Neutrophils represent the front-line defence cells in protecting organisms against infection and play an irreplaceable role in the proper performance of the immune system. As early as within the first minutes of stimulation, neutrophilic NADPH oxidase is activated, and cells release large quantities of highly toxic reactive oxygen species (ROS). These oxidants can be highly toxic not only for infectious agents but also for neighboring host tissues. Since flavonoids exhibit antioxidant and anti-inflammatory effects, they are subjects of interest for pharmacological modulation of ROS production. The present paper summarizes contemporary knowledge on the effects of various flavonoids on the respiratory burst of mammalian neutrophils. It can be summarized that the inhibitory effects of flavonoids on the respiratory burst of phagocytes are mediated via inhibition of enzymes involved in cell signaling as well as via modulation of redox status. However, the effects of flavonoids are even more complex, and several sites of action, depending upon the flavonoid structure and way of application, are included.

Institute of Biophysics Academy of Sciences of the Czech Republic vvi Brno Czech Republic

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Casbon AJ, Allen LA, Dunn KW, Dinauer MC. Macrophage NADPH oxidase flavocytochrome b localizes to the plasma membrane and Rab11-positive recycling endosomes. Journal of Immunology. 2009;182(4):2325–2339. PubMed PMC

Hajkova V, Svobodova A, Krejcova D, et al. Soluble glucomannan isolated from Candida utilis primes blood phagocytes. Carbohydrate Research. 2009;344(15):2036–2041. PubMed

Pekarova M, Lojek A, Martiskova H, et al. New role for L-arginine in regulation of inducible nitric-oxide-synthase-derived superoxide anion production in raw 264.7 macrophages. Scientific World Journal. 2011;11:2443–2457. PubMed PMC

Lojek A, Kubala L, Čížová H, Číž M. A comparison of whole blood neutrophil chemiluminescence measured with cuvette and microtitre plate luminometers. Luminescence. 2002;17(1):1–4. PubMed

Assari T. Chronic granulomatous disease; fundamental stages in our understanding of CGD. Medical Immunology. 2006;5, article 4 PubMed PMC

Genestra M. Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cellular Signalling. 2007;19(9):1807–1819. PubMed

Heumüller S, Wind S, Barbosa-Sicard E, et al. Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant. Hypertension. 2008;51(2):211–217. PubMed

Číž M, Čížová H, Denev P, Kratchanova M, Slavov A, Lojek A. Different methods for control and comparison of the antioxidant properties of vegetables. Food Control. 2010;21(4):518–523.

Denev P, Ciz M, Ambrozova G, Lojek A, Yanakieva I, Kratchanova M. Solid-phase extraction of berries’ anthocyanins and evaluation of their antioxidative properties. Food Chemistry. 2010;123(4):1055–1061.

Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients. 2010;2(12):1231–1246. PubMed PMC

Burke MF, Khera AV, Rader DJ. Polyphenols and cholesterol efflux: is coffee the next red wine? Circulation Research. 2010;106(4):627–629. PubMed PMC

Manach C, Williamson G, Morand C, Scalbert A, Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. The American Journal of Clinical Nutrition. 2005;81(1, supplement):230S–242S. PubMed

Halliwell B, Rafter J, Jenner A. Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? Antioxidant or not? The American Journal of Clinical Nutrition. 2005;81(1, supplement):268S–276S. PubMed

Sies H, Schewe T, Heiss C, Kelm M. Cocoa polyphenols and inflammatory mediators. The American Journal of Clinical Nutrition. 2005;81(1, supplement):304S–312S. PubMed

Pagonis C, Tauber AI, Pavlotsky N, Simons ER. Flavonoid impairment of neutrophil response. Biochemical Pharmacology. 1986;35(2):237–245. PubMed

Zielinska M, Kostrzewa A, Ignatowicz E. Antioxidative activity of flavonoids in stimulated human neutrophils. Folia Histochemica et Cytobiologica. 2000;38(1):25–30. PubMed

Wang JP, Chang LC, Hsu MF, Chen SC, Kuo SC. Inhibition of formyl-methionyl-leucyl-phenylalanine-stimulated respiratory burst by cirsimaritin involves inhibition of phospholipase D signaling in rat neutrophils. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2002;366(4):307–314. PubMed

Wang JP, Chang LC, Hsu MF, Lin CN. The blockade of formyl peptide-induced respiratory burst by 2′,5′-dihydroxy-2-furfurylchalcone involves phospholipase D signaling in neutrophils. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2003;368(3):166–174. PubMed

Chang LC, Huang TH, Chang CS, et al. Signaling mechanisms of inhibition of phospholipase D activation by CHS-111 in formyl peptide-stimulated neutrophils. Biochemical Pharmacology. 2011;81(2):269–278. PubMed

Selloum L, Reichl S, Muller M, Sebihi L, Arnhold J. Effects of flavonols on the generation of superoxide anion radicals by xanthine oxidase and stimulated neutrophils. Archives of Biochemistry and Biophysics. 2001;395(1):49–56. PubMed

Lee JP, Li YC, Chen HY, et al. Protective effects of luteolin against lipopolysaccharide-induced acute lung injury involves inhibition of MEK/ERK and PI3K/Akt pathways in neutrophils. Acta Pharmacologica Sinica. 2010;31(7):831–838. PubMed PMC

Pastene E, Speisky H, Troncoso M, Alarcón J, Figueroa G. In vitro inhibitory effect of apple peel extract on the growth of helicobacter pylori and respiratory burst induced on human neutrophils. Journal of Agricultural and Food Chemistry. 2009;57(17):7743–7749. PubMed

Kenny TP, Shu SA, Moritoki Y, Keen CL, Gershwin ME. Cocoa flavanols and procyanidins can modulate the lipopolysaccharide activation of polymorphonuclear cells in vitro. Journal of Medicinal Food. 2009;12(1):1–7. PubMed

Pincemail J, Thirion A, Dupuis M, et al. Ginkgo biloba extracts inhibits oxygen species production generated by phorbol myristate acetate stimulated human leukocytes. Experientia. 1987;43(2):181–184. PubMed

Ciz M, Pavelkova M, Gallova L, Kralova J, Kubala L, Lojek A. The influence of wine polyphenols on reactive oxygen and nitrogen species production by murine macrophages RAW 264.7. Physiological Research. 2008;57(3):393–402. PubMed

Scolaro B, Delwing- de Lima D, Pereira da Cruz JG, Delwing- Dal Magro D. Mate tea prevents oxidative stress in the blood and hippocampus of rats with acute or chronic ethanol administration. Oxidative Medicine and Cellular Longevity. 2012;2012:8 pages. Article ID 314758. PubMed PMC

Afanas'ev I. ROS and RNS signaling in heart disorders: could antioxidant treatment be successful? Oxidative Medicine and Cellular Longevity. 2011;2011:13 pages. Article ID 293769. PubMed PMC

Attia SM, Bakheet SA, Al-Rasheed NM. Proanthocyanidins produce significant attenuation of doxorubicin-induced mutagenicity via suppression of oxidative stress. Oxidative Medicine and Cellular Longevity. 2010;3(6):404–413. PubMed PMC

Daels-Rakotoarison DA, Gressier B, Trotin F, et al. Effects of Rosa canina fruit extract on neutrophil respiratory burst. Phytotherapy Research. 2002;16(2):157–161. PubMed

Ellinger S, Arendt BM, Fimmers R, Stehle P, Spengler U, Goerlich R. Bolus ingestion but not regular consumption of native or dealcoholized red wine modulates selected immunological functions of leukocytes in healthy volunteers. Annals of Nutrition and Metabolism. 2008;52(4):288–295. PubMed

Henson D, Nieman D, Davis JM, et al. Post-160-km race illness rates and decreases in granulocyte respiratory burst and salivary IgA output are not countered by quercetin ingestion. International Journal of Sports Medicine. 2008;29(10):856–863. PubMed

Kanashiro A, Kabeya LM, Martinello F, et al. Effect of rutin on polymorphonuclear leukocytes oxidative metabolism in hypercholesterolemia Golden Syrian hamsters: evaluation by chemiluminescence and flow cytometry. Pharmazie. 2007;62(4):295–298. PubMed

López D, Pavelkova M, Gallova L, et al. Dealcoholized red and white wines decrease oxidative stress associated with inflammation in rats. British Journal of Nutrition. 2007;98(3):611–619. PubMed

Williamson G, Manach C. Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. The American Journal of Cinical Nutrition. 2005;81(1):243s–255s. PubMed

Rabiskova M, Bautzova T, Gajdziok J, et al. Coated chitosan pellets containing rutin intended for the treatment of inflammatory bowel disease: in vitro characteristics and in vivo evaluation. International Journal of Pharmaceutics. 2012;422(1-2):151–159. PubMed

Williamson G. The use of flavonoid aglycones in in vitro systems to test biological activities: based on bioavailability data, is this a valid approach? Phytochemistry Reviews. 2002;1(2):215–222.

Study of possible mechanisms involved in the inhibitory effects of coumarin derivatives on neutrophil activity