簡易檢索 / 詳目顯示

研究生: 王春金
Anita - Carolina Suwandi
論文名稱: 鑑定蟻窩樹水萃取液中之生化活性物質
Identification of Bioactive Compounds in Water Extract of Sarang Semut (Myrmecodia pendans)
指導教授: 朱義旭
Yi-Hsu Ju
口試委員: 陳燿騰
Yaw-Terng Chern
Lien Huong Huynh
Lien Huong Huynh
Felycia Edi Soetaredjo
Felycia Edi Soetaredjo
Truong Chi Thanh
Truong Chi Thanh
學位類別: 碩士
Master
系所名稱: 工程學院 - 化學工程系
Department of Chemical Engineering
論文出版年: 2015
畢業學年度: 103
語文別: 英文
論文頁數: 90
中文關鍵詞: 蟻窩樹萃取酚化合物高效液相層析電噴霧質譜抗氧化物抗癌
外文關鍵詞: Sarang semut, Myrmecodia pendans, phenolic compound, High Performance Liquid Chromatography
相關次數: 點閱:317下載:2
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 蟻窩樹(Myrmecodia pendans)為一新發現有潛力之醫藥植物。眾所周知,此植物之水萃取液可治療多種疾病。據信其所含之植物化學物質(phytochemicals)為此植物具有健康效益之原因。然而,對此植物所含生物活性物質之知識十分有限;是以本研究之目的在於在最佳條件下得到蟻窩樹之萃取液,分離此萃取液並鑑定其中所含之生物活性物質。
    本研究利用100牵C水為萃取溶劑,再以DPPH評估萃取液之自由基清除活性以及萃取液對子宮頸癌細胞(HeLa)及乳癌細胞(MDA-MB-231)之毒性。結果顯示30分鐘之水萃取液具有最高活性,接著利用己烷、乙酸乙酯、丁醇及水將此萃取液做分級(fractionation)。對每一級分(fraction)量測其自由基清除活性、總酚含量、細胞毒活性及紫外線吸收,結果發現丁醇級分具有最高癌細胞抑制活性、最高總酚含量及最高DPPH活性。
    丁醇級分中生物活性物質之鑑定則是利用高效液相層析(HPLC)配合電噴霧質譜(ESI-MS)在負離子模式(negative ion mode)下為之。結果在蟻窩樹中共辨識出48種抗氧化物質, 其中大多數不曾在相關蟻窩樹文獻中被報導過。本研究證實蟻窩樹為一很好的抗氧化物來源。


    Sarang semut or ant-nest plant (Myrmecodia pendans) is a new potential medicinal plant. This water extract of this plant has been well-known for curing many kinds of diseases. Phytochemicals present in this plant are suspected as the reason of its health benefits. Nevertheless, detailed information on these bioactive compounds is very limited. Thus, this study was to determine optimum extraction time, explore bioactivity as well as separate and identify bioactive compounds of this plant.
    Extraction was done using water at 100牵C then its bioactivity of extracts were evaluated using DPPH for radical scavenging activity also cytotoxicity towards cervix cancer cells (HeLa) and breast cancer cells (MDA-MB-231). The highest activity was shown by 30 minutes water extracts, then it was fractionated using hexane, ethyl acetate, butanol, and water. Each solvent fractions were also evaluated for its radical scavenging activity, total phenolic content (TPC), cytotoxicity activity, and UV absorbance analysis.
    Butanol fraction possessed the highest cancer cell inhibition activity as well as the highest TPC and DPPH activities. Identification of bioactive compounds was performed with high-performance liquid chromatography coupled to electrospray ionization mass spectrometric (ESI-MS) detection in negative ion mode. In this present work, 48 antioxidant compounds are tentatively identified, most of them are reported herein in Myrmecodia pendans for the first time. These results indicate that Sarang semut is a good source of antioxidant compounds.

    RECOMMENDATION LETTER......................................ii QUALIFICATION LETTER......................................iii 摘要.......................................................iv ABSTRACT....................................................v ACKNOWLEDGEMENT............................................vi TABLE OF CONTENT...................................................vii LIST OF FIGURE ...........................................ix LIST OF TABLE...............................................x CHAPTER 1 INTRODUCTION 1.1. Research Background............................1 1.2. Objectives.....................................3 CHAPTER 2 LITERATURE REVIEW 2.1. Sarang Semut...................................4 2.2. Phenolic Compounds.............................5 2.3. Extraction....................................11 2.4. High-performance liquid chromatography(HPLC)..13 2.5. Mass spectrometer (MS)........................16 CHAPTER 3 EXPERIMENTAL SECTION 3.1. Materials and Tools...........................18 3.2. Instruments...................................19 3.3. Experimental Method...........................20 3.3.1. Sample preparation....................21 3.3.2. Extraction and Fractionation of Phenolic Compound.....................21 3.3.3. Total phenolic content (TPC)..........22 3.3.4. Radical Scavenging Activity...........22 3.3.5. Cytotoxicity Test.....................22 3.3.6. High Performance Liquid Chromatography and Mass Spectrometry(HPLC-MS)........24 CHAPTER 4 RESULTS AND DISCUSSION 4.1. Radical Scavenging Activity of Water Extracts 26 4.2. Cytotoxicity Test of Water Extracts...........27 4.3. Solvent Fractionation of Water Extracts.......29 4.4. UV analyses of solvent fractions..............32 4.5. HPLC-MS analysis of BF........................33 CHAPTER 5 CONCLUSION.......................................49 REFERENCES.................................................50 APPENDIX...................................................66

    1. Spačil, Z., Novakova, L., and Solich, P. (2008) Analysis of phenolic compounds by high performance liquid chromatography and ultra performance liquid chromatography, Talanta 76, 189-199.
    2. Ipek, E., Zeytinoglu, H., Okay, S., Tuylu, B. A., Kurkcuoglu, M., and Baser, K. H. C. (2005) Genotoxicity and antigenotoxicity of Origanum oil and carvacrol evaluated by Ames Salmonella/microsomal test, Food Chemistry 93, 551-556.
    3. Madari, H., and Jacobs, R. S. (2004) An analysis of cytotoxic botanical formulations used in traditional medicine of ancient Persia as abortifacients, Journal of Natural Products 67, 1204-1210.
    4. Harborne, J. B., and Williams, C. A. (2000) Advances in flavonoid research since 1992, Phytochemistry 55, 481-501.
    5. Havsteen, B. (1983) Flavonoids, a class of natural products of high pharmacological potency, Biochemical Pharmacology 32, 1141-1148.
    6. Lyons-Wall, P. M., and Samman, S. (1997) Flavonoids - dietary perspectives and health benefits, Nutrition Society of Australia 21, 106-114.
    7. Hung, H. C., Joshipura, K. J., Jiang, R., Hu, F. B., Hunter, D., Smith-Warner, S. A., Colditz, G. A., Rosner, B., Spiegelman, D., and Willett, W. C. (2004) Fruit and vegetable intake and risk of major chronic disease, Journal of the National Cancer Institute 96, 1577-1584.
    8. Hsu, C. L., and Yen, G. C. (2008) Phenolic compounds: Evidence for inhibitory effects against obesity and their underlying molecular signaling mechanisms, Molecular Nutrition and Food Research 52, 53-61.
    9. Cai, Y., Luo, Q., Sun, M., and Corke, H. (2004) Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer, Life Sciences 74, 2157-2184.
    10. Larson, R. A. (1988) The antioxidants of higher plants, Phytochemistry 27, 969–978.
    11. Zheng, W., and Wang, S. Y. (2001) Antioxidant activity and phenolic compounds in selected herbs, Journal of Agricultural and Food Chemistry 49, 5165-5170.
    12. Francis, G., Kerem, Z., Makkar, H. P. S., and Becker, K. (2002) The biological action of saponins in animal systems: A review, British Journal of Nutrition 88, 587-605.
    13. Chen, X. F., Wu, H. T., Tan, G. G., Zhu, Z. Y., and Chai, Y. F. (2011) Liquid chromatography coupled with time-of-flight and ion trap mass spectrometry for qualitative analysis of herbal medicines, Journal of Pharmaceutical Analysis 1, 235-245.
    14. Hertiani, T., Sasmito, E., Sumardi, and Ulfah, M. (2010) Preliminary study on immunomodulatory effect of Sarang-Semut tubers Myrmecodia tuberosa and Myrmecodia pendens, Online Journal of Biological Sciences 10, 136-141.
    15. Soeksmanto, A., Subroto, M. A., Wijaya, H., and Simanjuntak, P. (2010) Anticancer Activity Test for Extracts of Sarang Semut Plant (Myrmecodya pendens) to HeLa and MCM-B2 Cells, Pakistan Journal of Biological Sciences 13, 148-151.
    16. Sanjaya, R. E., Tedjo, Y. Y., Kurniawan, A., Ju, Y.-H., Ayucitra, A., and Ismadji, S. (2014) Investigation on supercritical CO2 extraction of phenolic-phytochemicals from an epiphytic plant tuber (Myrmecodia pendans), Journal of CO2 Utilization 6, 26-33.
    17. Engida, A. M., Kasim, N. S., Tsigie, Y. A., Ismadji, S., Huynh, L. H., and Ju, Y. H. (2013) Extraction, identification and quantitative HPLC analysis of flavonoids from sarang semut (Myrmecodia pendan), Industrial Crops and Products 41, 392-396.
    18. Engida, A. M., Faika, S., Nguyen-Thi, B. T., and Ju, Y. H. (2014) Analysis of major antioxidants from extracts of Myrmecodia pendans by UV/visible spectrophotometer, liquid chromatography/tandem mass spectrometry, and high-performance liquid chromatography/UV techniques, Journal of Food and Drug Analysis.
    19. Maurer, H. H. (2005) Advances in analytical toxicology: the current role of liquid chromatography-mass spectrometry in drug quantification in blood and oral fluid, Analytical and Bioanalytical Chemistry 381, 110-118.
    20. Qian, T., Cai, Z., Wong, R. N. S., Mak, N. K., and Jiang, Z. H. (2005) In vivo rat metabolism and pharmacokinetic studies of ginsenoside Rg3, Journal of Chromatography B 816, 223-232.
    21. Xing, J., Xie, C., and Lou, H. (2007) Recent applications of liquid chromatography–mass spectrometry in natural products bioanalysis, Journal of Pharmaceutical and Biomedical Analysis 44, 368-378.
    22. Nielsen, M. K. K., Johansen, S. S., Dalsgaard, P. W., and Linnet, K. (2010) Simultaneous screening and quantification of 52 common pharmaceuticals and drugs of abuse in hair using UPLC–TOF-MS, Forensic Science International 196, 85-92.
    23. Pelander, A., Ristimaa, J., Rasanen, I., Vuori, E., and Ojanpera, I. (2008) Screening for basic drugs in hair of drug addicts by liquid chromatography/time-of-flight mass spectrometry, Therapeutic Drug Monitoring 30, 717-724.
    24. Zhou, J.-L., Qi, L.-W., and Li, P. (2009) Herbal medicine analysis by liquid chromatography/time-of-flight mass spectrometry, Journal of Chromatography A 1216, 7582-7594.
    25. Wikipedia. (2013) Myrmecodia.
    26. Subroto, M. A., and Hendro. (2006) Gempur Penyakit dengan Sarang Semut, In Penebar Swadaya, Jakarta.
    27. Robbins, R. J. (2003) Phenolic acids in foods: an overview of analytical methodology, Journal of Agricultural and Food Chemistry 51, 2866-2887.
    28. Balasundram, N., Sundram, K., and Samman, S. (2006) Phenolic compounds in plants and agri-industrial by-products: Antioxidant activity, occurrence, and potential uses, Food Chemistry 99, 191-203.
    29. Ferreira, J. F., Luthria, D. L., Sasaki, T., and Heyerick, A. (2010) Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer, Molecules 15, 3135-3170.
    30. Mittova, V., Volokita, M., Guy, M., and Tal, M. (2000) Activities of SOD and the ascorbate- glutathione cycle enzymes in subcellular compartments in leaves and roots of the cultivated tomato and its wild salt-tolerant relative Lycopersicon pennellii, Physiologia Plantarum 110, 42-51.
    31. Popa, V. I., Dumitru, M., Volf, I., and Anghel, N. (2008) Lignin and polyphenols as allelochemicals, Industrial Crops and Products 27, 144-149.
    32. Naczk, M., and Shahidi, F. (2006) Phenolics in cereals, fruits and vegetables: Occurrence, extraction and analysis, Journal of Pharmaceutical and Biomedical Analysis 41, 1523-1542.
    33. Bravo, L. (1998) Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance, Nutrition Reviews 56, 317-333.
    34. Alasalvar, C., Grigor, J. M., Zhang, D., Quantick, P. C., and Shahidi, F. (2001) Comparison of volatiles, phenolics, sugars, antioxidant vitamins, and sensory quality of different colored carrot varieties, Journal of Agricultural and Food Chemistry 49, 1410-1416.
    35. Gordon, M. (1996) Dietary antioxidants in disease prevention, Natural Product Reports 13, 265-273.
    36. Benavente-Garcı́a, O., Castillo, J., Lorente, J., Ortuno, A., and Del Rio, J. A. (2000) Antioxidant activity of phenolics extracted from Olea europaea L. leaves, Food Chemistry 68, 457-462.
    37. Middleton, E., Kandaswami, C., and Theoharides, T. C. (2000) The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer, Pharmacological Reviews 52, 673-751.
    38. Puupponen-Pimia, R., Nohynek, L., Meier, C., Kahkonen, M., Heinonen, M., Hopia, A., and Oksman-Caldentey, K. M. (2001) Antimicrobial properties of phenolic compounds from berries, Journal of Applied Microbiology 90, 494-507.
    39. Ignat, I., Volf, I., and Popa, V. I. (2011) A critical review of methods for characterisation of polyphenolic compounds in fruits and vegetables, Food Chemistry 126, 1821-1835.
    40. Luthria, D. L. (2006) Significance of sample preparation in developing analytical methodologies for accurate estimation of bioactive compounds in functional foods, Journal of the Science of Food and Agriculture 86, 2266-2272.
    41. Escarpa, A., and Gonzalez, M. C. (2001) An overview of analytical chemistry of phenolic compounds in foods, Critical Reviews in Analytical Chemistry 31, 57–139.
    42. Croteau, R., Kutchan, T. M., and Lewis, N. G. (2000) Natural products (secondary metabolites), American Society of Plant Physiologists, Rockville.
    43. Hagerman, A. E. (2002) Tannin Handbook, Department of Chemistry and Biochemistry, Miami.
    44. Cook, N. C., and Samman, S. (1996) Flavonoids—Chemistry, metabolism, cardioprotective effects, and dietary sources, The Journal of Nutritional Biochemistry 7, 66-76.
    45. Kaufmann, B., and Christen, P. (2002) Recent extraction techniques for natural products: microwave-assisted extraction and pressurised solvent extraction, Phytochemical Analysis 13, 105-113.
    46. Handa, S. S., Khanuja, S. P. S., Longo, G., and Rakesh, D. D. (2008) Extraction Technologies for Medicinal and Aromatic Plants, International centre for science and high technology, Italy.
    47. Brusotti, G., Cesari, I., Dentamaro, A., Caccialanza, G., and Massolini, G. (2014) Isolation and characterization of bioactive compounds from plant resources: The role of analysis in the ethnopharmacological approach, Journal of Pharmaceutical and Biomedical Analysis 87, 218-228.
    48. Tohar, N., Syamsir, D. R., and Awang, K. Supercritical Carbon Dioxide Extraction of Mitragyna speciosa, Malaysia.
    49. Delazar, A., Nahar, L., Hamedeyazdan, S., and Sarker, S. D. (2012) Microwave-assisted extraction in natural products isolation, Methods in Molecular Biology 864, 89-115.
    50. Prathapa, B., Dey, A., Srinivasarao, G. H., P., J., and Arthanariswaran, P. (2013) A Review - Importance of RP-HPLC in Analytical Method Development International Journal of Novel Trends in Pharmaceutical Sciences 3, 15-23.
    51. Jeffery, G. H., Bassett, J., Mendham, J., and Denny, R. C. (1989) Vogel’s Textbook of Quantitative Chemical Analysis, 5 ed., Longman scientific & technical, Harlow.
    52. Gupta, V., Jain, A. D. K., Gill, N. S., and Gupta, K. (2012) Development and validation of HPLC method- a review, International Research Journal of Pharmaceutical and Applied Sciences 2, 17-25.
    53. Lindsay, S., and Kealey, D. (1987) High performance liquid chromatography, Wiley, USA.
    54. Malviya, R., Bansal, V., Pal, O. P., and Sharma, P. K. (2010) High performance liquid chromatography: A short review, Journal of Global Pharma Technology 2, 22-26.
    55. Aguilar, M. I. (2004) HPLC of Peptides and Proteins: Methods and Protocols, Humana Press Inc., Totowa.
    56. Wikipedia. (2014) High-performance liquid chromatography.
    57. Abidi, S. L. (1991) High-performance liquid chromatography of phosphatidic acids and related polar lipids, Journal of Chromatography A 587, 193-203.
    58. Lang, J. K. (2009) Handbook on Mass Spectrometry: Instrumentation, Data and Analysis, and Applications, Nova Science.
    59. Reusch, W. (2013) Mass Spectrometry.
    60. Dass, C. (2007) Fundamentals of Contemporary Mass Spectrometry, John Wiley & Sons, New Jersey.
    61. Eiceman, G. A. (2000) Encyclopedia of Analytical Chemistry: Applications, Theory, and Instrumentation, Wiley, Chichester.
    62. Pitt, J. J. (2009) Principles and Applications of Liquid Chromatography-Mass Spectrometry in Clinical Biochemistry, The Clinical Biochemist Reviews 30, 19-34.
    63. Singleton, V. L., and Rossi, J. A. (1965) Colorimetry of total phenolics with phosphomolybdicphosphotungstic acid reagents, American Journal of Enology and Viticulture 16, 144-158.
    64. Song, F. L., Gan, R. Y., Zhang, Y., Xiao, Q., Kuang, L., and Li, H. B. (2010) Total Phenolic Contents and Antioxidant Capacities of Selected Chinese Medicinal Plants, International Journal of Molecular Sciences 11, 2362-2372.
    65. Torey, A., Sasidharan, S., Latha, L. Y., Sudhakaran, S., and Ramanathan, S. (2010) Antioxidant activity and total phenolic content of methanol extracts of Ixora coccinea, Pharmaceutical Biology 48, 1119–1123.
    66. Fahmi, M. Z., and Chang, J. Y. (2013) Forming double layer-encapsulated quantum dots for bio-imaging and cell targeting, Nanoscale 5, 1517-1528.
    67. Mosmann, T. (1983) Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, Journal of Immunological Methods 65, 55-63.
    68. Fotakis, G., and Timbrell, J. A. (2006) In vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride, Toxicology Letters 160, 171-177.
    69. Servin, W. P., Chitra, D. B., Sarmad, M., and Sahaya, S. B. (2013) In vitro phytochemical screening, free radical scavenging activity and anticancer activity of abutilon hirtum (Lam.) sweet (Malvaceae), International Journal of PharmTech Research 5, 155-161.
    70. Du, L., Shen, Y., Zhang, X., Prinyawiwatkul, W., and Xu, Z. (2014) Antioxidant-rich phytochemicals in miracle berry (Synsepalum dulcificum) and antioxidant activity of its extracts, Food Chemistry 153, 279-284.
    71. Balogh, E., Hegedus, A., and Stefanovits-Banyai, E. (2010) Application of and correlation among antioxidant and antiradical assays for characterizing antioxidant capacity of berries, Scientia Horticulturae 125, 332-336.
    72. Naczk, M., and Shahidi, F. (2004) Extraction and analysis of phenolics in food, Journal of Chromatography A 1054, 95-111.
    73. Pavia, D. L., Lampman, G. M., and Kriz, G. S. (2001) Introduction to Spectroscopy, 3 ed., Thomson Learning, Inc., USA.
    74. Phillips, K. M., and Tarrago-Trani, M. T. (2010) Stability of vitamin C in frozen raw fruit and vegetable homogenates, Journal of Food Composition and Analysis 23, 243–259.
    75. Novakova, L., and Solich, P. (2008) HPLC methods for simultaneous determination of ascorbic and dehydroascorbic acids., Trends in Analytical Chemistry 27, 942–958.
    76. Spinola, V., Mendes, B., Camara, J., and Castilho, P. (2012) An improved and fast UHPLC-PDA methodology for determination of L-ascorbic and dehydroascorbic acids in fruits and vegetables. Evaluation of degradation rate during storage, Analytical and Bioanalytical Chemistry 403, 1049-1058.
    77. Szultka, M., Buszewska-Forajta, M., Kaliszan, R., and Buszewski, B. (2014) Determination of ascorbic acid and its degradation products by high-performance liquid chromatography-triple quadrupole mass spectrometry, Electrophoresis 35, 585-592.
    78. Tang, X., Liu, J., Dong, W., Li, P., Li, L., Lin, C., Zheng, Y., Hou, J., and Li, D. (2013) The cardioprotective effects of citric acid and L-malic acid on myocardial ischemia/reperfusion injury, Evidence-Based Complementary and Alternative Medicine 2013.
    79. Fernandez-Fernandez, R., Lopez-Martinez, J., Romero-Gonzalez, R., Martinez-Vidal, J., Alarcon Flores, M., and Garrido Frenich, A. (2010) Simple LC–MS Determination of Citric and Malic Acids in Fruits and Vegetables, Chroma 72, 55-62.
    80. Zhang, Q. C., Zhao, Y., and Bian, H. M. (2013) Antiplatelet activity of a novel formula composed of malic acid, succinic acid and citric acid from Cornus officinalis fruit, Phytotherapy Research 27, 1894-1896.
    81. Eswaranandam, S., Hettiarachchy, N. S., and Johnson, M. G. (2004) Antimicrobial activity of citric, lactic, malic, or tartaric acids and nisin-incorporated soy protein film against Listeria monocytogenes, Escherichia coli O157:H7, and Salmonella gaminara, Journal of Food Science 69, FMS79-FMS84.
    82. Abu-Reidah, I. M., Ali-Shtayeh, M. S., Jamous, R. M., Arraez-Roman, D., and Segura-Carretero, A. (2015) HPLC–DAD–ESI-MS/MS screening of bioactive components from Rhus coriaria L. (Sumac) fruits, Food Chemistry 166, 179-191.
    83. Chen, Y., Luo, H., Guo, X., Xian, Y., Luo, D., and Wu, Y. (2014) Determination of total maleic acid, fumaric acid, p-hydroxybenzoic acid and benzoic acid in food by ultra performance liquid chromatography-tandem mass spectrometry, Analytical Methods 6, 4803-4809.
    84. Akao, M., and Kuroda, K. (1991) Antifungal activity of fumaric acid in mice infected with Candida albicans, Chemical & Pharmaceutical Bulletin (Tokyo) 39, 3077-3078.
    85. Kuroda, K., and Akao, M. (1981) Antitumor and anti-intoxication activities of fumaric acid in cultured cells, Gann 72, 777-782.
    86. Footitt, E. J., Clayton, P. T., Mills, K., Heales, S. J., Neergheen, V., Oppenheim, M., and Mills, P. B. (2013) Measurement of plasma B6 vitamer profiles in children with inborn errors of vitamin B6 metabolism using an LC-MS/MS method, Journal of Inherited Metabolic Disease 36, 139-145.
    87. Urpi-Sarda, M., Zamora-Ros, R., Lamuela-Raventos, R., Cherubini, A., Jauregui, O., de la Torre, R., Covas, M. I., Estruch, R., Jaeger, W., and Andres-Lacueva, C. (2007) HPLC–Tandem mass spectrometric method to characterize resveratrol metabolism in humans, Clinical Chemistry 53, 292-299.
    88. Zhou, S., Yang, R., Teng, Z., Zhang, B., Hu, Y., Yang, Z., Huan, M., Zhang, X., and Mei, Q. (2009) Dose-dependent absorption and metabolism of trans-polydatin in rats, Journal of Agricultural and Food Chemistry 57, 4572-4579.
    89. Shan, C. W. (1988) Effects of polydatin on platelet aggregation in rabbits, Acta Pharmaceutica Sinica 23, 394-396.
    90. Pace-Asciak, C. R., Hahn, S., Diamandis, E. P., Soleas, G., and Goldberg, D. M. (1995) The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: Implications for protection against coronary heart disease, Clinica Chimica Acta 235, 207-219.
    91. Jayatilake, G. S., Jayasuriya, H., Lee, E. S., Koonchanok, N. M., Geahlen, R. L., Ashendel, C. L., McLaughlin, J. L., and Chang, C. J. (1993) Kinase Inhibitors from Polygonum cuspidatum, Journal of Natural Products 56, 1805-1810.
    92. Kostadinović, S., Wilkens, A., Stefova, M., Ivanova, V., Vojnoski, B., Mirhosseini, H., and Winterhalter, P. (2012) Stilbene levels and antioxidant activity of Vranec and Merlot wines from Macedonia: Effect of variety and enological practices, Food Chemistry 135, 3003-3009.
    93. Frankel, E. N., German, J. B., Kinsella, J. E., Parks, E., and Kanner, J. (1993) Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine, The Lancet 341, 454-457.
    94. Kimura, Y., Okuda, H., and Arichi, S. (1985) Effects of stilbenes on arachidonate metabolism in leukocytes, Biochimica et Biophysica Acta 834, 275-278.
    95. Arichi, H., Kimura, Y., Okuda, H., Baba, K., Kozawa, M., and Arichi, S. (1982) Effects of stilbene components of the roots of Polygonum cuspidatum Sieb. et Zucc. on lipid metabolism, Chemical & Pharmaceutical Bulletin (Tokyo) 30, 1766-1770.
    96. Lanzilli, G., Cottarelli, A., Nicotera, G., Guida, S., Ravagnan, G., and Fuggetta, M. P. (2012) Anti-inflammatory effect of resveratrol and polydatin by In vitro IL-17 modulation, Inflammation 35, 240-248.
    97. Orsini, F., Pelizzoni, F., Verotta, L., Aburjai, T., and Rogers, C. B. (1997) Isolation, synthesis, andantiplatelet aggregation activity of resveratrol 3-O-β-d-glucopyranoside and related compounds, Journal of Natural Products 60, 1082-1087.
    98. Romero-Perez, A. I., Ibern-Gomez, M., Lamuela-Raventos, R. M., and de la Torre-Boronat, M. C. (1999) Piceid, the Major Resveratrol Derivative in Grape Juices, Journal of Agricultural and Food Chemistry 47, 1533-1536.
    99. Yu, C. K. Y., Lam, C. N. W., Springob, K., Schmidt, J., Chu, I. K., and Lo, C. (2006) Constitutive Accumulation of cis-piceid in Transgenic Arabidopsis Overexpressing a Sorghum Stilbene Synthase Gene, Plant and Cell Physiology 47, 1017-1021.
    100. Zhao, H. Y., Fan, M. X., Wu, X., Wang, H. J., Yang, J., Si, N., and Bian, B. L. (2013) Chemical profiling of the chinese herb formula Xiao-Cheng-Qi decoction using liquid chromatography coupled with electrospray ionization mass spectrometry, Journal of Chromatographic Science 51, 273-285.
    101. Di Maio, I., Esposto, S., Taticchi, A., Selvaggini, R., Veneziani, G., Urbani, S., and Servili, M. (2011) HPLC–ESI-MS investigation of tyrosol and hydroxytyrosol oxidation products in virgin olive oil, Food Chemistry 125, 21-28.
    102. Sun, J., Liang, F., Bin, Y., Li, P., and Duan, C. (2007) Screening non-colored phenolics in red wines using liquid chromatography/ultraviolet and mass spectrometry/mass spectrometry libraries, Molecules 12, 679-693.
    103. Zhu, L., Zhang, Y., Deng, J., Li, H., and Lu, J. (2012) Phenolic concentrations and antioxidant properties of wines made from north american grapes grown in China, Molecules 17, 3304-3323.
    104. Restivo, A., Degano, I., Ribechini, E., and Colombini, M. P. (2014) Development and optimisation of an HPLC-DAD-ESI-Q-TOF method for the determination of phenolic acids and derivatives, PLOS ONE 9, e88762.
    105. Chen, Y., Peng, Y., Dai, C.-C., and Ju, Q. (2011) Biodegradation of 4-hydroxybenzoic acid by Phomopsis liquidambari, Applied Soil Ecology 51, 102-110.
    106. Vallverdu-Queralt, A., Jauregui, O., Di Lecce, G., Andres-Lacueva, C., and Lamuela-Raventos, R. M. (2011) Screening of the polyphenol content of tomato-based products through accurate-mass spectrometry (HPLC–ESI-QTOF), Food Chemistry 129, 877-883.
    107. Vallverdu-Queralt, A., Regueiro, J., Martinez-Huelamo, M., Rinaldi Alvarenga, J. F., Leal, L. N., and Lamuela-Raventos, R. M. (2014) A comprehensive study on the phenolic profile of widely used culinary herbs and spices: Rosemary, thyme, oregano, cinnamon, cumin and bay, Food Chemistry 154, 299-307.
    108. Stalmach, A., Mullen, W., Barron, D., Uchida, K., Yokota, T., Cavin, C., Steiling, H., Williamson, G., and Crozier, A. (2009) Metabolite profiling of hydroxycinnamate derivatives in plasma and urine after the ingestion of coffee by humans: identification of biomarkers of coffee consumption, Drug Metabolism and Disposition 37, 1749-1758.
    109. de Lourdes Mata-Bilbao, M., Andres-Lacueva, C., Roura, E., Jauregui, O., Torre, C., and Lamuela-Raventos, R. M. (2007) A new LC/MS/MS rapid and sensitive method for the determination of green tea catechins and their metabolites in biological samples, Journal of Agricultural and Food Chemistry 55, 8857-8863.
    110. Hilt, P., Schieber, A., Yildirim, C., Arnold, G., Klaiber, I., Conrad, J., Beifuss, U., and Carle, R. (2003) Detection of phloridzin in strawberries (Fragaria x ananassa Duch.) by HPLC-PDA-MS/MS and NMR spectroscopy, Journal of Agricultural and Food Chemistry 51, 2896-2899.
    111. Marles, M. A. S., Gruber, M. Y., Scoles, G. J., and Muir, A. D. (2003) Pigmentation in the developing seed coat and seedling leaves of Brassica carinata is controlled at the dihydroflavonol reductase locus, Phytochemistry 62, 663-672.
    112. Kajdžanoska, M., Gjamovski, V., and Stefova, M. (2010) HPLC-DAD-ESI-MSn identification of phenolic compounds in cultivated strawberries from Macedonia, Vol. 29.
    113. Huang, Y., Chen, L., Feng, L., Guo, F., and Li, Y. (2013) Characterization of total phenolic constituents from the stems of Spatholobus suberectus using LC-DAD-MSn and their inhibitory effect on human neutrophil elastase activity, Molecules 18, 7549-7556.
    114. Abu-Reidah, I. M., Arraez-Roman, D., Segura-Carretero, A., and Fernandez-Gutierrez, A. (2013) Profiling of phenolic and other polar constituents from hydro-methanolic extract of watermelon (Citrullus lanatus) by means of accurate-mass spectrometry (HPLC–ESI–QTOF–MS), Food Research International 51, 354-362.
    115. Liang, N. N., He, F., Bi, H. Q., Duan, C. Q., Reeves, M. J., and Wang, J. (2012) Evolution of flavonols in berry skins of different grape cultivars during ripening and a comparison of two vintages, Eur Food Res Technol 235, 1187-1197.
    116. Quifer-Rada, P., Vallverdu-Queralt, A., Martinez-Huelamo, M., Chiva-Blanch, G., Jauregui, O., Estruch, R., and Lamuela-Raventos, R. (2015) A comprehensive characterisation of beer polyphenols by high resolution mass spectrometry (LC–ESI-LTQ-Orbitrap-MS), Food Chemistry 169, 336-343.
    117. Maurya, D. K., Nandakumar, N., and Devasagayam, T. P. A. (2010) Anticancer property of gallic acid in A549, a human lung adenocarcinoma cell line, and possible mechanisms, Journal of Clinical Biochemistry and Nutrition 48, 85-90.
    118. Faried, A., Kurnia, D., Faried, L. S., Usman, N., Miyazaki, T., Kato, H., and Kuwano, H. (2007) Anticancer effects of gallic acid isolated from Indonesian herbal medicine, Phaleria macrocarpa (Scheff.) Boerl, on human cancer cell lines, International Journal of Oncology 30, 605-613.
    119. Salucci, M., Stivala, L. A., Maiani, G., Bugianesi, R., and Vannini, V. (2002) Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2), British Journal of Cancer 86, 1645-1651.
    120. Yoshioka, K., Kataoka, T., Hayashi, T., Hasegawa, M., Ishi, Y., and Hibasami, H. (2000) Induction of apoptosis by gallic acid in human stomach cancer KATO III and colon adenocarcinoma COLO 205 cell lines, Oncology Reports 7, 1221-1223.
    121. Kuo, C. L., Lai, K. C., Ma, Y. S., Weng, S. W., Lin, J. P., and Chung, J. G. (2014) Gallic acid inhibits migration and invasion of SCC-4 human oral cancer cells through actions of NF-κB, Ras and matrix metalloproteinase-2 and -9, Oncology Reports 32, 355-361.
    122. Francesko, A., Fernandes, M. M., and Tzanov, T. (2013) Gallic acid implications in health: Multi-therapeutic and protective agent, In Handbook on Gallic Acid: Natural Occurrences, Antioxidant Properties and Health Implications, pp 29-56.
    123. Abdelwahed, A., Bouhlel, I., Skandrani, I., Valenti, K., Kadri, M., Guiraud, P., Steiman, R., Mariotte, A. M., Ghedira, K., Laporte, F., Dijoux-Franca, M. G., and Chekir-Ghedira, L. (2007) Study of antimutagenic and antioxidant activities of Gallic acid and 1,2,3,4,6-pentagalloylglucose from Pistacia lentiscus. Confirmation by microarray expression profiling, Chemico-Biological Interactions 165, 1-13.
    124. Kim, Y. J. (2007) Antimelanogenic and antioxidant properties of gallic acid, Biological and Pharmaceutical Bulletin 30, 1052-1055.
    125. Ozcelik, B., Kartal, M., and Orhan, I. (2011) Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids, Pharmaceutical Biology 49, 396-402.
    126. Wang, K., Zhu, X., Zhang, K., Zhu, L., and Zhou, F. (2014) Investigation of gallic acid induced anticancer effect in human breast carcinoma MCF-7 cells, Journal of Biochemical and Molecular Toxicology 28, 387-393.
    127. You, B. R., Moon, H. J., Han, Y. H., and Park, W. H. (2010) Gallic acid inhibits the growth of HeLa cervical cancer cells via apoptosis and/or necrosis, Food and Chemical Toxicology 48, 1334-1340.
    128. Kaur, M., Velmurugan, B., Rajamanickam, S., Agarwal, R., and Agarwal, C. (2009) Gallic acid, an active constituent of grape seed extract, exhibits anti-proliferative, pro-apoptotic and anti-tumorigenic effects against prostate carcinoma xenograft growth in nude mice, Pharmaceutical Research 26, 2133-2140.
    129. Hollman, P. C. H. (2004) Absorption, bioavailability, and metabolism of flavonoids, Pharmaceutical Biology 42, 74-83.
    130. Kocacaliskan, I., Talan, I., and Terzi, I. (2006) Antimicrobial activity of catechol and pyrogallol as allelochemicals, Zeitschrift fur Naturforschung C 61, 639-642.
    131. Zheng, L. T., Ryu, G. M., Kwon, B. M., Lee, W. H., and Suk, K. (2008) Anti-inflammatory effects of catechols in lipopolysaccharide-stimulated microglia cells: Inhibition of microglial neurotoxicity, European Journal of Pharmacology 588, 106-113.
    132. Ma, Q., and Kinneer, K. (2002) Chemoprotection by phenolic antioxidants. Inhibition of tumor necrosis factor alpha induction in macrophages, The Journal of Biological Chemistry 277, 2477-2484.
    133. Giovannini, L., Migliori, M., Filippi, C., Origlia, N., Panichi, V., Falchi, M., Bertelli, A. A., and Bertelli, A. (2002) Inhibitory activity of the white wine compounds, tyrosol and caffeic acid, on lipopolysaccharide-induced tumor necrosis factor-alpha release in human peripheral blood mononuclear cells, International Journal of Tissue Reactions 24, 53-56.
    134. Lu, J., Huang, G., Wang, Z., Zhuang, S., Xu, L., Song, B., Xiong, Y., and Guan, S. (2013) Tyrosol exhibits negative regulatory effects on LPS response and endotoxemia, Food and Chemical Toxicology 62, 172-178.
    135. St-Laurent-Thibault, C., Arseneault, M., Longpre, F., and Ramassamy, C. (2011) Tyrosol and hydroxytyrosol, two main components of olive oil, protect N2a cells against amyloid-beta-induced toxicity. Involvement of the NF-kappaB signaling, Current Alzheimer Research 8, 543-551.
    136. Warleta, F., Quesada, C. S., Campos, M., Allouche, Y., Beltran, G., and Gaforio, J. J. (2011) Hydroxytyrosol protects against oxidative DNA damage in human breast cells, Nutrients 3, 839-857.
    137. Barontini, M., Bernini, R., Carastro, I., Gentili, P., and Romani, A. (2014) Synthesis and DPPH radical scavenging activity of novel compounds obtained from tyrosol and cinnamic acid derivatives, New Journal of Chemistry 38, 809-816.
    138. Alshatwi, A. A. (2010) Catechin hydrate suppresses MCF-7 proliferation through TP53/Caspase-mediated apoptosis, Journal of Experimental & Clinical Cancer Research 29, 167.
    139. Al-Hazzani, A. A., and Alshatwi, A. A. (2011) Catechin hydrate inhibits proliferation and mediates apoptosis of SiHa human cervical cancer cells, Food and Chemical Toxicology 49, 3281-3286.
    140. Rocha-Guzman, N. E., Gallegos-Infante, J. A., Gonzalez-Laredo, R. F., Reynoso-Camacho, R., Ramos-Gomez, M., Garcia-Gasca, T., Rodriguez-Munoz, M. E., Guzman-Maldonado, S. H., Medina-Torres, L., and Lujan-Garcia, B. A. (2009) Antioxidant activity and genotoxic effect on HeLa cells of phenolic compounds from infusions of Quercus resinosa leaves, Food Chemistry 115, 1320-1325.
    141. Ko, C. H., Lau, K. M., Choy, W. Y., and Leung, P. C. (2009) Effects of tea catechins, epigallocatechin, gallocatechin, and gallocatechin gallate, on bone metabolism, Journal of Agricultural and Food Chemistry 57, 7293-7297.
    142. Du, G. J., Zhang, Z., Wen, X. D., Yu, C., Calway, T., Yuan, C. S., and Wang, C. Z. (2012) Epigallocatechin gallate (EGCG) is the most effective cancer chemopreventive polyphenol in green tea, Nutrients 4, 1679-1691.
    143. Evacuasiany, E., Ratnawati, H., Liana, L. K., Widowati, W., Maesaroh, M., Mozef, T., and Risdian, C. (2014) Cytotoxic and antioxidant activities of catechins in inhibiting the malignancy of breast cancer, Oxidants and Antioxidants in Medical Science 3, 141-146.
    144. Wang, Z., Wang, D., Han, S., Wang, N., Mo, F., Loo, T. Y., Shen, J., Huang, H., and Chen, J. (2013) Bioactivity-guided identification and cell signaling technology to delineate the lactate dehydrogenase a inhibition effects of Spatholobus suberectus on breast cancer, PLOS ONE 8, e56631.
    145. Hayes, C. J., Whittaker, B. P., Watson, S. A., and Grabowska, A. M. (2006) Synthesis and preliminary anticancer activity studies of C4 and C8-modified derivatives of catechin gallate (CG) and epicatechin gallate (ECG), The Journal of Organic Chemistry 71, 9701-9712.
    146. Kurbitz, C., Heise, D., Redmer, T., Goumas, F., Arlt, A., Lemke, J., Rimbach, G., Kalthoff, H., and Trauzold, A. (2011) Epicatechin gallate and catechin gallate are superior to epigallocatechin gallate in growth suppression and anti-inflammatory activities in pancreatic tumor cells, Cancer Science 102, 728-734.
    147. Shih, P.-H., Yeh, C.-T., and Yen, G.-C. (2005) Effects of anthocyanidin on the inhibition of proliferation and induction of apoptosis in human gastric adenocarcinoma cells, Food and Chemical Toxicology 43, 1557-1566.
    148. Paixao, J., Dinis, T. C. P., and Almeida, L. M. (2012) Protective role of malvidin-3-glucoside on peroxynitrite-induced damage in endothelial cells by counteracting reactive species formation and apoptotic mitochondrial pathway, Oxidative Medicine and Cellular Longevity 2012, 12.
    149. Kahkonen, M. P., and Heinonen, M. (2003) Antioxidant activity of anthocyanins and their aglycons, Journal of Agricultural and Food Chemistry 51, 628-633.
    150. De Pascual-Teresa, S., Moreno, D. A., and Garcia-Viguera, C. (2010) Flavanols and anthocyanins in cardiovascular health: A review of current evidence, International Journal of Molecular Sciences 11, 1679-1703.
    151. Olsson, M. E., Gustavsson, K. E., Andersson, S., Nilsson, A., and Duan, R. D. (2004) Inhibition of cancer cell proliferation in vitro by fruit and berry extracts and correlations with antioxidant levels, Journal of Agricultural and Food Chemistry 52, 7264-7271.
    152. Zhang, Y., Vareed, S. K., and Nair, M. G. (2005) Human tumor cell growth inhibition by nontoxic anthocyanidins, the pigments in fruits and vegetables, Life Sciences 76, 1465-1472.
    153. Ho, L., Ferruzzi, M. G., Janle, E. M., Wang, J., Gong, B., Chen, T. Y., Lobo, J., Cooper, B., Wu, Q. L., Talcott, S. T., Percival, S. S., Simon, J. E., and Pasinetti, G. M. (2013) Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease, The FASEB Journal 27, 769-781.
    154. Meiers, S., Kemeny, M., Weyand, U., Gastpar, R., von Angerer, E., and Marko, D. (2001) The anthocyanidins cyanidin and delphinidin are potent inhibitors of the epidermal growth-factor receptor, Journal of Agricultural and Food Chemistry 49, 958-962.
    155. Liu, C., Kuei, C., Zhu, J., Yu, J., Zhang, L., Shih, A., Mirzadegan, T., Shelton, J., Sutton, S., Connelly, M. A., Lee, G., Carruthers, N., Wu, J., and Lovenberg, T. W. (2012) 3,5-Dihydroxybenzoic acid, a specific agonist for hydroxycarboxylic acid 1, inhibits lipolysis in adipocytes, Journal of Pharmacology and Experimental Therapeutics 341, 794-801.
    156. Rice-Evans, C. A., Miller, N. J., and Paganga, G. (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids, Free Radical Biology and Medicine 20, 933-956.
    157. Sroka, Z. (2005) Antioxidative and antiradical properties of plant phenolics, Zeitschrift fur Naturforschung C 60, 833-843.
    158. Sultana, N., Akhter, M., and Khatoon, Z. (2010) Nematicidal natural products from the aerial parts of Rubus niveus, Natural Product Research 24, 407-415.
    159. Chao, C. Y., and Yin, M. C. (2009) Antibacterial effects of roselle calyx extracts and protocatechuic acid in ground beef and apple juice, Foodborne Pathogens and Disease 6, 201-206.
    160. Li, X. C., Wang, X. Z., Chen, D. F., and Chen, S. Z. (2011) Antioxidant activity and mechanism of protocatechuic acid in vitro, Functional Foods in Health and Disease 7, 232-244.
    161. Shi, G.-F., An, L.-J., Jiang, B., Guan, S., and Bao, Y.-M. (2006) Alpinia protocatechuic acid protects against oxidative damage in vitro and reduces oxidative stress in vivo, Neuroscience Letters 403, 206-210.
    162. An, L. J., Guan, S., Shi, G. F., Bao, Y. M., Duan, Y. L., and Jiang, B. (2006) Protocatechuic acid from Alpinia oxyphylla against MPP+-induced neurotoxicity in PC12 cells, Food and Chemical Toxicology 44, 436-443.
    163. Ou, C. B., Pang, Q., Chen, X., Hou, N., and He, C. (2012) Protocatechuic acid, a new active substance against the challenge of avian infectious bursal disease virus, Poultry Science 91, 1604-1609.
    164. Kakkar, S., and Bais, S. (2014) A review on protocatechuic acid and its pharmacological potential, ISRN Pharmacology 2014.
    165. Juurlink, B. H., Azouz, H. J., Aldalati, A. M., AlTinawi, B. M., and Ganguly, P. (2014) Hydroxybenzoic acid isomers and the cardiovascular system, Nutrition Journal 13, 63.
    166. Tanaka, T., Tanaka, T., and Tanaka, M. (2011) Potential cancer chemopreventive activity of protocatechuic acid, Journal of Experimental & Clinical Medicine 3, 27-33.
    167. Khadem, S., and Marles, R. J. (2010) Monocyclic phenolic acids; hydroxy and polyhydroxybenzoic acids: Occurrence and recent bioactivity studies, Molecules 15, 7985-8005.
    168. Sharma, S., Khan, N., and Sultana, S. (2004) Study on prevention of two-stage skin carcinogenesis by Hibiscus rosa sinensis extract and the role of its chemical constituent, gentisic acid, in the inhibition of tumour promotion response and oxidative stress in mice, European Journal of Cancer Prevention 13, 53-63.
    169. Ashidate, K., Kawamura, M., Mimura, D., Tohda, H., Miyazaki, S., Teramoto, T., Yamamoto, Y., and Hirata, Y. (2005) Gentisic acid, an aspirin metabolite, inhibits oxidation of low-density lipoprotein and the formation of cholesterol ester hydroperoxides in human plasma, European Journal of Pharmacology 513, 173-179.
    170. Sappey, C., Boelaert, J. R., Legrandpoels, S., Grady, R. W., and Piette, J. (1995) NF-κB transcription factor activation by hydrogen peroxide can be decreased by 2,3-dihydroxybenzoic acid and its ethyl ester derivative, Archives of Biochemistry and Biophysics 321, 263-270.
    171. Sroka, Z., and Cisowski, W. (2003) Hydrogen peroxide scavenging, antioxidant and anti-radical activity of some phenolic acids, Food and Chemical Toxicology 41, 753-758.
    172. Pearce, R. A., Finley, R. J., Mustard, R. A., and Duff, J. H. (1985) 2,3-Dihydroxybenzoic acid : Effect on mortality rate in a septic rat model, Archives of Surgery 120, 937-940.
    173. Shibumon, G., Benny, P. J., Sunny, K., and Cincy, G. (2011) Antibiotic activity of 2,3-dihydroxybenzoic acid isolated from Flacourtia inermis fruit against multidrug resistant bacteria, Asian Journal of Pharmaceutical and Clinical Research 4, 126-130.
    174. Benny, P. J., Shibumon, G., Kuriakose, S., and Cincy, G. (2010) 2, 3-dihydroxybenzoic acid: an effective antifungal agent isolated from Flacourtia inermis fruit, International Journal of Pharmaceutical and Clinical Research 2, 101-105.
    175. Graziano, J. H., Grady, R. W., and Cerami, A. (1974) The identification of 2, 3-dihydroxybenzoic acid as a potentially useful iron-chelating drug, Journal of Pharmacology and Experimental Therapeutics 190, 570-575.
    176. Baldwin, S. R., Simon, R. H., Boxer, L. A., Till, G. O., and Kunkel, R. G. (1985) Attenuation by 2,3-dihydroxybenzoic acid of acute lung injury induced by cobra venom factor in the rat, The American Review of Respiratory Disease 132, 1288-1293.
    177. Graziano, J. H., Miller, D. R., Grady, R. W., and Cerami, A. (1976) Inhibition of membrane peroxidation in thalassaemic erythrocytes by 2,3-dihydroxybenzoic acid, British Journal of Haematology 32, 351-356.
    178. Ahire, J. J., Neppalli, R., Heunis, T. D., van Reenen, A. J., and Dicks, L. M. (2014) 2,3-dihydroxybenzoic acid electrospun into poly(D,L-lactide) (PDLLA)/Poly(ethylene oxide) (PEO) nanofibers inhibited the growth of gram-positive and gram-negative bacteria, Current Microbiology 69, 587-593.
    179. Spilioti, E., Jaakkola, M., Tolonen, T., Lipponen, M., Virtanen, V., Chinou, I., Kassi, E., Karabournioti, S., and Moutsatsou, P. (2014) Phenolic Acid Composition, Antiatherogenic and Anticancer Potential of Honeys Derived from Various Regions in Greece, PLOS ONE 9, e94860.
    180. Gitzinger, M., Kemmer, C., Fluri, D. A., El-Baba, M. D., Weber, W., and Fussenegger, M. (2012) The food additive vanillic acid controls transgene expression in mammalian cells and mice, Nucleic Acids Research 40, e37.
    181. Orabi, K. Y., Abaza, M. S., El Sayed, K. A., Elnagar, A. Y., Al-Attiyah, R., and Guleri, R. P. (2013) Selective growth inhibition of human malignant melanoma cells by syringic acid-derived proteasome inhibitors, Cancer Cell Int 13, 1-16.
    182. Abaza, M. S., Al-Attiyah, R., Bhardwaj, R., Abbadi, G., Koyippally, M., and Afzal, M. (2013) Syringic acid from Tamarix aucheriana possesses antimitogenic and chemo-sensitizing activities in human colorectal cancer cells, Pharm Biol. 51, 1110-1124.
    183. Huang, J., de Paulis, T., and May, J. M. (2004) Antioxidant effects of dihydrocaffeic acid in human EA.hy926 endothelial cells, The Journal of Nutritional Biochemistry 15, 722-729.
    184. Poquet, L., Clifford, M. N., and Williamson, G. (2008) Effect of dihydrocaffeic acid on UV irradiation of human keratinocyte HaCaT cells, Archives of Biochemistry and Biophysics 476, 196-204.
    185. Owen, R. W., Haubner, R., Mier, W., Giacosa, A., Hull, W. E., Spiegelhalder, B., and Bartsch, H. (2003) Isolation, structure elucidation and antioxidant potential of the major phenolic and flavonoid compounds in brined olive drupes, Food and Chemical Toxicology 41, 703-717.
    186. Liu, W., Xu, J., Wu, S., Liu, Y., Yu, X., Chen, J., Tang, X., Wang, Z., Zhu, X., and Li, X. (2013) Selective anti-proliferation of HER2-positive breast cancer cells by anthocyanins identified by high-throughput screening, PLOS ONE 8, e81586.
    187. Kamenickova, A., Anzenbacherova, E., Pavek, P., Soshilov, A. A., Denison, M. S., Zapletalova, M., Anzenbacher, P., and Dvorak, Z. (2013) Effects of anthocyanins on the AhR–CYP1A1 signaling pathway in human hepatocytes and human cancer cell lines, Toxicology Letters 221, 1-8.
    188. Avelar, M. M., and Gouvea, C. M. (2012) Procyanidin b2 cytotoxicity to mcf-7 human breast adenocarcinoma cells, Indian Journal of Pharmaceutical Sciences 74, 351-355.
    189. Miura, T., Chiba, M., Kasai, K., Nozaka, H., Nakamura, T., Shoji, T., Kanda, T., Ohtake, Y., and Sato, T. (2008) Apple procyanidins induce tumor cell apoptosis through mitochondrial pathway activation of caspase-3, Carcinogenesis 29, 585-593.
    190. Mackenzie, G. G., Adamo, A. M., Decker, N. P., and Oteiza, P. I. (2008) Dimeric procyanidin B2 inhibits constitutively active NF-κB in Hodgkin's lymphoma cells independently of the presence of IκB mutations, Biochemical Pharmacology 75, 1461-1471.
    191. Zhang, Z., Li, B. Y., Li, X. L., Cheng, M., Yu, F., Lu, W. D., Cai, Q., Wang, J. F., Zhou, R. H., Gao, H. Q., and Shen, L. (2013) Proteomic analysis of kidney and protective effects of grape seed procyanidin B2 in db/db mice indicate MFG-E8 as a key molecule in the development of diabetic nephropathy, Biochimica et Biophysica Acta 1832, 805-816.
    192. Park, Y. C., Rimbach, G., Saliou, C., Valacchi, G., and Packer, L. (2000) Activity of monomeric, dimeric, and trimeric flavonoids on NO production, TNF-α secretion, and NF-κB-dependent gene expression in RAW 264.7 macrophages, Federation of European Biochemical Societies Letter 465, 93-97.
    193. Kang, N. J., Lee, K. W., Lee, D. E., Rogozin, E. A., Bode, A. M., Lee, H. J., and Dong, Z. (2008) Cocoa procyanidins suppress transformation by inhibiting mitogen-activated protein kinase, Journal of Biological Chemistry 283, 20664-20673.
    194. Rodriguez-Ramiro, I., Ramos, S., Bravo, L., Goya, L., and Martin, M. (2012) Procyanidin B2 induces Nrf2 translocation and glutathione S-transferase P1 expression via ERKs and p38-MAPK pathways and protect human colonic cells against oxidative stress, Eur J Nutr 51, 881-892.
    195. Katoh, M., Oizumi, Y., Mohri, Y., Hirota, M., and Makabe, H. (2012) Synthesis of procyanidin B1, B2, and B4 and their anti-inflammatory activity: The effect of 4-alkoxy group of catechin and/or epicatechin electrophiles for condensation, Letters in Organic Chemistry 9, 233-238.
    196. Li, S., Kodama, E. N., Inoue, Y., Tani, H., Matsuura, Y., Zhang, J., Tanaka, T., and Hattori, T. (2010) Procyanidin B1 purified from Cinnamomi cortex suppresses hepatitis C virus replication, Antiviral Chemistry & Chemotherapy 20, 239-248.
    197. Zhuang, M., Jiang, H., Suzuki, Y., Li, X., Xiao, P., Tanaka, T., Ling, H., Yang, B., Saitoh, H., Zhang, L., Qin, C., Sugamura, K., and Hattori, T. (2009) Procyanidins and butanol extract of Cinnamomi Cortex inhibit SARS-CoV infection, Antiviral Research 82, 73-81.
    198. Jeong, W. S., and Kong, A. N. T. (2004) Biological properties of monomeric and polymeric catechins: Green tea catechins and procyanidins, Pharmaceutical Biology 42, 84-93.
    199. Zhang, X. Y., Bai, D. C., Wu, Y. J., Li, W. G., and Liu, N. F. (2005) Proanthocyanidin from grape seeds enhances anti-tumor effect of doxorubicin both in vitro and in vivo, Pharmazie 60, 533-538.
    200. Lu, J., Zhang, K., Chen, S., and Wen, W. (2009) Grape seed extract inhibits VEGF expression via reducing HIF-1alpha protein expression, Carcinogenesis 30, 636-644.
    201. Kaur, M., Agarwal, C., and Agarwal, R. (2009) Anticancer and cancer chemopreventive potential of grape seed extract and other grape-based products, Journal of Nutrition 139, 1806S-1812S.
    202. Li, X. L., Li, B. Y., Cheng, M., Yu, F., Yin, W. B., Cai, Q., Zhang, Z., Zhang, J. H., Wang, J. F., Zhou, R. H., and Gao, H. Q. (2013) PIMT prevents the apoptosis of endothelial cells in response to glycated low density lipoproteins and protective effects of grape seed procyanidin B2, PLOS ONE 8, e69979.
    203. Jeong, C. H., Jeong, H. R., Choi, G. N., Kim, D. O., Lee, U., and Heo, H. J. (2011) Neuroprotective and anti-oxidant effects of caffeic acid isolated from Erigeron annuus leaf, Chinese Medicine 6, 25.
    204. Chao, P. C., Hsu, C. C., and Yin, M. C. (2009) Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice, Nutrition & Metabolism 6, 33.
    205. Touaibia, M., Jean-Francois, J., and Doiron, J. (2011) Caffeic Acid, a versatile pharmacophore: an overview, Mini-Reviews in Medicinal Chemistry 11, 695-713.
    206. Magnani, C., Isaac, V. L. B., Correa, M. A., and Salgado, H. R. N. (2014) Caffeic acid: a review of its potential use in medications and cosmetics, Analytical Methods 6, 3203-3210.
    207. Gomez-Alonso, S., Collins, V. J., Vauzour, D., Rodriguez-Mateos, A., Corona, G., and Spencer, J. P. E. (2012) Inhibition of colon adenocarcinoma cell proliferation by flavonols is linked to a G2/M cell cycle block and reduction in cyclin D1 expression, Food Chemistry 130, 493-500.
    208. Hsu, Y. L., Liang, H. L., Hung, C. H., and Kuo, P. L. (2009) Syringetin, a flavonoid derivative in grape and wine, induces human osteoblast differentiation through bone morphogenetic protein-2/extracellular signal-regulated kinase 1/2 pathway, Molecular Nutrition and Food Research 53, 1452-1461.
    209. Wang, L., Li, Z. W., Zhang, W., Xu, R., Gao, F., Liu, Y. F., and Li, Y. J. (2014) Synthesis, crystal structure, and biological evaluation of a series of phloretin derivatives, Molecules 19, 16447-16457.
    210. Rossetti, L., Smith, D., Shulman, G. I., Papachristou, D., and DeFronzo, R. A. (1987) Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats, The Journal of Clinical Investigation 79, 1510-1515.
    211. Nićiforović, N., and Abramovič, H. (2014) Sinapic Acid and Its Derivatives: Natural Sources and Bioactivity, Comprehensive Reviews in Food Science and Food Safety 13, 34-51.
    212. Yoon, S. A., Kang, S. I., Shin, H. S., Kang, S. W., Kim, J. H., Ko, H. C., and Kim, S. J. (2013) p-Coumaric acid modulates glucose and lipid metabolism via AMP-activated protein kinase in L6 skeletal muscle cells, Biochemical and Biophysical Research Communications 432, 553-557.
    213. Hsu, C. L., Wu, C. H., Huang, S. L., and Yen, G. C. (2009) Phenolic compounds rutin and o-coumaric acid ameliorate obesity induced by high-fat diet in rats, Journal of Agricultural and Food Chemistry 57, 425-431.
    214. Sen, A., Atmaca, P., Terzioglu, G., and Arslan, S. (2013) Anticarcinogenic effect and carcinogenic potential of the dietary phenolic acid: o-coumaric acid, Natural Product Communications 8, 1269-1274.
    215. Szliszka, E., and Krol, W. (2013) Polyphenols isolated from propolis augment TRAIL-induced apoptosis in cancer cells, Evidence-Based Complementary and Alternative Medicine 2013.
    216. Malla, S., Koffas, M. A., Kazlauskas, R. J., and Kim, B. G. (2012) Production of 7-O-methyl aromadendrin, a medicinally valuable flavonoid, in Escherichia coli, Applied and Environmental Microbiology 78, 684-694.
    217. Stanojković, T., Kolundžija, B., Ćirić, A., Nikolić, D., and Kundaković, T. (2013) Cytotoxicity and antimicrobial activity of satureja kitaibelii wierzb. Ex heuff (Lamiaceae), Digest Journal of Nanomaterials and Biostructures 8, 845-854.
    218. Chen, H., Miao, Q., Geng, M., Liu, J., Hu, Y., Tian, L., Pan, J., and Yang, Y. (2013) Anti-tumor effect of rutin on human neuroblastoma cell lines through inducing G2/M cell cycle arrest and promoting apoptosis, The Scientific World Journal 2013.
    219. Lee, K. W., Kang, N. J., Rogozin, E. A., Kim, H. G., Cho, Y. Y., Bode, A. M., Lee, H. J., Surh, Y. J., Bowden, G. T., and Dong, Z. (2007) Myricetin is a novel natural inhibitor of neoplastic cell transformation and MEK1, Carcinogenesis 28, 1918-1927.
    220. Lin, Y., Shi, R., Wang, X., and Shen, H. M. (2008) Luteolin, a flavonoid with potential for cancer prevention and therapy, Current Cancer Drug Targets 8, 634-646.

    QR CODE