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Effects of Antioxidants on Periodontal Disease

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Studies on Periodontal Disease

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Abstract

Oxidative stress has been implicated in various diseases and syndromes, including periodontal disease, because of a weakening of the antioxidant defense or excess production of radicals that can overwhelm the scavenging capacity of cellular antioxidant systems. Antioxidants include vitamins (carotenoids, vitamins C and E), minerals (iron, copper, selenium, and zinc), or other compounds, and their effects on periodontal disease are one of the notable topics in periodontal research. Endogenous antioxidant enzymes (e.g., catalase, superoxide dismutases, reduced glutathione, and peroxiredoxins) and specific inhibitors of reactive oxygen/nitrogen species also have effects on periodontal disease. Numerous animal and in vitro studies have shown the effects of antioxidants on periodontal disease. However, there have been few randomized clinical trials on the effects in humans, and the use of adjunctive antioxidants therefore requires further investigation. In this chapter, we summarize the effects of antioxidants on periodontal disease. Traditional therapies in Asian regions are also discussed.

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References

  1. Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine, 4th edn. Oxford University Press, Oxford

    Google Scholar 

  2. Niki E (2012) Do antioxidants impair signaling by reactive oxygen species and lipid oxidation products? FEBS Lett 586:3767–3770. doi:10.1016/j.febslet.2012.09.025

    CAS  PubMed  Google Scholar 

  3. Saran M, Bors W (1989) Oxygen radicals acting as chemical messengers: a hypothesis. Free Radic Res Commun 7:213–220

    CAS  PubMed  Google Scholar 

  4. Suzuki YJ, Forman HJ, Sevanian A (1997) Oxidants as stimulators of signal transduction. Free Radic Biol Med 22:269–285

    CAS  PubMed  Google Scholar 

  5. Finkel T (2011) Signal transduction by reactive oxygen species. J Cell Biol 194:7–15. doi:10.1083/jcb.201102095

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Janssen-Heininger YMW, Mossman BT, Heintz NH et al (2008) Redox-based regulation of signal transduction: principles, pitfalls, and promises. Free Radic Biol Med 45:1–17. doi:10.1016/j.freeradbiomed.2008.03.011

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Winterbourn CC (2008) Reconciling the chemistry and biology of reactive oxygen species. Nat Chem Biol 4:278–286. doi:10.1038/nchembio.85

    CAS  PubMed  Google Scholar 

  8. Forman HJ, Maiorino M, Ursini F (2010) Signaling functions of reactive oxygen species. Biochemistry 49:835–842. doi:10.1021/bi9020378

    CAS  PubMed  Google Scholar 

  9. Murphy MP, Holmgren A, Larsson N et al (2011) Unraveling the biological roles of reactive oxygen species. Cell Metab 13:361–366. doi:10.1016/j.cmet.2011.03.010

    CAS  PubMed  Google Scholar 

  10. Niki E (2011) Assessment of antioxidant capacity in vitro and in vivo. Free Radic Biol Med 49:503–515. doi:10.1016/j.freeradbiomed.2010.04.016

    Google Scholar 

  11. Halliwell B (2012) Free radicals and antioxidants: updating a personal view. Nutr Rev 70:257–265. doi:10.1111/j.1753-4887.2012.00476.x

    PubMed  Google Scholar 

  12. Rhee SG, Woo HA (2011) Multiple functions of peroxiredoxins: peroxidases, sensors and regulators of the intracellular messenger H2O2, and protein chaperones. Antioxid Redox Signal 15:781–794. doi:10.1089/ars.2010.3393

    CAS  PubMed  Google Scholar 

  13. Woo HA, Yim SH, Shin DH et al (2010) Inactivation of peroxiredoxin I by phosphorylation allows localized H2O2 accumulation for cell signaling. Cell 140:517–528. doi:10.1016/j.cell.2010.01.009

    CAS  PubMed  Google Scholar 

  14. Barranco-Medina S, Lázaro JJ, Dietz KJ (2009) The oligomeric conformation of peroxiredoxins links redox state to function. FEBS Lett 583:1809–1816. doi:10.1016/j.febslet.2009.05.029

    CAS  PubMed  Google Scholar 

  15. Fisher AB (2011) Peroxiredoxin 6: a bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities. Antioxid Redox Signal 15:831–844. doi:10.1089/ars.2010.3412

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Gey KF (1998) Vitamins E plus C and interacting conutrients required for optimal health. A critical and constructive review of epidemiology and supplementation data regarding cardiovascular disease and cancer. Biofactors 7:113–174

    CAS  PubMed  Google Scholar 

  17. Cordero Z, Drogan D, Weikert C, Boeing H (2010) Vitamin E and risk of cardiovascular diseases: a review of epidemiologic and clinical trial studies. Crit Rev Food Sci Nutr 50:420–440. doi:10.1080/10408390802304230

    CAS  PubMed  Google Scholar 

  18. Gutteridge JM, Halliwell B (2010) Antioxidants: molecules, medicines, and myths. Biochem Biophys Res Commun 393:561–564. doi:10.1016/j.bbrc.2010.02.071

    CAS  PubMed  Google Scholar 

  19. Madianos PN, Bobetsis YA, Kinane DF (2005) Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva. J Clin Periodontol 32:57–71

    CAS  PubMed  Google Scholar 

  20. Komiya-Ito A, Ishihara K, Tomita S, Kato T, Yamada S (2010) Investigation of subgingival profile of periodontopathic bacteria using polymerase chain reaction. Bull Tokyo Dent Coll 51:139–144

    PubMed  Google Scholar 

  21. Xiong X, Buekens P, Fraser WD, Beck J, Offenbacher S (2006) Periodontal disease and adverse pregnancy outcomes: a systematic review. BJOG 113:135–143

    CAS  PubMed  Google Scholar 

  22. Page RC (1998) The pathobiology of periodontal diseases may affect systemic diseases: inversion of a paradigm. Ann Periodontol 3:108–120

    CAS  PubMed  Google Scholar 

  23. Parrish JH Jr, DeMarco TJ, Bissada NF (1977) Vitamin E and periodontitis in the rat. Oral Surg Oral Med Oral Pathol 44:210–218

    CAS  PubMed  Google Scholar 

  24. Kasuyama K, Tomofuji T, Ekuni D, Tamaki N, Azuma T, Irie K, Endo Y, Morita M (2011) Hydrogen-rich water attenuates experimental periodontitis in a rat model. J Clin Periodontol 38:1085–1090. doi:10.1111/j.1600-051X.2011.01801.x

    CAS  PubMed  Google Scholar 

  25. Maruyama T, Tomofuji T, Endo Y, Irie K, Azuma T, Ekuni D, Tamaki N, Yamamoto T, Morita M (2011) Supplementation of green tea catechins in dentifrices suppresses gingival oxidative stress and periodontal inflammation. Arch Oral Biol 56:48–53. doi:10.1016/j.archoralbio.2010.08.015

    CAS  PubMed  Google Scholar 

  26. Tomofuji T, Ekuni D, Irie K, Azuma T, Endo Y, Tamaki N, Sanbe T, Murakami J, Yamamoto T, Morita M (2009) Preventive effects of a cocoa-enriched diet on gingival oxidative stress in experimental periodontitis. J Periodontol 80:1799–1808. doi:10.1902/jop.2009.090270

    CAS  PubMed  Google Scholar 

  27. Ekuni D, Firth JD, Nayer T, Tomofuji T, Sanbe T, Irie K, Yamamoto T, Oka T, Liu Z, Vielkind J, Putnins EE (2009) Lipopolysaccharide-induced epithelial monoamine oxidase mediates alveolar bone loss in a rat chronic wound model. Am J Pathol 175:1398–1409. doi:10.2353/ajpath.2009.090108

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Tomofuji T, Ekuni D, Sanbe T, Irie K, Azuma T, Maruyama T, Tamaki N, Murakami J, Kokeguchi S, Yamamoto T (2009) Effects of vitamin C intake on gingival oxidative stress in rat periodontitis. Free Radic Biol Med 46:163–168. doi:10.1016/j.freeradbiomed.2008.09.040

    CAS  PubMed  Google Scholar 

  29. Duang XY, Wang Q, Zhou XD, Huang DM (2011) Mangiferin: a possible strategy for periodontal disease to therapy. Med Hypotheses 76:486–488. doi:10.1016/j.mehy.2010.11.029

    CAS  PubMed  Google Scholar 

  30. Narotzki B, Levy Y, Aizenbud D, Reznick AZ (2013) Green tea and its major polyphenol EGCG increase the activity of oral peroxidases. Adv Exp Med Biol 756:99–104. doi:10.1007/978-94-007-4549-0_13

    CAS  PubMed  Google Scholar 

  31. Zeidán-Chuliá F, Rybarczyk-Filho JL, Gursoy M, Könönen E, Uitto VJ, Gursoy OV, Cakmakci L, Moreira JC, Gursoy UK (2012) Bioinformatical and in vitro approaches to essential oil-induced matrix metalloproteinase inhibition. Pharm Biol 50:675–686. doi:10.3109/13880209.2012.677847

    PubMed  Google Scholar 

  32. Velliyagounder K, Ganeshnarayan K, Velusamy SK, Fine DH (2012) In vitro efficacy of diallyl sulfides against the periodontopathogen Aggregatibacter actinomycetemcomitans. Antimicrob Agents Chemother 56:2397–2407. doi:10.1128/AAC.00020-12

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Palmer LJ, Cooper PR, Ling MR, Wright HJ, Huissoon A, Chapple IL (2012) Hypochlorous acid regulates neutrophil extracellular trap release in humans. Clin Exp Immunol 167:261–268. doi:10.1111/j.1365-2249.2011.04518.x

    CAS  PubMed Central  PubMed  Google Scholar 

  34. O’Connor DJ, Wong RW, Rabie AB (2011) Resveratrol inhibits periodontal pathogens in vitro. Phytother Res 25:1727–1731. doi:10.1002/ptr.3501

    PubMed  Google Scholar 

  35. San Miguel SM, Opperman LA, Allen EP, Zielinski J, Svoboda KK (2011) Bioactive antioxidant mixtures promote proliferation and migration on human oral fibroblasts. Arch Oral Biol 56:812–822. doi:10.1016/j.archoralbio.2011.01.001

    CAS  PubMed  Google Scholar 

  36. Herrera BS, Martins-Porto R, Maia-Dantas A, Campi P, Spolidorio LC, Costa SK, Van Dyke TE, Gyurko R, Muscara MN (2011) iNOS-derived nitric oxide stimulates osteoclast activity and alveolar bone loss in ligature-induced periodontitis in rats. J Periodontol 82:1608–1615. doi:10.1902/jop.2011.100768

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Yamada M, Kubo K, Ueno T, Iwasa F, Att W, Hori N, Ogawa T (2010) Alleviation of commercial collagen sponge- and membrane-induced apoptosis and dysfunction in cultured osteoblasts by an amino acid derivative. Int J Oral Maxillofac Implants 25:939–946

    PubMed  Google Scholar 

  38. Núñez MJ, Novío S, Balboa J, Seoane J, Suárez JA, Freire-Garabal M (2010) Effects of resveratrol on expression of vascular endothelial growth factor in human gingival fibroblasts stimulated by periodontal pathogens. Acta Odontol Scand 68:239–247. doi:10.3109/00016357.2010.494269

    PubMed  Google Scholar 

  39. Staudte H, Güntsch A, Völpel A, Sigusch BW (2010) Vitamin C attenuates the cytotoxic effects of Porphyromonas gingivalis on human gingival fibroblasts. Arch Oral Biol 55:40–45. doi:10.1016/j.archoralbio.2009.11.009

    CAS  PubMed  Google Scholar 

  40. Geoghegan F, Wong RW, Rabie AB (2010) Inhibitory effect of quercetin on periodontal pathogens in vitro. Phytother Res 24:817–820. doi:10.1002/ptr.3014

    CAS  PubMed  Google Scholar 

  41. Nakamura H, Ukai T, Yoshimura A, Kozuka Y, Yoshioka H, Yoshinaga Y, Abe Y, Hara Y (2010) Green tea catechin inhibits lipopolysaccharide-induced bone resorption in vivo. J Periodontal Res 45:23–30. doi:10.1111/j.1600-0765.2008.01198.x

    CAS  PubMed  Google Scholar 

  42. Ohnishi T, Bandow K, Kakimoto K, Machigashira M, Matsuyama T, Matsuguchi T (2009) Oxidative stress causes alveolar bone loss in metabolic syndrome model mice with type 2 diabetes. J Periodontal Res 44:43–51. doi:10.1111/j.1600-0765.2007.01060.x

    CAS  PubMed  Google Scholar 

  43. Geoghegan F, Tsui VW, Wong RW, Rabie AB (2008) Inhibitory effect of quercetin on periodontal pathogens. Ann R Australas Coll Dent Surg 19:157–158. doi:10.1002/ptr.3014

    CAS  PubMed  Google Scholar 

  44. Argentin G, Cicchetti R (2006) Evidence for the role of nitric oxide in antiapoptotic and genotoxic effect of nicotine on human gingival fibroblasts. Apoptosis 11:1887–1897

    CAS  PubMed  Google Scholar 

  45. Inaba H, Tagashira M, Kanda T, Ohno T, Kawai S, Amano A (2005) Apple- and hop-polyphenols protect periodontal ligament cells stimulated with enamel matrix derivative from Porphyromonas gingivalis. J Periodontol 76:2223–2229

    CAS  PubMed  Google Scholar 

  46. Chang YC, Lai CC, Lin LF, Ni WF, Tsai CH (2005) The up-regulation of heme oxygenase-1 expression in human gingival fibroblasts stimulated with nicotine. J Periodontal Res 40:252–257

    CAS  PubMed  Google Scholar 

  47. Battino M, Ferreiro MS, Armeni T, Politi A, Bompadre S, Massoli A, Bullon P (2005) In vitro antioxidant activities of antioxidant-enriched toothpastes. Free Radic Res 39:343–350

    CAS  PubMed  Google Scholar 

  48. Battino M, Ferreiro MS, Fattorini D, Bullon P (2002) In vitro antioxidant activities of mouthrinses and their components. J Clin Periodontol 29:462–467

    CAS  PubMed  Google Scholar 

  49. Shokri F, Heidari M, Gharagozloo S, Ghazi-Khansari M (2000) In vitro inhibitory effects of antioxidants on cytotoxicity of T-2 toxin. Toxicology 146:171–176

    CAS  PubMed  Google Scholar 

  50. Babich H, Reisbaum AG, Zuckerbraun HL (2000) In vitro response of human gingival epithelial S-G cells to resveratrol. Toxicol Lett 114:143–153

    CAS  PubMed  Google Scholar 

  51. Babich H, Zuckerbraun HL, Hirsch ST, Blau L (1999) In vitro cytotoxicity of the nitric oxide donor, S-nitroso-N-acetyl-penicillamine, towards cells from human oral tissue. Pharmacol Toxicol 84:218–225

    CAS  PubMed  Google Scholar 

  52. Govindaraj J, Emmadi P, Deepalakshmi, Rajaram V, Prakash G, Puvanakrishnan R (2010) Protective effect of proanthocyanidins on endotoxin induced experimental periodontitis in rats. Indian J Exp Biol 48:133–142

    CAS  PubMed  Google Scholar 

  53. Cai X, Li C, Du G, Cao Z (2008) Protective effects of baicalin on ligature-induced periodontitis in rats. J Periodontal Res 43:14–21. doi:10.1111/j.1600-0765.2007.00989.x

    CAS  PubMed  Google Scholar 

  54. Ozdemir H, Kara MI, Erciyas K, Ozer H, Ay S (2012) Preventive effects of thymoquinone in a rat periodontitis model: a morphometric and histopathological study. J Periodontal Res 47:74–80. doi:10.1111/j.1600-0765.2011.01406.x

    CAS  PubMed  Google Scholar 

  55. Paola RD, Oteri G, Mazzon E, Crisafulli C, Galuppo M, Toso RD, Pressi G, Cordasco G, Cuzzocrea S (2011) Effects of verbascoside, biotechnologically purified by Syringa vulgaris plant cell cultures, in a rodent model of periodontitis. J Pharm Pharmacol 63:707–717. doi:10.1111/j.2042-7158.2011.01262.x

    CAS  PubMed  Google Scholar 

  56. Ku SK, Cho HR, Sung YS, Kang SJ, Lee YJ (2011) Effects of calcium gluconate on experimental periodontitis and alveolar bone loss in rats. Basic Clin Pharmacol Toxicol 108:241–250. doi:10.1111/j.1742-7843.2010.00646.x

    CAS  PubMed  Google Scholar 

  57. Lohinai Z, Benedek P, Fehér E, Györfi A, Rosivall L, Fazekas A, Salzman AL, Szabó C (1998) Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat. Br J Pharmacol 123:353–360

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Paquette DW, Rosenberg A, Lohinai Z, Southan GJ, Williams RC, Offenbacher S, Szabó C (2006) Inhibition of experimental gingivitis in beagle dogs with topical mercaptoalkylguanidines. J Periodontol 77:385–391

    CAS  PubMed  Google Scholar 

  59. Kador PF, O’Meara JD, Blessing K, Marx DB, Reinhardt RA (2011) Efficacy of structurally diverse aldose reductase inhibitors on experimental periodontitis in rats. J Periodontol 82:926–933. doi:10.1902/jop.2010.100442

    CAS  PubMed  Google Scholar 

  60. Toker H, Ozdemir H, Eren K, Ozer H, Sahin G (2009) N-acetylcysteine, a thiol antioxidant, decreases alveolar bone loss in experimental periodontitis in rats. J Periodontol 80:672–678. doi:10.1902/jop.2009.080509

    CAS  PubMed  Google Scholar 

  61. Di Paola R, Mazzon E, Zito D, Maiere D, Britti D, Genovese T, Cuzzocrea S (2005) Effects of Tempol, a membrane-permeable radical scavenger, in a rodent model periodontitis. J Clin Periodontol 32:1062–1068

    PubMed  Google Scholar 

  62. Di Paola R, Mazzon E, Rotondo F, Dattola F, Britti D, De Majo M, Genovese T, Cuzzocrea S (2005) Reduced development of experimental periodontitis by treatment with M40403, a superoxide dismutase mimetic. Eur J Pharmacol 516:151–157

    PubMed  Google Scholar 

  63. Petelin M, Pavlica Z, Ivanusa T, Sentjurc M, Skaleric U (2000) Local delivery of liposome-encapsulated superoxide dismutase and catalase suppress periodontal inflammation in beagles. J Clin Periodontol 27:918–925

    CAS  PubMed  Google Scholar 

  64. Abou Sulaiman AE, Shehadeh RM (2010) Assessment of total antioxidant capacity and the use of vitamin C in the treatment of non-smokers with chronic periodontitis. J Periodontol 81:1547–1554. doi:10.1902/jop.2010.100173

    CAS  PubMed  Google Scholar 

  65. Chandra RV, Sandhya YP, Nagarajan S, Reddy BH, Naveen A, Murthy KR (2012) Efficacy of lycopene as a locally delivered gel in the treatment of chronic periodontitis: smokers vs nonsmokers. Quintessence Int 43:401–411

    PubMed  Google Scholar 

  66. Chapple IL, Milward MR, Ling-Mountford N, Weston P, Carter K, Askey K, Dallal GE, De Spirt S, Sies H, Patel D, Matthews JB (2012) Adjunctive daily supplementation with encapsulated fruit, vegetable and berry juice powder concentrates and clinical periodontal outcomes: a double-blind RCT. J Clin Periodontol 39:62–72. doi:10.1111/j.1600-051X.2011.01793.x

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Harman D, Eddy DE (1979) Free radical theory of aging: beneficial effect of adding antioxidants to the maternal mouse diet on life span of offspring: possible explanation of the sex difference in longevity. Age 2:109–122

    CAS  Google Scholar 

  68. Comfort A (1979) The biology of senescence, 3rd edn. Elsevier Science, New York

    Google Scholar 

  69. Benzie IF, Szeto YT (1999) Total antioxidant capacity of teas by the ferric reducing/antioxidant power assay. J Agric Food Chem 47:633–636

    CAS  PubMed  Google Scholar 

  70. Prior RL, Wu X, Schaich K (2005) Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements. J Agric Food Chem 53:4290–4302

    CAS  PubMed  Google Scholar 

  71. Halliwell B, Rafter J, Jenner A (2005) Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? Antioxidant or not? Am J Clin Nutr 81:268S–276S

    CAS  PubMed  Google Scholar 

  72. Huxley RR, Neil HAW (2003) The relation between dietary flavonol intake and coronary heart disease mortality: a meta-analysis of prospective cohort studies. Eur J Clin Nutr 57:904–908

    CAS  PubMed  Google Scholar 

  73. Hertog MGL, Hollman PCH (1996) Potential health effects of the dietary flavonol quercetin. Eur J Clin Nutr 50:63–71

    CAS  PubMed  Google Scholar 

  74. Hertog MGL, Feskens EJM, Hollman PCH, Katan MB, Kromhout D (1993) Dietary antioxidant flavonoids and the risk of coronary heart diseases: the Zutphen Elderly Study. Lancet 342:1007–1011

    CAS  PubMed  Google Scholar 

  75. Sesso HD, Gaziano M, Buring JE, Hennekens CH (1999) Coffee and tea intake and the risk of myocardial infarction. Am J Epidemiol 149:162–167

    CAS  PubMed  Google Scholar 

  76. Hertog MGL, Bueno-de-Mesquita HB, Fehily AM, Sweetnam PM, Elwood PC, Kromhout D (1996) Fruit and vegetable consumption and cancer mortality in the Caerphilly Study. Cancer Epidemiol Biomarkers Prev 5:673–677

    CAS  PubMed  Google Scholar 

  77. Yochum L, Kushi LH, Meyer K, Folsom AR (1999) Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women. Am J Epidemiol 149:943–949

    CAS  PubMed  Google Scholar 

  78. Hirvonen T, Pietinen P, Virtanen M, Ovaskainen ML, Häkkinen S, Albanes D, Virtamo J (2001) Intake of flavonols and flavones and risk of coronary heart disease in male smokers. Epidemiology 12:62–67

    CAS  PubMed  Google Scholar 

  79. Geleijnse JM, Launer LJ, Van der Kuip DAM, Hofman A, Witteman JCM (2002) Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam Study. Am J Clin Nutr 75:880–886

    CAS  PubMed  Google Scholar 

  80. Mukamal KJ, Maclure M, Muller JE, Sherwood JB, Mittleman MA (2002) Tea consumption and mortality after acute myocardial infarction. Circulation 105:2476–2481

    PubMed  Google Scholar 

  81. Silva MM, Santos MR, Caroco G, Rocha R, Justino G, Mira L (2002) Structure-antioxidant activity relationships of flavonoids: a re-examination. Free Radic Res 36:1219–1227

    CAS  PubMed  Google Scholar 

  82. Pannala AS, Rice-Evans CA, Halliwell B, Singh S (1997) Inhibition of peroxynitrite-mediated tyrosine nitration by catechin polyphenols. Biochem Biophys Res Commun 232:164–168

    CAS  PubMed  Google Scholar 

  83. Paya M, Halliwell B, Hoult JRS (1992) Interaction of a series of coumarins with reactive oxygen species: scavenging of superoxide, hypochlorous acid and hydroxyl radicals. Biochem Pharmacol 44:205–214

    CAS  PubMed  Google Scholar 

  84. Boersma BJ, Patel RP, Kirk M, Jackson PL, Muccio D, Darley-Usmar VM, Barnes S (1999) Chlorination and nitration of soy isoflavones. Arch Biochem Biophys 368:265–275

    CAS  PubMed  Google Scholar 

  85. Halliwell B (2000) Antioxidant activity and other biological effects of flavonoids. In: Rice-Evans C (ed) Wake up to flavonoids. Royal Society of Medicine Press, London, pp 13–23

    Google Scholar 

  86. Mira L, Fernandez MT, Santos M, Rocha R, Florêncio MH, Jennings KR (2002) Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity. Free Radic Res 36:1199–1208

    CAS  PubMed  Google Scholar 

  87. Ketsawatsakul U, Whiteman M, Halliwell B (2000) A re-evaluation of the peroxynitrite scavenging activity of some dietary phenolics. Biochem Biophys Res Commun 279:692–699

    CAS  PubMed  Google Scholar 

  88. Talalay P (1989) Mechanisms of induction of enzymes that protect against chemical carcinogenesis. Adv Enzyme Regul 28:237–250

    CAS  PubMed  Google Scholar 

  89. Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236:313–322

    CAS  PubMed  Google Scholar 

  90. Ramos-Gomez M, Kwak MK, Dolan PM, Itoh K, Yamamoto M, Talalay P, Kensler TW (2001) Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in Nrf2 transcription factor-deficient mice. Proc Natl Acad Sci U S A 98:3410–3415

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Battino M, Bullon P, Wilson M, Newman H (1999) Oxidative injury and inflammatory periodontal diseases: the challenge of anti-oxidants to free radicals and reactive oxygen species. Crit Rev Oral Biol Med 10:458–476

    CAS  PubMed  Google Scholar 

  92. Chapple IL, Matthews JB (2007) The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000 43:160–232

    PubMed  Google Scholar 

  93. Rice-Evans C (1999) Implications of the mechanisms of action of tea polyphenols as antioxidants in vitro for chemoprevention in humans. Proc Soc Exp Biol Med 220:262–266

    CAS  PubMed  Google Scholar 

  94. Ramiro-Puig E, Castell M (2009) Cocoa: antioxidant and immunomodulator. Br J Nutr 101:931–940. doi:10.1017/S0007114508169896

    CAS  PubMed  Google Scholar 

  95. Dillinger TL, Barriga P, Escárcega S, Jimenez M, Salazar Lowe D, Grivetti LE (2000) Food of the gods: cure for humanity? A cultural history of the medicinal and ritual use of chocolate. J Nutr 130:2057S–2072S

    CAS  PubMed  Google Scholar 

  96. Vinson JA, Proch J, Zubik L (1999) Phenol antioxidant quantity and quality in foods: cocoa, dark chocolate, and milk chocolate. J Agric Food Chem 47:4821–4824

    CAS  PubMed  Google Scholar 

  97. Lee KW, Kim YJ, Lee HJ, Lee CY (2003) Cocoa has more phenolic phytochemicals and a higher antioxidant capacity than teas and red wine. J Agric Food Chem 51:7292–7295

    CAS  PubMed  Google Scholar 

  98. Vinson JA, Proch J, Bose P, Muchler S, Taffera P, Shuta D, Samman N, Agbor GA (2006) Chocolate is a powerful ex vivo and in vivo antioxidant, an antiatherosclerotic agent in an animal model, and a significant contributor to antioxidants in the European and American diets. J Agric Food Chem 54:8071–8076

    CAS  PubMed  Google Scholar 

  99. Gu L, House SE, Wu X, Ou B, Prior RL (2006) Procyanidin and catechin contents and antioxidant capacity of cocoa and chocolate products. J Agric Food Chem 54:4057–4061

    CAS  PubMed  Google Scholar 

  100. Arteel GE, Sies H (1999) Protection against peroxynitrite by cocoa polyphenol oligomers. FEBS Lett 462:167–170

    CAS  PubMed  Google Scholar 

  101. Counet C, Collin S (2003) Effect of the number of flavanol units on the antioxidant activity of procyanidin fractions isolated from chocolate. J Agric Food Chem 51:6816–6822

    CAS  PubMed  Google Scholar 

  102. Formica JV, Regelson W (1995) Review of the biology of quercetin and related bioflavonoids. Food Chem Toxicol 33:1061–1080

    CAS  PubMed  Google Scholar 

  103. Lamuela-Raventós RM, Andrés-Lacueva C, Permanyer J, Izquierdo-Pulido M (2001) More antioxidants in cocoa. J Nutr 131:834–835

    PubMed  Google Scholar 

  104. Azam S, Hadi N, Khan NU, Hadi SM (2003) Antioxidant and prooxidant properties of caffeine, theobromine and xanthine. Med Sci Monit 9:BR325–BR330

    CAS  PubMed  Google Scholar 

  105. Yilmaz Y, Toledo RT (2004) Major flavonoids in grape seeds and skins: antioxidant capacity of catechin, epicatechin, and gallic acid. J Agric Food Chem 52:255–260

    CAS  PubMed  Google Scholar 

  106. Spencer JP, Schroeter H, Rechner AR, Rice-Evans C (2001) Bioavailability of flavan-3-ols and procyanidins: gastrointestinal tract influences and their relevance to bioactive forms in vivo. Antioxid Redox Signal 3:1023–1039

    CAS  PubMed  Google Scholar 

  107. Natsume M, Osakabe N, Yasuda A, Baba S, Tokunaga T, Kondo K, Osawa T, Terao J (2004) In vitro antioxidative activity of (2)-epicatechin glucuronide metabolites present in human and rat plasma. Free Radic Res 38:1341–1348

    CAS  PubMed  Google Scholar 

  108. Erlejman AG, Fraga CG, Oteiza PI (2006) Procyanidins protect Caco-2 cells from bile acid- and oxidant-induced damage. Free Radic Biol Med 41:1247–1256

    CAS  PubMed  Google Scholar 

  109. Lee KW, Kundu JK, Kim SO, Chun KS, Lee HJ, Surh YJ (2006) Cocoa polyphenols inhibit phorbol ester-induced superoxide anion formation in cultured HL-60 cells and expression of cyclooxygenase-2 and activation of NF-kB and MAPKs in mouse skin in vivo. J Nutr 136:1150–1155

    CAS  PubMed  Google Scholar 

  110. Baba S, Osakabe N, Natsume M, Yasuda A, Takizawa T, Nakamura T, Terao J (2000) Cocoa powder enhances the level of antioxidative activity in rat plasma. Br J Nutr 84:673–680

    CAS  PubMed  Google Scholar 

  111. Wang JF, Schramm DD, Holt RR, Ensunsa JL, Fraga CG, Schmitz HH, Keen CL (2000) A dose–response effect from chocolate consumption on plasma epicatechin and oxidative damage. J Nutr 130:2115S–2119S

    CAS  PubMed  Google Scholar 

  112. Lecumberri E, Mateos R, Ramos S, Alía M, Rúperez P, Goya L, Izquierdo-Pulido M, Bravo L (2006) Characterization of cocoa fiber and its effect on the antioxidant capacity of serum in rats. Nutr Hosp 21:622–628

    CAS  PubMed  Google Scholar 

  113. Ramiro-Puig E, Urpí-Sardà M, Pérez-Cano FJ, Franch A, Castellote C, Andrés-Lacueva C, Izquierdo-Pulido M, Castell M (2007) Cocoa-enriched diet enhances antioxidant enzyme activity and modulates lymphocyte composition in thymus from young rats. J Agric Food Chem 55:6431–6438

    CAS  PubMed  Google Scholar 

  114. Mateos R, Lecumberri E, Ramos S, Goya L, Bravo L (2005) Determination of malondialdehyde (MDA) by high-performance liquid chromatography in serum and liver as a biomarker for oxidative stress. Application to a rat model for hypercholesterolemia and evaluation of the effect of diets rich in phenolic antioxidants from fruits. J Chromatogr B Analyt Technol Biomed Life Sci 827:76–82

    CAS  PubMed  Google Scholar 

  115. Fraga CG, Actis-Goretta L, Ottaviani JI, Carrasquedo F, Lotito SB, Lazarus S, Schmitz HH, Keen CL (2005) Regular consumption of a flavanol-rich chocolate can improve oxidant stress in young soccer players. Clin Dev Immunol 12:11–17

    CAS  PubMed Central  PubMed  Google Scholar 

  116. Cooper KA, Donovan JL, Waterhouse AL, Williamson G (2008) Cocoa and health: a decade of research. Br J Nutr 99:1–11

    CAS  PubMed  Google Scholar 

  117. Fisher ND, Hollenberg NK (2005) Flavanols for cardiovascular health: the science behind the sweetness. J Hypertens 23:1453–1459

    CAS  PubMed  Google Scholar 

  118. Osakabe N (2005) Cacao polyphenols and atherosclerosis. J Clin Biochem Nutr 37:67–72

    CAS  Google Scholar 

  119. Heptinstall S, May J, Fox S, Kwik-Uribe C, Zhao L (2006) Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo studies in healthy adults. J Cardiovasc Pharmacol 47:S197–S205

    CAS  PubMed  Google Scholar 

  120. Hodgson JM, Croft KD (2006) Dietary flavonoids: effects on endothelial function and blood pressure. J Sci Food Agric 86:2492–2498

    CAS  Google Scholar 

  121. Hackman RM, Polagruto JA, Zhu QY (2008) Flavanols: digestion, absorption and bioactivity. Phytochem Rev 7:195–208

    CAS  Google Scholar 

  122. Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79:727–747

    CAS  PubMed  Google Scholar 

  123. de Boer VC, Dihal AA, van der Woude H, Arts IC, Wolffram S, Alink GM, Rietjens IM, Keijer J, Hollman PC (2005) Tissue distribution of quercetin in rats and pigs. J Nutr 135:1718–1725

    PubMed  Google Scholar 

  124. Mak JC (2012) Potential role of green tea catechins in various disease therapies: progress and promise. Clin Exp Pharmacol Physiol 39:265–273. doi:10.1111/j.1440-1681.2012.05673.x

    CAS  PubMed  Google Scholar 

  125. Pandey M, Gupta S (2009) Green tea and prostate cancer: from bench to clinic. Front Biosci 1:13–25

    Google Scholar 

  126. Morel I, Lescoat G, Cogrel P, Sergent O, Pasdeloup N, Brissot P, Cillard P, Cillard J (1993) Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem Pharmacol 45:13–19

    CAS  PubMed  Google Scholar 

  127. Hatano T, Miyatake H, Natsume M, Osakabe N, Takizawa T, Ito H, Yoshida T (2002) Proanthocyanidin glycosides and related polyphenols from cacao liquor and their antioxidant effects. Phytochemistry 59:749–758

    CAS  PubMed  Google Scholar 

  128. Pollard SE, Kuhnle GG, Vauzour D, Vafeiadou K, Tzounis X, Whiteman M, Rice-Evans C, Spencer JP (2006) The reaction of flavonoid metabolites with peroxynitrite. Biochem Biophys Res Commun 350:960–968

    CAS  PubMed  Google Scholar 

  129. Narotzki B, Reznick AZ, Aizenbud D, Levy Y (2012) Green tea: a promising natural product in oral health. Arch Oral Biol 57:429–435. doi:10.1016/j.archoralbio.2011.11.017

    CAS  PubMed  Google Scholar 

  130. McKay DL, Blumberg JB (2002) The role of tea in human health: an update. J Am Coll Nutr 21:1–13

    CAS  PubMed  Google Scholar 

  131. Johnson JJ, Bailey HH, Mukhtar H (2010) Green tea polyphenols for prostate cancer chemoprevention: a translational perspective. Phytomedicine 17:3–13. doi:10.1016/j.phymed.2009.09.011

    CAS  PubMed Central  PubMed  Google Scholar 

  132. Andrade JP, Assunção M (2012) Protective effects of chronic green tea consumption on age-related neurodegeneration. Curr Pharm Des 18:4–14

    CAS  PubMed  Google Scholar 

  133. Islam MA (2012) Cardiovascular effects of green tea catechins: progress and promise. Recent Pat Cardiovasc Drug Discov 7:88–99

    CAS  PubMed  Google Scholar 

  134. Davinelli S, Sapere N, Zella D, Bracale R, Intrieri M, Scapagnini G (2012) Pleiotropic protective effects of phytochemicals in Alzheimer’s disease. Oxid Med Cell Longev 2012:386527. doi:10.1155/2012/386527

    PubMed Central  PubMed  Google Scholar 

  135. Hurt RT, Wilson T (2012) Geriatric obesity: evaluating the evidence for the use of flavonoids to promote weight loss. J Nutr Gerontol Geriatr 31:269–289. doi:10.1080/21551197.2012.698222

    PubMed  Google Scholar 

  136. Cimino S, Sortino G, Favilla V, Castelli T, Madonia M, Sansalone S, Russo GI, Morgia G (2012) Polyphenols: key issues involved in chemoprevention of prostate cancer. Oxid Med Cell Longev 2012:632959. doi:10.1155/2012/632959

    PubMed Central  PubMed  Google Scholar 

  137. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC (2006) Multiple biological activities of curcumin: a short review. Life Sci 78:2081–2087

    CAS  PubMed  Google Scholar 

  138. Grynkiewicz G, Ślifirski P (2012) Curcumin and curcuminoids in quest for medicinal status. Acta Biochim Pol 59:201–212

    CAS  PubMed  Google Scholar 

  139. Esatbeyoglu T, Huebbe P, Ernst IM, Chin D, Wagner AE, Rimbach G (2012) Curcumin—from molecule to biological function. Angew Chem Int Ed Engl 51:5308–5332. doi:10.1002/anie.201107724

    CAS  PubMed  Google Scholar 

  140. Pan MH, Huang TM, Lin JK (1999) Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos 27:486–494

    CAS  PubMed  Google Scholar 

  141. Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21:2895–2900

    CAS  PubMed  Google Scholar 

  142. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS (1998) Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 64:353–356

    CAS  PubMed  Google Scholar 

  143. Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, Pirmohamed M, Marnett LJ, Gescher AJ, Steward WP (2001) Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res 7:1894–1900

    CAS  PubMed  Google Scholar 

  144. Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, Marczylo TH, Morgan B, Hemingway D, Plummer SM, Pirmohamed M, Gescher AJ, Steward WP (2004) Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 10:6847–6854

    CAS  PubMed  Google Scholar 

  145. Lao CD, Ruffin MT 4th, Normolle D, Heath DD, Murray SI, Bailey JM, Boggs ME, Crowell J, Rock CL, Brenner DE (2006) Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 6:10

    PubMed Central  PubMed  Google Scholar 

  146. Garcea G, Jones DJ, Singh R, Dennison AR, Farmer PB, Sharma RA, Steward WP, Gescher AJ, Berry DP (2004) Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration. Br J Cancer 90:1011–1015

    CAS  PubMed Central  PubMed  Google Scholar 

  147. Garcea G, Berry DP, Jones DJ, Singh R, Dennison AR, Farmer PB, Sharma RA, Steward WP, Gescher AJ (2005) Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev 14:120–125

    CAS  PubMed  Google Scholar 

  148. Ireson C, Orr S, Jones DJ, Verschoyle R, Lim CK, Luo JL, Howells L, Plummer S, Jukes R, Williams M, Steward WP, Gescher A (2001) Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit Phorbol ester-induced prostaglandin E2 production. Cancer Res 61:1058–1064

    CAS  PubMed  Google Scholar 

  149. Asai A, Miyazawa T (2000) Occurrence of orally administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma. Life Sci 67:2785–2793

    CAS  PubMed  Google Scholar 

  150. Schiborr C, Eckert GP, Rimbach G, Frank J (2010) A validated method for the quantification of curcumin in plasma and brain tissue by fast narrow-bore high-performance liquid chromatography with fluorescence detection. Anal Bioanal Chem 397:1917–1925

    CAS  PubMed  Google Scholar 

  151. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4:807–818

    CAS  PubMed  Google Scholar 

  152. Vareed SK, Kakarala M, Ruffin MT, Crowell JA, Normolle DP, Djuric Z, Brenner DE (2008) Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomarkers Prev 17:1411–1417. doi:10.1158/1055-9965.EPI-07-2693

    CAS  PubMed  Google Scholar 

  153. Wahlström B, Blennow G (1978) A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol 43:86–92

    Google Scholar 

  154. Yang KY, Lin LC, Tseng TY, Wang SC, Tsai TH (2007) Oral bioavailability of curcumin in rat and the herbal analysis from curcuma longa by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 853:183–189

    CAS  PubMed  Google Scholar 

  155. Priyadarsini KI, Maity DK, Naik GH, Kumar MS, Unnikrishnan MK, Satav JG, Mohan H (2003) Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin. Free Radic Biol Med 35:475–484

    CAS  PubMed  Google Scholar 

  156. Ak T, Gülçin I (2008) Antioxidant and radical scavenging properties of curcumin. Chem Biol Interact 174:27–37. doi:10.1016/j.cbi.2008.05.003

    CAS  PubMed  Google Scholar 

  157. Surh YJ (2003) Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 3:768–780

    CAS  PubMed  Google Scholar 

  158. Slocum SL, Kensler TW (2011) Nrf2: control of sensitivity to carcinogens. Arch Toxicol 85:273–284. doi:10.1007/s00204-011-0675-4

    CAS  PubMed  Google Scholar 

  159. Goel A, Aggarwal BB (2010) Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer 62:919–930. doi:10.1080/01635581.2010.509835

    CAS  PubMed  Google Scholar 

  160. Donnez D, Jeandet P, Clément C, Courot E (2009) Bioproduction of resveratrol and stilbene derivatives by plant cells and microorganisms. Trends Biotechnol 27:706–713. doi:10.1016/j.tibtech.2009.09.005

    CAS  PubMed  Google Scholar 

  161. Paredes-López O, Cervantes-Ceja ML, Vigna-Pérez M, Hernández-Pérez T (2010) Berries: improving human health and healthy aging, and promoting quality life - a review. Plant Foods Hum Nutr 65:299–308. doi:10.1007/s11130-010-0177-1

    PubMed  Google Scholar 

  162. Castrejón ADR, Eichholz I, Rohn S, Kroh LW, Huyskens-Keil S (2008) Phenolic profile and antioxidant activity of high bush blueberry (Vaccinium corymbosum L.) during fruit maturation and ripening. Food Chem 109:564–572. doi:10.1016/j.foodchem.2008.01.007

    Google Scholar 

  163. Vitrac X, Moni JP, Vercauteren J, Deffieux G, Mérillon JM (2002) Direct liquid chromatography analysis of resveratrol derivatives and flavanonols in wines with absorbance and fluorescence detection. Anal Chim Acta 458:103–110. doi:10.1016/S0003-2670(01)01498-2

    CAS  Google Scholar 

  164. Gupta SC, Kannappan R, Reuter S, Kim JH, Aggarwal BB (2011) Chemosensitization of tumors by resveratrol. Ann N Y Acad Sci 1215:150–160. doi:10.1111/j.1749-6632.2010.05852.x

    CAS  PubMed Central  PubMed  Google Scholar 

  165. Frei B (2004) Efficacy of dietary antioxidants to prevent oxidative damage and inhibit chronic disease. J Nutr 134:3196–3198

    Google Scholar 

  166. Kundu JK, Surh YJ (2008) Cancer chemopreventive and therapeutic potential of resveratrol: mechanistic perspectives. Cancer Lett 269:243–261. doi:10.1016/j.canlet.2008.03.057

    CAS  PubMed  Google Scholar 

  167. Kundu JK, Shin YK, Kim SH, Surh YJ (2006) Resveratrol inhibits Phorbol ester-induced expression of COX-2 and activation of NFkappaB in mouse skin by blocking IkappaB kinase activity. Carcinogenesis 27:1465–1474

    CAS  PubMed  Google Scholar 

  168. Subbaramaiah K, Chung WJ, Michaluart P, Telang N, Tanabe T, Inoue H, Jang M, Pezzuto JM, Dannenberg AJ (1998) Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J Biol Chem 273:21875–21882

    CAS  PubMed  Google Scholar 

  169. Carluccio MA, Ancora MA, Massaro M, Carluccio M, Scoditti E, Distante A, Storelli C, De Caterina R (2007) Homocysteine induces VCAM-1 gene expression through NF-kappaB and NAD(P)H oxidase activation: protective role of Mediterranean diet polyphenolic antioxidants. Am J Physiol Heart Circ Physiol 293:2344–2354

    Google Scholar 

  170. Csiszar A, Smith K, Labinsky N, Orosz Z, Rivera A, Ungvari Z (2006) Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells: role of NF-kappaB inhibition. Am J Physiol Heart Circ Physiol 291:1694–1699

    Google Scholar 

  171. Shankar S, Nall D, Tang SN, Meeker D, Passarini J, Sharma J, Srivastava RK (2011) Resveratrol inhibits pancreatic cancer stem cell characteristics in human and KrasG12D transgenic mice by inhibiting pluripotency maintaining factors and epithelialmesenchymal transition. PLoS One 6:e16530. doi:10.1371/journal.pone.0016530

    CAS  PubMed Central  PubMed  Google Scholar 

  172. Vergara D, Simeone P, Toraldo D, Del Boccio P, Vergaro V, Leporatti S, Pieragostino D, Tinelli A, De Domenico S, Alberti S, Urbani A, Salzet M, Santino A, Maffia M (2012) Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells. Mol Biosyst 8:1078–1087. doi:10.1039/c2mb05486h

    CAS  PubMed  Google Scholar 

  173. Sharma S, Chopra K, Kulkarni SK (2007) Effect of insulin and its combination with resveratrol or curcumin in attenuation of diabetic neuropathic pain: participation of nitric oxide F TNF-alpha. Phytother Res 21:278–283

    CAS  PubMed  Google Scholar 

  174. Giovinazzo G, Ingrosso I, Paradiso A, De Gara L, Santino A (2012) Resveratrol biosynthesis: plant metabolic engineering for nutritional improvement of food. Plant Foods Hum Nutr 67:191–199

    CAS  PubMed  Google Scholar 

  175. Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK (2004) High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 32:1377–1382

    CAS  PubMed  Google Scholar 

  176. Walle T (2011) Bioavailability of resveratrol. Ann N Y Acad Sci 1215:9–15. doi:10.1111/j.1749-6632.2010.05842.x

    CAS  PubMed  Google Scholar 

  177. Hertog MG, Hollman PC, Katan MB, Kromhout D (1993) Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Nutr Cancer 20:21–29

    CAS  PubMed  Google Scholar 

  178. Bischoff SC (2008) Quercetin: potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Care 11:733–740. doi:10.1097/MCO.0b013e32831394b8

    CAS  PubMed  Google Scholar 

  179. Chen C, Zhou J, Ji C (2010) Quercetin: a potential drug to reverse multidrug resistance. Life Sci 87:333–338. doi:10.1016/j.lfs.2010.07.004

    CAS  PubMed  Google Scholar 

  180. Kressler J, Millard-Stafford M, Warren GL (2011) Quercetin and endurance exercise capacity: a systematic review and meta-analysis. Med Sci Sports Exerc 43:2396–2404. doi:10.1249/MSS.0b013e31822495a7

    CAS  PubMed  Google Scholar 

  181. Mendoza EE, Burd R (2011) Quercetin as a systemic chemopreventative agent: structural and functional mechanisms. Mini Rev Med Chem 11:1216–1221

    CAS  PubMed  Google Scholar 

  182. Larson AJ, Symons JD, Jalili T (2010) Quercetin: a treatment for hypertension? a review of efficacy and mechanisms. Pharmaceuticals 3:237–250. doi:10.3390/ph3010237

    CAS  PubMed Central  Google Scholar 

  183. Russo M, Spagnuolo C, Tedesco I, Bilotto S, Russo GL (2012) The flavonoid quercetin in disease prevention and therapy: facts and fancies. Biochem Pharmacol 83:6–15. doi:10.1016/j.bcp.2011.08.010

    CAS  PubMed  Google Scholar 

  184. Vissiennon C, Nieber K, Kelber O, Butterweck V (2012) Route of administration determines the anxiolytic activity of the flavonols kaempferol, quercetin and myricetin - are they prodrugs? J Nutr Biochem 23:733–740. doi:10.1016/j.jnutbio.2011.03.017

    CAS  PubMed  Google Scholar 

  185. Dajas F (2012) Life or death: neuroprotective and anticancer effects of quercetin. J Ethnopharmacol 143:383–396. doi:10.1016/j.jep.2012.07.005

    CAS  PubMed  Google Scholar 

  186. Lamson DW, Brignall MS (2000) Antioxidants and cancer part3: quercetin. Altern Med Rev 5:196–208

    CAS  PubMed  Google Scholar 

  187. Kelly GS (2011) Quercetin. Monograph. Altern Med Rev 16:172–194

    PubMed  Google Scholar 

  188. Manach C, Morand C, Texier O, Favier ML, Agullo G, Demigné C, Régérat F, Rémésy C (1995) Quercetin metabolites in plasma of rats fed diets. J Nutr 125:1911–1922

    CAS  PubMed  Google Scholar 

  189. Paulke A, Nöldner M, Schubert-Zsilavecz M, Wurglics M (2008) St. John’s wort flavonoids and their metabolites show antidepressant activity and accumulate in brain after multiple oral doses. Pharmazie 63:296–302

    CAS  PubMed  Google Scholar 

  190. Rangel-Ordóñez L, Nöldner M, Schubert-Zsilavecz M, Wurglics M (2010) Plasma levels and distribution of flavonoids in rat brain after single and repeated doses of standardized Ginkgo biloba extract EGb 761®. Planta Med 76:1683–1690. doi:10.1055/s-0030-1249962

    PubMed  Google Scholar 

  191. Banerjee S, Li Y, Wang Z, Sarkar FH (2008) Multi-targeted therapy of cancer by genistein. Cancer Lett 269:226–242. doi:10.1016/j.canlet.2008.03.052

    CAS  PubMed Central  PubMed  Google Scholar 

  192. Perabo FG, Von Löw EC, Ellinger J, von Rücker A, Müller SC, Bastian PJ (2008) Soy isoflavone genistein in prevention and treatment of prostate cancer. Prostate Cancer Prostatic Dis 11:6–12

    CAS  PubMed  Google Scholar 

  193. Si H, Liu D (2007) Phytochemical genistein in the regulation of vascular function: new insights. Curr Med Chem 14:2581–2589

    CAS  PubMed  Google Scholar 

  194. Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, Gaudio A, Mazzaferro S, Frisina A, Frisina N, Lubrano C, Bonaiuto M, D’Anna R, Cannata ML, Corrado F, Adamo EB, Wilson S, Squadrito F (2007) Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med 146:839–847

    PubMed  Google Scholar 

  195. Adlercreutz H, Markkanen H, Watanabe S (1993) Plasma concentrations of phyto-oestrogens in Japanese men. Lancet 342:1209–1210

    CAS  PubMed  Google Scholar 

  196. Mills PK, Beeson WL, Phillips RL, Fraser GE (1989) Cohort study of diet lifestyle and prostate cancer in Adventist men. Cancer 64:598–604

    CAS  PubMed  Google Scholar 

  197. Knight DC, Eden JA (1996) A review of the clinical effects of phytoestrogens. Obstet Gynecol 87:897–904

    CAS  PubMed  Google Scholar 

  198. Zava DT, Dollbaum CM, Blen M (1998) Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med 217:369–378

    CAS  PubMed  Google Scholar 

  199. Konishi T (2009) Brain oxidative stress as basic target of antioxidant traditional oriental medicines. Neurochem Res 34:711–716. doi:10.1007/s11064-008-9872-9

    CAS  PubMed  Google Scholar 

  200. Cheng JT (2000) Review: drug therapy in Chinese traditional medicine. J Clin Pharmacol 40:445–450

    CAS  PubMed  Google Scholar 

  201. Liu J, Edamatsu R, Kabuto H, Mori A (1990) Antioxidant action of guilingji in the brain of rats with FeCl3-induced epilepsy. Free Radic Biol Med 9:451–454

    CAS  PubMed  Google Scholar 

  202. Ou B, Huang D, Hampsch-woodill M, Flanagan JA (2003) When east meets west: the relationship between yin-yang and antioxidation-oxidation. FASEB J 17:127–129

    CAS  PubMed  Google Scholar 

  203. Rausch WD, Liu S, Gille G, Radad K (2006) Neuroprotective effects of ginsenosides. Acta Neurobiol Exp 66:369–375

    Google Scholar 

  204. Tang SY, Whiteman M, Peng ZF, Jenner A, Young EL, Halliwell B (2004) Characterization of antioxidant and antiglycation properties and isolation of active ingredients from traditional Chinese medicines. Free Radic Biol Med 36:1575–1587

    CAS  PubMed  Google Scholar 

  205. Stickel F, Schuppan D (2007) Herbal medicine in the treatment of liver diseases. Dig Liver Dis 39:293–304

    CAS  PubMed  Google Scholar 

  206. Surathu N, Kurumathur AV (2011) Traditional therapies in the management of periodontal disease in India and China. Periodontol 2000 56:14–24. doi:10.1111/j.1600-0757.2010.00369.x

    PubMed  Google Scholar 

  207. Chava VK, Vedula BD (2012) Thermo reversible green tea catechin gel for local application in chronic periodontitis - a 4 week clinical trial. J Periodontol. doi:10.1902/jop.2012.120425

    PubMed  Google Scholar 

  208. Hirasawa M, Takada K, Makimura M, Otake S (2002) Improvement of periodontal status by green tea catechin using a local delivery system: a clinical pilot study. J Periodontal Res 37:433–438

    CAS  PubMed  Google Scholar 

  209. Krahwinkel T, Willershausen B (2000) The effect of sugar-free green tea chew candies on the degree of inflammation of the gingiva. Eur J Med Res 5:463–467

    CAS  PubMed  Google Scholar 

  210. Tamura M, Saito H, Kikuchi K, Ishigami T, Toyama Y, Takami M, Ochiai K (2011) Antimicrobial activity of Gel-entrapped catechins toward oral microorganisms. Biol Pharm Bull 34:638–643

    CAS  PubMed  Google Scholar 

  211. Taylor PW, Hamilton-Miller JM, Stapleton PD (2005) Antimicrobial properties of green tea catechins. Food Sci Technol Bull 2:71–81

    PubMed Central  PubMed  Google Scholar 

  212. Okamoto M, Sugimoto A, Leung KP, Nakayama K, Kamaguchi A, Maeda N (2004) Inhibitory effect of green tea catechins on cysteine proteinases in Porphyromonas gingivalis. Oral Microbiol Immunol 19:118–120

    CAS  PubMed  Google Scholar 

  213. Petti S, Scully C (2009) Polyphenols, oral health and disease: a review. J Dent 37:413–423. doi:10.1016/j.jdent.2009.02.003

    CAS  PubMed  Google Scholar 

  214. Ho KY, Tsai CC, Huang JS, Chen CP, Lin TC, Lin CC (2001) Antimicrobial activity of tannin components from Vaccinium vitis-idaea L. J Pharm Pharmacol 53:187–191

    CAS  PubMed  Google Scholar 

  215. Yang F, de Villiers WJ, McClain CJ, Varilek GW (1998) Green tea polyphenols block endotoxin-induced tumor necrosis factor-production and lethality in a murine model. J Nutr 128:2334–2340

    CAS  PubMed  Google Scholar 

  216. Crouvezier S, Powell B, Keir D, Yaqoob P (2001) The effects of phenolic components of tea on the production of pro- and anti-inflammatory cytokines by human leukocytes in vitro. Cytokine 13:280–286

    CAS  PubMed  Google Scholar 

  217. Hosokawa Y, Hosokawa I, Ozaki K, Nakanishi T, Nakae H, Matsuo T (2010) Tea polyphenols inhibit IL-6 production in tumor necrosis factor superfamily 14-stimulated human gingival fibroblasts. Mol Nutr Food Res 54(Suppl 2):S151–S158. doi:10.1002/mnfr.200900549

    CAS  PubMed  Google Scholar 

  218. Hosokawa Y, Hosokawa I, Ozaki K, Nakanishi T, Nakae H, Matsuo T (2010) Catechins inhibit CXCL10 production from oncostatin M-stimulated human gingival fibroblasts. J Nutr Biochem 21:659–664. doi:10.1016/j.jnutbio.2009.04.005

    CAS  PubMed  Google Scholar 

  219. Hosokawa Y, Hosokawa I, Ozaki K, Nakanishi T, Nakae H, Matsuo T (2009) Catechins inhibit CCL20 production in IL-17A-stimulated human gingival fibroblasts. Cell Physiol Biochem 24:391–396. doi:10.1159/000257431

    CAS  PubMed  Google Scholar 

  220. Yun JH, Kim CS, Cho KS, Chai JK, Kim CK, Choi SH (2007) (−)-Epigallocatechin gallate induces apoptosis, via caspase activation, in osteoclasts differentiated from RAW 264.7 cells. J Periodontal Res 42:212–218

    CAS  PubMed  Google Scholar 

  221. Yun JH, Pang EK, Kim CS, Yoo YJ, Cho KS, Chai JK, Kim CK, Choi SH (2004) Inhibitory effects of green tea polyphenol (−)-epigallocatechin gallate on the expression of matrix metalloproteinase-9 and on the formation of osteoclasts. J Periodontal Res 39:300–307

    CAS  PubMed  Google Scholar 

  222. Chen YW, Yang WH, Wong MY, Chang HH, Yen-Ping Kuo M (2012) Curcumin inhibits thrombin-stimulated connective tissue growth factor (CTGF/CCN2) production through c-Jun NH2-terminal kinase suppression in human gingival fibroblasts. J Periodontol 83:1546–1553. doi:10.1902/jop.2012.110641

    CAS  PubMed  Google Scholar 

  223. Atsumi T, Tonosaki K, Fujisawa S (2006) Induction of early apoptosis and ROS-generation activity in human gingival fibroblasts (HGF) and human submandibular gland carcinoma (HSG) cells treated with curcumin. Arch Oral Biol 51:913–921

    CAS  PubMed  Google Scholar 

  224. Atsumi T, Fujisawa S, Tonosaki K (2005) Relationship between intracellular ROS production and membrane mobility in curcumin- and tetrahydrocurcumin-treated human gingival fibroblasts and human submandibular gland carcinoma cells. Oral Dis 11:236–242

    CAS  PubMed  Google Scholar 

  225. Zhou T, Chen D, Li Q, Sun X, Song Y, Wang C (2013) Curcumin inhibits inflammatory response and bone loss during experimental periodontitis in rats. Acta Odontol Scand 71:349–356. doi:10.3109/00016357.2012.682092

    CAS  PubMed  Google Scholar 

  226. Guimarães MR, Coimbra LS, de Aquino SG, Spolidorio LC, Kirkwood KL, Rossa C Jr (2011) Potent anti-inflammatory effects of systemically administered curcumin modulate periodontal disease in vivo. J Periodontal Res 46:269–279

    PubMed Central  PubMed  Google Scholar 

  227. Guimarães MR, de Aquino SG, Coimbra LS, Spolidorio LC, Kirkwood KL, Rossa C Jr (2012) Curcumin modulates the immune response associated with LPS-induced periodontal disease in rats. Innate Immun 18:155–163. doi:10.1177/1753425910392935

    PubMed Central  PubMed  Google Scholar 

  228. Kim SJ (2011) Curcumin suppresses the production of interleukin-6 in Prevotella intermedia lipopolysaccharide-activated RAW 264.7 cells. J Periodontal Implant Sci 41:157–163. doi:10.5051/jpis.2011.41.3.157

    PubMed Central  PubMed  Google Scholar 

  229. Chen D, Nie M, Fan MW, Bian Z (2008) Anti-inflammatory activity of curcumin in macrophages stimulated by lipopolysaccharides from Porphyromonas gingivalis. Pharmacology 82:264–269. doi:10.1159/000161127

    CAS  PubMed  Google Scholar 

  230. Watanabe A, Takeshita A, Kitano S, Hanazawa S (1996) CD14-mediated signal pathway of Porphyromonas gingivalis lipopolysaccharide in human gingival fibroblasts. Infect Immun 64:4488–4494

    CAS  PubMed Central  PubMed  Google Scholar 

  231. Casati MZ, Algayer C, Cardoso da Cruz G, Ribeiro FV, Casarin RC, Pimentel SP, Cirano FR (2013) Resveratrol decreases periodontal breakdown and modulate local levels of cytokines during periodontitis in rats. J Periodontol. doi:10.1902/jop.2013.120746

    Google Scholar 

  232. Park GJ, Kim YS, Kang KL, Bae SJ, Baek HS, Auh QS, Chun YH, Park BH, Kim EC (2012) Effects of sirtuin 1 activation on nicotine and lipopolysaccharide-induced cytotoxicity and inflammatory cytokine production in human gingival fibroblasts. J Periodontal Res. doi:10.1111/jre.12030

    Google Scholar 

  233. Rizzo A, Bevilacqua N, Guida L, Annunziata M, Romano Carratelli C, Paolillo R (2012) Effect of resveratrol and modulation of cytokine production on human periodontal ligament cells. Cytokine 60:197–204. doi:10.1016/j.cyto.2012.06.004

    CAS  PubMed  Google Scholar 

  234. Park HJ, Jeong SK, Kim SR, Bae SK, Kim WS, Jin SD, Koo TH, Jang HO, Yun I, Kim KW, Bae MK (2009) Resveratrol inhibits Porphyromonas gingivalis lipopolysaccharide-induced endothelial adhesion molecule expression by suppressing NF-kappaB activation. Arch Pharm Res 32:583–591. doi:10.1007/s12272-009-1415-7

    CAS  PubMed  Google Scholar 

  235. Andreou V, D’Addario M, Zohar R, Sukhu B, Casper RF, Ellen RP, Tenenbaum HC (2004) Inhibition of osteogenesis in vitro by a cigarette smoke-associated hydrocarbon combined with Porphyromonas gingivalis lipopolysaccharide: reversal by resveratrol. J Periodontol 75:939–948

    CAS  PubMed  Google Scholar 

  236. Takahama U, Hirota S, Oniki T (2006) Quercetin-dependent scavenging of reactive nitrogen species derived from nitric oxide and nitrite in the human oral cavity: interaction of quercetin with salivary redox components. Arch Oral Biol 51:629–639

    CAS  PubMed  Google Scholar 

  237. Cheng WC, Huang RY, Chiang CY, Chen JK, Liu CH, Chu CL, Fu E (2010) Ameliorative effect of quercetin on the destruction caused by experimental periodontitis in rats. J Periodontal Res 45:788–795. doi:10.1111/j.1600-0765.2010.01301.x

    CAS  PubMed  Google Scholar 

  238. Gutiérrez-Venegas G, Jiménez-Estrada M, Maldonado S (2007) The effect of flavonoids on transduction mechanisms in lipopolysaccharide-treated human gingival fibroblasts. Int Immunopharmacol 7:1199–1210

    PubMed  Google Scholar 

  239. Li M, Xu Z (2008) Quercetin in a lotus leaves extract may be responsible for antibacterial activity. Arch Pharm Res 31:640–644. doi:10.1007/s12272-001-1206-5

    CAS  PubMed  Google Scholar 

  240. Sosroseno W, Bird PS, Seymour GJ (2011) Nitric oxide production by a murine macrophage cell line (RAW264.7 cells) stimulated with Aggregatibacter actinomycetemcomitans surface-associated material. Anaerobe 17:246–251. doi:10.1016/j.anaerobe.2011.06.006

    CAS  PubMed  Google Scholar 

  241. Gutiérrez-Venegas G, Kawasaki-Cárdenas P, Arroyo-Cruz SR, Maldonado-Frías S (2006) Luteolin inhibits lipopolysaccharide actions on human gingival fibroblasts. Eur J Pharmacol 541:95–105

    PubMed  Google Scholar 

  242. Gutiérrez-Venegas G, Kawasaki-Cárdenas P, Cruz-Arroyo SR, Pérez-Garzón M, Maldonado-Frías S (2006) Actinobacillus actinomycetemcomitans lipopolysaccharide stimulates the phosphorylation of p44 and p42 MAP kinases through CD14 and TLR-4 receptor activation in human gingival fibroblasts. Life Sci 78:2577–2583

    PubMed  Google Scholar 

  243. Luo LJ, Liu F, Lin ZK, Xie YF, Xu JL, Tong QC, Shu R (2012) Genistein regulates the IL-1 beta induced activation of MAPKs in human periodontal ligament cells through G protein-coupled receptor 30. Arch Biochem Biophys 522:9–16. doi:10.1016/j.abb.2012.04.007

    CAS  PubMed  Google Scholar 

  244. Kubo M, Matsuda H, Tanaka M, Kimura Y, Okuda H, Higashino M, Tani T, Namba K, Arichi S (1984) Studies on Scutellariae radix: VII. Anti-arthritic and anti-inflammatory actions of methanolic extract and flavonoid components from Scutellariae radix. Chem Pharm Bull (Tokyo) 32:2724–2729

    CAS  Google Scholar 

  245. Tominari T, Hirata M, Matsumoto C, Inada M, Miyaura C (2012) Polymethoxy flavonoids, nobiletin and tangeretin, prevent lipopolysaccharide-induced inflammatory bone loss in an experimental model for periodontitis. J Pharmacol Sci 119:390–394

    CAS  PubMed  Google Scholar 

  246. Feghali K, Feldman M, La VD, Santos J, Grenier D (2011) Cranberry proanthocyanidins: natural weapons against periodontal diseases. J Agric Food Chem 60:5728–5735. doi:10.1021/jf203304v

    PubMed  Google Scholar 

  247. La VD, Howell AB, Grenier D (2010) Anti-Porphyromonas gingivalis and anti-inflammatory activities of A-type cranberry proanthocyanidins. Antimicrob Agents Chemother 54:1778–1784. doi:10.1128/AAC.01432-09

    CAS  PubMed Central  PubMed  Google Scholar 

  248. La VD, Howell AB, Grenier D (2009) Cranberry proanthocyanidins inhibit MMP production and activity. J Dent Res 88:627–632. doi:10.1177/0022034509339487

    CAS  PubMed  Google Scholar 

  249. Tanabe S, Santos J, La VD, Howell AB, Grenier D (2011) A-type cranberry proanthocyanidins inhibit the RANKL-dependent differentiation and function of human osteoclasts. Molecules 16:2365–2374. doi:10.3390/molecules16032365

    CAS  PubMed  Google Scholar 

  250. Lo’pez-La’zaro M (2009) Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem 9:31–59

    Google Scholar 

  251. Choi EY, Jin JY, Choi JI, Choi IS, Kim SJ (2011) Effects of luteolin on the release of nitric oxide and interleukin-6 by macrophages stimulated with lipopolysaccharide from Prevotella intermedia. J Periodontol 82:1509–1517. doi:10.1902/jop.2011.100759

    CAS  PubMed  Google Scholar 

  252. Jeong GS, Lee SH, Jeong SN, Kim YC, Kim EC (2009) Anti-inflammatory effects of apigenin on nicotine- and lipopolysaccharide-stimulated human periodontal ligament cells via heme oxygenase-1. Int Immunopharmacol 9:1374–1380. doi:10.1016/j.intimp.2009.08.015

    CAS  PubMed  Google Scholar 

  253. Dar A, Faizi S, Naqvi S, Roome T, Zikr-ur-Rehman S, Ali M, Firdous S, Moin ST (2005) Analgesic and antioxidant activity of mangiferin and its derivatives: the structure activity relationship. Biol Pharm Bull 28:596–600

    CAS  PubMed  Google Scholar 

  254. Anton R (1988) Flavonoids and traditional medicine. Prog Clin Biol Res 280:423–439

    CAS  PubMed  Google Scholar 

  255. Kim HK, Park HR, Lee JS, Chung TS, Chung HY, Chung J (2007) Down-regulation of iNOS and TNF-alpha expression by kaempferol via NF-kappaB inactivation in aged rat gingival tissues. Biogerontology 8:399–408

    CAS  PubMed  Google Scholar 

  256. Kimbrough C, Chun M, dela Roca G, Lau BH (2002) PYCNOGENOL chewing gum minimizes gingival bleeding and plaque formation. Phytomedicine 9:410–413

    CAS  PubMed  Google Scholar 

  257. Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S (2007) Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 13:688–694

    CAS  PubMed  Google Scholar 

  258. Ekuni D, Tomofuji T, Endo Y, Kasuyama K, Irie K, Azuma T, Tamaki N, Mizutani S, Kojima A, Morita M (2012) Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model. Arch Oral Biol 57:1615–1622. doi:10.1016/j.archoralbio.2012.04.013

    CAS  PubMed  Google Scholar 

  259. Biswas K, Chattopadhyay I, Banerjee RK, Bandyopadhyay U (2002) Biological activities and medicinal properties of neem (Azadirachta indica). Curr Sci 82:1336–1345

    CAS  Google Scholar 

  260. Botelho MA, Santos RA, Martins JG, Carvalho CO, Paz MC, Azenha C, Ruela RS, Queiroz DB, Ruela WS, Marinho G, Ruela FI (2008) Efficacy of a mouthrinse based on leaves of the neem tree (Azadirachta indica) in the treatment of patients with chronic gingivitis: a doubleblind, randomized, controlled trial. J Med Plants Res 2:341–346

    Google Scholar 

  261. Pai MR, Acharya LD, Udupa N (2004) The effect of two different dental gels and a mouthwash on plaque and gingival scores: a six-week clinical study. Int Dent J 54:219–223

    CAS  PubMed  Google Scholar 

  262. Sharma S, Saimbi CS, Koirala B, Shukla R (2008) Effect of various mouthwashes on the levels of interleukin-2 and interferongamma in chronic gingivitis. J Clin Pediatr Dent 32:111–114

    PubMed  Google Scholar 

  263. Vanka A, Tandon S, Rao SR, Udupa N, Ramkumar P (2001) The effect of indigenous Neem Azadirachta indica [correction of (Adirachta indica)] mouth wash on Streptococcus mutans and lactobacilli growth. Indian J Dent Res 12:133–144

    CAS  PubMed  Google Scholar 

  264. Abraham S, Kumar MS, Sehgal PK, Nitish S, Jayakumar ND (2005) Evaluation of the inhibitory effect of triphala on PMN-type matrix metalloproteinase (MMP-9). J Periodontol 76:497–502

    CAS  PubMed  Google Scholar 

  265. Asokan S, Emmadi P, Chamundeswari R (2009) Effect of oil pulling on plaque induced gingivitis: a randomized, controlled, triple-blind study. Indian J Dent Res 20:47–51

    PubMed  Google Scholar 

  266. Sankar D, Sambandam G, Rao R, Pugalendi KV (2005) Modulation of blood pressure, lipid profiles and redox status in hypertensive patients taking different edible oils. Clin Chim Acta 355:97–104

    CAS  PubMed  Google Scholar 

  267. Zhang JZ, Yang XX, Tong YH (1992) Clinical study on using Guchiwan and spiromycin to treat periodontal disease. Chin J Integr Chin Western Med 12:83–85

    Google Scholar 

  268. Song H, Zhao RF, Zhou YJ (1996) The effect of Guchigao on gingival crevicular fluid IL-8 in periodontitis patients. In: Proceedings of the 3rd national conference on integrated Chinese and western medicine stomatology, Xianen, pp 25–28

    Google Scholar 

  269. Mullally BH, James JA, Coulter WA, Linden GJ (1995) The efficacy of a herbal-based toothpaste on the control of plaque and gingivitis. J Clin Periodontol 22:686–689

    CAS  PubMed  Google Scholar 

  270. Van der Weijden GA, Timmer CJ, Timmerman MF, Reijerse E, Mantel MS, van der Velden U (1998) The effect of herbal extracts in an experimental mouthrinse on established plaque and gingivitis. J Clin Periodontol 25:399–403

    PubMed  Google Scholar 

  271. Wu SJ, Ng LT, Lin CC (2004) Antioxidant activities of some common ingredients of traditional Chinese medicine, Angelica sinensis, Lycium barbarum and Poria cocos. Phytother Res 18:1008–1012

    PubMed  Google Scholar 

  272. Chan Y, Lai CH, Yang HW, Lin YY, Chan CH (2003) The evaluation of Chinese herbal medicine effectiveness on periodontal pathogens. Am J Chin Med 31:751–761

    PubMed  Google Scholar 

  273. Asman B, Wijkander P, Hjerpe A (1994) Reduction of collagen degradation in experimental granulation tissue by vitamin E and selenium. J Clin Periodontol 21:45–47

    CAS  PubMed  Google Scholar 

  274. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C (2004) Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and etaanalysis. Lancet 364:1219–1228

    CAS  PubMed  Google Scholar 

  275. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C (2008) Systematic review: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements. Aliment Pharmacol Ther 28:689–703

    CAS  PubMed  Google Scholar 

  276. Dietrich M, Traber MG, Jacques PF, Cross CE, Hu Y, Block G (2006) Does gamma-tocopherol play a role in the primary prevention of heart disease and cancer? A review. J Am Coll Nutr 25:292–299

    Google Scholar 

  277. Halliwell B (2009) The wanderings of a free radical. Free Radic Biol Med 46:531–542. doi:10.1016/j.freeradbiomed.2008.11.008

    CAS  PubMed  Google Scholar 

  278. Hercberg S, Ezzedine K, Guinot C, Preziosi P, Galan P, Bertrais S, Estaquio C, Briançon S, Favier A, Latreille J, Malvy D (2007) Antioxidant supplementation increases the risk of skin cancers in women but not in men. J Nutr 137:2098–2105

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Takaaki Tomofuji, Daisuke Ekuni, Shinsuke Mizutani & Manabu Morita

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  1. Takaaki Tomofuji
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  2. Daisuke Ekuni
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  3. Shinsuke Mizutani
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  4. Manabu Morita
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Correspondence to Takaaki Tomofuji .

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Editors and Affiliations

  1. Department of Preventive Dentistry, Okayama University Graduate School of Medicine and Pharmaceutical Sciences, Okayama, Japan

    Daisuke Ekuni

  2. Dept of Science and Clinical Specialty Odontostomatology & Biochemistry, Polytechnical University of Marche Faculty of Medicine, Ancona, Italy

    Maurizio Battino

  3. Department of Preventive Dentistry, Okayama Univ Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Takaaki Tomofuji

  4. Dept of Oral Biological & Medical Scienc Laboratory of Periodontal Biology, University of British Columbia Faculty of Dentistry, Vancouver, British Columbia, Canada

    Edward E. Putnins

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Tomofuji, T., Ekuni, D., Mizutani, S., Morita, M. (2014). Effects of Antioxidants on Periodontal Disease. In: Ekuni, D., Battino, M., Tomofuji, T., Putnins, E. (eds) Studies on Periodontal Disease. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-9557-4_18

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