Health-beneficial nutraceuticals—myth or reality?

Applied Microbiology and Biotechnology

Volumn 101, Issue 3, 2017, Pages 951-961

  Sauer, Sascha ^a   Plauth, Annabell ^a  

^a MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

Author keywords

Hormesis; Nutrition; Omics; Pharmacology; Polyphenols; Resveratrol

Indexed keywords

NUTRITION; PHYSIOLOGY; RESVERATROL;

EXPERIMENTAL APPROACHES; HORMESIS; NUTRACEUTICAL PRODUCTS; OMICS; PHARMACOLOGY; POLYPHENOLS; SCIENTIFIC EVIDENCE; SCIENTIFIC FOUNDATIONS;

HEALTH;

NUTRACEUTICAL; BIOLOGICAL PRODUCT; POLYPHENOL; RESVERATROL; STILBENE DERIVATIVE;

BIOACTIVITY; DRUG; EPIDEMIOLOGY; HEALTH IMPACT; NUTRIENT AVAILABILITY; PHYSIOLOGY;

DIET SUPPLEMENTATION; HEALTH; HUMAN; NUTRITION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SYSTEMS BIOLOGY; DIET; DIETARY SUPPLEMENT; HORMESIS; ISOLATION AND PURIFICATION; METABOLISM;

BIOLOGICAL PRODUCTS; DIET; DIETARY SUPPLEMENTS; HEALTH; HORMESIS; HUMANS; POLYPHENOLS; STILBENES;

EID: 85008655890     PISSN: 01757598     EISSN: 14320614     Source Type: Journal    
DOI: 10.1007/s00253-016-8068-5     Document Type: Review

References (112)

1. Agrawal DK, Mishra PK (2010) Curcumin and its analogues: potential anticancer agents. Med Res Rev 30(5):818–860. doi:10.1002/med.20188
2. Andlauer W, Furst P (2002) Nutraceuticals: a piece of history, present status and outlook. Food Res Int 35(2–3):171–176. doi:10.1016/S0963-9969(01)00179-X
3. Apak R, Guclu K, Demirata B, Ozyurek M, Celik SE, Bektasoglu B, Berker KI, Ozyurt D (2007) Comparative evaluation of various total antioxidant capacity assays applied to phenolic compounds with the CUPRAC assay. Molecules (Basel, Switzerland) 12(7):1496–1547. doi:10.3390/12071496
4. Arias N, Miranda J, Macarulla MT, Aguirre L, Fernandez-Quintela A, Andres-Lacueva C, Urpi-Sarda M, Portillo MP (2014) The combination of resveratrol and conjugated linoleic acid attenuates the individual effects of these molecules on triacylglycerol metabolism in adipose tissue. Eur J Nutr 53:575–582. doi:10.1007/s00394-013-0566-y
5. Aruoma OI (1998) Free radicals, oxidative stress, and antioxidants in human health and disease. J Am Oil Chem Soc 75(2):199–212. doi:10.1007/s11746-998-0032-9
6. Asensi M, Medina I, Ortega A, Carretero J, Bano MC, Obrador E, Estrela JM (2002) Inhibition of cancer growth by resveratrol is related to its low bioavailability. Free Radic Biol Med 33(3):387–398. doi:10.1016/S0891-5849(02)00911-5
7. Augustin MA, Sanguansri L, Lockett T (2013) Nano- and micro-encapsulated systems for enhancing the delivery of resveratrol. Ann N Y Acad Sci 1290:107–112. doi:10.1111/nyas.12130
8. Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell’s functional organization. Nat Rev Genet 5(2):101–113. doi:10.1038/nrg1272
9. Beart JE, Lilley TH, Haslam E (1985) Plant polyphenols—secondary metabolism and chemical defence: some observations. Phytochemistry 24(1):33–38. doi:10.1016/s0031-9422(00)80802-x
10. Belem MAF (1999) Application of biotechnology in the product development of nutraceuticals in Canada. Trends Food Sci Tech 10(3):101–106. doi:10.1016/S0924-2244(99)00029-1
11. Bhat KPL, Pezzuto JM (2002) Cancer chemopreventive activity of resveratrol. Ann N Y Acad Sci 957(1):210–229. doi:10.1111/j.1749-6632.2002.tb02918.x
12. Bode LM, Bunzel D, Huch M, Cho GS, Ruhland D, Bunzel M, Bub A, Franz CM, Kulling SE (2013) In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. Am J Clin Nutr 97(2):295–309. doi:10.3945/ajcn.112.049379
13. Botden IP, Oeseburg H, Durik M, Leijten FP, Van Vark-Van Der Zee LC, Musterd-Bhaggoe UM, Garrelds IM, Seynhaeve AL, Langendonk JG, Sijbrands EJ, Danser AH, Roks AJ (2012) Red wine extract protects against oxidative-stress-induced endothelial senescence. Clin Sci (Lond) 123(8):499–507. doi:10.1042/CS20110679
14. Brglez Mojzer E, Knez Hrncic M, Skerget M, Knez Z, Bren U (2016) Polyphenols: extraction methods, antioxidative action, bioavailability and anticarcinogenic effects. Molecules (Basel, Switzerland) 21(7). doi:10.3390/molecules21070901
15. Brower V (2005) A nutraceutical a day may keep the doctor away. Consumers are turning increasingly to food supplements to improve well-being when pharmaceuticals fail. EMBO Rep 6(8):708–711. doi:10.1038/sj.embor.7400498
16. Calabrese EJ, Baldwin LA (2003) Hormesis: the dose-response revolution. Annu Rev Pharmacol Toxicol 43:175–197. doi:10.1146/annurev.pharmtox.43.100901.140223
17. Cao G, Sofic E, Prior RL (1997) Antioxidant and prooxidant behavior of flavonoids: structure-activity relationships. Free Radic Biol Med 22(5):749–760. doi:10.1016/s0891-5849(96)00351-6
18. Chauhan B, Kumar G, Kalam N, Ansari SH (2013) Current concepts and prospects of herbal nutraceutical: a review. J Adv Pharm Technol Res 4(1):4–8. doi:10.4103/2231-4040.107494
19. D’Archivio M, Filesi C, Vari R, Scazzocchio B, Masella R (2010) Bioavailability of the polyphenols: status and controversies. Int J Mol Sci 11(4):1321–1342. doi:10.3390/ijms11041321
20. Dai J, Mumper RJ (2010) Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules (Basel, Switzerland) 15(10):7313–7352. doi:10.3390/molecules15107313
21. Defelice SL (1995) The nutraceutical revolution—its impact on food-industry R-and-D. Trends Food Sci Tech 6(2):59–61. doi:10.1016/S0924-2244(00)88944-X
22. Duthie GG, Duthie SJ, Kyle JA (2000) Plant polyphenols in cancer and heart disease: implications as nutritional antioxidants. Nutr Res Rev 13(1):79–106. doi:10.1079/095442200108729016
23. Espin JC, Garcia-Conesa MT, Tomas-Barberan FA (2007) Nutraceuticals: facts and fiction. Phytochemistry 68(22–24):2986–3008. doi:10.1016/j.phytochem.2007.09.014
24. Etcheverry P, Grusak MA, Fleige LE (2012) Application of in vitro bioaccessibility and bioavailability methods for calcium, carotenoids, folate, iron, magnesium, polyphenols, zinc, and vitamins B(6), B(12), D, and E. Front Physiol 3:317. doi:10.3389/fphys.2012.00317
25. Fang M, Chen D, Yang CS (2007) Dietary polyphenols may affect DNA methylation. J Nutr 137(1 Suppl):223S–228S
26. Fantini M, Benvenuto M, Masuelli L, Frajese GV, Tresoldi I, Modesti A, Bei R (2015) In vitro and in vivo antitumoral effects of combinations of polyphenols, or polyphenols and anticancer drugs: perspectives on cancer treatment. Int J Mol Sci 16(5):9236–9282. doi:10.3390/ijms16059236
27. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408(6809):239–247. doi:10.1038/35041687
28. Fiatarone MA, O’Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, Roberts SB, Kehayias JJ, Lipsitz LA, Evans WJ (1994) Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med 330(25):1769–1775. doi:10.1056/NEJM199406233302501
29. Fresco P, Borges F, Diniz C, Marques MP (2006) New insights on the anticancer properties of dietary polyphenols. Med Res Rev 26(6):747–766. doi:10.1002/med.20060
30. Gambini J, Ingles M, Olaso G, Lopez-Grueso R, Bonet-Costa V, Gimeno-Mallench L, Mas-Bargues C, Abdelaziz KM, Gomez-Cabrera MC, Vina J, Borras C (2015) Properties of resveratrol: in vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxidative Med Cell Longev 2015:837042. doi:10.1155/2015/837042
31. Gems D, Partridge L (2008) Stress-response hormesis and aging: “that which does not kill us makes us stronger”. Cell Metab 7(3):200–203. doi:10.1016/j.cmet.2008.01.001
32. Goh K-I, Cusick ME, Valle D, Childs B, Vidal M, Barabási A-L (2007) The human disease network. Proc Natl Acad Sci 104(21):8685–8690. doi:10.1073/pnas.0701361104
33. Gonzalez-Vallinas M, Gonzalez-Castejon M, Rodriguez-Casado A, Ramirez de Molina A (2013) Dietary phytochemicals in cancer prevention and therapy: a complementary approach with promising perspectives. Nutr Rev 71(9):585–599. doi:10.1111/nure.12051
34. Gupta S, Chauhan D, Mehla K, Sood P, Nair A (2010) An overview of nutraceuticals: current scenario. J Basic Clin Pharm 1(2):55–62
35. Halliwell B (2008) Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies? Arch Biochem Biophys 476(2):107–112. doi:10.1016/j.abb.2008.01.028
36. Haslam E (1996) Natural polyphenols (vegetable tannins) as drugs: possible modes of action. J Nat Prod 59(2):205–215. doi:10.1021/np960040+
37. Hayes DP (2007) Nutritional hormesis. Eur J Clin Nutr 61(2):147–159. doi:10.1038/sj.ejcn.1602507
38. Huang H, Chen G, Liao D, Zhu Y, Pu R, Xue X (2016) The effects of resveratrol intervention on risk markers of cardiovascuklar health in overweight and obese subjects: a pooled analysis of randomized controlled trials. Obesity Rev 17:1329–1340. doi:10.1111/obr. 12458
39. Huq T, Khan A, Khan RA, Riedl B, Lacroix M (2013) Encapsulation of probiotic bacteria in biopolymeric system. Crit Rev Food Sci Nutr 53(9):909–916. doi:10.1080/10408398.2011.573152
40. Iqbal MA, Bamezai RN (2012) Resveratrol inhibits cancer cell metabolism by down regulating pyruvate kinase M2 via inhibition of mammalian target of rapamycin. PLoS One 7(5):e36764. doi:10.1371/journal.pone.0036764
41. Jiang YL, Liu ZP (2011) Natural products as anti-invasive and anti-metastatic agents. Curr Med Chem 18(6):808–829. doi:10.2174/092986711794927711
42. Kampa M, Nifli AP, Notas G, Castanas E (2007) Polyphenols and cancer cell growth. Rev Physiol Biochem Pharmacol 159:79–113. doi:10.1007/112_2006_0702
43. Khan N, Afaq F, Mukhtar H (2008) Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal 10(3):475–510. doi:10.1089/ars.2007.1740
44. Khan N, Mukhtar H (2008) Multitargeted therapy of cancer by green tea polyphenols. Cancer Lett 269(2):269–280. doi:10.1016/j.canlet.2008.04.014
45. Kim HS, Quon MJ, Kim JA (2014) New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate. Redox Biol 2:187–195. doi:10.1016/j.redox.2013.12.022
46. Kris-Etherton PM, Hecker KD, Bonanome A, Coval SM, Binkoski AE, Hilpert KF, Griel AE, Etherton TD (2002) Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer. Am J Med 113(9):71–88. doi:10.1016/s0002-9343(01)00995-0
47. Lall RK, Syed DN, Adhami VM, Khan MI, Mukhtar H (2015) Dietary polyphenols in prevention and treatment of prostate cancer. Int J Mol Sci 16(2):3350–3376. doi:10.3390/ijms16023350
48. Lambert JD, Hong J, Yang GY, Liao J, Yang CS (2005) Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. Am J Clin Nutr 81(1 Suppl):284S–291S
49. Landete JM (2011) Ellagitannins, ellagic acid and their derived metabolites: a review about source, metabolism, functions and health. Food Res Int 44(5):1150–1160. doi:10.1016/j.foodres.2011.04.027
50. Lee KW, Lee HJ (2006) The roles of polyphenols in cancer chemoprevention. Biofactors 26(2):105–121. doi:10.1002/biof.5520260202
51. Leu TH, Maa MC (2002) The molecular mechanisms for the antitumorigenic effect of curcumin. Curr Med Chem Anticancer Agents 2(3):357–370. doi:10.2174/1568011024606370
52. Lewandowska H, Kalinowska M, Lewandowski W, Stepkowski TM, Brzoska K (2016) The role of natural polyphenols in cell signaling and cytoprotection against cancer development. J Nutr Biochem 32:1–19. doi:10.1016/j.jnutbio.2015.11.006
53. Link A, Balaguer F, Goel A (2010) Cancer chemoprevention by dietary polyphenols: promising role for epigenetics. Biochem Pharmacol 80(12):1771–1792. doi:10.1016/j.bcp.2010.06.036
54. Long LH, Clement MV, Halliwell B (2000) Artifacts in cell culture: rapid generation of hydrogen peroxide on addition of (−)-epigallocatechin, (−)-epigallocatechin gallate, (+)-catechin, and quercetin to commonly used cell culture media. Biochem Biophys Res Commun 273(1):50–53. doi:10.1006/bbrc.2000.2895
55. Long LH, Halliwell B (2009) Artefacts in cell culture: pyruvate as a scavenger of hydrogen peroxide generated by ascorbate or epigallocatechin gallate in cell culture media. Biochem Biophys Res Commun 388(4):700–704. doi:10.1016/j.bbrc.2009.08.069
56. Manach C, Williamson G, Morand C, Scalbert A, Remesy C (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 81(1 Suppl):230S–242S
57. Manson MM (2003) Cancer prevention—the potential for diet to modulate molecular signalling. Trends Mol Med 9(1):11–18. doi:10.1016/s1471-4914(02)00002-3
58. McClements DJ (2015) Enhancing nutraceutical bioavailability through food matrix design. Curr Opin Food Sci 4:1–6. doi:10.1016/j.cofs.2014.12.008
59. McClements DJ, Li F, Xiao H (2015) The nutraceutical bioavailability classification scheme: classifying nutraceuticals according to factors limiting their oral bioavailability. Annu Rev Food Sci Technol 6(1):299–327. doi:10.1146/annurev-food-032814-014043
60. Meierhofer D, Weidner C, Hartmann L, Mayr JA, Han CT, Schroeder FC, Sauer S (2013) Protein sets define disease states and predict in vivo effects of drug treatment. Mol Cell Proteomics 12(7):1965–1979. doi:10.1074/mcp.M112.025031
61. Meierhofer D, Weidner C, Sauer S (2014) Integrative analysis of transcriptomics, proteomics, and metabolomics data of white adipose and liver tissue of high-fat diet and rosiglitazone-treated insulin-resistant mice identified pathway alterations and molecular hubs. J Prot Res 13(12):5592–5602. doi:10.1021/pr5005828
62. Meierhofer D, Weidner C, Sauer S (2015) Correction to “integrative analysis of transcriptomics, proteomics, and metabolomics data of white adipose and liver tissue of high-fat diet and rosiglitazone-treated insulin-resistant mice identified pathway alterations and molecular hubs”. J Prot Res 14(3):1643–1644. doi:10.1021/acs.jproteome.5b00137
63. Muller M, Kersten S (2003) Nutrigenomics: goals and strategies. Nat Rev Genet 4(4):315–322. doi:10.1038/nrg1047
64. Munin A, Edwards-Levy F (2011) Encapsulation of natural polyphenolic compounds; a review. Pharmaceutics 3(4):793–829. doi:10.3390/pharmaceutics3040793
65. Murakami I, Chaleckis R, Pluskal T, Ito K, Hori K, Ebe M, Yanagida M, Kondoh H (2014) Metabolism of skin-absorbed resveratrol into its glucuronized form in mouse skin. PLoS One 9:e115359. doi:10.1371/journal.pone.0115359
66. Ohara M, Ohyama Y (2014) Delivery and application of dietary polyphenols to target organs, tissues and intracellular organelles. Curr Drug Metab 15(1):37–47. doi:10.2174/1389200214666131210143407
67. Osorio-Tobón JF, Carvalho PIN, Rostagno MA, Petenate AJ, Meireles MAA (2014) Extraction of curcuminoids from deflavored turmeric (Curcuma longa L.) using pressurized liquids: process integration and economic evaluation. J Supercrit Fluids 95:167–174. doi:10.1016/j.supflu.2014.08.012
68. Pandey RP, Parajuli P, Shin JY, Lee J, Lee S, Hong YS, Park YI, Kim JS, Sohng JK (2014) Enzymatic biosynthesis of novel resveratrol glucoside and glycoside derivatives. Appl Environ Microbiol 80:7235–7243. doi:10.1128/AEM.02076-14
69. Park EJ, Pezzuto JM (2015) The pharmacology of resveratrol in animals and humans. Biochim Biophys Acta 1852(6):1071–1113. doi:10.1016/j.bbadis.2015.01.014
70. Plauth A, Geikowski A, Cichon S, Wowro SJ, Liedgens L, Rousseau M, Weidner C, Fuhr L, Kliem M, Jenkins G, Lotito S, Wainwright LJ, Sauer S (2016a) Hormetic shifting of redox environment by pro-oxidative resveratrol protects cells against stress. Free Radic Biol Med. doi:10.1016/j.freeradbiomed.2016.08.006
71. Plauth A, Geikowski A, Cichon S, Wowro SJ, Liedgens L, Rousseau M, Weidner C, Fuhr L, Kliem M, Jenkins G, Lotito S, Wainwright LJ, Sauer S (2016b) Oxygen and pH-dependent oxidation of resveratrol. Data in Brief. doi:10.1016/j.dib.2016.09.012
72. Ristow M, Zarse K, Oberbach A, Kloting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Bluher M (2009) Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Nat Acad Sci U S A 106(21):8665–8670. doi:10.1073/pnas.0903485106
73. Rolls BJ, Ello-Martin JA, Tohill BC (2004) What can intervention studies tell us about the relationship between fruit and vegetable consumption and weight management? Nutr Rev 62(1):1–17. doi:10.1111/j.1753-4887.2004.tb00001.x
74. Sang S, Yang I, Buckley B, Ho CT, Yang CS (2007) Autoxidative quinone formation in vitro and metabolite formation in vivo from tea polyphenol (−)-epigallocatechin-3-gallate: studied by real-time mass spectrometry combined with tandem mass ion mapping. Free Radic Biol Med 43(3):362–371. doi:10.1016/j.freeradbiomed.2007.04.008
75. Santos IS, Ponte BM, Boonme P, Silva AM, Souto EB (2013) Nanoencapsulation of polyphenols for protective effect against colon-rectal cancer. Biotechnol Adv 31(5):514–523. doi:10.1016/j.biotechadv.2012.08.005
76. Sauer S (2013) Protein set analyses: how could this impact the clinic? Expert Rev Proteomics 10(4):305–307. doi:10.1586/14789450.2013.814883
77. Sauer S (2014) Amorfrutins: a promising class of natural products that are beneficial to health. Chembiochem 15(9):1231–1238. doi:10.1002/cbic.201402124
78. Sauer S, Luge T (2015) Nutriproteomics: facts, concepts, and perspectives. Proteomics 15(5–6):997–1013. doi:10.1002/pmic.201400383
79. Serrano A, Palacios C, Roy G, Cespon C, Villar ML, Nocito M, Gonzalez-Porque P (1998) Derivatives of gallic acid induce apoptosis in tumoral cell lines and inhibit lymphocyte proliferation. Arch Biochem Biophys 350(1):49–54. doi:10.1006/abbi.1997.0474
80. Seyed MA, Jantan I, Bukhari SN, Vijayaraghavan K (2016) A comprehensive review on the chemotherapeutic potential of piceatannol for cancer treatment, with mechanistic insights. J Agric Food Chem 64(4):725–737. doi:10.1021/acs.jafc.5b05993
81. Sharma RA, Gescher AJ, Steward WP (2005) Curcumin: the story so far. Eur J Cancer 41(13):1955–1968. doi:10.1016/j.ejca.2005.05.009
82. Sharmila G, Bhat FA, Arunkumar R, Elumalai P, Raja Singh P, Senthilkumar K, Arunakaran J (2014) Chemopreventive effect of quercetin, a natural dietary flavonoid on prostate cancer in in vivo model. Clin Nutr 33(4):718–726. doi:10.1016/j.clnu.2013.08.011
83. Shrikanta A, Kumar A, Govindaswamy V (2015) Resveratrol content and antioxidant properties of underutilized fruits. J Food Sci Technol 52(1):383–390. doi:10.1007/s13197-013-0993-z
84. Siddiqui IA, Sanna V, Ahmad N, Sechi M, Mukhtar H (2015) Resveratrol nanoformulation for cancer prevention and therapy. Ann N Y Acad Sci 1348(1):20–31. doi:10.1111/nyas.12811
85. Siegrist M, Stampfli N, Kastenholz H (2008) Consumers’ willingness to buy functional foods. The influence of carrier, benefit and trust. Appetite 51(3):526–529. doi:10.1016/j.appet.2008.04.003
86. Sinatra ST, DeMarco J (1995) Free radicals, oxidative stress, oxidized low density lipoprotein (LDL), and the heart: antioxidants and other strategies to limit cardiovascular damage. Conn Med 59(10):579–588
87. Siro I, Kapolna E, Kapolna B, Lugasi A (2008) Functional food. Product development, marketing and consumer acceptance—a review. Appetite 51(3):456–467. doi:10.1016/j.appet.2008.05.060
88. Soural I, Vrchotova N, Triska J, Balik J, Hornik S, Curinova P, Sykora J (2015) Various extraction methods for obtaining stilbenes from grape cane of Vitis vinifera L. Molecules (Basel, Switzerland) 20(4):6093–6112. doi:10.3390/molecules20046093
89. Stivala LA, Savio M, Carafoli F, Perucca P, Bianchi L, Maga G, Forti L, Pagnoni UM, Albini A, Prosperi E, Vannini V (2001) Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol. J Biol Chem 276(25):22586–22594. doi:10.1074/jbc.M101846200
90. Stoner GD, Mukhtar H (1995) Polyphenols as cancer chemopreventive agents. J Cell Biochem 59(S22):169–180. doi:10.1002/jcb.240590822
91. Sugihara G, May R, Ye H, Hsieh CH, Deyle E, Fogarty M, Munch S (2012) Detecting causality in complex ecosystems. Science 338(6106):496–500. doi:10.1126/science.1227079
92. Summerlin N, Soo E, Thakur S, Qu Z, Jambhrunkar S, Popat A (2015) Resveratrol nanoformulations: challenges and opportunities. Int J Pharm 479(2):282–290. doi:10.1016/j.ijpharm.2015.01.003
93. Surh YJ (2003) Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 3(10):768–780. doi:10.1038/nrc1189
94. Tabrez S, Priyadarshini M, Urooj M, Shakil S, Ashraf GM, Khan MS, Kamal MA, Alam Q, Jabir NR, Abuzenadah AM, Chaudhary AG, Damanhouri GA (2013) Cancer chemoprevention by polyphenols and their potential application as nanomedicine. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 31(1):67–98. doi:10.1080/10590501.2013.763577
95. Tome-Carneiro J, Larrosa M, Gonzalez-Sarrias A, Tomas-Barberan FA, Garcia-Conesa MT, Espin JC (2013) Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Curr Pharm Des 19:6064–6093. doi:10.2174/13816128113199990407
96. Tripoli E, Guardia ML, Giammanco S, Majo DD, Giammanco M (2007) Citrus flavonoids: molecular structure, biological activity and nutritional properties: a review. Food Chem 104(2):466–479. doi:10.1016/j.foodchem.2006.11.054
97. Turner RS, Thomas RG, Craft S, van Dyck CH, Mintzer J, Reynolds BA, Brewer JB, Rissman RA, Raman R, Aisen PS, Alzheimer’s Disease Cooperative S (2015) A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology 85(16):1383–1391. doi:10.1212/WNL.0000000000002035
98. van Kleef E, van Trijp HCM, Luning P, Jongen WMF (2002) Consumer-oriented functional food development: how well do functional disciplines reflect the ‘voice of the consumer’? Trends Food Sci Tech 13(3):93–101. doi:10.1016/s0924-2244(02)00068-7
99. Verma S, Singh A, Mishra A (2013) Gallic acid: molecular rival of cancer. Environ Toxicol Pharmacol 35(3):473–485. doi:10.1016/j.etap.2013.02.011
100. Wagner H, Ulrich-Merzenich G (2009) Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine 16(2–3):97–110. doi:10.1016/j.phymed.2008.12.018
101. Weidner C, de Groot JC, Prasad A, Freiwald A, Quedenau C, Kliem M, Witzke A, Kodelja V, Han CT, Giegold S, Baumann M, Klebl B, Siems K, Muller-Kuhrt L, Schurmann A, Schuler R, Pfeiffer AF, Schroeder FC, Bussow K, Sauer S (2012) Amorfrutins are potent antidiabetic dietary natural products. Proc Nat Acad Sci U S A 109(19):7257–7262. doi:10.1073/pnas.1116971109
102. Weidner C, Wowro SJ, Freiwald A, Kawamoto K, Witzke A, Kliem M, Siems K, Muller-Kuhrt L, Schroeder FC, Sauer S (2013) Amorfrutin B is an efficient natural peroxisome proliferator-activated receptor gamma (PPARgamma) agonist with potent glucose-lowering properties. Diabetologia 56:1802–1812. doi:10.1007/s00125-013-2920-2
103. Weidner C, Rousseau M, Plauth A, Wowro SJ, Fischer C, Abdel-Aziz H, Sauer S (2015) Melissa officinalis extract induces apoptosis and inhibits proliferation in colon cancer cells through formation of reactive oxygen species. Phytomedicine 22(2):262–270. doi:10.1016/j.phymed.2014.12.008
104. Weidner C, Rousseau M, Micikas RJ, Fischer C, Plauth A, Wowro SJ, Siems K, Hetterling G, Kliem M, Schroeder FC, Sauer S (2016a) Amorfrutin C induces apoptosis and inhibits proliferation in colon cancer cells through targeting mitochondria. J Nat Prod 79(1):2–12. doi:10.1021/acs.jnatprod.5b00072
105. Weidner C, Rousseau M, Plauth A, Wowro SJ, Fischer C, Abdel-Aziz H, Sauer S (2016b) Iberis amara extract induces intracellular formation of reactive oxygen species and inhibits colon cancer. PLoS One 11(4):e0152398. doi:10.1371/journal.pone.0152398
106. Weinberg R (2010) Point: hypotheses first. Nature 464(7289):678. doi:10.1038/464678a
107. Weiskirchen S, Weiskirchen R (2016) Resveratrol: how much wine do you have to drink to stay healthy? Adv Nutr 7(4):706–718. doi:10.3945/an.115.011627
108. Wu J-C, Lai C-S, Lee P-S, Ho C-T, Liou W-S, Wang Y-J, Pan M-H (2016) Anti-cancer efficacy of dietary polyphenols is mediated through epigenetic modifications. Curr Opin Food Sci 8:1–7. doi:10.1016/j.cofs.2016.01.009
109. Xue YQ, Di JM, Luo Y, Cheng KJ, Wei X, Shi Z (2014) Resveratrol oligomers for the prevention and treatment of cancers. Oxidative Med Cell Longev 2014:765832. doi:10.1155/2014/765832
110. Yang CS, Landau JM, Huang MT, Newmark HL (2001) Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu Rev Nutr 21:381–406. doi:10.1146/annurev.nutr.21.1.381
111. Yang NC, Lee CH, Song TY (2010) Evaluation of resveratrol oxidation in vitro and the crucial role of bicarbonate ions. Biosci Biotechnol Biochem 74(1):63–68. doi:10.1271/bbb.90549
112. Zlotogorski A, Dayan A, Dayan D, Chaushu G, Salo T, Vered M (2013) Nutraceuticals as new treatment approaches for oral cancer: II. Green tea extracts and resveratrol. Oral Oncol 49(6):502–506. doi:10.1016/j.oraloncology.2013.02.011