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Treatment with Rutin - A Therapeutic Strategy for Neutrophil-Mediated Inflammatory and Autoimmune Diseases - Anti-inflammatory Effects of Rutin on Neutrophils -

  • Nikfarjam, Bahareh Abd (Cellular and Molecular Research Center, Qazvin University of Medical Sciences) ;
  • Adineh, Mohtaram (Department of Immunology, Qazvin University of Medical Sciences) ;
  • Hajiali, Farid (Cellular and Molecular Research Center, Qazvin University of Medical Sciences) ;
  • Nassiri-Asl, Marjan (Cellular and Molecular Research Center, Qazvin University of Medical Sciences)
  • Received : 2017.01.04
  • Accepted : 2017.02.03
  • Published : 2017.03.31

Abstract

Objectives: Neutrophils represent the front line of human defense against infections. Immediately after stimulation, neutrophilic enzymes are activated and produce toxic mediators such as pro-inflammatory cytokines, nitric oxide (NO) and myeloperoxidase (MPO). These mediators can be toxic not only to infectious agents but also to host tissues. Because flavonoids exhibit antioxidant and anti-inflammatory effects, they are subjects of interest for pharmacological modulation of inflammation. In the present study, the effects of rutin on stimulus-induced NO and tumor necrosis factor $(TNF)-{\alpha}$ productions and MPO activity in human neutrophils were investigated. Methods: Human peripheral blood neutrophils were isolated using Ficoll-Hypaque density gradient centrifugation coupled with dextran T500 sedimentation. The cell preparations containing > 98% granulocytes were determined by morphological examination through Giemsa staining. Neutrophils were cultured in complete Roswell Park Memorial Institute (RPMI) medium, pre-incubated with or without rutin ($25{\mu}M$) for 45 minutes, and stimulated with phorbol 12-myristate 13-acetate (PMA). Then, the $TNF-{\alpha}$, NO and MPO productions were analyzed using enzyme-linked immunosorbent assay (ELISA), Griess Reagent, and MPO assay kits, respectively. Also, the viability of human neutrophils was assessed using tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and neutrophils were treated with various concentrations of rutin ($1-100{\mu}M$), after which MTT was appended and incubated at $37^{\circ}C$ for 4 hour. Results: Rutin at concentrations up to $100{\mu}M$ did not affect neutrophil viability during the 4-hour incubation period. Rutin significantly decreased the NO and $TNF-{\alpha}$ productions in human peripheral blood neutrophils compared to PMA-control cells (P < 0.001). Also, MPO activity was significantly reduced by rutin (P < 0.001). Conclusion: In this in vitro study, rutin had an anti-inflammatory effect due to its inhibiting NO and $TNF-{\alpha}$ productions, as well as MPO activity, in activated human neutrophils. Treatment with rutin may be considered as a therapeutic strategy for neutrophil-mediated inflammatory/autoimmune diseases.

Acknowledgement

Supported by : Qazvin University of Medical Sciences

References

  1. Faurschou M, Borregaard N. Neutrophil granules and secretory vesicles in inflammation. Microbes Infect. 2003;5(14):1317-27. https://doi.org/10.1016/j.micinf.2003.09.008
  2. Powers SK, Jackson MJ. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev. 2008;88(4):1243-76. https://doi.org/10.1152/physrev.00031.2007
  3. Deby-Dupont G, Deby C, Lamy M. Neutrophil myeloperoxidase revisited: it's role in health and disease. Intensivmed Notfallmed. 1999;36(6):500-13. https://doi.org/10.1007/s003900050270
  4. Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem. 2002;13(10): 572-84. https://doi.org/10.1016/S0955-2863(02)00208-5
  5. Fabjan N, Rode J, Kosir IJ, Wang Z, Zhang Z, Kreft I. Tartary buckwheat (Fagopyrum tataricum Gaertn) as a source of dietary rutin and quercitrin. J Agric Food Chem. 2003;51(22):6452-5. https://doi.org/10.1021/jf034543e
  6. Wang M, Tadmor Y, Wu QL, Chin CK, Garrison SA, Simon JE. Quantification of protodioscin and rutin in asparagus shoots by LC⁄MS and HPLC methods. J Agric Food Chem. 2003;51(21):6132-6. https://doi.org/10.1021/jf0344587
  7. Yoo H, Ku SK, Baek YD, Bae JS. Anti-inflammatory effects of rutin on HMGB1-induced inflammatory responses in vitro and in vivo. Inflamm Res. 2014;63(3):197-206. https://doi.org/10.1007/s00011-013-0689-x
  8. Nassiri-Asl M, Naserpour Farivar T, Abbasi E, Sadeghnia HR, Sheikhi M, Lotfizadeh M, et al. Effects of rutin on oxidative stress in mice with kainic acid-induced seizure. J Integr Med. 2013;11(5):337-42. https://doi.org/10.3736/jintegrmed2013042
  9. Morimoto Y, Yasuhara T, Sugimoto A, Inoue A, Hide I, Akiyama M, et al. Anti-allergic substances contained in the pollen of Cryptomeria japonica possess diverse effects on the degranulation of RBL-2H3 cells. J Pharmacol Sci. 2003;92(3):291-5. https://doi.org/10.1254/jphs.92.291
  10. Moghbelinejad S, Nassiri-Asl M, Farivar TN, Abbasi E, Sheikhi M, Taghiloo M, et al. Rutin activates the MAPK pathway and BDNF gene expression on beta-amyloid induced neurotoxicity in rats. Toxicol Lett. 2014;224(1):108-13. https://doi.org/10.1016/j.toxlet.2013.10.010
  11. Motamedshariaty VS, Amel Farzad S, Nassiri-Asl M, Hosseinzadeh H. Effects of rutin on acrylamide-induced neurotoxicity. Daru. 2014;22(1):27. https://doi.org/10.1186/2008-2231-22-27
  12. Kim DS, Ji HD, Rhee MH, Sung YY, Yang WK, Kim SH, et al. Antiplatelet activity of Morus alba leaves extract, mediated via inhibiting granule secretion and blocking the phosphorylation of extracellular-signal-regulated kinase and Akt. Evid Based Complement Alternat Med. 2014;2014:DOI: 10.1155/2014/639548. https://doi.org/10.1155/2014/639548
  13. Huang YC, Horng CT, Chen ST, Lee SS, Yang ML, Lee CY, et al. Rutin improves endotoxin-induced acute lung injury via inhibition of iNOS and VCAM-1 expression. Environ Toxicol. 2016;31(2):185-91. https://doi.org/10.1002/tox.22033
  14. Arjumand W, Seth A, Sultana S. Rutin attenuates cisplatin induced renal inflammation and apoptosis by reducing $NF{\kappa}B$, $TNF-{\alpha}$ and caspase-3 expression in wistar rats. Food Chem Toxicol. 2011;49(9):2013-21. https://doi.org/10.1016/j.fct.2011.05.012
  15. Maqbool M, Vidyadaran S, George E, Ramasamy R. Optimisation of laboratory procedures for isolating human peripheral blood derived neutrophils. Med J Malaysia. 2011;66(4):296-9.
  16. 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.
  17. Chen JW, Zhu ZQ, Hu TX, Zhu DY. Structure-activity relationship of natural flavonoids in hydroxyl radical-scavenging effects. Acta Pharmacol Sin. 2002;23(7):667-72.
  18. Kauss T, Moynet D, Rambert J, Al-Kharrat A, Brajot S, Thiolat D, et al. Rutoside decreases human macrophage derived inflammatory mediators and improves clinical signs in adjuvant induced arthritis. Arthritis Res Ther. 2008;10(1):DOI: 10.1186/ar2372. https://doi.org/10.1186/ar2372
  19. Lago JH, Toledo-Arruda AC, Mernak M, Barrosa KH, Martins MA, Tiberio IF, et al. Structure-activity association of flavonoids in lung diseases. Molecules. 2014;19(3):3570-95. https://doi.org/10.3390/molecules19033570
  20. Lee W, Ku SK, Bae JS. Barrier protective effects of rutin in LPS-induced inflammation in vitro and in vivo. Food Chem Toxicol. 2012;50(9):3048-55. https://doi.org/10.1016/j.fct.2012.06.013
  21. Shiba Y, Kinoshita T, Chuman H, Taketani Y, Takeda E, Kato Y, et al. Flavonoids as substrates and inhibitors of myeloperoxidase: molecular actions of aglycone and metabolites. Chem Res Toxicol. 2008;21(8):1600-9. https://doi.org/10.1021/tx8000835
  22. Yeh CH, Yang JJ, Yang ML, Li YC, Kuan YH. Rutin decreases lipopolysaccharide-induced acute lung injury via inhibition of oxidative stress and the MAPK-$NF-{\kappa}B$ pathway. Free Radic Biol Med. 2014;69:249-57. https://doi.org/10.1016/j.freeradbiomed.2014.01.028
  23. Arruda-Silva F, Nascimento MV, Luz AB, Venzke D, Queiroz GS, Frode TS, et al. Polygala molluginifolia A. St.-Hil. and Moq. prevent inflammation in the mouse pleurisy model by inhibiting $NF-{\kappa}B$ activation. Int Immunopharmacol. 2014;19(2):334-41. https://doi.org/10.1016/j.intimp.2014.02.010
  24. Shin YK, Sohn UD, Choi MS, Kum C, Sim SS, Lee MY. Effects of rutin and harmaline on rat reflux oesophagitis. Auton Autacoid Pharmacol. 2002;22(1):47-55. https://doi.org/10.1046/j.1474-8673.2002.00241.x

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