Plant Phenolics: Extraction, Analysis and Their Antioxidant and Anticancer Properties

Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro and in-vivo animal models are viewed, including recent human intervention studies. Finally, possible mechanisms of action involving antioxidant and pro-oxidant activity as well as interference with cellular functions are discussed.

[1]  P. Dugo,et al.  Inhibition of nitric oxide biosynthesis by anthocyanin fraction of blackberry extract. , 2006, Nitric oxide : biology and chemistry.

[2]  K. Murakami,et al.  Interaction of iron with polyphenolic compounds: application to antioxidant characterization. , 1998, Analytical biochemistry.

[3]  M. C. García-Parrilla,et al.  Antioxidant capacity of plasma after red wine intake in human volunteers. , 2005, Journal of agricultural and food chemistry.

[4]  A. Oliveira‐Brett,et al.  Ultrasound extracted flavonoids from four varieties of Portuguese red grape skins determined by reverse-phase high-performance liquid chromatography with electrochemical detection. , 2008, Analytica chimica acta.

[5]  M. Ogasawara,et al.  Differential effects of antioxidants on the in vitro invasion, growth and lung metastasis of murine colon cancer cells. , 2007, Biological & pharmaceutical bulletin.

[6]  K. Grohmann,et al.  Biological properties of citrus flavonoids pertaining to cancer and inflammation. , 2001, Current medicinal chemistry.

[7]  Xianli Wu,et al.  In vitro and in vivo antioxidant and anti-inflammatory capacities of an antioxidant-rich fruit and berry juice blend. Results of a pilot and randomized, double-blinded, placebo-controlled, crossover study. , 2008, Journal of agricultural and food chemistry.

[8]  K. Lee,et al.  Antiproliferative effects of dietary phenolic substances and hydrogen peroxide. , 2005, Journal of agricultural and food chemistry.

[9]  P. O'Brien,et al.  Cancer Chemoprevention and Apoptosis Mechanisms Induced by Dietary Polyphenolics , 2000, Drug metabolism and drug interactions.

[10]  H. Ashida,et al.  Simultaneous determination of all polyphenols in vegetables, fruits, and teas. , 2003, Journal of agricultural and food chemistry.

[11]  H. Mukhtar,et al.  Protective effect of pomegranate‐derived products on UVB‐mediated damage in human reconstituted skin , 2009, Experimental dermatology.

[12]  D. Marko,et al.  Do anthocyanins and anthocyanidins, cancer chemopreventive pigments in the diet, merit development as potential drugs? , 2009, Cancer Chemotherapy and Pharmacology.

[13]  H. Daniel,et al.  Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines , 1999, European journal of nutrition.

[14]  E. Ibáñez,et al.  Use of compressed fluids for sample preparation: food applications. , 2007, Journal of chromatography. A.

[15]  Pierre Brat,et al.  Rapid determination of polyphenols and vitamin C in plant-derived products. , 2005, Journal of agricultural and food chemistry.

[16]  Brittany L. White,et al.  Release of bound procyanidins from cranberry pomace by alkaline hydrolysis. , 2010, Journal of agricultural and food chemistry.

[17]  G. Jones,et al.  High Molecular Weight Plant Polyphenolics (Tannins) as Biological Antioxidants. , 1998, Journal of agricultural and food chemistry.

[18]  D. Dickinson,et al.  Roles of Catalase and Hydrogen Peroxide in Green Tea Polyphenol-Induced Chemopreventive Effects , 2004, Journal of Pharmacology and Experimental Therapeutics.

[19]  S. Lazarus,et al.  Identification of procyanidins and anthocyanins in blueberries and cranberries (Vaccinium spp.) using high-performance liquid chromatography/mass spectrometry. , 2001, Journal of agricultural and food chemistry.

[20]  M. Netzel,et al.  The excretion and biological antioxidant activity of elderberry antioxidants in healthy humans , 2005 .

[21]  N. Seeram,et al.  Isolation and identification of strawberry phenolics with antioxidant and human cancer cell antiproliferative properties. , 2008, Journal of agricultural and food chemistry.

[22]  D. Hou,et al.  Green tea proanthocyanidins inhibit cyclooxygenase-2 expression in LPS-activated mouse macrophages: molecular mechanisms and structure-activity relationship. , 2007, Archives of biochemistry and biophysics.

[23]  A. Ferro-Luzzi,et al.  Alcohol-free red wine enhances plasma antioxidant capacity in humans. , 1998, The Journal of nutrition.

[24]  L. Goya,et al.  Influence of quercetin and rutin on growth and antioxidant defense system of a human hepatoma cell line (HepG2) , 2006, European journal of nutrition.

[25]  L. T. Taylor,et al.  Feasibility study of online supercritical fluid extraction-liquid chromatography-UV absorbance-mass spectrometry for the determination of proanthocyanidins in grape seeds. , 2005, Journal of chromatographic science.

[26]  R. Wrolstad,et al.  Characterization and Measurement of Anthocyanins by UV‐Visible Spectroscopy , 2001 .

[27]  F. Lajolo,et al.  Polyphenols and antioxidant capacity of seed coat and cotyledon from Brazilian and Peruvian bean cultivars (Phaseolus vulgaris L.). , 2007, Journal of agricultural and food chemistry.

[28]  Fereidoon Shahidi,et al.  Phenolics in cereals, fruits and vegetables: occurrence, extraction and analysis. , 2006, Journal of pharmaceutical and biomedical analysis.

[29]  A. Ebringerová,et al.  Comparison of conventional and ultrasound-assisted extraction of phenolics-rich heteroxylans from wheat bran. , 2008, Ultrasonics sonochemistry.

[30]  A. Azmi,et al.  Plant polyphenols mobilize endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: A putative mechanism for anticancer properties , 2006, FEBS letters.

[31]  R. Mumper,et al.  Effects of a Topically Applied Bioadhesive Berry Gel on Loss of Heterozygosity Indices in Premalignant Oral Lesions , 2008, Clinical Cancer Research.

[32]  Xiao-hua Xiao,et al.  Application of ionic liquids in the microwave-assisted extraction of trans-resveratrol from Rhizma Polygoni Cuspidati. , 2007, Journal of chromatography. A.

[33]  S. Katiyar,et al.  Proanthocyanidins from grape seeds inhibit expression of matrix metalloproteinases in human prostate carcinoma cells, which is associated with the inhibition of activation of MAPK and NF kappa B. , 2004, Carcinogenesis.

[34]  F. J. Francis,et al.  SOLVENT EXTRACTION OF ANTHOCYANINS FROM WINE POMACE , 1980 .

[35]  R. Mumper,et al.  Topical application of a bioadhesive black raspberry gel modulates gene expression and reduces cyclooxygenase 2 protein in human premalignant oral lesions. , 2008, Cancer research.

[36]  F. W. Albert,et al.  Anthocyanin/Polyphenolic–Rich Fruit Juice Reduces Oxidative Cell Damage in an Intervention Study with Patients on Hemodialysis , 2008, Cancer Epidemiology Biomarkers & Prevention.

[37]  E. Schleicher,et al.  The Chemopreventive Polyphenol Curcumin Prevents Hematogenous Breast Cancer Metastases in Immunodeficient Mice , 2006, Cellular Physiology and Biochemistry.

[38]  M. Hamburger,et al.  Pressurized liquid extraction of medicinal plants. , 1999, Journal of chromatography. A.

[39]  H. Ross,et al.  Berry extracts exert different antiproliferative effects against cervical and colon cancer cells grown in vitro. , 2008, Journal of agricultural and food chemistry.

[40]  W. Bors,et al.  Chemistry of the Antioxidant Effect of Polyphenols , 2002, Annals of the New York Academy of Sciences.

[41]  M Vinatoru,et al.  The use of ultrasound for the extraction of bioactive principles from plant materials. , 1997, Ultrasonics sonochemistry.

[42]  O. Padilla-Zakour,et al.  Chemical characterization of red wine grape (Vitis vinifera and Vitis interspecific hybrids) and pomace phenolic extracts and their biological activity against Streptococcus mutans. , 2007, Journal of agricultural and food chemistry.

[43]  A. Hagerman,et al.  Determination of gallotannin with rhodanine. , 1988, Analytical biochemistry.

[44]  A. Gérard,et al.  Acoustic bubble cavitation at low frequencies , 1998 .

[45]  M. Chung,et al.  Comparison of the antioxidant activities of nine different fruits in human plasma. , 2005, Journal of medicinal food.

[46]  S. Chu,et al.  Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and u-PA expression. , 2006, Chemico-biological interactions.

[47]  G. Beecher,et al.  Measurement of food flavonoids by high-performance liquid chromatography: A review. , 2000, Journal of agricultural and food chemistry.

[48]  L. Stanley Molecular aspects of chemical carcinogenesis: the roles of oncogenes and tumour suppressor genes. , 1995, Toxicology.

[49]  V. Cheynier,et al.  Analysis of phenolic compounds in two blackberry species (Rubus glaucus and Rubus adenotrichus) by high-performance liquid chromatography with diode array detection and electrospray ion trap mass spectrometry. , 2007, Journal of agricultural and food chemistry.

[50]  Y. Lou,et al.  Effects of tea, decaffeinated tea, and caffeine on UVB light-induced complete carcinogenesis in SKH-1 mice: demonstration of caffeine as a biologically important constituent of tea. , 1997, Cancer research.

[51]  Y. Lou,et al.  Inhibitory effects of black tea, green tea, decaffeinated black tea, and decaffeinated green tea on ultraviolet B light-induced skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated SKH-1 mice. , 1994, Cancer research.

[52]  Liliana Jiménez,et al.  Polyphenols: food sources and bioavailability. , 2004, The American journal of clinical nutrition.

[53]  C. Rice-Evans,et al.  Antioxidant activity applying an improved ABTS radical cation decolorization assay. , 1999, Free radical biology & medicine.

[54]  R. K. Bhattacharya,et al.  Protective effect of rutin, a flavonol glycoside, on the carcinogen-induced DNA damage and repair enzymes in rats. , 1996, Cancer letters.

[55]  E. Castanas,et al.  Potent inhibitory action of red wine polyphenols on human breast cancer cells , 2000, Journal of cellular biochemistry.

[56]  M. Pinelo,et al.  A simple method to separate red wine nonpolymeric and polymeric phenols by solid-phase extraction. , 2006, Journal of agricultural and food chemistry.

[57]  M B Katan,et al.  Dietary flavonoids: intake, health effects and bioavailability. , 1999, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[58]  T J Mason,et al.  Potential for the use of ultrasound in the extraction of antioxidants from Rosmarinus officinalis for the food and pharmaceutical industry. , 2004, Ultrasonics sonochemistry.

[59]  B. Ames,et al.  Oxidants, antioxidants, and the degenerative diseases of aging. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[60]  J. Pezzuto,et al.  Composition of a chemopreventive proanthocyanidin-rich fraction from cranberry fruits responsible for the inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity. , 2002, Journal of agricultural and food chemistry.

[61]  V. Krutovskikh,et al.  Lack of tumor-promoting effects of flavonoids: studies on rat liver preneoplastic foci and on in vivo and in vitro gap junctional intercellular communication. , 1996, Nutrition and cancer.

[62]  M. Kobori,et al.  Induction of apoptosis in cancer cells by Bilberry (Vaccinium myrtillus) and the anthocyanins. , 2003, Journal of agricultural and food chemistry.

[63]  R. Doll,et al.  The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. , 1981, Journal of the National Cancer Institute.

[64]  L. Butler,et al.  Condensed tannin purification and characterization of tannin-associated proteins. , 1980, Journal of agricultural and food chemistry.

[65]  M. Palma,et al.  Investigation on phenolic compounds stability during microwave-assisted extraction. , 2007, Journal of chromatography. A.

[66]  O. Aruoma,et al.  Characterization of the phenolic constituents in Mauritian endemic plants as determinants of their antioxidant activities in vitro. , 2006, Journal of plant physiology.

[67]  J. Rivas-Gonzalo,et al.  Analysis of flavanols in beverages by high-performance liquid chromatography with chemical reaction detection , 1998 .

[68]  R. Dambergs,et al.  High throughput analysis of red wine and grape phenolics-adaptation and validation of methyl cellulose precipitable tannin assay and modified Somers color assay to a rapid 96 well plate format. , 2007, Journal of agricultural and food chemistry.

[69]  M. Hirayama,et al.  Antioxidant activity of black currant anthocyanin aglycons and their glycosides measured by chemiluminescence in a neutral pH region and in human plasma. , 2002, Journal of agricultural and food chemistry.

[70]  Fusheng Yang,et al.  Prevention of Alzheimer's disease: Omega-3 fatty acid and phenolic anti-oxidant interventions , 2005, Neurobiology of Aging.

[71]  C. Ho,et al.  Effects of purified green and black tea polyphenols on cyclooxygenase- and lipoxygenase-dependent metabolism of arachidonic acid in human colon mucosa and colon tumor tissues. , 2001, Biochemical pharmacology.

[72]  F. Shahidi,et al.  Extraction and analysis of phenolics in food. , 2004, Journal of chromatography. A.

[73]  K. Belkacemi,et al.  Anthocyanins in wild blueberries of Quebec: extraction and identification. , 2007, Journal of agricultural and food chemistry.

[74]  S. Spechler,et al.  Clinical practice. Barrett's Esophagus. , 2002, The New England journal of medicine.

[75]  A. Meyer,et al.  Enzyme-assisted extraction of antioxidative phenols from black currant juice press residues (Ribes nigrum). , 2001, Journal of agricultural and food chemistry.

[76]  R. Agarwal,et al.  Fractionation of high molecular weight tannins in grape seed extract and identification of procyanidin B2-3,3'-di-O-gallate as a major active constituent causing growth inhibition and apoptotic death of DU145 human prostate carcinoma cells. , 2007, Carcinogenesis.

[77]  Rickey Y. Yada,et al.  ANTHOCYANINS AS FOOD COLORANTS —A REVIEW , 1987 .

[78]  K. Yamaki,et al.  Inhibitory effect of some flavonoids on tumor necrosis factor-alpha production in lipopolysaccharide-stimulated mouse macrophage cell line J774.1. , 2003, Journal of medicinal food.

[79]  Nathan R. Perron,et al.  A Review of the Antioxidant Mechanisms of Polyphenol Compounds Related to Iron Binding , 2009, Cell Biochemistry and Biophysics.

[80]  F. J. Francis,et al.  Quantitative Methods for Anthocyanins. , 1968 .

[81]  D. Mitchell,et al.  Effects of chronic low-dose ultraviolet B radiation on DNA damage and repair in mouse skin. , 1999, Cancer research.

[82]  M. Serafini,et al.  Plasma antioxidants from chocolate , 2003, Nature.

[83]  T. C. Wilson,et al.  Quantitative determination of ellagic acid , 1990 .

[84]  K. Danno,et al.  Role of oxygen intermediates in UV-induced epidermal cell injury. , 1984, The Journal of investigative dermatology.

[85]  W. Oleszek,et al.  Quali-quantitative analyses of Flavonoids of Morus nigra L. and Morus alba L. (Moraceae) fruits. , 2008, Journal of agricultural and food chemistry.

[86]  Liliana Jiménez,et al.  Dietary Polyphenols and the Prevention of Diseases , 2005, Critical reviews in food science and nutrition.

[87]  A. Wu,et al.  Automated assay of oxygen radical absorbance capacity with the COBAS FARA II. , 1995, Clinical chemistry.

[88]  Patrik R. Jones,et al.  Quantification of condensed tannins by precipitation with methyl cellulose: development and validation of an optimised tool for grape and wine analysis , 2006 .

[89]  K. Mı́ková,et al.  Heat Stability of Anthocyanins , 1985 .

[90]  F. Saura-calixto,et al.  Antioxidant activity of dietary polyphenols as determined by a modified ferric reducing/antioxidant power assay. , 2000, Journal of agricultural and food chemistry.

[91]  H. Ross,et al.  Antiproliferative activity is predominantly associated with ellagitannins in raspberry extracts. , 2007, Phytochemistry.

[92]  M. Herderich,et al.  Rapid isolation of red wine polymeric polyphenols by solid-phase extraction. , 2008, Journal of agricultural and food chemistry.

[93]  C. Gerhauser Cancer Chemopreventive Potential of Apples, Apple Juice, and Apple Components , 2008, Planta medica.

[94]  B. Meibohm,et al.  Pharmacokinetics of anthocyanins and antioxidant effects after the consumption of anthocyanin-rich acai juice and pulp (Euterpe oleracea Mart.) in human healthy volunteers. , 2008, Journal of agricultural and food chemistry.

[95]  S. Guyot,et al.  Thiolysis-HPLC characterization of apple procyanidins covering a large range of polymerization states. , 2001, Journal of agricultural and food chemistry.

[96]  H. Mukhtar,et al.  Pomegranate Fruit Extract Modulates UV-B–mediated Phosphorylation of Mitogen-activated Protein Kinases and Activation of Nuclear Factor Kappa B in Normal Human Epidermal Keratinocytes¶ , 2005, Photochemistry and photobiology.

[97]  E. Castanas,et al.  Wine Antioxidant Polyphenols Inhibit the Proliferation of Human Prostate Cancer Cell Lines , 2000, Nutrition and cancer.

[98]  C. Guzmán,et al.  Optimization of extraction of phenolic antioxidants from peanut skins , 2005 .

[99]  F. Tomás-Barberán,et al.  Characterization and quantitation of phenolic compounds in new apricot (Prunus armeniaca L.) varieties. , 2005, Journal of agricultural and food chemistry.

[100]  P. Mattila,et al.  Determination of flavonoids in plant material by HPLC with diode-array and electro-array detections. , 2000, Journal of agricultural and food chemistry.

[101]  C. Rice-Evans,et al.  Antioxidant properties of phenolic compounds , 1997 .

[102]  I R Rowland,et al.  Anti-cancer properties of phenolics from apple waste on colon carcinogenesis in vitro. , 2007, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[103]  C. Fraga,et al.  A dose-response effect from chocolate consumption on plasma epicatechin and oxidative damage. , 2000, The Journal of nutrition.

[104]  B. Frei,et al.  Tea Catechins and Polyphenols: Health Effects, Metabolism, and Antioxidant Functions , 2003, Critical reviews in food science and nutrition.

[105]  T. Swain,et al.  Changes in tannins in ripening fruits , 1963 .

[106]  M. Cristani,et al.  In vitro protective effect of a Jacquez grapes wine extract on UVB-induced skin damage. , 2006, Toxicology in vitro : an international journal published in association with BIBRA.

[107]  T. McMillan,et al.  The green tea polyphenol, epigallocatechin‐3‐gallate, protects against the oxidative cellular and genotoxic damage of UVA radiation , 2002, International journal of cancer.

[108]  Chung S. Yang,et al.  Cancer chemopreventive activity and bioavailability of tea and tea polyphenols. , 2003, Mutation research.

[109]  A. Meyer,et al.  Selective release of phenols from apple skin : Mass transfer kinetics during solvent and enzyme-assisted extraction , 2008 .

[110]  B. Hudson,et al.  Polyhydroxy chalcones and flavanones as antioxidants for edible oils , 1983 .

[111]  L. Nie,et al.  Solvent effects on focused microwave assisted extraction of polyphenolic acids from Eucommia ulmodies. , 2004, Phytochemical analysis : PCA.

[112]  C. Rice-Evans,et al.  Structure-antioxidant activity relationships of flavonoids and phenolic acids. , 1996, Free radical biology & medicine.

[113]  M. Pinelo,et al.  Effect of solvent, temperature, and solvent-to-solid ratio on the total phenolic content and antiradical activity of extracts from different components of grape pomace. , 2005, Journal of agricultural and food chemistry.

[114]  J. Young,et al.  Improved high performance liquid chromatographic separation of anthocyanin compounds from grapes using a novel mixed-mode ion-exchange reversed-phase column. , 2007, Journal of chromatography. A.

[115]  B. Klejdus,et al.  High performance liquid chromatographic determination of phenolic compounds in seed exudates of Festuca arundinacea and F. pratense , 2000 .

[116]  C. Fraga,et al.  Epicatechin in human plasma: in vivo determination and effect of chocolate consumption on plasma oxidation status. , 2000, The Journal of nutrition.

[117]  C. Cavaliere,et al.  Rapid-resolution liquid chromatography/mass spectrometry for determination and quantitation of polyphenols in grape berries. , 2008, Rapid communications in mass spectrometry : RCM.

[118]  M. Ishikawa,et al.  Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice. , 2005, Biological & pharmaceutical bulletin.

[119]  E. Feskens,et al.  Dietary flavonoids and cancer risk in the Zutphen Elderly Study. , 1994, Nutrition and cancer.

[120]  M. Palma,et al.  Ultrasound-assisted extraction of soy isoflavones. , 2003, Journal of chromatography. A.

[121]  M. de Castro,et al.  Ultrasound-assisted extraction of phenolic compounds from strawberries prior to liquid chromatographic separation and photodiode array ultraviolet detection. , 2005, Journal of chromatography. A.

[122]  J. Harnly,et al.  A screening method for the identification of glycosylated flavonoids and other phenolic compounds using a standard analytical approach for all plant materials. , 2007, Journal of agricultural and food chemistry.

[123]  M. Palma,et al.  Microwave assisted extraction of soy isoflavones. , 2007, Analytica chimica acta.

[124]  M. Kampa,et al.  Polyphenols and cancer cell growth. , 2007, Reviews of physiology, biochemistry and pharmacology.

[125]  I. Kostova,et al.  Antiangiogenic effects of flavonoids and chalcones. , 2008, Pharmacological research.

[126]  Chung S. Yang Inhibition of carcinogenesis by tea , 1997, Nature.

[127]  A. J. Ryan,et al.  Comparison of Several Procedures Used for the Extraction of Anthocyanins from Red Grapes , 1998 .

[128]  L. Goya,et al.  Comparative effects of food-derived polyphenols on the viability and apoptosis of a human hepatoma cell line (HepG2). , 2005, Journal of agricultural and food chemistry.

[129]  R. Karjalainen,et al.  High-performance liquid chromatography analysis of black currant (Ribes nigrum L.) fruit phenolics grown either conventionally or organically. , 2006, Journal of agricultural and food chemistry.

[130]  V. Cheynier,et al.  Quantitative fractionation of grape proanthocyanidins according to their degree of polymerization. , 1999, Journal of agricultural and food chemistry.

[131]  S. Katiyar,et al.  Grape seed proanthocyanidins inhibit UV-radiation-induced oxidative stress and activation of MAPK and NF-kappaB signaling in human epidermal keratinocytes. , 2006, Free radical biology & medicine.

[132]  Kamil Kuca,et al.  Condensed and hydrolysable tannins as antioxidants influencing the health. , 2008, Mini reviews in medicinal chemistry.

[133]  Yi Yang,et al.  Ultrasound-assisted extraction of rutin and quercetin from Euonymus alatus (Thunb.) Sieb. , 2008, Ultrasonics sonochemistry.

[134]  M. Jung,et al.  Characterization and quantification of anthocyanins in grape juices obtained from the grapes cultivated in Korea by HPLC/DAD, HPLC/MS, and HPLC/MS/MS. , 2008, Journal of food science.

[135]  L. Butler,et al.  Characterization of the condensed tannin (proanthocyanidin) from a group II sorghum , 1983 .

[136]  P. Bose,et al.  MegaNatural((R)) Gold Grapeseed Extract: In Vitro Antioxidant and In Vivo Human Supplementation Studies. , 2001, Journal of medicinal food.

[137]  R. Lamuela-Raventós,et al.  Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent , 1999 .

[138]  M. Polášek,et al.  Recent trends in the determination of polyphenols by electromigration methods. , 2006, Journal of pharmaceutical and biomedical analysis.

[139]  M. Heinonen,et al.  Berry anthocyanins: isolation, identification and antioxidant activities , 2003 .

[140]  Xianglin Shi,et al.  Cyanidin-3-glucoside, a Natural Product Derived from Blackberry, Exhibits Chemopreventive and Chemotherapeutic Activity* , 2006, Journal of Biological Chemistry.

[141]  B. Klejdus,et al.  Supercritical fluid extraction of isoflavones from biological samples with ultra-fast high-performance liquid chromatography/mass spectrometry. , 2005, Journal of separation science.

[142]  A. Yanagida,et al.  Analytical separation of tea catechins and food-related polyphenols by high-speed counter-current chromatography. , 2006, Journal of chromatography. A.

[143]  H. S. Scheuller,et al.  Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro. , 2006, Journal of agricultural and food chemistry.

[144]  R. J. Robbins,et al.  Phenolic acids in foods: an overview of analytical methodology. , 2003, Journal of agricultural and food chemistry.

[145]  M. Caboni,et al.  Free and bound phenolic compounds in barley (Hordeum vulgare L.) flours. evaluation of the extraction capability of different solvent mixtures and pressurized liquid methods by micellar electrokinetic chromatography and spectrophotometry. , 2004, Journal of chromatography. A.

[146]  M. Pinelo,et al.  Optimization of continuous phenol extraction from Vitis vinifera byproducts , 2005 .

[147]  F. Shahidi,et al.  Phenolic antioxidants. , 1992, Critical reviews in food science and nutrition.

[148]  R. Reiter,et al.  DNA oxidatively damaged by chromium(III) and H(2)O(2) is protected by the antioxidants melatonin, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine, resveratrol and uric acid. , 2001, The international journal of biochemistry & cell biology.

[149]  H. Mukhtar,et al.  Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice , 2005, International journal of cancer.

[150]  N. Cotelle Role of flavonoids in oxidative stress. , 2001, Current topics in medicinal chemistry.

[151]  F. Tomás-Barberán,et al.  HPLC-DAD-MS/MS ESI characterization of unusual highly glycosylated acylated flavonoids from cauliflower (Brassica oleracea L. var. botrytis) agroindustrial byproducts. , 2003, Journal of agricultural and food chemistry.

[152]  P. Winterhalter,et al.  Separation and purification of anthocyanins by high-speed countercurrent chromatography and screening for antioxidant activity. , 2000, Journal of agricultural and food chemistry.

[153]  Jianlin Huang,et al.  Microwave-assisted extraction of quercetin and acid degradation of its glycosides in Psidium guajava leaves. , 2004, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.

[154]  J. Zhang,et al.  Effect of six flavonoids on proliferation of hepatic stellate cells in vitro. , 2000, Acta pharmacologica Sinica.

[155]  Y. Miura,et al.  Effects of green, oolong and black teas and related components on the proliferation and invasion of hepatoma cells in culture , 1999, Cytotechnology.

[156]  V. L. Singleton,et al.  Colorimetry of Total Phenolics with Phosphomolybdic-Phosphotungstic Acid Reagents , 1965, American Journal of Enology and Viticulture.

[157]  Dejian Huang,et al.  Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays: a comparative study. , 2002, Journal of agricultural and food chemistry.

[158]  D. Barrett,et al.  Comparison of the total phenolic and ascorbic acid content of freeze-dried and air-dried marionberry, strawberry, and corn grown using conventional, organic, and sustainable agricultural practices. , 2003, Journal of agricultural and food chemistry.

[159]  B. G. Chan,et al.  The conversion of procyanidins and prodelphinidins to cyanidin and delphinidin , 1985 .

[160]  G. Perriello,et al.  Acute effects of lyophilised red wine on total antioxidant capacity in healthy volunteers. , 2003, Diabetes, nutrition & metabolism.

[161]  M. Palma,et al.  Determination of trans-resveratrol in grapes by pressurised liquid extraction and fast high-performance liquid chromatography. , 2006, Journal of chromatography. A.

[162]  C. Fraga Plant polyphenols: How to translate their in vitro antioxidant actions to in vivo conditions , 2007, IUBMB life.

[163]  M. Stiborová,et al.  Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. , 2002, Chemico-biological interactions.

[164]  B. Hudson,et al.  Polyhydroxy flavonoid antioxidants for edible oils. structural criteria for activity , 1983 .

[165]  Ilja C W Arts,et al.  Polyphenols and disease risk in epidemiologic studies. , 2005, The American journal of clinical nutrition.

[166]  M Vinatoru,et al.  An overview of the ultrasonically assisted extraction of bioactive principles from herbs. , 2001, Ultrasonics sonochemistry.

[167]  Jungmin Lee,et al.  Determination of total monomeric anthocyanin pigment content of fruit juices, beverages, natural colorants, and wines by the pH differential method: collaborative study. , 2005, Journal of AOAC International.

[168]  Rebecca E. Forkner,et al.  Determination of hydrolyzable tannins (gallotannins and ellagitannins) after reaction with potassium iodate. , 2002, Journal of agricultural and food chemistry.

[169]  H. Frederiksen,et al.  Dietary proanthocyanidins: occurrence, dietary intake, bioavailability, and protection against cardiovascular disease. , 2005, Molecular nutrition & food research.

[170]  M. D'Archivio,et al.  Polyphenols, dietary sources and bioavailability. , 2007, Annali dell'Istituto superiore di sanita.

[171]  W. Berger,et al.  Green tea extract and (−)‐epigallocatechin‐3‐gallate, the major tea catechin, exert oxidant but lack antioxidant activities , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[172]  L. Butler,et al.  Choosing appropriate methods and standards for assaying tannin , 1989, Journal of Chemical Ecology.

[173]  J. Trosko,et al.  Prevention of the down-regulation of gap junctional intercellular communication by green tea in the liver of mice fed pentachlorophenol. , 2000, Carcinogenesis.

[174]  Jae Heun Lee,et al.  Protective effect of anthocyanins from black soybean seed coats on UVB-induced apoptotic cell death in vitro and in vivo. , 2008, Journal of agricultural and food chemistry.

[175]  H. Babich,et al.  In vitro cytotoxicity of epigallocatechin gallate and tea extracts to cancerous and normal cells from the human oral cavity. , 2004, Basic & clinical pharmacology & toxicology.

[176]  Kazuhiko Yoshida,et al.  Effects of blue honeysuckle (Lonicera caerulea L.) extract on lipopolysaccharide-induced inflammation in vitro and in vivo. , 2006, Experimental eye research.

[177]  C. Rice-Evans,et al.  The relative antioxidant activities of plant-derived polyphenolic flavonoids. , 1995, Free radical research.

[178]  P. Bose,et al.  Phenol antioxidant quantity and quality in foods: fruits. , 2001, Journal of agricultural and food chemistry.

[179]  J. Exon,et al.  A Review of the Effects and Mechanisms of Polyphenolics in Cancer , 2006, Critical reviews in food science and nutrition.

[180]  I. Mcmurrough,et al.  Chromatographic separation and automated analysis of flavanols. , 1978, Analytical biochemistry.

[181]  M. Downey,et al.  Simultaneous separation by reversed-phase high-performance liquid chromatography and mass spectral identification of anthocyanins and flavonols in Shiraz grape skin. , 2008, Journal of chromatography. A.

[182]  S. Guyot,et al.  Reversed-Phase HPLC following Thiolysis for Quantitative Estimation and Characterization of the Four Main Classes of Phenolic Compounds in Different Tissue Zones of a French Cider Apple Variety (Malus domestica Var. Kermerrien) , 1998 .

[183]  S. Guyot,et al.  Characterization and estimation of proanthocyanidins and other phenolics in coffee pulp (Coffea arabica) by thiolysis-high-performance liquid chromatography. , 2004, Journal of agricultural and food chemistry.

[184]  G. Mazza,et al.  Extraction of anthocyanins and other phenolics from black currants with sulfured water. , 2002, Journal of agricultural and food chemistry.

[185]  A. Pell,et al.  Analysis of condensed tannins: a review , 2001 .

[186]  P. Autio,et al.  In‐vivo effects of solar‐simulated ultraviolet irradiation on antioxidant enzymes and lipid peroxidation in human epidermis , 1991, The British journal of dermatology.

[187]  R. Russell,et al.  Serum antioxidant capacity is increased by consumption of strawberries, spinach, red wine or vitamin C in elderly women. , 1998, The Journal of nutrition.

[188]  Baojun Xu,et al.  A comparative study on phenolic profiles and antioxidant activities of legumes as affected by extraction solvents. , 2007, Journal of food science.

[189]  S. Mattila,et al.  Characterization of phenolic compounds from lingonberry (Vaccinium vitis-idaea). , 2006, Journal of agricultural and food chemistry.

[190]  M. Glomb,et al.  Characterization of phenolic compounds in rooibos tea. , 2008, Journal of agricultural and food chemistry.

[191]  G. Mittal,et al.  Extraction of Polyphenolics from Plant Material for Functional Foods—Engineering and Technology , 2005 .

[192]  Dejian Huang,et al.  The chemistry behind antioxidant capacity assays. , 2005, Journal of agricultural and food chemistry.

[193]  R. M. Alonso-Salces,et al.  Pressurized liquid extraction for the determination of polyphenols in apple. , 2001, Journal of chromatography. A.

[194]  K. Hostettmann,et al.  On-line identification of the bioactive compounds from Blumea gariepina by HPLC-UV-MS and HPLC-UV-NMR, combined with HPLC-micro-fractionation. , 2005, Phytochemical analysis : PCA.

[195]  Timothy J. Mason,et al.  The uses of ultrasound in food technology , 1996 .

[196]  N. O'Brien,et al.  Protection by the flavonoids myricetin, quercetin, and rutin against hydrogen peroxide-induced DNA damage in Caco-2 and Hep G2 cells. , 1999, Nutrition and cancer.

[197]  Fulvio Mattivi,et al.  Quantitation of polyphenols in different apple varieties. , 2004, Journal of agricultural and food chemistry.

[198]  S. Ramos Cancer chemoprevention and chemotherapy: dietary polyphenols and signalling pathways. , 2008, Molecular nutrition & food research.

[199]  S. Amin,et al.  Inhibition of lung carcinogenesis by black tea in Fischer rats treated with a tobacco-specific carcinogen: caffeine as an important constituent. , 1998, Cancer research.

[200]  Anne S. Meyer,et al.  Upgrading of grape skins: Significance of plant cell-wall structural components and extraction techniques for phenol release , 2006 .

[201]  M. Ortega-Heras,et al.  Optimization of a solid-phase extraction method using copolymer sorbents for isolation of phenolic compounds in red wines and quantification by HPLC. , 2008, Journal of agricultural and food chemistry.

[202]  R. Prior,et al.  Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements. , 2005, Journal of agricultural and food chemistry.

[203]  A. Berthod,et al.  Polyphenols in countercurrent chromatography. An example of large scale separation , 1999 .

[204]  M. Lean,et al.  The effects of dietary phenolic compounds on cytokine and antioxidant production by A549 cells. , 2008, Journal of medicinal food.

[205]  Mary G. Chisholm,et al.  HPLC determination of non-flavonoid phenols in vidal blanc wine using electrochemical detection , 1990 .

[206]  H. Hibasami,et al.  Sesamin and episesamin induce apoptosis in human lymphoid leukemia Molt 4B cells. , 2000, International journal of molecular medicine.

[207]  B. Magnuson,et al.  Anthocyanin-Rich Extracts Inhibit Multiple Biomarkers of Colon Cancer in Rats , 2006, Nutrition and cancer.

[208]  V. Menon,et al.  Ellagic acid, a natural polyphenol protects rat peripheral blood lymphocytes against nicotine-induced cellular and DNA damage in vitro: with the comparison of N-acetylcysteine. , 2007, Toxicology.

[209]  M. Palma,et al.  Stability of phenolic compounds during extraction with superheated solvents. , 2001, Journal of chromatography. A.

[210]  Luis Cisneros-Zevallos,et al.  Screening methods to measure antioxidant activity of sorghum (sorghum bicolor) and sorghum products. , 2003, Journal of agricultural and food chemistry.

[211]  L. Butler,et al.  Assay of condensed tannins or flavonoid oligomers and related flavonoids in plants. , 1994, Methods in enzymology.

[212]  Christopher A. Pohl,et al.  Accelerated Solvent Extraction: A Technique for Sample Preparation , 1996 .

[213]  W. Frankel,et al.  Transitioning From Preclinical to Clinical Chemopreventive Assessments of Lyophilized Black Raspberries: Interim Results Show Berries Modulate Markers of Oxidative Stress in Barrett's Esophagus Patients , 2006, Nutrition and cancer.

[214]  Yung-Sheng Huang,et al.  Green Tea Polyphenols Modulate Secretion of Urokinase Plasminogen Activator (uPA) and Inhibit Invasive Behavior of Breast Cancer Cells , 2005, Nutrition and cancer.

[215]  L. Howard,et al.  Effects of solvent and temperature on pressurized liquid extraction of anthocyanins and total phenolics from dried red grape skin. , 2003, Journal of agricultural and food chemistry.

[216]  F. J. Francis,et al.  Quantitative methods for anthocyanins. 2. Determination of total anthocyanin and degradation index for cranberry juice. , 1968 .

[217]  G. Eisenbrand,et al.  Modulation of oxidative cell damage by reconstituted mixtures of phenolic apple juice extracts in human colon cell lines. , 2006, Molecular nutrition & food research.

[218]  R. Ruch,et al.  Resveratrol reverses tumor-promoter-induced inhibition of gap-junctional intercellular communication. , 2000, Biochemical and biophysical research communications.

[219]  E. Björklund,et al.  Analytical-scale microwave-assisted extraction. , 2000, Journal of chromatography. A.

[220]  T. Kanda,et al.  Characterization of Polymerized Polyphenols by Size-exclusion HPLC , 2002, Bioscience, biotechnology, and biochemistry.

[221]  Jae Heun Lee,et al.  Anthocyanins from black soybean seed coats inhibit UVB-induced inflammatory cylooxygenase-2 gene expression and PGE2 production through regulation of the nuclear factor-kappaB and phosphatidylinositol 3-kinase/Akt pathway. , 2008, Journal of agricultural and food chemistry.

[222]  Y. S. Moreno,et al.  Characterization of anthocyanin extracts from maize kernels. , 2005, Journal of chromatographic science.

[223]  Á. Ríos,et al.  Bioguided extraction of polyphenols from grape marc by using an alternative supercritical-fluid extraction method based on a liquid solvent trap , 2004, Analytical and bioanalytical chemistry.

[224]  S. Gupta,et al.  Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of apigenin in normal versus human prostate carcinoma cells. , 2001, Biochemical and biophysical research communications.

[225]  Yiwei Li,et al.  Mechanisms of Cancer Chemoprevention by Soy Isoflavone Genistein , 2004, Cancer and Metastasis Reviews.

[226]  E. Yarnell,et al.  The effect of freeze‐drying and its implications for botanical medicine: a review , 2005, Phytotherapy research : PTR.

[227]  M. Netzel,et al.  In vivo antioxidative capacity of a composite berry juice , 2002 .

[228]  S. Bennett,et al.  A single HPLC-PAD-APCI/MS method for the quantitative comparison of phenolic compounds found in leaf, stem, root and fruit extracts of Vaccinium angustifolium. , 2007, Phytochemical analysis : PCA.

[229]  P. Kroon,et al.  High contents of nonextractable polyphenols in fruits suggest that polyphenol contents of plant foods have been underestimated. , 2009, Journal of agricultural and food chemistry.

[230]  Sonia Ramos,et al.  Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. , 2007, The Journal of nutritional biochemistry.

[231]  A. U. Khan,et al.  Reactive oxygen species as cellular messengers. , 1995, Chemistry & biology.

[232]  P. Laake,et al.  Anthocyanins inhibit nuclear factor-kappaB activation in monocytes and reduce plasma concentrations of pro-inflammatory mediators in healthy adults. , 2007, The Journal of nutrition.

[233]  C. Rémésy,et al.  Comparative effects of flavonoids on the growth, viability and metabolism of a colonic adenocarcinoma cell line (HT29 cells). , 1996, Cancer letters.

[234]  K. Robards Strategies for the determination of bioactive phenols in plants, fruit and vegetables. , 2003, Journal of chromatography. A.

[235]  M. Kohno,et al.  Suppression of tumor cell invasiveness by hydrolyzable tannins (plant polyphenols) via the inhibition of matrix metalloproteinase-2/-9 activity. , 2005, Biochemical and biophysical research communications.

[236]  R. Durst,et al.  Analysis of Anthocyanins in Nutraceuticals , 2001 .

[237]  C. Stalikas Extraction, separation, and detection methods for phenolic acids and flavonoids. , 2007, Journal of separation science.

[238]  M. D. Luque de Castro,et al.  Dynamic superheated liquid extraction of anthocyanins and other phenolics from red grape skins of winemaking residues. , 2007, Bioresource technology.

[239]  C. Diniz,et al.  New insights on the anticancer properties of dietary polyphenols , 2006, Medicinal research reviews.

[240]  S. Khokhar,et al.  Iron binding characteristics of phenolic compounds: some tentative structure–activity relations , 2003 .

[241]  M. Moyer,et al.  Anthocyanin-Rich Extract From Aronia meloncarpa E. Induces a Cell Cycle Block in Colon Cancer but Not Normal Colonic Cells , 2003, Nutrition and cancer.

[242]  G. Mazza,et al.  Optimization of Extraction of Anthocyanins from Black Currants with Aqueous Ethanol , 2003 .

[243]  P. Dais,et al.  Detection and quantification of phenolic compounds in olive oil by high resolution 1H nuclear magnetic resonance spectroscopy. , 2009, Analytica chimica acta.

[244]  L. Howard,et al.  Pressurized liquid extraction of flavonoids from spinach. , 2008, Journal of food science.

[245]  R. Pedreschi,et al.  Antimutagenic and antioxidant properties of phenolic fractions from Andean purple corn (Zea mays L.). , 2006, Journal of agricultural and food chemistry.

[246]  Devanand L. Luthria,et al.  Influence of sample preparation on assay of phenolic acids from eggplant. , 2006, Journal of agricultural and food chemistry.

[247]  Y. Sasaki,et al.  Tea tannin components modify the induction of sister-chromatid exchanges and chromosome aberrations in mutagen-treated cultured mammalian cells and mice. , 1991, Mutation research.

[248]  M. D. Luque de Castro,et al.  Ultrasound-assisted extraction for the analysis of phenolic compounds in strawberries , 2004, Analytical and bioanalytical chemistry.

[249]  A. Rodríguez-Bernaldo de Quirós,et al.  Analysis of non-anthocyanin phenolic compounds in wine samples using high performance liquid chromatography with ultraviolet and fluorescence detection. , 2007, Journal of separation science.

[250]  C. Thompson,et al.  Apoptosis in the pathogenesis and treatment of disease , 1995, Science.

[251]  G. Loo,et al.  Effects of epigallocatechin gallate and quercetin on oxidative damage to cellular DNA. , 2000, Mutation research.

[252]  Carrita A. Hightower,et al.  Flavonoids Suppress Androgen-Independent Human Prostate Tumor Proliferation , 2000, Nutrition and cancer.

[253]  Colin D Kay,et al.  Absorption of anthocyanins from blueberries and serum antioxidant status in human subjects. , 2002, Journal of agricultural and food chemistry.

[254]  R. Mumper,et al.  Formulation and In-Vitro and In-Vivo Evaluation of a Mucoadhesive Gel Containing Freeze Dried Black Raspberries: Implications for Oral Cancer Chemoprevention , 2007, Pharmaceutical Research.

[255]  D. Hou,et al.  Anthocyanidins inhibit cyclooxygenase-2 expression in LPS-evoked macrophages: structure-activity relationship and molecular mechanisms involved. , 2005, Biochemical pharmacology.

[256]  T. van Ree,et al.  Tannins: classification and definition. , 2001, Natural product reports.