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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

Research Article

Quercetin Decreased Alveolar Bone Loss and Apoptosis in Experimentally Induced Periodontitis Model in Wistar Rats

Author(s): Mehmet Murat Taskan* and Fikret Gevrek

Volume 19, Issue 4, 2020

Page: [436 - 448] Pages: 13

DOI: 10.2174/1871523019666200124114503

Price: $65

Abstract

Background: Quercetin is a flavonoid which has potent anti-inflammatory, antibacterial, and antioxidant effect. Purpose of this study was to evaluate effects of quercetin on alveolar bone loss and histopathological changes in ligature-induced periodontitis in rats.

Methods: Wistar rats were divided into four experimental groups: non-ligated control (C, n=8) group; periodontitis (P, n=8) group; ligature and low dose quercetin group (75 mg/kg/day quercetin, Q75 group, n=8); ligature and high dose quercetin group (150 mg/kg/day quercetin, Q150 group, n=8). Silk ligatures were placed at gingival margin of lower first molars of mandibular right quadrant. Study duration was 15 days, and animals were sacrificed end of this period. Changes in alveolar bone levels were clinically measured and tissues were immunohistochemically examined, matrix metalloproteinase 8 (MMP 8), inducible nitric oxide synthase (iNOS), tissue inhibitor of metalloproteinase 1 (TIMP 1), Cysteine-aspartic proteases 3 (Caspase 3), and tartrate-resistant acid phosphatase (TRAP) positive osteoclast cells, osteoblast, and neutrophil counts were also determined.

Results and Discussion: Alveolar bone loss was highest in P group, and differences among P, Q75, and Q150 groups were significant. Both doses of quercetin decreased TRAP+ osteoclast cells and increased osteoblast cells. Inflammation in P group was also higher than those of C, Q75, and Q150 groups indicating anti-inflammatory effect of quercetin. iNOS, MMP-8, and caspase-3 levels were highest, and TIMP-1 expression was lowest in P group; differences were statistically significant.

Conclusion: Within limits of this study, it can be suggested that quercetin administration may reduce alveolar bone loss by increasing osteoblastic activity, decreasing osteoclastic activity, apoptosis, and inflammation in an experimental model of periodontitis.

Keywords: Anti-inflammatory, antioxidants, experimental periodontitis, iNOS, MMP-8, quercetin.

Graphical Abstract
[1]
Orihuela-Campos, R.C.; Tamaki, N.; Mukai, R.; Fukui, M.; Miki, K.; Terao, J.; Ito, H-O. Biological impacts of resveratrol, quercetin, and N-acetylcysteine on oxidative stress in human gingival fibroblasts. J. Clin. Biochem. Nutr., 2015, 56(3), 220-227.
[http://dx.doi.org/10.3164/jcbn.14-129] [PMID: 26060353]
[2]
Zhang, J-M.; An, J. Cytokines, inflammation, and pain. Int. Anesthesiol. Clin., 2007, 45(2), 27-37.
[http://dx.doi.org/10.1097/AIA.0b013e318034194e] [PMID: 17426506]
[3]
Mantovani, A.; Sica, A.; Sozzani, S.; Allavena, P.; Vecchi, A.; Locati, M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol., 2004, 25(12), 677-686.
[http://dx.doi.org/10.1016/j.it.2004.09.015] [PMID: 15530839]
[4]
Xiao, C-J.; Yu, X-J.; Xie, J-L.; Liu, S.; Li, S. Protective effect and related mechanisms of curcumin in rat experimental periodontitis. Head Face Med., 2018, 14(1), 12.
[http://dx.doi.org/10.1186/s13005-018-0169-1] [PMID: 30115081]
[5]
Sasaki, S.; Takeda, K.; Takewaki, M.; Ouhara, K.; Kajiya, M.; Mizuno, N.; Fujita, T.; Kurihara, H. BDNF/HMW‐HA complex as an adjunct to nonsurgical periodontal treatment of ligature‐induced periodontitis in dogs. J. Periodontol., 2018, 90(1), 98-109.
[PMID: 30030840]
[6]
Callaway, D.A.; Riquelme, M.A.; Sharma, R.; Lopez-Cruzan, M.; Herman, B.A.; Jiang, J.X. Caspase-2 modulates osteoclastogenesis through down-regulating oxidative stress. Bone, 2015, 76, 40-48.
[http://dx.doi.org/10.1016/j.bone.2015.03.006] [PMID: 25796569]
[7]
Schieber, M.; Chandel, N.S. ROS function in redox signaling and oxidative stress. Curr. Biol., 2014, 24(10), R453-R462.
[http://dx.doi.org/10.1016/j.cub.2014.03.034] [PMID: 24845678]
[8]
Zhou, J.; Lei, Y.; Chen, J.; Zhou, X. Potential ameliorative effects of epigallocatechin-3-gallate against testosterone-induced benign prostatic hyperplasia and fibrosis in rats. Int. Immunopharmacol., 2018, 64, 162-169.
[http://dx.doi.org/10.1016/j.intimp.2018.08.038] [PMID: 30179845]
[9]
Kurutas, E.B. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr. J., 2016, 15(1), 71.
[http://dx.doi.org/10.1186/s12937-016-0186-5] [PMID: 27456681]
[10]
Anand David, A.V.; Arulmoli, R.; Parasuraman, S. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn. Rev., 2016, 10(20), 84-89.
[http://dx.doi.org/10.4103/0973-7847.194044] [PMID: 28082789]
[11]
Li, Y.; Yao, J.; Han, C.; Yang, J.; Chaudhry, M.T.; Wang, S.; Liu, H.; Yin, Y. Quercetin, inflammation and immunity. Nutrients, 2016, 8(3), 167.
[http://dx.doi.org/10.3390/nu8030167] [PMID: 26999194]
[12]
Wang, S.; Yao, J.; Zhou, B.; Yang, J.; Chaudry, M.T.; Wang, M.; Xiao, F.; Li, Y.; Yin, W. Bacteriostatic effect of Quercetin as an antibiotic alternative in vivo and its antibacterial mechanism in vitro. J. Food Prot., 2018, 81(1), 68-78.
[http://dx.doi.org/10.4315/0362-028X.JFP-17-214] [PMID: 29271686]
[13]
Comalada, M.; Camuesco, D.; Sierra, S.; Ballester, I.; Xaus, J.; Gálvez, J.; Zarzuelo, A. In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway. Eur. J. Immunol., 2005, 35(2), 584-592.
[http://dx.doi.org/10.1002/eji.200425778] [PMID: 15668926]
[14]
Gutiérrez-Venegas, G.; Torras-Ceballos, A.; Gómez-Mora, J.A.; Fernández-Rojas, B. Luteolin, quercetin, genistein and quercetagetin inhibit the effects of lipopolysaccharide obtained from Porphyromonas gingivalis in H9c2 cardiomyoblasts. Cell. Mol. Biol. Lett., 2017, 22(1), 19.
[http://dx.doi.org/10.1186/s11658-017-0047-z] [PMID: 28878808]
[15]
Lee, M.; Yun, S.; Lee, H.; Yang, J. Quercetin mitigates inflammatory responses induced by vascular endothelial growth factor in mouse retinal photoreceptor cells through suppression of nuclear factor Kappa B. Int. J. Mol. Sci., 2017, 18(11), 2497.
[http://dx.doi.org/10.3390/ijms18112497] [PMID: 29165402]
[16]
Gutiérrez-Venegas, G.; Bando-Campos, C.G. The flavonoids luteolin and quercetagetin inhibit lipoteichoic acid actions on H9c2 cardiomyocytes. Int. Immunopharmacol., 2010, 10(9), 1003-1009.
[http://dx.doi.org/10.1016/j.intimp.2010.05.012] [PMID: 20685402]
[17]
Cheng, W.C.; Huang, R.Y.; Chiang, C.Y.; Chen, J.K.; Liu, C.H.; Chu, C.L.; Fu, E. Ameliorative effect of quercetin on the destruction caused by experimental periodontitis in rats. J. Periodontal Res., 2010, 45(6), 788-795.
[http://dx.doi.org/10.1111/j.1600-0765.2010.01301.x] [PMID: 20663021]
[18]
Kador, P.F.; O’Meara, J.D.; Blessing, K.; Marx, D.B.; Reinhardt, R.A. Efficacy of structurally diverse aldose reductase inhibitors on experimental periodontitis in rats. J. Periodontol., 2011, 82(6), 926-933.
[http://dx.doi.org/10.1902/jop.2010.100442] [PMID: 21189083]
[19]
Ouhara, K.; Munenaga, S.; Kajiya, M.; Takeda, K.; Matsuda, S.; Sato, Y.; Hamamoto, Y.; Iwata, T.; Yamasaki, S.; Akutagawa, K.; Mizuno, N.; Fujita, T.; Sugiyama, E.; Kurihara, H. The induced RNA-binding protein, HuR, targets 3′-UTR region of IL-6 mRNA and enhances its stabilization in periodontitis. Clin. Exp. Immunol., 2018, 192(3), 325-336.
[http://dx.doi.org/10.1111/cei.13110] [PMID: 29393507]
[20]
Chen, B.; He, T.; Xing, Y.; Cao, T. Effects of quercetin on the expression of MCP-1, MMP-9 and VEGF in rats with diabetic retinopathy. Exp. Ther. Med., 2017, 14(6), 6022-6026.
[http://dx.doi.org/10.3892/etm.2017.5275] [PMID: 29285153]
[21]
Silva, F.C.; Bramatti, I.C.; Toledo, A.G.; Salles, F.M.; Itinose, A.M.; Marek, C.B. Antihyperglycemic effect of quercetin in ovariectomized rats treated with tamoxifen. J. Med. Food, 2017, 20(3), 235-242.
[http://dx.doi.org/10.1089/jmf.2016.0078] [PMID: 28121480]
[22]
Leong, N.L.; Hurng, J.M.; Djomehri, S.I.; Gansky, S.A.; Ryder, M.I.; Ho, S.P. Age-related adaptation of bone-PDL-tooth complex: Rattus-Norvegicus as a model system. PLoS One, 2012, 7(4) e35980
[http://dx.doi.org/10.1371/journal.pone.0035980]] [PMID: 22558292]
[23]
Balci Yuce, H.; Karatas, Ö.; Tulu, F.; Altan, A.; Gevrek, F. Effect of diabetes on collagen metabolism and hypoxia in human gingival tissue: a stereological, histopathological, and immunohistochemical study. Biotech. Histochem., 2019, 94(1), 65-73.
[http://dx.doi.org/10.1080/10520295.2018.1508745] [PMID: 30317872]
[24]
Toker, H.; Balci Yuce, H.; Lektemur Alpan, A.; Gevrek, F.; Elmastas, M. Morphometric and histopathological evaluation of the effect of grape seed proanthocyanidin on alveolar bone loss in experimental diabetes and periodontitis. J. Periodontal Res., 2018, 53(3), 478-486.
[http://dx.doi.org/10.1111/jre.12536] [PMID: 29446089]
[25]
Kang, S.J.; Lee, E.K.; Han, C.H.; Lee, B.H.; Lee, Y.J.; Ku, S.K. Inhibitory effects of Persicariae rhizoma aqueous extracts on experimental periodontitis and alveolar bone loss in Sprague-Dawley rats. Exp. Ther. Med., 2016, 12(3), 1563-1571.
[http://dx.doi.org/10.3892/etm.2016.3499] [PMID: 27588077]
[26]
Teixeira, A.H.; Freire, J.M.O.; de Sousa, L.H.T.; Parente, A.T.; de Sousa, N.A.; Arriaga, A.M.C.; Lopes da Silva, F.R.; Melo, I.M.; Castro da Silva, I.I.; Pereira, K.M.A.; Goes, P.; Costa, J.J.D.N.; Cristino-Filho, G.; Pinto, V.P.T.; Chaves, H.V.; Bezerra, M.M. Stemodia maritima L. extract decreases inflammation, oxidative stress, and alveolar bone loss in an experimental periodontitis rat model. Front. Physiol., 2017, 8, 988.
[http://dx.doi.org/10.3389/fphys.2017.00988] [PMID: 29249988]
[27]
Damgaard, C.; Holmstrup, P.; Van Dyke, T.E.; Nielsen, C.H. The complement system and its role in the pathogenesis of periodontitis: current concepts. J. Periodontal Res., 2015, 50(3), 283-293.
[http://dx.doi.org/10.1111/jre.12209] [PMID: 25040158]
[28]
Guo, C.; Hou, G.Q.; Li, X.D.; Xia, X.; Liu, D.X.; Huang, D.Y.; Du, S.X. Quercetin triggers apoptosis of lipopolysaccharide (LPS)-induced osteoclasts and inhibits bone resorption in RAW264.7 cells. Cell. Physiol. Biochem., 2012, 30(1), 123-136.
[http://dx.doi.org/10.1159/000339052] [PMID: 22759961]
[29]
Qiu, L.; Luo, Y.; Chen, X. Quercetin attenuates mitochondrial dysfunction and biogenesis via upregulated AMPK/SIRT1 signaling pathway in OA rats. Biomed. Pharmacother., 2018, 103, 1585-1591.
[http://dx.doi.org/10.1016/j.biopha.2018.05.003] [PMID: 29864946]
[30]
Walker, E.H.; Pacold, M.E.; Perisic, O.; Stephens, L.; Hawkins, P.T.; Wymann, M.P.; Williams, R.L. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol. Cell, 2000, 6(4), 909-919.
[http://dx.doi.org/10.1016/S1097-2765(05)00089-4] [PMID: 11090628]
[31]
Sicheri, F.; Moarefi, I.; Kuriyan, J. Crystal structure of the Src family tyrosine kinase Hck. Nature, 1997, 385(6617), 602-609.
[http://dx.doi.org/10.1038/385602a0] [PMID: 9024658]
[32]
Park, C.H.; Chang, J.Y.; Hahm, E.R.; Park, S.; Kim, H-K.; Yang, C.H. Quercetin, a potent inhibitor against β-catenin/Tcf signaling in SW480 colon cancer cells. Biochem. Biophys. Res. Commun., 2005, 328(1), 227-234.
[http://dx.doi.org/10.1016/j.bbrc.2004.12.151] [PMID: 15670774]
[33]
Wiseman, R.L.; Zhang, Y.; Lee, K.P.; Harding, H.P.; Haynes, C.M.; Price, J.; Sicheri, F.; Ron, D. Flavonol activation defines an unanticipated ligand-binding site in the kinase-RNase domain of IRE1. Mol. Cell, 2010, 38(2), 291-304.
[http://dx.doi.org/10.1016/j.molcel.2010.04.001] [PMID: 20417606]
[34]
Endale, M.; Park, S-C.; Kim, S.; Kim, S-H.; Yang, Y.; Cho, J.Y.; Rhee, M.H. Quercetin disrupts tyrosine-phosphorylated phosphatidylinositol 3-kinase and myeloid differentiation factor-88 association, and inhibits MAPK/AP-1 and IKK/NF-κB-induced inflammatory mediators production in RAW 264.7 cells. Immunobiology, 2013, 218(12), 1452-1467.
[http://dx.doi.org/10.1016/j.imbio.2013.04.019] [PMID: 23735482]
[35]
Naasani, I.; Oh-Hashi, F.; Oh-Hara, T.; Feng, W.Y.; Johnston, J.; Chan, K.; Tsuruo, T. Blocking telomerase by dietary polyphenols is a major mechanism for limiting the growth of human cancer cells in vitro and in vivo. Cancer Res., 2003, 63(4), 824-830.
[PMID: 12591733]
[36]
Russo, M.; Spagnuolo, C.; Tedesco, I.; Bilotto, S.; Russo, G.L. The flavonoid quercetin in disease prevention and therapy: facts and fancies. Biochem. Pharmacol., 2012, 83(1), 6-15.
[http://dx.doi.org/10.1016/j.bcp.2011.08.010] [PMID: 21856292]
[37]
Wang, X-C.; Zhao, N-J.; Guo, C.; Chen, J-T.; Song, J-L.; Gao, L. Quercetin reversed lipopolysaccharide-induced inhibition of osteoblast differentiation through the mitogen-activated protein kinase pathway in MC3T3-E1 cells. Mol. Med. Rep., 2014, 10(6), 3320-3326.
[http://dx.doi.org/10.3892/mmr.2014.2633] [PMID: 25323558]
[38]
Messer, J.G.; Hopkins, R.G.; Kipp, D.E. Quercetin metabolites up‐regulate the antioxidant response in osteoblasts isolated from fetal rat calvaria. J. Cell. Biochem., 2015, 116(9), 1857-1866.
[http://dx.doi.org/10.1002/jcb.25141] [PMID: 25716194]
[39]
Forte, L.; Torricelli, P.; Boanini, E.; Gazzano, M.; Rubini, K.; Fini, M.; Bigi, A. Antioxidant and bone repair properties of quercetin-functionalized hydroxyapatite: An in vitro osteoblast-osteoclast-endothelial cell co-culture study. Acta Biomater., 2016, 32, 298-308.
[http://dx.doi.org/10.1016/j.actbio.2015.12.013] [PMID: 26689470]
[40]
Kang, J.; de Brito Bezerra, B.; Pacios, S.; Andriankaja, O.; Li, Y.; Tsiagbe, V.; Schreiner, H.; Fine, D. H.; Graves, D. T. Aggregatibacter actinomycetemcomitans infection enhances apoptosis in vivo through a caspase-3 dependent mechanism in experimental periodontitis. Infect Immun , 2012. IAI., 2012, 06371-11..
[41]
Pradeep, A.R.; Suke, D.K.; Prasad, M.V.; Singh, S.P.; Martande, S.S.; Nagpal, K.; Naik, S.B.; Guruprasad, C.N.; Raju, A.P.; Singh, P.; Siddaya, M. Expression of key executioner of apoptosis caspase-3 in periodontal health and disease. J. Investig. Clin. Dent., 2016, 7(2), 174-179.
[http://dx.doi.org/10.1111/jicd.12134] [PMID: 25388853]
[42]
Curylofo-Zotti, F.A.; Elburki, M.S.; Oliveira, P.A.; Cerri, P.S.; Santos, L.A.; Lee, H-M.; Johnson, F.; Golub, L.M.; Rossa, C.; Guimarães-Stabili, M.R. Differential effects of natural Curcumin and chemically modified curcumin on inflammation and bone resorption in model of experimental periodontitis. Arch. Oral Biol., 2018, 91, 42-50.
[http://dx.doi.org/10.1016/j.archoralbio.2018.04.007] [PMID: 29669267]
[43]
Bureau, G.; Longpré, F.; Martinoli, M.G. Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J. Neurosci. Res., 2008, 86(2), 403-410.
[http://dx.doi.org/10.1002/jnr.21503] [PMID: 17929310]
[44]
Napimoga, M.H.; Clemente-Napimoga, J.T.; Macedo, C.G.; Freitas, F.F.; Stipp, R.N.; Pinho-Ribeiro, F.A.; Casagrande, R.; Verri, W.A., Jr Quercetin inhibits inflammatory bone resorption in a mouse periodontitis model. J. Nat. Prod., 2013, 76(12), 2316-2321.
[http://dx.doi.org/10.1021/np400691n] [PMID: 24246038]
[45]
Chang, Y-C.; Li, P-C.; Chen, B-C.; Chang, M-S.; Wang, J-L.; Chiu, W-T.; Lin, C-H. Lipoteichoic acid-induced nitric oxide synthase expression in RAW 264.7 macrophages is mediated by cyclooxygenase-2, prostaglandin E2, protein kinase A, p38 MAPK, and nuclear factor-kappaB pathways. Cell. Signal., 2006, 18(8), 1235-1243.
[http://dx.doi.org/10.1016/j.cellsig.2005.10.005] [PMID: 16289764]
[46]
Green, S.J.; Scheller, L.F.; Marletta, M.A.; Seguin, M.C.; Klotz, F.W.; Slayter, M.; Nelson, B.J.; Nacy, C.A. Nitric oxide: cytokine-regulation of nitric oxide in host resistance to intracellular pathogens. Immunol. Lett., 1994, 43(1-2), 87-94.
[http://dx.doi.org/10.1016/0165-2478(94)00158-8] [PMID: 7537721]
[47]
Knowles, R.G.; Moncada, S. Nitric oxide synthases in mammals. Biochem. J., 1994, 298(Pt 2), 249-258.
[http://dx.doi.org/10.1042/bj2980249] [PMID: 7510950]
[48]
Kim, H.P.; Mani, I.; Iversen, L.; Ziboh, V.A. Effects of naturally-occurring flavonoids and biflavonoids on epidermal cyclooxygenase and lipoxygenase from guinea-pigs. Prostaglandins Leukot. Essent. Fatty Acids, 1998, 58(1), 17-24.
[http://dx.doi.org/10.1016/S0952-3278(98)90125-9] [PMID: 9482162]
[49]
Lee, K.M.; Hwang, M.K.; Lee, D.E.; Lee, K.W.; Lee, H.J. Protective effect of quercetin against arsenite-induced COX-2 expression by targeting PI3K in rat liver epithelial cells. J. Agric. Food Chem., 2010, 58(9), 5815-5820.
[http://dx.doi.org/10.1021/jf903698s] [PMID: 20377179]
[50]
Suganthy, N.; Devi, K.P.; Nabavi, S.F.; Braidy, N.; Nabavi, S.M. Bioactive effects of quercetin in the central nervous system: Focusing on the mechanisms of actions. Biomed. Pharmacother., 2016, 84, 892-908.
[http://dx.doi.org/10.1016/j.biopha.2016.10.011] [PMID: 27756054]
[51]
Kreft, M. Buckwheat phenolic metabolites in health and disease. Nutr. Res. Rev., 2016, 29(1), 30-39.
[http://dx.doi.org/10.1017/S0954422415000190] [PMID: 27046048]
[52]
Ishizawa, K.; Yoshizumi, M.; Kawai, Y.; Terao, J.; Kihira, Y.; Ikeda, Y.; Tomita, S.; Minakuchi, K.; Tsuchiya, K.; Tamaki, T. Pharmacology in health food: metabolism of quercetin in vivo and its protective effect against arteriosclerosis. J. Pharmacol. Sci., 2011, 115(4), 466-470.
[http://dx.doi.org/10.1254/jphs.10R38FM] [PMID: 21436601]

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