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Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease

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Abstract

Chronic inflammation is being shown to be increasingly involved in the onset and development of several pathological disturbances such as arteriosclerosis, obesity, diabetes, neurodegenerative diseases and even cancer. Treatment for chronic inflammatory disorders has not been solved, and there is an urgent need to find new and safe anti-inflammatory compounds. Flavonoids belong to a group of natural substances occurring normally in the diet that exhibit a variety of beneficial effects on health. The anti-inflammatory properties of flavonoids have been studied recently, in order to establish and characterize their potential utility as therapeutic agents in the treatment of inflammatory diseases. Several mechanisms of action have been proposed to explain in vivo flavonoid anti-inflammatory actions, such as antioxidant activity, inhibition of eicosanoid generating enzymes or the modulation of the production of proinflammatory molecules. Recent studies have also shown that some flavonoids are modulators of proinflammatory gene expression, thus leading to the attenuation of the inflammatory response. However, much work remains to be done in order to achieve definitive conclusions about their potential usefulness. This review summarizes the known mechanisms involved in the anti-inflammatory activity of flavonoids and the implications of these effects on the protection against cancer and cardiovascular disease.

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References

  1. Nathan C. Points of control in inflammation. Nature. 2002;420:846–52.

    Article  PubMed  CAS  Google Scholar 

  2. Barton GM. A calculated response: control of inflammation by the innate immune system. J Clin Invest. 2008;118:413–20.

    Article  PubMed  CAS  Google Scholar 

  3. Haddad PS, Azar GA, Groom S, Boivin M. Natural health products, modulation of immune function and prevention of chronic disease. Evid Based Complement Alternat Med. 2005;2:513–20.

    Article  PubMed  Google Scholar 

  4. Yoon J-H, Baek SJ. Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med J. 2005;46:585–96.

    Article  PubMed  CAS  Google Scholar 

  5. Robak J, Gryglewski RJ. Bioactivity of flavonoids. Pol J Pharmacol. 1996;48:555–64.

    PubMed  CAS  Google Scholar 

  6. Russo A, Acquaviva R, Campisi A, Sorrenti V, Di Giacomo C, Virgata G, et al. Bioflavonoids as antiradicals, antioxidants and DNA cleavage protectors. Cell Biol Toxicol. 2000;16:91–8.

    Article  PubMed  CAS  Google Scholar 

  7. Havsteen B. The biochemistry and medical significance of the flavonoids. Pharmacol Ther. 2002;96:67–202.

    Article  PubMed  CAS  Google Scholar 

  8. Rotelli AE, Guardia T, Juárez AO, de la Rocha NE. Comparative study of flavonoids in experimental models of inflammation. Pharmacol Res. 2003;48:601–6.

    Article  PubMed  CAS  Google Scholar 

  9. Wang L, Tu YC, Lian TW, Hung JT, Yen JH, Wu MJ. Distinctive antioxidant and anti-inflammatory effects of flavonols. J Agric Food Chem. 2006;54:9798–804.

    Article  PubMed  CAS  Google Scholar 

  10. Bazzano LA, He J, Ogden LG, Loria CM, Vupputuri S, Myers L, et al. Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic follow-up study. Am J Clin Nutr. 2002;76:93–9.

    PubMed  CAS  Google Scholar 

  11. Joshipura KJ, Hu HB, Manson JE, Stampfer MJ, Rimm EB, Speizer FE, et al. The effect of fruit and vegetable intake on risk for coronary heart disease. Ann Intern Med. 2001;134:1106–14.

    PubMed  CAS  Google Scholar 

  12. Liu S, Manson JE, Lee I-M, Cole SR, Hennekens CH, Willett WC, et al. Fruit and vegetable intake and risk of cardiovascular disease: the Women’s Health Study. Am J Clin Nutr. 2000;72:922–8.

    PubMed  CAS  Google Scholar 

  13. Gandini S, Merzenich H, Robertson C, Boyle P. Meta-analysis of studies on breast cancer risk and diet: the role of fruit and vegetable consumption and the intake of associated micronutrients. Eur J Cancer. 2000;36:636–46.

    Article  PubMed  CAS  Google Scholar 

  14. Kolonel LN, Hankin J, Whittemore AS, Wu AH, Gallagher RP, Wilkens L, et al. Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study. Cancer Epidemiol Biomark Prev. 2000;9:795–804.

    CAS  Google Scholar 

  15. Feskanich D, Ziegler RG, Michaud DS, Giovannucci EL, Speizer FE, Willett WC, et al. Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women. J Natl Cancer Inst. 2000;92:1812–23.

    Article  PubMed  CAS  Google Scholar 

  16. Jiang F, Dusting GJ. Natural phenolic compounds as cardiovascular therapeutics: potential role of their anti-inflammatory effects. Curr Vasc Pharmacol. 2003;1:135–56.

    Article  PubMed  CAS  Google Scholar 

  17. Kim HP, Kun HS, Chang HW, Kang SS. Anti-inflammatory plant flavonoids and cellular action mechanisms. J Pharmacol Sci. 2004;96:229–45.

    Article  PubMed  CAS  Google Scholar 

  18. Beecher GR. Overview of dietary flavonoids: nomenclature, occurrence and intake. J Nutr. 2003;133:3248S–54S.

    PubMed  CAS  Google Scholar 

  19. Paradkar PN, Blum PS, Berhow MA, Bauman H, Kuo SM. Dietary isoflavones suppress endotoxin-induced inflammatory reaction in liver and intestine. Cancer Lett. 2004;215:21–8.

    Article  PubMed  CAS  Google Scholar 

  20. Duan W, Kuo C, Selvarajan S, Chua KY, Bay BH, Wong WS. Anti-inflammatory effects of genistein, a tyrosine kinase inhibitor, on a guinea pig model of asthma. Am J Respir Crit Care Med. 2003;167:185–92.

    Article  PubMed  Google Scholar 

  21. Ruetten HT. Effects of tyrphostins and genistein on the circulatory failure and organ dysfunction caused by endotoxin in the rat: a possible role for protein tyrosine kinase. Br J Pharmacol. 1997;122:59–70.

    Article  PubMed  CAS  Google Scholar 

  22. Verdrengh M, Jonsson IM, Holmdahl R, Tarkowski A. Genistein as an anti-inflammatory agent. Inflamm Res. 2003;52:341–6.

    Article  PubMed  CAS  Google Scholar 

  23. Guardia T, Rotelli AE, Juárez AO, Pelzer LE. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmacol. 2001;56:683–7.

    Article  CAS  Google Scholar 

  24. Nishikawa M. Reactive oxygen species in tumor metastasis. Cancer Lett. 2008;266:53–9.

    Article  PubMed  CAS  Google Scholar 

  25. Willcox JK, Ash SL, Catignani GL. Antioxidants and prevention of chronic disease. Crit Rev Food Sci Nutr. 2004;44:275–95.

    Article  PubMed  CAS  Google Scholar 

  26. Halliwell B. Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med. 1991;91:14S–22S.

    Article  PubMed  CAS  Google Scholar 

  27. Sies H. Oxidative stress: from basic research to clinical application. Am J Med. 1991;91:31S–8S.

    Article  PubMed  CAS  Google Scholar 

  28. de Groot H, Rauen U. Tissue injury by reactive oxygen species and the protective effects of flavonoids. Fundam Clin Pharmacol. 1998;12:249–55.

    PubMed  Google Scholar 

  29. Fantone JC, Ward PA. Role of oxygen-derived free-radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol. 1982;107:395–418.

    PubMed  CAS  Google Scholar 

  30. Hart BA, Ram T, Vai Ching IP, Van DI H, Labodie RP. How flavonoids inhibit the generation of luminal-dependent chemiluminescence by activated human neutrophils. Chem Biol Interact. 1990;73:323–35.

    Article  Google Scholar 

  31. Limasset B, Le Doucen C, Dore J-C, Ojasoo T, Damon M, De Paulet AC. Effects of flavonoid on the release of reactive oxygen species by stimulated human neutrophils. Multivariate analysis of structure activity relationships (SAR). Biochem Pharmacol. 1993;46:1257–71.

    Article  PubMed  CAS  Google Scholar 

  32. Jung HA, Jung MJ, Kim JY, Chung HY, Choi JS. Inhibitory activity of flavonoids from Prunus davidiana and other flavonoids on total ROS and hydroxyl radical generation. Arch Pharm Res. 2003;26:809–15.

    Article  PubMed  CAS  Google Scholar 

  33. Korkina LG, Afanas’ev IB. Antioxidant and chelating properties of flavonoids. Adv Pharmacol. 1997;38:151–63.

    Article  PubMed  CAS  Google Scholar 

  34. Haenen GR, Paquay JB, Korthouwer RE, Bast A. Peroxynitrite scavenging by flavonoids. Biochem Biophys Res Commun. 1997;236:591–3.

    Article  PubMed  CAS  Google Scholar 

  35. Lai HH, Yen GC. Inhibitory effect of isoflavones on peroxynitrite-mediated low density lipoprotein oxidation. Biosci Biotechnol Biochem. 2002;66:22–8.

    Article  PubMed  CAS  Google Scholar 

  36. Hanaski Y, Ogawa S, Fukui S. The correlation between active oxygen scavenging and antioxidative effects of flavonoids. Free Radic Biol Med. 1994;16:845–50.

    Article  Google Scholar 

  37. Keery NL, Abbey M. Red wine and fractionated phenolic compounds prepared from red wine inhibit low density lipoprotein oxidation in vitro. Atherosclerosis. 1997;135:93–102.

    Article  Google Scholar 

  38. Shutenko Z, Henry Y, Pinard E, Seylaz J, Potier P, Berthet F, et al. Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion. Biochem Pharmacol. 1999;57:199–208.

    Article  PubMed  CAS  Google Scholar 

  39. Van Acker SA, Tromp MN, Haenen GR, Van der Vijgh WJ, Bast A. Flavonoids as scavengers of nitric oxide radical. Biochem Biophys Res Commun. 1995;214:755–9.

    Article  PubMed  Google Scholar 

  40. Yen GC, Lai HH. Inhibition of reactive nitrogen species effects in vitro and in vivo isoflavones and soy-based food extracts. J Agric Food Chem. 2003;51:7892–900.

    Article  PubMed  CAS  Google Scholar 

  41. Sarkar A, Bhaduri A. Black tea is a powerful chemopreventor of reactive oxygen and nitrogen species: comparison with its individual constituents and green tea. Biochem Biophys Res Commun. 2001;284:173–8.

    Article  PubMed  CAS  Google Scholar 

  42. Chan MM, Fong D, Ho CT, Huang HT. Inhibition of inducible nitric oxide synthase gene expression and enzyme activity by epigallocatechin gallate, a natural product from green tea. Biochem Pharmacol. 1997;54:1281–6.

    Article  PubMed  CAS  Google Scholar 

  43. Hong J, Smith TJ, Ho CT, August DA, Yang CS. Effects of purified green and black tea polyphenols on cyclooxygenase and lipoxygenase-dependent metabolism of arachidonic acid in human colon mucosa and colon tumor tissues. Biochem Pharmacol. 2001;62:1175–83.

    Article  PubMed  CAS  Google Scholar 

  44. Agarwal SK, Agarwal R, Wood GS, Mukhtar H. Protection against ultraviolet B radiation induced effects in the skin of SKH-1 hairless mice by a polyphenolic fraction isolated from green tea. Photochem Photobiol. 1993;58:695–700.

    Article  PubMed  CAS  Google Scholar 

  45. Laughton MJ, Evans PJ, Moroney MA, Hoult JR, Halliwell B. Inhibition of mammalian 5-lipoxygenase and cyclooxygenase by flavonoids and phenolic dietary additives. Relationship to antioxidant activity to iron-reducing ability. Biochem Pharmacol. 1991;42:1673–81.

    Article  PubMed  CAS  Google Scholar 

  46. Nagao A, Seki M, Kobayashi H. Inhibition of xanthine oxidase by flavonoids. Biosci Biotechnol Biochem. 1999;63:1787–90.

    Article  PubMed  CAS  Google Scholar 

  47. Jolly CA. Diet manipulation and prevention of aging, cancer and autoimmune disease. Curr Opin Clin Nutr Metab Care. 2005;8:382–7.

    PubMed  CAS  Google Scholar 

  48. Hance KW, Rogers CJ, Hursting SD, Greiner JW. Combination of physical activity, nutrition, or other metabolic factors and vaccine response. Front Biosci. 2007;12:4997–5029.

    Article  PubMed  CAS  Google Scholar 

  49. Volman JJ, Ramakers JD, Plat J. Dietary modulation of immune function by beta-glucans. Physiol Behav. 2008;94:276–84.

    Article  PubMed  CAS  Google Scholar 

  50. Middleton E, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacol Rev. 2000;52:673–751.

    PubMed  CAS  Google Scholar 

  51. Rudd CE. CD4, CD8 and the TCR-CD3 complex: a novel class of protein-tyrosine kinase receptor. Immunol Today. 1990;11:400–6.

    Article  PubMed  CAS  Google Scholar 

  52. Mustelin T, Abraham RT, Rudd CE, Alonso A, Merlo JJ. Protein tyrosine phosphorylation in T cell signaling. Front Biosci. 2002;1:918–69.

    Article  Google Scholar 

  53. Campbell M-A, Sefton CM. Protein tyrosine phosphorylation is induced in murine B lymphocytes in response to stimulation with anti-immunoglobulin. EMBO J. 1990;9:2125–31.

    PubMed  CAS  Google Scholar 

  54. Geng JY, Zhang B, Lotz M. Protein tyrosine kinase activation is required for lipopolysaccharide induction of cytokines in human blood monocytes. J Immunol. 1993;151:6692–700.

    PubMed  CAS  Google Scholar 

  55. Akiyama T, Ishida J, Nakagawa S, Ogawara H, Wanatabe S, Itoh N, et al. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem. 1987;262:5592–5.

    PubMed  CAS  Google Scholar 

  56. Trevillyan JM, Lu YL, Atluru D, Phillips CA, Bjorndahl JM. Differential inhibition of T cell receptor signal transduction and early activation events by selective inhibitor of protein-tyrosine kinase. J Immunol 1990;145.

  57. Shapira L, Takashiba S, Champagne C, Amar S, Van Dyke TE. Involvement of protein kinase C and protein tyrosine kinase in lipopolysaccharide-induced TNF-alpha and IL-1 beta production by human monocytes. J Immunol. 1994;153:1818–24.

    PubMed  CAS  Google Scholar 

  58. Atluru D, Jackson TM, Atluru S. Genistein, a selective protein tyrosine kinase inhibitor, inhibits interleukin-2 and leukotriene B4 production from human mononuclear cells. Clin Immunol Immunopathol. 1991;59:379–87.

    Article  PubMed  CAS  Google Scholar 

  59. Comalada M, Ballester I, Bailón E, Sierra S, Xaus J, Gálvez J, et al. Inhibition of pro-inflammatory markers in primary bone marrow-derived mouse macrophages by naturally occurring flavonoids: analysis of the structure-activity relationship. Biochem Pharmacol. 2006;72:1010–21.

    Article  PubMed  CAS  Google Scholar 

  60. Bennet JP, Gomperst BD, Wollenweber E. Inhibitory effects of natural flavonoids on secretion from mast cells and neutrophils. Arzneimittelforschung. 1981;31:433–7.

    Google Scholar 

  61. Berton G, Schneider C, Romeo D. Inhibition by quercetin of activation of polymorphonuclear leukocyte functions. Stimulus-specific effects. Biochim Biophys Acta. 1980;595:47–55.

    Article  PubMed  CAS  Google Scholar 

  62. Kanashiro A, Souza JG, Kabeya LM, Azzolini AE, Lucisano-Valim YM. Elastase release by stimulet neutrophils inhibited by flavonoids: importance of the catechol group. Z Naturforsch 2007;62.

  63. Selloum L, Bouriche H, Tigrine C, Boudoukha C. Anti-inflammatory effect of rutin on rat paw oedema, and on neutrophils chemotaxis and degranulation. Exp Toxicol Pathol. 2003;54:313–8.

    Article  PubMed  CAS  Google Scholar 

  64. Tordera M, Ferrándiz ML, Alcaraz MJ. 1994. Influence of anti-inflammatory flavonoids on degranulation and arachidonic acid release in rat neutrophils. Z Naturforsch [C]. 49:235–40.

  65. Chang HW, Baek SH, Chung KW, Son KH, Kim HP, Kang SS. Inactivation of phospholipase A2 by naturally ocurring biflavonoid, ochnaflavone. Biochem Biophys Res Commun. 1994;205:843–9.

    Article  PubMed  CAS  Google Scholar 

  66. Gil B, Sanz MJ, Terencio MC, Giunasegaran R, Playa M, Alcaraz MJ. Morelloflavone, a novel biflavonoid inhibitor of human secretory phospholipase a2 with anti-inflammatory activity. Biochem Pharmacol. 1997;53:733–40.

    Article  PubMed  CAS  Google Scholar 

  67. Chi YS, Jong HG, Son KH, Chang HW, Kang SS, Kim HP. Effects of naturally prenylated flavonoids on enzymes metabolizing arachidonic acid: cyclooxygenases and lipoxygenases. Biochem Pharmacol. 2001;62:1185–91.

    Article  PubMed  CAS  Google Scholar 

  68. Kobuchi H, Virgili F, Packer L. Assay of inducible form of nitric oxide synthase activity: effect of flavonoids and plant extracts. Methods Enzymol. 1999;301:504–13.

    Article  PubMed  CAS  Google Scholar 

  69. Cheon BS, Kim YH, Son KS, Chang HW, Kang SS, Kim HP. Effects of prenilated flavonoids and biflavonoids on lipopolysaccharide-induced nitric oxide production from the mouse macrophage cell line RAW 264.7. Planta Med 2000; 66:596–600.

    Google Scholar 

  70. Lee T-P, Matteliano ML, Middleton E. Effect of quercitin on human polymorphonuclear leukocyte lysosomal enzyme release and phospholipid metabolism. Life Sci. 1982;31:2765–74.

    Article  PubMed  CAS  Google Scholar 

  71. Lanni C, Becker EL. Inhibition of neutrophil phospholipase A2 by p-bromophenylacyl bromide, nordihydroguaiaretic acid, 5,8,11,14-eicosatetrayenoic acid and quercetin. Inst Archs Allergy Appl Immunol. 1985;76:214–7.

    CAS  Google Scholar 

  72. Lindahl M, Tagesson C. Selective inhibition of group II phospholipase A2 by quercetin. Inflammation. 1993;17:573–82.

    Article  PubMed  CAS  Google Scholar 

  73. Süleyman H, Demircan B, Karagöz Y. Anti-inflammatory and side effects of cyclooxygenase inhibitors. Pharmacol Rep. 2007;59:247–58.

    PubMed  Google Scholar 

  74. Khanapure SP, Garvey DS, Janero DR, Letts LG. Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers. Curr Top Med Chem. 2007;7:311–40.

    Article  PubMed  CAS  Google Scholar 

  75. Kuhn H. Biologic relevance of lipoxygenase isoforms in atherogenesis. Expert Rev Cardiovasc Ther. 2005;3:1099–110.

    Article  PubMed  CAS  Google Scholar 

  76. Bauman J, von Bruchhausen FV, Wurm G. Flavonoids and related compounds as inhibitors of arachidonic acid peroxidation. Prostaglandins. 1980;20:627–39.

    Article  Google Scholar 

  77. Landorfi R, Mower RL, Steiner M. Modification of platelet function and arachidonic acid metabolism by biflavonoids. Structure–activity relations. Biochem Pharmacol. 1984;33:1525–30.

    Article  Google Scholar 

  78. Wakabayashi I, Yasui K. Wogonin inhibits inducible prostaglandin E2 production in macrophages. Eur J Pharmacol. 2000;406:477–81.

    Article  PubMed  CAS  Google Scholar 

  79. Chi YS, Cheon BS, Kim HP. Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxigenase-2 and the induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 264.7 cells. Biochem Pharmacol 2001; 61:1195–203.

    Google Scholar 

  80. You KM, Jong HG, Kim HP. Inhibition of cyclooxygenase/lipoxygenase from human platelets by polyhydroxylated/methoxylated flavonoids isolated from medicinal plants. Arch Pharm Res. 1999;22:18–24.

    Article  PubMed  CAS  Google Scholar 

  81. Chung CP, Park JB, Bae KH. Pharmacological effects of methanolic extract from root of Scutellaria baicalensis and its flavonoids on human gingival fibroblasts. Planta Med. 1995;61:150–3.

    Article  PubMed  CAS  Google Scholar 

  82. Mashesha HG, Singh SA, Rao AR. Inhibition of lipoxygenase by soy isoflavones: Evidence of isoflavones as redox inhibitors. Arch Biochem Biophys. 2007;461:176–85.

    Article  CAS  Google Scholar 

  83. Hong J, Bose M, Ju J, Ryu JH, Chen X, Sang S, et al. Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivates: effects on cytosolic phospholipase A2, cyclooxygenases and 5-lipoxygenase. Carcinogenesis. 2004;25:1671–9.

    Article  PubMed  CAS  Google Scholar 

  84. Moncada S, Palmer MJ, Higgs DA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1992;43:109–42.

    Google Scholar 

  85. Liang YC, Huang YT, Tsai SH, Lin-Shiau SY, Chen CF, Lin JK. 1999. Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis. 20:1945–52.

    Google Scholar 

  86. Autore G, Rastrelli L, Lauro MR, Marzocco S, Sorrentino R, Pinto A, et al. Inhibition of nitric oxide synthase expression by a methanolic extract of Crescencia alata and its derived flavonols. Life Sci. 2001;70:523–34.

    Article  PubMed  CAS  Google Scholar 

  87. Kim HK, Cheon BS, Kim YH, Kim SY, Kim HP. Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure–activity relationships. Biochem Pharmacol 1999;58.

  88. Raso GM, Meli R, Di Carlo G, Pacilio M, Di Carlo R. Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by flavonoids in macrophage J774A.1. Life Sci 2001; 68:921–31.

    Google Scholar 

  89. Sheu F, Lai HH, Yen GC. Suppression of effect of soy isoflavones on nitric oxide production in RAW 264.7 macrophages. J Agric Food Chem. 2001;49:1767–72.

    Article  PubMed  CAS  Google Scholar 

  90. Chen YC, Shen SC, Lee WR, Hou WC, Yang LL, Lee TJ. Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced inducible NOS and cyclooxygenase-2 gene expression by rutin, quercetin, and quercetin pentaacetate in RAW 264.7 macrophages. J Cell Biochem. 2001;82:537–48.

    Article  PubMed  CAS  Google Scholar 

  91. Chen XW, FGraner SC, Anderson JJ. Isoflavones regulate interleukin-6 and osteoprotegerin synthesis during osteoblast cell differentiation via an estrogen-receptor-dependent pathway. Biochem Biophys Res Commun. 2002;295:417–22.

    Article  PubMed  CAS  Google Scholar 

  92. Ding SZ, Cho CH, Lam SK. Regulation of interleukin-6 production in a human gastric epithelial cell line MKN-28. Cytokine. 2000;12:1129–35.

    Article  PubMed  CAS  Google Scholar 

  93. Xagorari A, Papapetropoulos A, Mauromatis A, Economou M, Fostis T, Roussos C. Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. J Pharmacol Exp Therap. 2001;296:181–7.

    CAS  Google Scholar 

  94. Cho JY, Kim PS, Park JB, Yoo ES, Baik KU, Kim YK, et al. Inhibitor of tumor necrosis factor-alpha production in lipopolysaccharide-stimulated RAW264.7 cells from Amorpha fruticosa. J Ethnopharmacol. 2000;70:127–33.

    Article  PubMed  CAS  Google Scholar 

  95. Cho SY, Park SJ, Kwon MJ, Jeong TS, Bok SH, Choi WY, et al. Quercetin suppresses proinflammatory cytokines production through MAP kinases and NF-kappaB pathway in lipopolysaccharide-stimulated macrophage. Mol Cell Biochem. 2003;243:153–60.

    Article  PubMed  CAS  Google Scholar 

  96. Van Dien M, Takahashi K, Mu MM, Koide N, Sugiyama T, Mori I, et al. Protective effect of wogonin on endotoxin-induced lethal shock in d-galactosamine-sensitized mice. Microbiol Immunol. 2001;45:751–6.

    PubMed  Google Scholar 

  97. Santangelo C, Vari R, Scazzocchio B, Di Benedetto R, Filesi C, Masella R. Polyphenols, intracellular signalling and inflammation. Ann Ist Super Sanita. 2007;43:394–405.

    PubMed  CAS  Google Scholar 

  98. Mutoh M, Takahashi M, Fukuda K, Komatsu H, Enya T, Matsushima-Hibiya Y, et al. Suppression by flavonoids of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells: structure–activity relationship. Jpn J Cancer Res. 2000;91:686–91.

    PubMed  CAS  Google Scholar 

  99. Hooshmand S, Soung do Y, Lucas EA, Madihally SV, Levenson CW, Arjmandi BH. Genistein reduces the production of proinflammatory molecules in human chondrocytes. J Nutr Biochem 2007; 18:609–14.

    Google Scholar 

  100. Chen CY, Peng WH, Tsai KD, Hsu SL. Luteolin suppresses inflammation-associated gene expression by blocking NF-kappaB and AP-1 activation pathway in mouse alveolar macrophages. Life Sci. 2007;81:1602–14.

    Article  PubMed  CAS  Google Scholar 

  101. Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E. Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediat Inflamm 2007; 2007:45673.

  102. Su B, Karin M. Mitogen-activated protein kinase cascades and regulation of gene expression. Curr Opin Immunol. 1996;8:402–11.

    Article  PubMed  CAS  Google Scholar 

  103. Dong C, Davis RJ, Flavell RA. MAP kinases in the immune response. Annu Rev Immunol. 2002;20:55–72.

    Article  PubMed  CAS  Google Scholar 

  104. Herlaar E, Brown Z. MAPK signaling cascades in inflammatory disease. Mol Med Today. 1999;5:439–47.

    Article  PubMed  CAS  Google Scholar 

  105. Ono K, Han J. The p38 signal transduction pathway: activation and function. Cell Signal. 2000;12:1–13.

    Article  PubMed  CAS  Google Scholar 

  106. Branger J, van den Blink B, Weijer S, Madwed J, Bos CL, Gupta A, et al. The p38 signal transduction pathway: activation and function. J Immunol. 2002;168:4070–7.

    PubMed  CAS  Google Scholar 

  107. Nieminen R, Leinonen S, Lahti A, Vuolteenaho K, Jalonen U, Kankaanranta H, et al. Inhibitors of mitogen-activated protein kinases downregulate COX-2 expression in human chondrocytes. Mediat Inflamm. 2005;5:249–55.

    Article  CAS  Google Scholar 

  108. Feng GJ, Goodridge HS, Harnett MM, Wei SQ, Nikolaev AV, Higson AP, et al. Extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases differentially regulate the lipopolysaccharide-mediated induction of inducible nitric oxide synthase and IL-12 in macrophages: Leishmania phosphoglycans subvert macrophage IL-12 production by targeting ERK MAP kinase. J Immunol 1999; 163:6403–6412.

    Google Scholar 

  109. Xagorari A, Roussos C, Papapetropoulos A. Inhibition of LPS-stimulated pathways in macrophages by the flavonoid luteolin. Br J Pharmacol. 2002;136:1058–64.

    Article  PubMed  CAS  Google Scholar 

  110. Means TK, Pavlovich RP, Roca D, Vermuelen MW, Fenton MJ. Activation of TNF-alpha transcription utilizes distinct MAP kinase pathways in different macrophage populations. J Leuk Biol. 2000;67:885–93.

    CAS  Google Scholar 

  111. Baldassare JJ, Bi Y, Bellone CJ. The role of p38 mitogen-activated protein kinase in IL-1 beta transcription. J Immunol. 1999;162:5367–73.

    PubMed  CAS  Google Scholar 

  112. van den Blink B, Juffermans NP, ten Hove T, Schultz MJ, van Deventer SJ, van der Poll T, et al. p38 mitogen-activated protein kinase inhibition increases cytokine release by macrophages in vitro and during infection in vivo. J Immunol. 2001;166:582–7.

    PubMed  Google Scholar 

  113. Kontoyiannis D, Pasparakis M, Pizarro TT, Cominelli F, Kollias G. Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut associated immunopathologies. Immunity. 1999;10:387–98.

    Article  PubMed  CAS  Google Scholar 

  114. Carter AB, Monick MM, Hunninghake GW. Both Erk and p38 kinases are necessary for cytokine gene transcription. Am J Resp Cell Mol Biol. 1999;20:751–8.

    CAS  Google Scholar 

  115. Pereira SG, Oakley F. Nuclear factor-kappaB1: regulation and function. Int J Biochem Cell Biol. 2008;40:1425–30.

    Article  PubMed  CAS  Google Scholar 

  116. Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336:1066–71.

    Article  PubMed  CAS  Google Scholar 

  117. Park E, Kum S, Wang C, Park SY, Kim BS, Schuller-Levis G. Anti-inflammatory activity of herbal medicines: inhibition of nitric oxide production and tumor necrosis factor-alpha secretion in an activated macrophage-like cell line. Am J Chin Med. 2005;33:415–24.

    Article  PubMed  Google Scholar 

  118. Kotanidou A, Xagorari A, Bagli E, Kitsanta P, Fostis T, Papapetropoulos A, et al. Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of proinflammatory molecules in mice. Am J Resp Crit Care Med. 2002;165:818–23.

    PubMed  Google Scholar 

  119. Kim JS, Jobin C. The flavonoid luteolin prevents lipopolysaccharide-induced NK-kappaB signaling and gene expression by blocking I-kappaB kinase activity in intestinal epithelial cells and bone-marrow derived dendritic cells. Immunology. 2005;115:373–87.

    Article  CAS  Google Scholar 

  120. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.

    Article  PubMed  CAS  Google Scholar 

  121. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.

    Article  PubMed  CAS  Google Scholar 

  122. Shacter E, Weitzman SA. Chronic inflammation and cancer. Oncology. 2002;16:217–26.

    PubMed  Google Scholar 

  123. Fox JG, Wang TC. Inflammation, atrophy and gastric cancer. J Clin Invest. 2007;117:60–9.

    Article  PubMed  CAS  Google Scholar 

  124. Dobrovolskaia MA, Kozlov SV. Inflammation and cancer: when NF-kappaB amalgamates the perilous partnership. Curr Cancer Drug Targets. 2005;5:325–544.

    Article  PubMed  CAS  Google Scholar 

  125. YC Xiao H. Combination regimen with statins and NSAIDs: a promising strategy for cancer chemoprevention. Int J Cancer. 2008;123:983–90.

    Article  CAS  Google Scholar 

  126. Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer cell. 2005;7:211–7.

    Article  PubMed  CAS  Google Scholar 

  127. de Visser KE, Coussens LM. The inflammatory tumor microenvironment and its impact on cancer development. Contrib Microbiol. 2006;13:118–37.

    Article  PubMed  Google Scholar 

  128. Rivoli E, Norat T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am J Clin Nutr. 2003;78:559S–69S.

    Google Scholar 

  129. Vainio H, Weiderpass E. Fruit and vegetables in cancer prevention. Nutr Cancer. 2006;54:111–42.

    Article  PubMed  CAS  Google Scholar 

  130. Yang CS, Landau JM, Huang MT, Newmark HL. Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu Rev Nutr. 2001;21:381–406.

    Article  PubMed  CAS  Google Scholar 

  131. Le Marchand L. Cancer preventive effects of flavonoids—a review. Biomed Pharmacother. 2002;56:269–301.

    Article  Google Scholar 

  132. Wang ZY, Huang HT, Lou YR, Xie JG, Reuhl KR, Newmark HL, et al. Inhibitory effects of black tea, green tea, decaffeinated black tea, and decaffeinated green tea on ultraviolet B light-induce skin carcinogenesis in 7,12-dimethylbenz(a)anthracene-initiated SKH-1 mice. Cancer Res. 1994;52:1162–70.

    Google Scholar 

  133. Lu YP, Lou YR, Lin Y, Shih WJ, Huang MT, Yang CS, et al. Inhibitory effects of orally administered green tea, black tea, and caffeine on skin carcinogenesis in mice previously treated with ultraviolet light (light-risk mice): relationship to decreased tissue fat. Cancer Res. 2001;61:5002–9.

    PubMed  CAS  Google Scholar 

  134. Yamane T, Hagiwara N, Tateishi M, Akachi S, Kim M, Okuzumi J, et al. Inhibition of azoxymethane-induced colon carcinogenesis in rat by green tea polyphenol fraction. Jpn J Cancer Res. 1991;82:1336–9.

    PubMed  CAS  Google Scholar 

  135. Kawabata K, Tanaka T, Honjo S, Kakumoto M, Hara A, Makita H, et al. Chemopreventive effects of dietary flavonoid morin on chemically induced rat tongue carcinogenesis. Int J Cancer. 1999;83:381–6.

    Article  PubMed  CAS  Google Scholar 

  136. Deschner EE, Ruperto J, Wong G, Newmark HL. Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis. 1991;12:1193–6.

    Article  PubMed  CAS  Google Scholar 

  137. Messina MJ, Persky V, Setchell KD, Barnes S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer. 1994;21:113–31.

    Article  PubMed  CAS  Google Scholar 

  138. Wietrzyk J, Opolski A, Madej J, Radzikowski C. Antitumor and antimetastatic effect of genistein alone of combined with cyclophosphamide in mice transplanted with various tumors depends on the route of tumor transplantation. In Vivo. 2000;14:357–62.

    PubMed  CAS  Google Scholar 

  139. Pollard M, Suckow MA. Dietary prevention of hormone refractory prostate cancer in Lobund–Wistar rats: a review of studies in a relevant animal model. Comp Med. 2006;56:461–7.

    PubMed  CAS  Google Scholar 

  140. Birt DF, Hendrich S, Wang W. Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol Therapeutics. 2001;90:157–77.

    Article  CAS  Google Scholar 

  141. Fresco P, Borges F, Diniz C, Marques MPM. New insights on the anticancer properties of dietary polyphenols. Med Res Rev. 2006;26:747–66.

    Article  PubMed  CAS  Google Scholar 

  142. Kamaraj S, Vinodhkumar R, Anandakumar P, Jagan S, Ramakrishnan G, Devaki T. The effects of quercetin on antioxidant status and tumor markers in the lung and serum of mice treated with benzo(a)pyrene. Biol Pharm Bull 2007;30:2268–73.

    Article  PubMed  CAS  Google Scholar 

  143. D’Alessandro TL, Prasain J, Benton MR, Botting N, Moore R, Darley-Usmar V, et al. Polyphenols, inflammatory response, and cancer prevention: chlorination of isoflavones by human neutrophils. J Nutr 2003;133:3773S–7S.

    Google Scholar 

  144. Vanamala J, Leonardi T, Patil BS, Taddeo SS, Murphy ME, Pike LM, et al. Suppression of colon carcinogenesis by bioactive compounds in grapefruit. Carcinogenesis 2006;27:1257–65.

    Article  PubMed  CAS  Google Scholar 

  145. Cai H, Al-Fayez M, Tunstall RG, Platton S, Greaves P, Steward WP, et al. The rice bran constituent tricin potently inhibits cyclooxygenase enzymes and interferes with intestinal carcinogenesisin Apc Min mice. Mol Cancer Ther 2005;4:1287–92.

    Article  PubMed  CAS  Google Scholar 

  146. Horia E, Watkins BA. Complementary actions of docosahexanoic acid and genistein on COX-2, PGE2, and invasiveness in MDA-MB-231 breast cancer cells. Carcinogenesis 2007;28:809–15.

    Article  PubMed  CAS  Google Scholar 

  147. Van Dross RT, Hong X, Essengue S, Fischer SM, Pelling JC. Modulation of UVB-induced and basal cyclooxygenase-2 (COX-2) expression by apigenin in mouse keratinocytes: role of USF transcription factors. Mol Carcinog 2007;46:303–14.

    Article  PubMed  CAS  Google Scholar 

  148. Lin JK, Chen YC, Huang YT, Lin-Shiau SY. Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin. J Cell Biochem 1997;Suppl 28–29:39–48.

  149. Lee LT, Huang YT, Hwang JJ, Lee PP, Ke FC, Nair MP, et al. Blockade of the epidrmal growth factor receptor tyrosine kinase activity by quercetin and luteolin leads to growth inhibition and apoptosis of pancreatic tumor cells. Anticancer Res 2002;22:1615–27.

    PubMed  CAS  Google Scholar 

  150. Khan N, Afaq F, Mukhtar H. Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal 2008;10:475–510.

    Article  PubMed  CAS  Google Scholar 

  151. Shukla S, Gupta S. Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retinoblastoma dephosphorylation in human prostate cancer cells. Cell cycle 2007;6:1102–14.

    PubMed  CAS  Google Scholar 

  152. Yin F, Giuliano AE, Law RE, Van Herle AJ. Apigenin inhibits growth and induces G2/M arrest by modulating cyclin-CDK regulators and ERK MAP kinase activation in breast carcinoma cells. Anticancer Res 2001;21:413–20.

    PubMed  CAS  Google Scholar 

  153. Manna SK, Aggarwal RS, Sethi G, Agarwall BB, Ramesh GT. Morin (3,5,7,2′,4′-pentahydroxyflavone) abolishes nuclear factor-kappa B activation induced by various carcinogens and inflammatory stimuli, leading to suppression of nuclear factor-kappaB-regulated gene expression and up-regulation of apoptosis. Clin Cancer Res 2007;8:2290–7.

    Google Scholar 

  154. Li Y, Sarkar FH. Inhibition of nuclear factor kappaB activation in PC3 cells by genistenin is mediated via Akt signalling pathway. Clin Cancer Res 2002;8:2369–77.

    PubMed  CAS  Google Scholar 

  155. Davis JN, Kucuk O, Sarkar FH. Genistein inhibits NF-kappaB activation in prostate cancer cells. Nutr Cancer 1999;35:167–74.

    Article  PubMed  CAS  Google Scholar 

  156. Rahman KW, Li Y, Sarkar FH. Inactivation of Akt and NF-kappaB play important roles during indole-3-carbinol-induced apoptosis in breast cancer cells. Nutr Cancer 2004;48:84–94.

    Article  PubMed  CAS  Google Scholar 

  157. Shukla S, Gupta S. Suppression of constitutive and tumor necrosis factor alpha-induced nuclear factor (NF)-kappaB activation and induction of apoptosis by apigenin in human prostate carcinoma PC-3 cells: correlation with down-regulation of NF-kappaB-responsive genes. Clin Cancer Res 2004;10:3169–78.

    Article  PubMed  CAS  Google Scholar 

  158. Kelloff GJ. Perspectives on cancer chemoprevention research and drug development. Adv Cancer Res. 2000;78:199–334.

    Article  PubMed  CAS  Google Scholar 

  159. Libby P. Inflammation and atherosclerosis. Nature. 2002;420:868–74.

    Article  PubMed  CAS  Google Scholar 

  160. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105:1135–43.

    Article  PubMed  CAS  Google Scholar 

  161. Dong ZM, Chapman SM, Brown AA, Frenette PS, Hynes RO, Wagner DD. The combined role of P- and E-selectins in atherosclerosis. J Clin Invest. 1998;102:145–52.

    Article  PubMed  CAS  Google Scholar 

  162. Libby P. Changing concepts of atherogenesis. J Intern Med. 2000;247:349–58.

    Article  PubMed  CAS  Google Scholar 

  163. Bonomini F, Tengattin IS, Fabiano A, Bianchi R, Rezzani R. Atherosclerosis and oxidative stress. Histol Histopathol. 2008;23:381–90.

    PubMed  CAS  Google Scholar 

  164. Hofnagel O, Luechtenborg B, Weissen-Plenz G, Robenek H. Statins and foam cell formation: impact on LDL oxidation and uptake of oxidized lipoproteins via scavenger receptors. Biochim Biophys Acta. 2007;1771:1117–24.

    PubMed  CAS  Google Scholar 

  165. Charo IF, Taubman MB. Chemokines in the pathogenesis of vascular disease. Circ Res. 2004;95:858–66.

    Article  PubMed  CAS  Google Scholar 

  166. Szekanecz Z. Pro-inflammatory cytokines in atherosclerosis. Isr Med Assoc J. 2008;10:529–30.

    PubMed  Google Scholar 

  167. Ohsuzu F. The roles of cytokines, inflammation and immunity in vascular diseases. J Atheroscler Thromb. 2004;11:313–21.

    PubMed  CAS  Google Scholar 

  168. Mallat Z, Gojova A, Marchiol-Fournigault C, Esposito B, Kamaté C, Merval R, et al. Inhibition of transforming growth factor-beta signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice. Circ Res. 2001;89:930–4.

    Article  PubMed  CAS  Google Scholar 

  169. Kaperonis EA, Liapis CD, Kakisis JD, Dimitroulis D, Papavassiliou VG. Inflammation and atherosclerosis. Eur J Vasc Endovasc Surg 2006;31.

  170. Schonbeck U, Mach F, Sukhova GK, Murphy C, Bonnefoy JY, Fabunmi RP, et al. Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes: a role for CD40 signaling in plaque rupture? Circ Res. 1997;81:448–54.

    PubMed  CAS  Google Scholar 

  171. Wu L, Fan J, Matsumoto S, Watanabe T. Induction and regulation of matrix metalloproteinase-12 by cytokines and CD40 signaling in monocyte/macrophages. Biochem Biophys Res Commun. 2000;269:808–15.

    Article  PubMed  CAS  Google Scholar 

  172. Zebrack JS, Anderson JL. Role of inflammation in cardiovascular disease: how to use C-reactive protein in clinical practice. Prog Cardivasc Nurs. 2002;17:174–85.

    Article  Google Scholar 

  173. Shishehbor MH, Bhatt DL. Inflammation and atherosclerosis. Curr Atheroscler Rep. 2004;6:131–9.

    Article  PubMed  Google Scholar 

  174. Hertog MGL, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med. 1995;155:381–6.

    Article  PubMed  CAS  Google Scholar 

  175. Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ. 1996;312:478–81.

    PubMed  CAS  Google Scholar 

  176. Knekt P, Kumpulainen J, Järvinen R, Rissanen H, Heliövaara M, Reunanen A, et al. Flavonoid intake and risk of chronic diseases. Am J Clin Nutr. 2002;76:560–8.

    PubMed  CAS  Google Scholar 

  177. Yochum L, Kushi LH, Meyer K, Folsom AR. Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women. Am J Epidemiol. 1999;149:943–9.

    PubMed  CAS  Google Scholar 

  178. Rimm E, Katan M, Ascherio A, Stampfer MJ, Willett WC. Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann Intern Med. 1996;125:384–9.

    PubMed  CAS  Google Scholar 

  179. Sesso HD, Gaziano JM, Liu S, Buring JE. Flavonoid intake and the risk of cardiovascular disease in women. Am J Clin Nutr. 2003;77:1400–8.

    PubMed  CAS  Google Scholar 

  180. Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong CP, Nettleton JA, et al. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr. 2007;85:895–909.

    PubMed  CAS  Google Scholar 

  181. Hooper L, Kroon PA, Rimm EB, Cohn JS, Harvey I, Le Cornu KA, et al. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2008;88:38–50.

    PubMed  CAS  Google Scholar 

  182. Mukamal KJ, Maclure M, Muller JE, Sherwood JB, Mittleman MA. Tea consumption and mortality after acute myocardial infarction. Circulation. 2002;105:2476–81.

    Article  PubMed  Google Scholar 

  183. Wiswedel I, Hirsch D, Kropf S, Gruening M, Pfister E, Schewe T, et al. Flavanol-rich cocoa drink lowers plasma F(2)-isoprostane concentrations in humans. Free Radic Biol Med. 2004;37:411–21.

    Article  PubMed  CAS  Google Scholar 

  184. Droke EA, Hager KA, Lerner MR, Lightfoot SA, Stoecker BJ, Brackett DJ, et al. Soy isoflavone averts chronic inflammation-induced bone loss and vascular disease. J Inflamm 2007;4:17.

    Google Scholar 

  185. Lotito SB, Frei B. Dietary flavonoids attenuate tumor necrosis factor alpha–induced adhesion molecule expression in human aortic endothelial cells. Structure–function relationships and activity after pass metabolism. J Biol Chem. 2006;281:37102–10.

    Article  PubMed  CAS  Google Scholar 

  186. Chacko BK, Chandler RT, D’Alessandro TL, Mundhekar A, Khoo NKH, Botting N, et al. Anti-inflammatory effects of isoflavones are dependent on flow and human endothelial cell PPAR-gamma. J Nutr. 2007;137:351–6.

    PubMed  CAS  Google Scholar 

  187. Osiecki H. The role of chronic inflammation in cardiovascular disease and its regulation by nutrients. Altern Med Rev. 2004;9:32–53.

    PubMed  Google Scholar 

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Acknowledgments

The authors acknowledge funding from the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA) project AT07-003.

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  1. Centro para la Calidad de los Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Campus Universitario “Duques de Soria”, 42071, Soria, Spain

    Ana García-Lafuente, Eva Guillamón, Ana Villares, Mauricio A. Rostagno & José Alfredo Martínez

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  1. Ana García-Lafuente
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García-Lafuente, A., Guillamón, E., Villares, A. et al. Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease. Inflamm. Res. 58, 537–552 (2009). https://doi.org/10.1007/s00011-009-0037-3

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