Advertisement

Molecular and Cellular Biochemistry

, Volume 444, Issue 1–2, pp 63–75 | Cite as

Pretreatment with quercetin prevents changes in lymphocytes E-NTPDase/E-ADA activities and cytokines secretion in hyperlipidemic rats

  • Josiane B. S. Braun
  • Jader B. Ruchel
  • Alessandra G. Manzoni
  • Fátima H. Abdalla
  • Emerson A. Casalli
  • Lívia G. Castilhos
  • Daniela F. Passos
  • Daniela B. R. Leal
Article
  • 56 Downloads

Abstract

Hyperlipidemia (HL) is a condition associated with endothelial dysfunction and inflammatory disorders. Purinergic system ectoenzymes play an important role in modulating the inflammatory and immune response. This study investigated whether the preventive treatment with quercetin is able to prevent changes caused by hyperlipidemia in the purinergic system, through the activities of E-NTPDase and E-ADA in lymphocytes, and quantify the nucleotides and nucleoside, and the secretion of anti- and proinflammatory cytokines. Animals were divided into saline/control, saline/quercetin 5 mg/kg, saline/quercetin 25 mg/kg, saline/quercetin 50 mg/kg, saline/simvastatin (0.04 mg/kg), hyperlipidemia, hyperlipidemia/quercetin 5 mg/kg, hyperlipidemia/quercetin 25 mg/kg, hyperlipidemia/quercetin 50 mg/kg, and hyperlipidemia/simvastatin. Animals were pretreated with quercetin for 30 days and hyperlipidemia was subsequently induced by intraperitoneal administration of 500 mg/kg of poloxamer-407. Simvastatin was administered after the induction of hyperlipidemia. Lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated for the cytokines and nucleotide/nucleoside quantification. E-NTPDase and E-ADA activities were increased in lymphocytes from hyperlipidemic rats and pretreatment with quercetin was able to prevent the increase in the activities of these enzymes caused by hyperlipidemia. Hyperlipidemic rats when receiving pretreatment with quercetin and treatment with simvastatin showed decreased levels of ATP and ADP when compared to the untreated hyperlipidemic group. The IFN-γ and IL-4 cytokines were increased in the hyperlipidemic group when compared with control group, and decreased when hyperlipidemic rats received the pretreatment with quercetin. However, pretreatment with quercetin was able to prevent the alterations caused by hyperlipidemia probably by regulating the inflammatory process. We can suggest that the quercetin is a promising compound to be used as an adjuvant in the treatment of hyperlipidemia.

Keywords

Flavonoid Cholesterol Ectoenzymes Cytokines 

Notes

Acknowledgements

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundo de Incentivo a Pesquisa (FIPE/UFSM), Brazil.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

References

  1. 1.
    Navar-Boggan AM, Peterson ED, D’Agostino RB et al (2015) Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease. Circ 131:451–458Google Scholar
  2. 2.
    Ahmad S, Beg ZH (2013) Hypolipidemic and antioxidant activities of thymoquinone and limonene in atherogenic suspension fed rats. Food Chem 138:1116–1124PubMedGoogle Scholar
  3. 3.
    Ong SL, Nalamolu KR, Lai HY (2017) Potential lipid-lowering effects of Eleusine indica (L) Gaertn. Extract on high-fat-diet-induced hyperlipidemic rats. Pharmacogn Magn 13:1–9Google Scholar
  4. 4.
    Shafik NM, Baalash A, Ebeid AM (2017) Synergistic cardioprotective effects of combined chromium picolinate and atorvastatin treatment in triton X-100-induced hyperlipidemia in rats: impact on some biochemical markers. Biol Trace Elem Res 13:1–10Google Scholar
  5. 5.
    Braun JBS, Ruchel JB, Adefegha SA et al (2017) Neuroprotective effects of pretreatment with quercetin as assessed by acetylcholinesterase assay and behavioral testing in poloxamer-407 induced hyperlipidemic rats. Biomed Pharmacot 88:1054–1063Google Scholar
  6. 6.
    Chaudhary HR, Brocks DR (2013) The single dose poloxamer 407 model of hyperlipidemia; systemic effects on lipids assessed using pharmacokinetic methods, and its effects on adipokines. J Pharm Pharmaceut Sci 16:65–73Google Scholar
  7. 7.
    Johnston TP, Palmer WK (1993) Mechanism of poloxamer 407-induced hypertriglyceridemia in the rat. Biochem Pharmacol 46:1037–1042PubMedGoogle Scholar
  8. 8.
    Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874PubMedGoogle Scholar
  9. 9.
    Hansson GK, Libby P, Schonbeck U et al (2002) Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 91:281–291PubMedGoogle Scholar
  10. 10.
    McMurray H, Parthasarathy S, Steinberg D (1993) Oxidatively modified low density lipoprotein is a chemoattractant for human T lymphocytes. J Clin Invest 92:1004–1008PubMedPubMedCentralGoogle Scholar
  11. 11.
    Riwanto M, Landmesser U (2013) High density lipoproteins and endothelial functions: mechanistic insights and alterations in cardiovascular disease. J Lipid Res 54:3227–3243PubMedPubMedCentralGoogle Scholar
  12. 12.
    Dichtl W, Nilsson L, Goncalves I et al (1999) Very low-density lipoprotein activates nuclear factor-kB in endothelial cells. Circ Res 84:1085–1094PubMedGoogle Scholar
  13. 13.
    Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circ 105:1135–1143Google Scholar
  14. 14.
    Libby P, Geng YJ, Aikawa M et al (1996) Macrophages and atherosclerotic plaque stability. Curr Opin Lipid 7:330–335Google Scholar
  15. 15.
    Libby P (2001) Current concepts of the pathogenesis of the acute coronary syndromes. Circ 104:365–372Google Scholar
  16. 16.
    Libby P, Simon DI (2001) Inflammation and thrombosis: the clot thickens. Circ 103:1718–1720Google Scholar
  17. 17.
    Biasillo G, Leo M, Della Bona R et al (2010) Inflammatory biomarkers and coronary heart disease: from bench to bedside and back. Inter Emerg Med 5:225–233Google Scholar
  18. 18.
    Galkina E, Ley K (2009) Immune and inflammatory mechanism of atherosclerosis. Annu Rev Immunol 27:165–197PubMedPubMedCentralGoogle Scholar
  19. 19.
    Walch L, Massade L, Dufilho M et al (2006) Pro-atherogenic effect of interleukin-4 in endothelial cells: modulation of oxidative stress, nitric oxide and monocyte chemoattractant protein-1 expression. Atheroscl 187:285–291Google Scholar
  20. 20.
    Delves PJ, Roitt M (2000) The immune system. Second of two parts. N Engl J Med 343:108–117PubMedGoogle Scholar
  21. 21.
    Rock KL, Hearn A, Chen JC et al (2005) Natural endogenous adjuvants. Springer Semin Immunopathol 26:231–246PubMedGoogle Scholar
  22. 22.
    Mancino G, Placido RD, Virgilio F (2001) P2×7 receptors and apoptosis in tuberculosis infection. J Biol Regul Homeost Agents 15:286–293PubMedGoogle Scholar
  23. 23.
    Bours MJ, Swennen EL, Di Virgilio F et al (2006) Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Ther 112:358–404PubMedGoogle Scholar
  24. 24.
    Ralevic V, Burnstock G (2003) Involvement of purinergic signaling in cardiovascular diseases. Drug News Perspect 16:133–140PubMedGoogle Scholar
  25. 25.
    Zimmermann H, Mishra S, Shukla V et al (2007) Ecto-nucleotidases, molecular properties and functional impact. An Real Acad Nac Farm 73:537–566Google Scholar
  26. 26.
    Robson SC, Sevigny J, Zimmermann H (2006) The E-NTPDase family of ectonucleotidases: structure function relationships and pathophysiological significance. Purinergic Signal 2:409–430PubMedPubMedCentralGoogle Scholar
  27. 27.
    Maliszewski CR, Delespesse GJ, Schoenborn MA et al (1994) The CD39 lymphoid cell activation antigen. Molecular cloning and structural characterization. J Immunol 153:3574–3583PubMedGoogle Scholar
  28. 28.
    Zimmermann H (1992) 5′-Nucleotidase: molecular structure and functional aspects. Biochem J 285:345–365PubMedPubMedCentralGoogle Scholar
  29. 29.
    Ishizawa K, Yoshizumi M, Kawai Y et al (2011) Pharmacology in health food: metabolism of quercetin in vivo and its protective effect against arteriosclerosis. J Pharmacol Sci 115:466–470PubMedGoogle Scholar
  30. 30.
    Garelnabi M, Mahini H, Wilson T (2014) Quercetin intake with exercise modulates lipoprotein metabolism and reduces atherosclerosis. Plaque Formation JIISN 11:2–8Google Scholar
  31. 31.
    Xue F, Nie X, Shi J et al (2017) Quercetin inhibits LPS-induced inflammation and ox-LDL-induced lipid deposition. Front Pharmacol 8:1–40Google Scholar
  32. 32.
    Lin X, Lin C, Zhao T et al (2017) Quercetin protects against heat stroke-induced myocardial injury in male rats: antioxidative and antiinflammatory mechanisms. Chem Biol Interact 265:47–54PubMedGoogle Scholar
  33. 33.
    Rupasinghe HV, Kathirvel P, Huber GM (2011) Ultrasonication-assisted solvent extraction of quercetin glycosides from ‘Idared’ apple peels. Molecules 16:9783–9791Google Scholar
  34. 34.
    Aguirre L, Arias N, Macarulla MT et al (2011) Beneficial effects of quercetin on obesity and diabetes. Open Nutraceut J 4:189–198Google Scholar
  35. 35.
    Abdalla FH, Cardoso AM, Schmatz R et al (2014) Protective effect of quercetin in ecto-enzymes, cholinesterases, and myeloperoxidase activities in the lymphocytes of rats exposed to cadmium. Mol Cell Biochem 396:201–211PubMedGoogle Scholar
  36. 36.
    Palmer WK, Eugene EE, Thomas PJ (1998) Poloxamer 407-induced atherogenesis in the C57BL/6 mouse. Atherosclerosis 136:115–123PubMedGoogle Scholar
  37. 37.
    Reigner BG, Blesch K (2002) Estimating the starting dose for entry into humans: principles and practice. Eur J Clin Pharmacol 57:835–845PubMedGoogle Scholar
  38. 38.
    Böyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl 97:77–89PubMedGoogle Scholar
  39. 39.
    Jaques JA, Rezer JFP, Ruchel JB et al (2011) A method for isolation of rat lymphocyte-rich mononuclear cells from lung tissue useful for determination of nucleoside triphosphate diphosphohydrolase activity. Anal Biochem 410:34–39PubMedGoogle Scholar
  40. 40.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254PubMedGoogle Scholar
  41. 41.
    Leal DBR, Streher CA, Neu TN et al (2005) Characterization of NTPDase (NTPDase1; ecto-apyrase; ecto-diphosphohydrolase; CD39; E.C. 3.6.1.5) activity in humans lymphocytes. Biochim Biophys Acta 1721:9–15PubMedGoogle Scholar
  42. 42.
    Chan KM, Delfert D, Junger KD (1986) A direct colorimetric assay for Ca2+ stimulated ATPase activity. Anal Biochem 157:375–380PubMedGoogle Scholar
  43. 43.
    Giusti G, Galanti B (1984) Colorimetric method. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Verlag Chemie, Weinheim, pp 315–323Google Scholar
  44. 44.
    Voelter W, Zech K, Arnold P et al (1980) Determination of selected pyrimidines, purines and their metabolites in serum and urine by reverse-phase ion-pair chromatography. J Chromatogr 199:345–354PubMedGoogle Scholar
  45. 45.
    Xiong H, Xu Y, Tan G et al (2015) Glycyrrhizin ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice and inhibits TNF-alpha-induced ICAM-1 expression via NF-kappaB/MAPK in HaCaT cells. Cell Physiol Biochem 35:1335–1346PubMedGoogle Scholar
  46. 46.
    Nabavi SF, Russo GL, Daglia M et al (2015) Role of quercetin as an alternative for obesity treatment: you are what you eat! Food Chem 179:305–310PubMedGoogle Scholar
  47. 47.
    Arai Y, Watanabe S, Kimira M et al (2000) Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. J Nutr 130:2243–2250PubMedGoogle Scholar
  48. 48.
    Choi EJ, Chee KM, Lee BL (2003) Anti- and prooxidant effects of chronic quercetin administration in rats. Eur J Pharmacol 482:281–285PubMedGoogle Scholar
  49. 49.
    Lu J, Zheng YL, Luo L et al (2006) Quercetin reverses D-galactose induced neurotoxicity in mouse brain. Behav Brain Res 171:251–260PubMedGoogle Scholar
  50. 50.
    Amit G, Vandana S, Sidharth M (2011) Hyperlipidemia: an updated review. Inter J Biopharma Toxicol Res 1:81–89Google Scholar
  51. 51.
    Rocha VZ, Libby P (2009) Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol 6:399–409PubMedGoogle Scholar
  52. 52.
    Miyara M, Sakaguchi S (2007) Natural regulatory T cells: mechanisms of suppression. Trends Mol Med 13:108–116PubMedGoogle Scholar
  53. 53.
    Duarte MMF, Loro VL, Rocha JBT et al (2007) Enzymes that hydrolyze adenine nucleotides of patients with hypercholesterolemia and inflammatory processes. FEBS J 274:2707–2714PubMedGoogle Scholar
  54. 54.
    Robson SC, Daoud S, Bégin M et al (1997) Modulation of vascular ATP diphosphohydrolase by fatty acids. Blood Coagul Fibrinolysis 8:21–27PubMedGoogle Scholar
  55. 55.
    Papanikolaou A, Papafotika A, Murphy C et al (2005) Cholesterol-dependent lipid assemblies regulate the activity of the ecto-nucleotidase CD39. J Biol Chem 280:26406–26414PubMedGoogle Scholar
  56. 56.
    Ataman OV (1991) Ectonucleotidase activity of isolated strips of arteries and veins of experimental animals. Influence of various damaging agents on ecto-ATPase activity of blood vessels. Fiziol Zh 37:32–37PubMedGoogle Scholar
  57. 57.
    Moritz CEJ, Vieira GA, Piroli C et al (2012) Physical training normalizes nucleotide hydrolysis and biochemical parameters in blood serum from streptozotocin-diabetic rats. Arch Physiol Biochem 118:253–259PubMedGoogle Scholar
  58. 58.
    Di Virgilio F (1995) The P2Z purinoreceptor: an intriguing role in immunity, inflammation and cell death. Immunol Today 16:524–528PubMedGoogle Scholar
  59. 59.
    Dwyer K, Deaglio S, Gao W et al (2007) CD39 and control of cellular immune responses. Purinergic Signal 3:171–180PubMedPubMedCentralGoogle Scholar
  60. 60.
    Di Virgilio F, Chiozzi P, Ferrari D et al (2001) Nucleotide receptors: an emerging family of regulatory molecules in blood cells. Blood 97:587–600PubMedGoogle Scholar
  61. 61.
    Zimmermann H (1999) Nucleotides and cd39: principal modulatory players in hemostasis and thrombosis. Nat Med 5:987–988PubMedGoogle Scholar
  62. 62.
    Gessi S, Varani K, Merighi S et al (2007) Adenosine and lymphocyte regulation. Purinergic Signal 3:109–116PubMedPubMedCentralGoogle Scholar
  63. 63.
    Rodrigues R, Debom G, Soares F et al (2014) Alterations of ectonucleotidases and acetylcholinesterase activities in lymphocytes of down syndrome subjects: relation with inflammatory parameters. Clin Chim Acta 433:105–110PubMedGoogle Scholar
  64. 64.
    Baldissarelli J, Santi A, Schmatz R et al (2016) Quercetin changes purinergic enzyme activities and oxidative profile in platelets of rats with hypothyroidism. Biomed Pharm 84:1849–1857Google Scholar
  65. 65.
    Pourshari WP, Saghiri R, Ebrahimi-Rad M et al (2009) Adenosine deaminase in patients with primary immunodeficiency syndromes: the analysis of serum ADA1 and ADA2 activities. Clin Biochem 42:1438–1443Google Scholar
  66. 66.
    Aldrich M, Blackburn M, Kellems R (2000) The importance of adenosine deaminase for lymphocyte development and function. Biochem Biophys Res 272:311–335Google Scholar
  67. 67.
    Kvist TM, Schwarz P, Jorgensen NR (2014) The P2 × 7 receptor: a key player in immune-mediated bone loss? Sci World J 2014:1–10Google Scholar
  68. 68.
    Nair MP, Mahajan S, Reynolds JL et al (2006) The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-kappa beta system. Clin Vaccine Immunol 13:319–328PubMedPubMedCentralGoogle Scholar
  69. 69.
    Chen JC, Ho FM, Lee CPD et al (2005) Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IkappaB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia. Eur J Pharmacol 521:9–20PubMedGoogle Scholar
  70. 70.
    Kuno M, Seki N, Tsujimoto S et al (2006) Anti-inflammatory activity of non-nucleoside adenosine deaminase inhibitor FR234938. Eur J Pharmacol 534:241–249PubMedGoogle Scholar
  71. 71.
    Vargas AJ, Burd R (2010) Hormesis and synergy: pathways and mechanisms of quercetin in cancer prevention and management. Nutr Rev 68:418–428PubMedGoogle Scholar
  72. 72.
    Jacob F, Novo CP, Bachert C et al (2013) Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses. Purinergic Signal 84:154–160Google Scholar
  73. 73.
    Trautmann A (2009) Extracellular ATP in immune system: more than a just a danger signal. Sci Signal 2:1–3Google Scholar
  74. 74.
    Langston H, Ke Y, Gewirtz A et al (2003) Secretion of IL-2 and IFN-y, but not IL-4, by antigen-specific T cells requires extracellular ATP. J Immunol 170:2962–2970PubMedGoogle Scholar
  75. 75.
    Hulthe J, Fagerberg B (2002) Circulating oxidized LDL is associated with subclinical atherosclerosis development and inflammatory cytokines. Arterioscler Tromb Vasc Biol 22:1162–1167Google Scholar
  76. 76.
    King VL, Cassis LA, Daugherty A (2007) Interleukin-4 does not influence development of hypercholesterolemia or angiotensin II-induced atherosclerotic lesions in mice. Am J Pathol 171:2040–2047PubMedPubMedCentralGoogle Scholar
  77. 77.
    Buono C, Come CE, Stavrakis G et al (2003) Influence of interferon-gamma on the extent and phenotype of diet-induced atherosclerosis in the LDLR-deficient mouse. Arterioscler Thromb Vasc Biol 23:454–460PubMedGoogle Scholar
  78. 78.
    Packard RRS, Lichtman AH, Libby P (2009) Innate and adaptive immunity in atherosclerosis. Semin Immunopathol 31:1–5Google Scholar
  79. 79.
    Santi A, Da Cruz IBM, Loro VL et al (2016) Overt hypothyroidism is associated with blood inflammatory biomarkers dependent of lipid profile. J Appl Biom 14:119–124Google Scholar
  80. 80.
    Mirhafez SR, Tajfard M, Avan A et al (2016) Association between serum cytokine concentrations and the presence of hypertriglyceridemia. Clin Biochem 49:750–755PubMedGoogle Scholar
  81. 81.
    Girn HRS, Orsi NM, Vanniasinkam SH (2007) An overview of cytokines interactions in atherosclerosis and implications for peripheral arterial disease. Vascul Med 12:299–309Google Scholar
  82. 82.
    Leon ML, Zuckerman SH (2005) Gamma interferon: a central mediator in atherosclerosis. Inflamm Res 54:395–411PubMedGoogle Scholar
  83. 83.
    Robertson AKL, Hansson GKT (2006) Cells in atherogenesis. For better or for worse? Atherioscler Tromb Vasc Biol 26:2421–2432Google Scholar
  84. 84.
    Zahedi M, Ghiasvand R, Feizi A et al (2013) Does quercetin improve cardiovascular risk factors and inflammatory biomarkers in women with type 2 diabetes: a double-blind randomized controlled clinical trial. Int J Prev Med 4:777–785PubMedPubMedCentralGoogle Scholar
  85. 85.
    Yu ES, Min HJ, An SY et al (2008) Regulatory mechanisms of IL-2 and IFN-γ suppression by Quercetin in T helper Cells. Biochem Pharmacol 76:70–78PubMedGoogle Scholar
  86. 86.
    Kumazawa Y, Kawaguchi K, Takimoto H (2006) Immunomodulating effects of flavonoids on acute and chronic inflammatory responses caused by tumor necrosis factor alpha. Curr Pharm Des 12:4271–4279PubMedGoogle Scholar
  87. 87.
    Ruiz PA, Braune A, Holzlwimmer G et al (2007) Quercetin inhibits TNF-induced NF-kappaB transcription factor recruitment to proinflammatory gene promoters in murine intestinal epithelial cells. J Nutr 137:1208–1215PubMedGoogle Scholar
  88. 88.
    Steinberg D, Lewis A (1997) Conner memorial lecture. Oxidative modification of LDL and atherogenesis. Circulation 95:1062–1071PubMedGoogle Scholar
  89. 89.
    Lee YW, Kuhn H, Hennig B et al (2001) IL-4-induced oxidative stress upregulates VCAM-1 gene expression in human endothelial cells. J Mol Cell Cardiol 33:83–94PubMedGoogle Scholar
  90. 90.
    King VL, Szilvassy SJ, Daugherty A (2002) Interleukin-4 deficiency decreases atherosclerotic lesion formation in a site-specific manner in female LDL receptor–/–mice. Arterioscler Thromb Vasc Biol 22:456–461PubMedGoogle Scholar
  91. 91.
    Rollins BJ, Pober JS (1991) Interleukin-4 induces the synthesis and secretion of mcp-1/je by human endothelial cells. Am J Pathol 138:1315–1319PubMedPubMedCentralGoogle Scholar
  92. 92.
    Xu MX, Wang M, Yang WW (2017) Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR 4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice. Int J Nanomed 12:327–345Google Scholar
  93. 93.
    Tsao CH, Shiau MY, Chuang PH et al (2014) Interleukin-4 regulates lipid metabolism by inhibiting adipogenesis and promoting lipolysis. J Lipid Res 55:385–397PubMedPubMedCentralGoogle Scholar
  94. 94.
    Rogerio AP, Dora CL, Andrade EL et al (2010) Anti-inflammatory effect of quercetin-loaded microemulsion in the airways allergic inflammatory model in mice. Pharmacol Res 61:288–297PubMedGoogle Scholar
  95. 95.
    Chirumbolo S (2010) The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflamm Allergy Drug Targets 9:263–285PubMedGoogle Scholar
  96. 96.
    Kaneko M, Takimoto H, Sugiyama T et al (2008) Suppressive effects of the flavonoids quercetin and luteolin on the accumulation of lipid rafts after signal transduction via receptors. Immunopharmacol Immunotoxicol 30:867–882PubMedGoogle Scholar
  97. 97.
    Wleklik M, Luczak M, Panasiak W et al (1988) Structural basis for antiviral activity of flavonoids naturally occurring compounds. Acta Virol 32:522–525PubMedGoogle Scholar
  98. 98.
    Wang L, Tu YC, Lian TW et al (2006) Distinctive antioxidant and anti-inflammatory effects of flavonols. J Agric Food Chem 54:9798–9804PubMedGoogle Scholar
  99. 99.
    Tsuchiya H (2010) Structure-dependent membrane interaction of flavonoids associated with their bioactivity. Food Chem 120:1089–1096Google Scholar
  100. 100.
    Sugiyama T, Kawaguchi K, Dobashi H et al (2008) Quercetin but not luteolin suppresses the induction of lethal shock upon infection of mice with Salmonella typhimurium. FEMS Immunol Med Microbiol 53:306–313PubMedGoogle Scholar
  101. 101.
    Kempuraj D, Madhappan B, Christodoulou S et al (2005) Flavonols inhibit pro-inflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells. Br J Pharmacol 145:934–944PubMedPubMedCentralGoogle Scholar
  102. 102.
    Comalada M, Ballester I, Bailon E et al (2006) Inhibition of pro-inflammatory markers in primary bone marrow-derived mouse macrophages by naturally occurring flavonoids: analysis of the structure-activity relationship. Biochem Pharmacol 72:1010–1021PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Josiane B. S. Braun
    • 1
    • 2
  • Jader B. Ruchel
    • 1
    • 2
  • Alessandra G. Manzoni
    • 2
  • Fátima H. Abdalla
    • 1
  • Emerson A. Casalli
    • 3
  • Lívia G. Castilhos
    • 4
  • Daniela F. Passos
    • 2
  • Daniela B. R. Leal
    • 1
    • 2
    • 4
  1. 1.Programa de Pós Graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e ExatasUniversidade Federal de Santa MariaSanta MariaBrazil
  2. 2.Laboratório de Imunobiologia Experimental e Aplicada, Departamento de Microbiologia e Parasitologia, Centro de Ciências da SaúdeUniversidade Federal de Santa MariaSanta MariaBrazil
  3. 3.Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde (ICBS)Universidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  4. 4.Programa de Pós Graduação em Ciências Farmacêuticas, Centro de Ciências da SaúdeUniversidade Federal de Santa MariaSanta MariaBrazil

Personalised recommendations