tea consumption and breast cancer risk or recurrence: a meta-analysis[J]. Breast Cancer Research and Treatment, 2010, 119(2): 477-484.
[9]	Dai Q, Shu X O, Li H, et al.Is green tea drinking associated with a later onset of breast cancer?[J]. Annals of Epidemiology, 2010, 20(1): 74-81.
[10]	Onakpoya I, Spencer E, Heneghan C, et al.The effect of green tea on blood pressure and lipid profile: a systematic review and meta-analysis of randomized clinical trials[J]. Nutrition Metabolism and Cardiovascular Diseases, 2014, 24(8): 823-836.
[11]	Khalesi S, Sun J, Buys N, et al.Green tea catechins and blood pressure: a systematic review and meta-analysis of randomised controlled trials[J]. European Journal of Nutrition, 2014, 53(6): 1299-1311.
[12]	Dong X, Yang C, Cao S, et al.Tea consumption and the risk of depression: a meta-analysis of observational studies[J]. Australian and New Zealand Journal of Psychiatry, 2015, 49(4): 334-345.
[13]	Lambert J D, Yang C S. Cancer chemopreventive activity and bioavailability of tea and tea polyphenols [J]. Mutation Research, 2003, 523/524(1): 201-208.
[14]	Higdon J V, Frei B.Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions[J]. Critical Reviews in Food Science and Nutrition, 2003, 43(1): 89-143.
[15]	Vuong Q V.Epidemiological evidence linking tea consumption to human health: a review[J]. Critical Reviews in Food Science and Nutrition, 2014, 54(4): 523-536.
[16]	Johnson R, Bryant S, Huntley A L.Green tea and green tea catechin extracts: an overview of the clinical evidence[J]. Maturitas, 2012, 73(4): 280-287.
[17]	Seely D, Mills E J, Wu P, et al.The effects of green tea consumption on incidence of breast cancer and recurrence of breast cancer: a systematic review and meta-analysis[J]. Integrative Cancer Therapies, 2005, 4(2): 144-155.
[18]	Yuan J M, Sun C, Butler L M.Tea and cancer prevention: epidemiological studies[J]. Pharmacological Research, 2011, 64(2): 123-135.
[19]	Wang J S, Haitao L, Wang P W, et al.Validation of green tea polyphenol biomarkers in a phase II human intervention trial[J]. Food and Chemical Toxicology, 2008, 46(1): 232-240.
[20]	Zamora Ros R, Rabassa M, Llorach R, et al.Application of dietary phenolic biomarkers in epidemiology: past, present and future[J]. Journal of Agricultural and Food Chemistry, 2012, 60(27): 6648-6657.
[21]	Li W, He N, Tian L, et al.Inhibitory effects of polyphenol-enriched extract from Ziyang tea against human breast cancer MCF-7 cells through reactive oxygen species-dependent mitochondria molecular mechanism[J]. Journal of Food and Drug Analysis, 2016, 24(3): 527-538.
[22]	Daglia M, Di Lorenzo A, Nabavi S F, et al.Polyphenols: well beyond the antioxidant capacity: gallic acid and related compounds as neuroprotective agents: you are what you eat![J]. Current Pharmaceutical Biotechnology, 2014, 15(4): 362-372.
[23]	Diniz P H, Pistonesi M F, Alvarez M, et al.Simplified tea classification based on a reduced chemical composition profile via successive projections algorithm linear discriminant analysis (SPA-LDA)[J]. Journal of Food Composition and Analysis, 2015, 39: 103-110.
[24]	Jenab M, Slimani N, Bictash M, et al.Biomarkers in nutritional epidemiology: applications, needs and new horizons[J]. Human Genetics, 2009, 125(5/6): 507-525.
[25]	Llorach R, Garcia Aloy M, Tulipani S, et al.Nutrimetabolomic strategies to develop new biomarkers of intake and health effects[J]. Journal of Agricultural and Food Chemistry, 2012, 60(36): 8797-8808.
[26]	Strimbu K, Tavel J A.What are biomarkers?[J]. Current Opinion in Hiv and Aids, 2010, 5(6): 463-466.
[27]	Potischman N.Biologic and methodologic issues for nutritional biomarkers[J]. Journal of Nutrition, 2003, 133(3): 875S-880S.
[28]	Sun C L, Yuan J M, Lee M J, et al.Urinary tea polyphenols in relation to gastric and esophageal cancers: a prospective study of men in Shanghai, China[J]. Carcinogenesis, 2002, 23(9): 1497-1503.
[29]	Ottaviani J I, Borges G, Momma T Y, et al.The metabolome of [2-C-14] (-)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives[J]. Scientific Reports, 2016, 6: 29034.
[30]	Spencer J P, Mohsen M M, Minihane A, et al.Biomarkers of the intake of dietary polyphenols: strengths, limitations and application in nutrition research[J]. British Journal of Nutrition, 2008, 99(1): 12-22.
[31]	Yang J, Liu R H.The phenolic profiles and antioxidant activity in different types of tea[J]. International Journal of Food Science and Technology, 2013, 48(1): 163-171.
[32]	Row K H, Jin Y.Recovery of catechin compounds from Korean tea by solvent extraction[J]. Bioresource Technology, 2006, 97(5): 790-793.
[33]	Luo H, Stephen B C, Gao W M, et al.Metabolic profiling in validation of plasma biomarkers for green tea polyphenols[J]. Metabolomics, 2006, 2(4): 235-241.
[34]	Pietta P, Paolo S, Claudio G, et al.Relationship between rate and extent of catechin absorption and plasma antioxidant status[J]. IUBMB Life, 1998, 46(5): 895-903.
[35]	Yuan J M, Gao Y T, Yang C S, et al.Urinary biomarkers of tea polyphenols and risk of colorectal cancer in the Shanghai cohort study[J]. International Journal of Cancer, 2007, 120(6): 1344-1350.
[36]	Fung S T, Ho C K, Choi S W, et al.Comparison of catechin profiles in human plasma and urine after single dosing and regular intake of green tea (Camellia sinensis)[J]. British Journal of Nutrition, 2013, 109(12): 2199-2207.
[37]	Chow H H, Cai Y, Hakim I A, et al.Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals[J]. Clinical Cancer Research, 2003, 9(9): 3312-3319.
[38]	Bell J R, Donovan J L, Wong R, et al.(+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine[J]. American Journal of Clinical Nutrition, 2000, 71(1): 103-108.
[39]	Richelle M, Tavazzi I, Enslen M, et al.Plasma kinetics in man of epicatechin from black chocolate[J]. European Journal of Clinical Nutrition, 1999, 53(1): 22-26.
[40]	张梁, 陈欣, 陈博, 等. 茶多酚体内吸收、分布、代谢和排泄研究进展[J]. 安徽农业大学学报, 2016, 43(5): 667-675.
[41]	Feng W Y.Metabolism of green tea catechins: an overview[J]. Current Drug Metabolism, 2006, 7(7): 755-809.
[42]	Lee M J, Wang Z Y, Li H, et al.Analysis of plasma and urinary tea polyphenols in human subjects[J]. Cancer Epidemiology Biomarkers & Prevention, 1995, 4(4): 393-399.
[43]	Meng X, Sang S, Zhu N, et al.Identification and characterization of methylated and ringfission metabolites of tea catechins formed in humans, mice, and rats[J]. Chemical Research in Toxicology, 2002, 15(8): 1042-1050.
[44]	Lee M J, Maliakal P, Chen L, et al.Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability[J]. Cancer Epidemiology, Biomarkers & Prevention, 2002, 11(10): 1025-1032.
[45]	Sang S, Mao Jung Lee, Brian B, et al.Human urinary metabolite profile of tea polyphenols analyzed by liquid chromatography/electrospray ionization tandem mass spectrometry with data‐dependent acquisition[J]. Rapid Communications in Mass Spectrometry, 2008, 22(10): 1567-1578.
[46]	Butler L M, Joyce Y H, Wang R, et al.Urinary biomarkers of catechins and risk of hepatocellular carcinoma in the Shanghai cohort study[J]. American Journal of Epidemiology, 2015, 181(6): 397-405.
[47]	Tomonori Unno K K, Hiroshige I, Tadakazu T. Analysis of (-)-Epigallocatechin gallate in human serum obtained after ingesting green tea[J]. Bioscience, Biotechnology, and Biochemistry, 1996, 60(12): 2066-2068.
[48]	Masukawa Y, Matsui Y, Shimizu N, et al.Determination of green tea catechins in human plasma using liquid chromatography-electrospray ionization mass spectrometry[J]. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2006, 834(1/2): 26-34.
[49]	Nakagawa K, Okuda S, Miyazawa T.Dose-dependent incorporation of tea catechins, (-)-epigallocatechin-3-gallate and (-)-epigallocatechin, into human plasma[J]. Bioscience Biotechnology and Biochemistry, 1997, 61(12): 1981-1985.
[50]	Miyazawa T.Absorption, metabolism and antioxidative effects of tea catechin in humans[J]. Biofactors, 2000, 13(1/4): 55-59.
[51]	Zhang L, Han Y H, Shan J J, et al.Simultaneous determination of seven catechins in rat plasma by ultra-high performance liquid chromatography tandem mass spectrometry and its application to a pharmacokinetics study[J]. Analytical Methods, 2015, 7(22): 9415-9420.
[52]	Huo Y S, Zhang Q, Li Q, et al.Development of a UFLC-MS/MS method for the simultaneous determination of seven tea catechins in rat plasma and its application to a pharmacokinetic study after administration of green tea extract[J]. Journal of Pharmaceutical and Biomedical Analysis, 2016, 125: 229-235.
[53]	Lee M J, Prabhu S, Meng X, et al.An improved method for the determination of green and black tea polyphenols in biomatrices by high-performance liquid chromatography with coulometric array detection[J]. Analytical Biochemistry, 2000, 279(2): 164-169.
[54]	Van Amelsvoort J M M, Hof K H V, Mathot J N J J, et al. Plasma concentrations of individual tea catechins after a single oral dose in humans[J]. Xenobiotica, 2001, 31(12): 891-901.
[55]	Unno T, Sagesaka Y M, Kakuda T.Analysis of tea catechins in human plasma by high-performance liquid chromatography with solid-phase extraction[J]. Journal of Agricultural and Food Chemistry, 2005, 53(26): 9885-9889.
[56]	Luo H, Tang L, Tang M, et al.Phase IIa chemoprevention trial of green tea polyphenols in high-risk individuals of liver cancer: modulation of urinary excretion of green tea polyphenols and 8-hydroxydeoxyguanosine[J]. Carcinogenesis, 2006, 27(2): 262-268.
[57]	Manach C, Scalbert A, Morand C, et al.Polyphenols: food sources and bioavailability[J]. American Journal of Clinical Nutrition, 2004, 79(5): 727-747.
[58]	Toutain P L, Bousquet-Melou A.Bioavailability and its assessment[J]. Journal of Veterinary Pharmacology and Therapeutics, 2004, 27(6): 455-466.
[59]	Cai Y, Anavy N D, Chow H H.Contribution of presystemic hepatic extraction to the low oral bioavailability of green tea catechins in rats[J]. Drug Metabolism and Disposition, 2002, 30(11): 1246-1249.
[60]	Li N, Taylor L S, Ferruzzi M G, et al.Kinetic study of catechin stability: effects of pH, concentration, and temperature[J]. Journal of Agricultural and Food Chemistry, 2012, 60(51): 12531-12539.
[61]	Wu L Y, Sanguansri L, Augustin M A.Protection of epigallocatechin gallate against degradation during in vitro digestion using apple pomace as a carrier[J]. Journal of Agricultural and Food Chemistry, 2014, 62(50): 12265-12270.
[62]	Rodrigues C F, Ascencao K, Silva F A, et al.Drug-delivery systems of green tea catechins for improved stability and bioavailability[J]. Current Medicinal Chemistry, 2013, 20(37): 4744-4757.
[63]	Benshitrit R C, Levi C S, Tal S L, et al.Development of oral food-grade delivery systems: current knowledge and future challenges[J]. Food & Function, 2012, 3(1): 10-21.
[64]	Kadowaki M, Sugihara N, Tagashira T, et al.Presence or absence of a gallate moiety on catechins affects their cellular transport[J]. Journal of Pharmacy and Pharmacology, 2008, 60(9): 1189-1195.
[65]	Ullmann U, Haller J, Decourt J P, et al.A single ascending dose study of epigallocatechin gallate in healthy volunteers[J]. Journal of International Medical Research, 2003, 31(2): 88-101.
[66]	Bhushani J A, Karthik P, Anandharamakrishnan C.Nanoemulsion based delivery system for improved bioaccessibility and Caco-2 cell monolayer permeability of green tea catechins[J]. Food Hydrocolloids, 2016, 56: 372-382.
[67]	Mario G F, Catrina M P, Andrew P N, et al.The influence of food formulation on digestive behavior and bioavailability of catechin polyphenols[J]. Acta Horticulturae, 2009, 841(841): 121-128.
[68]	Tomas Barberan F A, Selma M V, Espin J C. Interactions of gut microbiota with dietary polyphenols and consequences to human health[J]. Current Opinion in Clinical Nutrition and Metabolic Care, 2016, 19(6): 471-476.
[69]	Takechi R, Alfonso H, Hiramatsu N, et al.Elevated plasma and urinary concentrations of green tea catechins associated with improved plasma lipid profile in healthy Japanese women[J]. Nutrition Research, 2016, 36(3): 220-226.
[70]	Luo J F, Gao Y T, Chow W H, et al.Urinary polyphenols and breast cancer risk: results from the Shanghai women's health study[J]. Breast Cancer Research and Treatment, 2010, 120(3): 693-702.
[71]	Iwasaki M, Inoue M, Sasazuki S, et al.Plasma tea polyphenol levels and subsequent risk of breast cancer among Japanese women: a nested case-control study[J]. Breast Cancer Research and Treatment, 2010, 124(3): 827-834.
[72]	Sun C L, Yuan J M, Lee M J, et al.Urinary tea polyphenols in relation to gastric and esophageal cancers: a prospective study of men in Shanghai, China[J]. Carcinogenesis, 2002, 23(9): 1497-1503.
[73]	Yuan J M, Gao Y T, Yang C S, et al.Urinary biomarkers of tea polyphenols and risk of colorectal cancer in the Shanghai cohort study[J]. International Journal of Cancer, 2007, 120(6): 1344-1350.
[74]	Xie G, Zhao A, Zhao L, et al.Metabolic fate of tea polyphenols in humans[J]. Journal of Proteome Research, 2012, 11(6): 3449-3457.
[75]	Ishii T, Ichikawa T, Minoda K, et al.Human serum albumin as an antioxidant in the oxidation of (-)-epigallocatechin gallate: participation of reversible covalent binding for interaction and stabilization[J]. Bioscience Biotechnology and Biochemistry, 2011, 75(1): 100-106.
[76]	Maiti T K, Ghosh K S, Dasgupta S.Interaction of (-)-epigallocatechin-3-gallate with human serum albumin: fluorescence, fourier transform infrared, circular dichroism, and docking studies[J]. Proteins-Structure Function and Bioinformatics, 2006, 64(2): 355-362.
[77]	Kim S, Lee M J, Hong J, et al.Plasma and tissue levels of tea catechins in rats and mice during chronic consumption of green tea polyphenols[J]. Nutrition and Cancer, 2000, 37(1): 41-48.
[78]	Chen L, Lee M J, Li H, et al.Absorption, distribution, elimination of tea polyphenols in rats[J]. Drug Metabolism and Disposition, 1997, 25(9): 1045-1050.
[79]	Senechal S, Kussmann M, Nutriproteomics. Technologies and applications for identification and quantification of biomarkers and ingredients[J]. Proceedings of the Nutrition Society, 2011, 70(3): 351-364.
[80]	Van Velzen E J, Westerhuis J A, Van Duynhoven J P, et al. Phenotyping tea consumers by nutrikinetic analysis of polyphenolic end-metabolites[J]. Journal of Proteome Research, 2009, 8(7): 3317-3330.
[81]	Holmes E, Loo R L, Stamler J, et al.Human metabolic phenotype diversity and its association with diet and blood pressure[J]. Nature, 2008, 453(7193): 396-400.
[82]	Zanesco A, da Silva C V, Delbin M A, et al. Interactions between L-arginine supplementation and physical training in the mitochondrial biomarkers and nitric oxide bioavailability in rat skeletal muscle[J]. The FASEB Journal, 2013, 27: 1.
[83]	Roowi S, Stalmach A, Mullen W, et al.Green tea flavan-3-ols: colonic degradation and urinary excretion of catabolites by humans[J]. Journal of Agricultural and Food Chemistry, 2010, 58(2): 1296-1304.
[84]	Cardona F, Andreslacueva C, Tulipani S, et al.Benefits of polyphenols on gut microbiota and implications in human health[J]. Journal of Nutritional Biochemistry, 2013, 24(8): 1415-1422.
[85]	Misaka S, Kawabe K, Onoue S, et al.Development of rapid and simultaneous quantitative method for green tea catechins on the bioanalytical study using UPLC/ESI-MS[J]. Biomedical Chromatography, 2013, 27(1): 1-6.