Anti-inflammatory Effects of Quercetin and Vitexin on Activated Human Peripheral Blood Neutrophils - The effects of quercetin and vitexin on human neutrophils -

  • Nikfarjam, Bahareh Abd (Cellular and Molecular Research Center, Qazvin University of Medical Sciences) ;
  • Hajiali, Farid (Cellular and Molecular Research Center, Qazvin University of Medical Sciences) ;
  • Adineh, Mohtaram (Department of Immunology, School of Medicine, Qazvin University of Medical Sciences) ;
  • Nassiri-Asl, Marjan (Cellular and Molecular Research Center, Qazvin University of Medical Sciences)
  • Received : 2017.05.23
  • Accepted : 2017.06.20
  • Published : 2017.06.30


Objectives: Polymorphonuclear neutrophils (PMNs) constitute the first line of defense against invading microbial pathogens. Early events in inflammation involve the recruitment of neutrophils to the site of injury or damage where changes in intracellular calcium can cause the activation of pro-inflammatory mediators from neutrophils including superoxide generation, degranulation and release of myeloperoxidase (MPO), productions of interleukin (IL)-8 and tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$), and adhesion to the vascular endothelium. To address the anti-inflammatory role of flavonoids, in the present study, we investigated the effects of the flavonoids quercetin and vitexin on the stimulus-induced nitric oxide (NO), $TNF-{\alpha}$, and MPO productions in human neutrophils. Methods: Human peripheral blood neutrophils were isolated, and their viabilities were determined by using the Trypan Blue exclusion test. The polymorphonuclear leukocyte (PMNL) preparations contained more than 98% neutrophils as determined by morphological examination with Giemsa staining. The viabilities of cultured neutrophils with various concentrations of quercetin and vitexin ($1-100{\mu}M$) were studied using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. Neutrophils were cultured in complete Roswell Park Memorial Institute (RPMI) medium, pre-incubated with or without quercetin and vitexin ($25{\mu}M$) for 45 min, and stimulated with phorbol 12-myristate 13-acetate (PMA) ($10^{-7}M$). NO production was carried out through nitrite determination by using the Griess method. Also, the $TNF-{\alpha}$ and the MPO productions were measured using enzyme-linked immunosorbent assay (ELISA) kits and MPO assay kits. Results: Neutrophil viability was not affected up to a concentration of $100{\mu}M$ of quercetin or vitexin. Both quercetin and vitexin significantly inhibited $TNF-{\alpha}$, NO, and MPO productions in human neutrophils (P < 0.001). Conclusion:The present study showed that both quercetin and vitexin had significant anti-inflammatory effects. Thus, treatment with either quercetin or vitexin may be considered as a therapeutic strategy for treating patients with neutrophil-mediated inflammatory diseases.


Supported by : Qazvin University of Medical Sciences


  1. Mayadas TN, Cullere X, Lowell CA. The multifaceted functions of neutrophils. Annu Rev Pathol. 2014;9:181-218.
  2. Davies MJ. Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention. J Clin Biochem Nutr. 2011;48(1):8-19.
  3. Yang JH, Kim SC, Shin BY, Jin SH, Jo MJ, Jegal KH, et al. O-methylated flavonol isorhamnetin prevents acute inflammation through blocking of $NF-{\kappa}B$ activation. Food Chem Toxicol. 2013;59:362-72.
  4. Middleton E Jr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev. 2000;52(4):673-751.
  5. Nikfarjam BA, Adineh M, Hajiali F, Nassiri-Asl M. Treatment with rutin - a therapeutic strategy for neutrophil-mediated inflammatory and autoimmune diseases. J Pharmacopuncture. 2017;20(1):52-6.
  6. Gonzalez R, Ballester I, Lopez-Posadas R, Suarez MD, Zarzuelo A, Martinez-Augustin O, et al. Effects of flavonoids and other polyphenols on inflammation. Crit Rev Food Sci Nutr. 2011;51(4):331-62.
  7. Abbasi E, Nassiri-Asl M, Shafeei M, Sheikhi M. Neuroprotective effects of vitexin, a flavonoid, on pentylenetetrazole-induced seizure in rats. Chem Biol Drug Des. 2012;80(2):274-8.
  8. Nassiri-Asl M, Hajiali F, Taghiloo M, Abbasi E, Mohseni F, Yousefi F. Comparison between the effects of quercetin on seizure threshold in acute and chronic seizure models. Toxicol Ind Health. 2016;32(5):936-44.
  9. Huang R, Zhong T, Wu H. Quercetin protects against lipopolysaccharide-induced acute lung injury in rats through suppression of inflammation and oxidative stress. Arch Med Sci. 2015;11(2):427-32.
  10. Borghi SM, Carvalho TT, Staurengo-Ferrari L, Hohmann MS, Pinge-Filho P, Casagrande R, et al. Vitexin inhibits inflammatory pain in mice by targeting TRPV1, oxidative stress, and cytokines. J Nat Prod. 2013;76(6):1141-9.
  11. Ding AH, Nathan CF, Stuehr DJ. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. comparison of activating cytokines and evidence for independent production. J Immunol. 1988;141(7):2407-12.
  12. Eguchi K, Nagai R. Islet inflammation in type 2 diabetes and physiology. J Clin Invest. 2017;127(1):14-23.
  13. Moore MM, Chua W, Charles KA, Clarke SJ. Inflammation and cancer: causes and consequences. Clin Pharmacol Ther. 2010;87(4):504-8.
  14. Perez-Cerda F, Sanchez-Gomez MV, Matute C. The link of inflammation and neurodegeneration in progressive multiple sclerosis. Mult Scler Demyelinating Disord. 2016;1:9.
  15. Lirk P, Hoffmann G, Rieder J. Inducible nitric oxide synthase-time for reappraisal. Curr Drug Targets Inflamm Allergy. 2002;1(1):89-108.
  16. Yang Y, Yu T, Jang HJ, Byeon SE, Song SY, Lee BH, et al. In vitro and in vivo anti-inflammatory activities of Polygonum hydropiper methanol extract. J Ethnopharmacol. 2012;139(2):616-25.
  17. Endale M, Park SC, Kim S, Kim SH, Yang Y, Cho JY, et al. Quercetin disrupts tyrosine-phosphorylated phosphatidylinositol 3-kinase and myeloid differentiation factor-88 association, and inhibits MAPK/AP-1 and IKK/$NF-{\kappa}B$-induced inflammatory mediators production in RAW 264.7 cells. Immunobiology. 2013;218(12):1452-67.
  18. Rosa SI, Rios-Santos F, Balogun SO, Martins DT. Vitexin reduces neutrophil migration to inflammatory focus by down-regulating pro-inflammatory mediators via inhibition of p38, ERK1/2 and JNK pathway. Phytomedicine. 2016;23(1):9-17.
  19. Liu H, Xue JX, Li X, Ao R, Lu Y. Quercetin liposomes protect against radiation-induced pulmonary injury in a murine model. Oncol Lett. 2013;6(2):453-9.
  20. Liao YR, Lin JY. Quercetin intraperitoneal administration ameliorates lipopolysaccharide-induced systemic inflammation in mice. Life Sci. 2015;137:89-97.
  21. Pfeuffer M, Auinger A, Bley U, Kraus-Stojanowic I, Laue C, Winkler P, et al. Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammation in men with different APOE isoforms. Nutr Metab Cardiovasc Dis. 2013;23(5):403-9.
  22. Dong L, Fan Y, Shao X, Chen Z. Vitexin protects against myocardial ischemia/reperfusion injury in Langendorff-perfused rat hearts by attenuating inflammatory response and apoptosis. Food Chem Toxicol. 2011;49(12):3211-6.
  23. Dong LY, Li S, Zhen YL, Wang YN, Shao X, Luo ZG. Cardioprotection of vitexin on myocardial ischemia/reperfusion injury in rat via regulating inflammatory cytokines and MAPK pathway. Am J Chin Med. 2013;41(6):1251-66.
  24. Ma Z, Ji W, Fu Q, Ma S. Formononetin inhibited the inflammation of LPS-induced acute lung injury in mice associated with induction of PPAR gamma expression. Inflammation. 2013;36(6):1560-6.
  25. Bhaskar S, Sudhakaran, PR, Helen A. Quercetin attenuates atherosclerotic inflammation and adhesion molecule expression by modulating TLR-$NF-{\kappa}B$ signaling pathway. Cell Immunol. 2016;310:131-40.
  26. Pecivova J, Macickova T, Svitekova K, Nosal' R. Quercetin inhibits degranulation and superoxide generation in PMA stimulated neutrophils. Interdiscip Toxicol. 2012;5(2):81-3.
  27. Schultke E, Griebel RW, Juurlink BH. Quercetin attenuates inflammatory processes after spinal cord injury in an animal model. Spinal Cord. 2010;48(12):857-61.
  28. Sun Z, Yan B, Yu WY, Yao X, Ma X, Sheng G, et al. Vitexin attenuates acute doxorubicin cardiotoxicity in rats via the suppression of oxidative stress, inflammation and apoptosis and the activation of FOXO3a. Exp Ther Med. 2016;12(3):1879-84.