Skip to main content
Top
Published in: Inflammation Research 9/2009

01-09-2009 | Review

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

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

Published in: Inflammation Research | Issue 9/2009

Login to get access

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.
Literature
2.
go back to reference Barton GM. A calculated response: control of inflammation by the innate immune system. J Clin Invest. 2008;118:413–20.PubMedCrossRef Barton GM. A calculated response: control of inflammation by the innate immune system. J Clin Invest. 2008;118:413–20.PubMedCrossRef
3.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference Yoon J-H, Baek SJ. Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med J. 2005;46:585–96.PubMedCrossRef Yoon J-H, Baek SJ. Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med J. 2005;46:585–96.PubMedCrossRef
5.
go back to reference Robak J, Gryglewski RJ. Bioactivity of flavonoids. Pol J Pharmacol. 1996;48:555–64.PubMed Robak J, Gryglewski RJ. Bioactivity of flavonoids. Pol J Pharmacol. 1996;48:555–64.PubMed
6.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
7.
go back to reference Havsteen B. The biochemistry and medical significance of the flavonoids. Pharmacol Ther. 2002;96:67–202.PubMedCrossRef Havsteen B. The biochemistry and medical significance of the flavonoids. Pharmacol Ther. 2002;96:67–202.PubMedCrossRef
8.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference 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 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
11.
go back to reference 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 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
12.
go back to reference 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 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
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference 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. 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.
15.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference Jiang F, Dusting GJ. Natural phenolic compounds as cardiovascular therapeutics: potential role of their anti-inflammatory effects. Curr Vasc Pharmacol. 2003;1:135–56.PubMedCrossRef Jiang F, Dusting GJ. Natural phenolic compounds as cardiovascular therapeutics: potential role of their anti-inflammatory effects. Curr Vasc Pharmacol. 2003;1:135–56.PubMedCrossRef
17.
go back to reference Kim HP, Kun HS, Chang HW, Kang SS. Anti-inflammatory plant flavonoids and cellular action mechanisms. J Pharmacol Sci. 2004;96:229–45.PubMedCrossRef Kim HP, Kun HS, Chang HW, Kang SS. Anti-inflammatory plant flavonoids and cellular action mechanisms. J Pharmacol Sci. 2004;96:229–45.PubMedCrossRef
18.
go back to reference Beecher GR. Overview of dietary flavonoids: nomenclature, occurrence and intake. J Nutr. 2003;133:3248S–54S.PubMed Beecher GR. Overview of dietary flavonoids: nomenclature, occurrence and intake. J Nutr. 2003;133:3248S–54S.PubMed
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference Verdrengh M, Jonsson IM, Holmdahl R, Tarkowski A. Genistein as an anti-inflammatory agent. Inflamm Res. 2003;52:341–6.PubMedCrossRef Verdrengh M, Jonsson IM, Holmdahl R, Tarkowski A. Genistein as an anti-inflammatory agent. Inflamm Res. 2003;52:341–6.PubMedCrossRef
23.
go back to reference 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.CrossRef 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.CrossRef
24.
25.
go back to reference Willcox JK, Ash SL, Catignani GL. Antioxidants and prevention of chronic disease. Crit Rev Food Sci Nutr. 2004;44:275–95.PubMedCrossRef Willcox JK, Ash SL, Catignani GL. Antioxidants and prevention of chronic disease. Crit Rev Food Sci Nutr. 2004;44:275–95.PubMedCrossRef
26.
go back to reference Halliwell B. Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med. 1991;91:14S–22S.PubMedCrossRef Halliwell B. Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med. 1991;91:14S–22S.PubMedCrossRef
27.
28.
go back to reference 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 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
29.
go back to reference 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 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
30.
go back to reference 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.CrossRef 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.CrossRef
31.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
32.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
33.
go back to reference Korkina LG, Afanas’ev IB. Antioxidant and chelating properties of flavonoids. Adv Pharmacol. 1997;38:151–63.PubMedCrossRef Korkina LG, Afanas’ev IB. Antioxidant and chelating properties of flavonoids. Adv Pharmacol. 1997;38:151–63.PubMedCrossRef
34.
go back to reference Haenen GR, Paquay JB, Korthouwer RE, Bast A. Peroxynitrite scavenging by flavonoids. Biochem Biophys Res Commun. 1997;236:591–3.PubMedCrossRef Haenen GR, Paquay JB, Korthouwer RE, Bast A. Peroxynitrite scavenging by flavonoids. Biochem Biophys Res Commun. 1997;236:591–3.PubMedCrossRef
35.
go back to reference Lai HH, Yen GC. Inhibitory effect of isoflavones on peroxynitrite-mediated low density lipoprotein oxidation. Biosci Biotechnol Biochem. 2002;66:22–8.PubMedCrossRef Lai HH, Yen GC. Inhibitory effect of isoflavones on peroxynitrite-mediated low density lipoprotein oxidation. Biosci Biotechnol Biochem. 2002;66:22–8.PubMedCrossRef
36.
go back to reference 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.CrossRef 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.CrossRef
37.
go back to reference 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.CrossRef 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.CrossRef
38.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
39.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
40.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
41.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
42.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
43.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
44.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
45.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
46.
go back to reference Nagao A, Seki M, Kobayashi H. Inhibition of xanthine oxidase by flavonoids. Biosci Biotechnol Biochem. 1999;63:1787–90.PubMedCrossRef Nagao A, Seki M, Kobayashi H. Inhibition of xanthine oxidase by flavonoids. Biosci Biotechnol Biochem. 1999;63:1787–90.PubMedCrossRef
47.
go back to reference Jolly CA. Diet manipulation and prevention of aging, cancer and autoimmune disease. Curr Opin Clin Nutr Metab Care. 2005;8:382–7.PubMed Jolly CA. Diet manipulation and prevention of aging, cancer and autoimmune disease. Curr Opin Clin Nutr Metab Care. 2005;8:382–7.PubMed
48.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
49.
go back to reference Volman JJ, Ramakers JD, Plat J. Dietary modulation of immune function by beta-glucans. Physiol Behav. 2008;94:276–84.PubMedCrossRef Volman JJ, Ramakers JD, Plat J. Dietary modulation of immune function by beta-glucans. Physiol Behav. 2008;94:276–84.PubMedCrossRef
50.
go back to reference 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 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
51.
go back to reference Rudd CE. CD4, CD8 and the TCR-CD3 complex: a novel class of protein-tyrosine kinase receptor. Immunol Today. 1990;11:400–6.PubMedCrossRef Rudd CE. CD4, CD8 and the TCR-CD3 complex: a novel class of protein-tyrosine kinase receptor. Immunol Today. 1990;11:400–6.PubMedCrossRef
52.
go back to reference Mustelin T, Abraham RT, Rudd CE, Alonso A, Merlo JJ. Protein tyrosine phosphorylation in T cell signaling. Front Biosci. 2002;1:918–69.CrossRef Mustelin T, Abraham RT, Rudd CE, Alonso A, Merlo JJ. Protein tyrosine phosphorylation in T cell signaling. Front Biosci. 2002;1:918–69.CrossRef
53.
go back to reference 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 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
54.
go back to reference 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 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
55.
go back to reference 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 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
56.
go back to reference 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. 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.
go back to reference 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 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
58.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
59.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
60.
go back to reference Bennet JP, Gomperst BD, Wollenweber E. Inhibitory effects of natural flavonoids on secretion from mast cells and neutrophils. Arzneimittelforschung. 1981;31:433–7. Bennet JP, Gomperst BD, Wollenweber E. Inhibitory effects of natural flavonoids on secretion from mast cells and neutrophils. Arzneimittelforschung. 1981;31:433–7.
61.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
62.
go back to reference 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. 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.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
64.
go back to reference 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. 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.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
66.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
67.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
68.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
69.
go back to reference 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. 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.
70.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
71.
go back to reference 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. 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.
72.
go back to reference Lindahl M, Tagesson C. Selective inhibition of group II phospholipase A2 by quercetin. Inflammation. 1993;17:573–82.PubMedCrossRef Lindahl M, Tagesson C. Selective inhibition of group II phospholipase A2 by quercetin. Inflammation. 1993;17:573–82.PubMedCrossRef
73.
go back to reference Süleyman H, Demircan B, Karagöz Y. Anti-inflammatory and side effects of cyclooxygenase inhibitors. Pharmacol Rep. 2007;59:247–58.PubMed Süleyman H, Demircan B, Karagöz Y. Anti-inflammatory and side effects of cyclooxygenase inhibitors. Pharmacol Rep. 2007;59:247–58.PubMed
74.
go back to reference Khanapure SP, Garvey DS, Janero DR, Letts LG. Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers. Curr Top Med Chem. 2007;7:311–40.PubMedCrossRef Khanapure SP, Garvey DS, Janero DR, Letts LG. Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers. Curr Top Med Chem. 2007;7:311–40.PubMedCrossRef
75.
go back to reference Kuhn H. Biologic relevance of lipoxygenase isoforms in atherogenesis. Expert Rev Cardiovasc Ther. 2005;3:1099–110.PubMedCrossRef Kuhn H. Biologic relevance of lipoxygenase isoforms in atherogenesis. Expert Rev Cardiovasc Ther. 2005;3:1099–110.PubMedCrossRef
76.
go back to reference Bauman J, von Bruchhausen FV, Wurm G. Flavonoids and related compounds as inhibitors of arachidonic acid peroxidation. Prostaglandins. 1980;20:627–39.CrossRef Bauman J, von Bruchhausen FV, Wurm G. Flavonoids and related compounds as inhibitors of arachidonic acid peroxidation. Prostaglandins. 1980;20:627–39.CrossRef
77.
go back to reference 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.CrossRef 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.CrossRef
78.
go back to reference Wakabayashi I, Yasui K. Wogonin inhibits inducible prostaglandin E2 production in macrophages. Eur J Pharmacol. 2000;406:477–81.PubMedCrossRef Wakabayashi I, Yasui K. Wogonin inhibits inducible prostaglandin E2 production in macrophages. Eur J Pharmacol. 2000;406:477–81.PubMedCrossRef
79.
go back to reference 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. 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.
80.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
81.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
82.
go back to reference 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.CrossRef 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.CrossRef
83.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
84.
go back to reference Moncada S, Palmer MJ, Higgs DA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1992;43:109–42. Moncada S, Palmer MJ, Higgs DA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1992;43:109–42.
85.
go back to reference 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. 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.
86.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
87.
go back to reference 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. 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.
go back to reference 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. 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.
89.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
90.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
91.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
92.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
93.
go back to reference 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. 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.
94.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
95.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
96.
go back to reference 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 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
97.
go back to reference 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 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
98.
go back to reference 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 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
99.
go back to reference 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. 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.
100.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
101.
go back to reference 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. 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.
go back to reference Su B, Karin M. Mitogen-activated protein kinase cascades and regulation of gene expression. Curr Opin Immunol. 1996;8:402–11.PubMedCrossRef Su B, Karin M. Mitogen-activated protein kinase cascades and regulation of gene expression. Curr Opin Immunol. 1996;8:402–11.PubMedCrossRef
103.
go back to reference Dong C, Davis RJ, Flavell RA. MAP kinases in the immune response. Annu Rev Immunol. 2002;20:55–72.PubMedCrossRef Dong C, Davis RJ, Flavell RA. MAP kinases in the immune response. Annu Rev Immunol. 2002;20:55–72.PubMedCrossRef
104.
go back to reference Herlaar E, Brown Z. MAPK signaling cascades in inflammatory disease. Mol Med Today. 1999;5:439–47.PubMedCrossRef Herlaar E, Brown Z. MAPK signaling cascades in inflammatory disease. Mol Med Today. 1999;5:439–47.PubMedCrossRef
105.
go back to reference Ono K, Han J. The p38 signal transduction pathway: activation and function. Cell Signal. 2000;12:1–13.PubMedCrossRef Ono K, Han J. The p38 signal transduction pathway: activation and function. Cell Signal. 2000;12:1–13.PubMedCrossRef
106.
go back to reference 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 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
107.
go back to reference 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.CrossRef 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.CrossRef
108.
go back to reference 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. 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.
109.
go back to reference Xagorari A, Roussos C, Papapetropoulos A. Inhibition of LPS-stimulated pathways in macrophages by the flavonoid luteolin. Br J Pharmacol. 2002;136:1058–64.PubMedCrossRef Xagorari A, Roussos C, Papapetropoulos A. Inhibition of LPS-stimulated pathways in macrophages by the flavonoid luteolin. Br J Pharmacol. 2002;136:1058–64.PubMedCrossRef
110.
go back to reference 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. 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.
111.
go back to reference 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 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
112.
go back to reference 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 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
113.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
114.
go back to reference 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. 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.
115.
go back to reference Pereira SG, Oakley F. Nuclear factor-kappaB1: regulation and function. Int J Biochem Cell Biol. 2008;40:1425–30.PubMedCrossRef Pereira SG, Oakley F. Nuclear factor-kappaB1: regulation and function. Int J Biochem Cell Biol. 2008;40:1425–30.PubMedCrossRef
116.
go back to reference Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336:1066–71.PubMedCrossRef Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336:1066–71.PubMedCrossRef
117.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
118.
go back to reference 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 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
119.
go back to reference 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.CrossRef 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.CrossRef
122.
go back to reference Shacter E, Weitzman SA. Chronic inflammation and cancer. Oncology. 2002;16:217–26.PubMed Shacter E, Weitzman SA. Chronic inflammation and cancer. Oncology. 2002;16:217–26.PubMed
123.
124.
go back to reference Dobrovolskaia MA, Kozlov SV. Inflammation and cancer: when NF-kappaB amalgamates the perilous partnership. Curr Cancer Drug Targets. 2005;5:325–544.PubMedCrossRef Dobrovolskaia MA, Kozlov SV. Inflammation and cancer: when NF-kappaB amalgamates the perilous partnership. Curr Cancer Drug Targets. 2005;5:325–544.PubMedCrossRef
125.
go back to reference YC Xiao H. Combination regimen with statins and NSAIDs: a promising strategy for cancer chemoprevention. Int J Cancer. 2008;123:983–90.CrossRef YC Xiao H. Combination regimen with statins and NSAIDs: a promising strategy for cancer chemoprevention. Int J Cancer. 2008;123:983–90.CrossRef
126.
go back to reference Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer cell. 2005;7:211–7.PubMedCrossRef Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer cell. 2005;7:211–7.PubMedCrossRef
127.
go back to reference de Visser KE, Coussens LM. The inflammatory tumor microenvironment and its impact on cancer development. Contrib Microbiol. 2006;13:118–37.PubMedCrossRef de Visser KE, Coussens LM. The inflammatory tumor microenvironment and its impact on cancer development. Contrib Microbiol. 2006;13:118–37.PubMedCrossRef
128.
go back to reference 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. 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.
129.
130.
go back to reference Yang CS, Landau JM, Huang MT, Newmark HL. Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu Rev Nutr. 2001;21:381–406.PubMedCrossRef Yang CS, Landau JM, Huang MT, Newmark HL. Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu Rev Nutr. 2001;21:381–406.PubMedCrossRef
131.
go back to reference Le Marchand L. Cancer preventive effects of flavonoids—a review. Biomed Pharmacother. 2002;56:269–301.CrossRef Le Marchand L. Cancer preventive effects of flavonoids—a review. Biomed Pharmacother. 2002;56:269–301.CrossRef
132.
go back to reference 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. 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.
133.
go back to reference 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 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
134.
go back to reference 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 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
135.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
136.
go back to reference Deschner EE, Ruperto J, Wong G, Newmark HL. Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis. 1991;12:1193–6.PubMedCrossRef Deschner EE, Ruperto J, Wong G, Newmark HL. Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis. 1991;12:1193–6.PubMedCrossRef
137.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
138.
go back to reference 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 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
139.
go back to reference 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 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
140.
go back to reference Birt DF, Hendrich S, Wang W. Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol Therapeutics. 2001;90:157–77.CrossRef Birt DF, Hendrich S, Wang W. Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol Therapeutics. 2001;90:157–77.CrossRef
141.
go back to reference Fresco P, Borges F, Diniz C, Marques MPM. New insights on the anticancer properties of dietary polyphenols. Med Res Rev. 2006;26:747–66.PubMedCrossRef Fresco P, Borges F, Diniz C, Marques MPM. New insights on the anticancer properties of dietary polyphenols. Med Res Rev. 2006;26:747–66.PubMedCrossRef
142.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
143.
go back to reference 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. 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.
144.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
145.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
146.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
147.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
148.
go back to reference 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. 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.
go back to reference 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 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
150.
go back to reference Khan N, Afaq F, Mukhtar H. Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal 2008;10:475–510.PubMedCrossRef Khan N, Afaq F, Mukhtar H. Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal 2008;10:475–510.PubMedCrossRef
151.
go back to reference 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 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
152.
go back to reference 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 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
153.
go back to reference 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. 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.
154.
go back to reference 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 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
155.
go back to reference Davis JN, Kucuk O, Sarkar FH. Genistein inhibits NF-kappaB activation in prostate cancer cells. Nutr Cancer 1999;35:167–74.PubMedCrossRef Davis JN, Kucuk O, Sarkar FH. Genistein inhibits NF-kappaB activation in prostate cancer cells. Nutr Cancer 1999;35:167–74.PubMedCrossRef
156.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
157.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
158.
go back to reference Kelloff GJ. Perspectives on cancer chemoprevention research and drug development. Adv Cancer Res. 2000;78:199–334.PubMedCrossRef Kelloff GJ. Perspectives on cancer chemoprevention research and drug development. Adv Cancer Res. 2000;78:199–334.PubMedCrossRef
160.
161.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
163.
go back to reference Bonomini F, Tengattin IS, Fabiano A, Bianchi R, Rezzani R. Atherosclerosis and oxidative stress. Histol Histopathol. 2008;23:381–90.PubMed Bonomini F, Tengattin IS, Fabiano A, Bianchi R, Rezzani R. Atherosclerosis and oxidative stress. Histol Histopathol. 2008;23:381–90.PubMed
164.
go back to reference 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 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
165.
go back to reference Charo IF, Taubman MB. Chemokines in the pathogenesis of vascular disease. Circ Res. 2004;95:858–66.PubMedCrossRef Charo IF, Taubman MB. Chemokines in the pathogenesis of vascular disease. Circ Res. 2004;95:858–66.PubMedCrossRef
166.
go back to reference Szekanecz Z. Pro-inflammatory cytokines in atherosclerosis. Isr Med Assoc J. 2008;10:529–30.PubMed Szekanecz Z. Pro-inflammatory cytokines in atherosclerosis. Isr Med Assoc J. 2008;10:529–30.PubMed
167.
go back to reference Ohsuzu F. The roles of cytokines, inflammation and immunity in vascular diseases. J Atheroscler Thromb. 2004;11:313–21.PubMed Ohsuzu F. The roles of cytokines, inflammation and immunity in vascular diseases. J Atheroscler Thromb. 2004;11:313–21.PubMed
168.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
169.
go back to reference Kaperonis EA, Liapis CD, Kakisis JD, Dimitroulis D, Papavassiliou VG. Inflammation and atherosclerosis. Eur J Vasc Endovasc Surg 2006;31. Kaperonis EA, Liapis CD, Kakisis JD, Dimitroulis D, Papavassiliou VG. Inflammation and atherosclerosis. Eur J Vasc Endovasc Surg 2006;31.
170.
go back to reference 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 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
171.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
172.
go back to reference 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.CrossRef 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.CrossRef
173.
174.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
175.
go back to reference Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ. 1996;312:478–81.PubMed Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ. 1996;312:478–81.PubMed
176.
go back to reference 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 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
177.
go back to reference 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 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
178.
go back to reference 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 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
179.
go back to reference 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 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
180.
go back to reference 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 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
181.
go back to reference 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 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
182.
go back to reference Mukamal KJ, Maclure M, Muller JE, Sherwood JB, Mittleman MA. Tea consumption and mortality after acute myocardial infarction. Circulation. 2002;105:2476–81.PubMedCrossRef Mukamal KJ, Maclure M, Muller JE, Sherwood JB, Mittleman MA. Tea consumption and mortality after acute myocardial infarction. Circulation. 2002;105:2476–81.PubMedCrossRef
183.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
184.
go back to reference 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. 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.
185.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
186.
go back to reference 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 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
187.
go back to reference Osiecki H. The role of chronic inflammation in cardiovascular disease and its regulation by nutrients. Altern Med Rev. 2004;9:32–53.PubMed Osiecki H. The role of chronic inflammation in cardiovascular disease and its regulation by nutrients. Altern Med Rev. 2004;9:32–53.PubMed
Metadata
Title
Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease
Authors
Ana García-Lafuente
Eva Guillamón
Ana Villares
Mauricio A. Rostagno
José Alfredo Martínez
Publication date
01-09-2009
Publisher
SP Birkhäuser Verlag Basel
Published in
Inflammation Research / Issue 9/2009
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-009-0037-3

Other articles of this Issue 9/2009

Inflammation Research 9/2009 Go to the issue