Abstract
Asthma is an inflammatory disease that affects many people around the world, especially persons at paediatric age group. The effectiveness of tyrosol, a natural phenolic compound, was examined in the asthma model induced by ovalbumin (OVA). For this purpose, four groups, each consisting of eight rats, were arranged. For 21 days, physiological saline solution was treated to the control group and OVA was treated to the groups of OVA, OVA + dexamethasone (Dexa) and OVA + tyrosol groups, intraperitoneally and through inhalation. Additionally, 0.25 mg/kg Dexa was treated to the OVA + Dexa group and 20 mg/kg tyrosol to the OVA + tyrosol group by oral gavage. Serum, blood, bronchoalveolar lavage fluid (BALF) and lung tissues of the rats were examined. It was observed that MDA level decreased, GSH level and GPx activity increased, and there was no change in CAT activity in lung tissues of the tyrosol treatment groups. It was also observed that NF-κB, TNF-α, IL-4, IL-5, IL-13, IFN-γ and IgE levels decreased compared to the OVA group in lung tissue and serum samples except for serum NF-κB and IL-4. However, no effect on IL-1 β level was observed. In addition, it was determined that tyrosol treatment increased the IL-10 level on both tissue samples. The results of the histopathological investigation of lung tissue showed that tyrosol significantly ameliorated OVA-induced histopathological lesions. Additionally, PAS staining showed that mucus hypersecretion was significantly reduced with the use of tyrosol. In addition, it was determined that the number of eosinophils decreased significantly in blood and BALF samples. The obtained results showed that tyrosol possessed antioxidant and anti-inflammatory features on OVA-induced rats and preserved tissue architecture.
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27 September 2021
A Correction to this paper has been published: https://doi.org/10.1007/s00210-021-02157-4
References
Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126. https://doi.org/10.1016/S0076-6879(84)05016-3
Atochin DN, Chernysheva GA, Smolyakova VI et al (2016) Neuroprotective effects of p-tyrosol after the global cerebral ischemia in rats. Phytomedicine 23:784–792. https://doi.org/10.1016/j.phymed.2016.03.015
Barnes PJ (2008a) Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 8:183–192. https://doi.org/10.1038/nri2254
Barnes PJ (2008b) The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest 118:3546–3556. https://doi.org/10.1172/JCI36130
Beutler E (1975) Red cell metabolism. In: A manual of biochemical methods. Grune Strottan, New York
Beutler E, Dubon O, Kelly B (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888
Bolandi SM, Abdolmaleki Z, Assarehzadegan M-A (2021) Bevacizumab regulates inflammatory cytokines and inhibits VEGFR2 signaling pathway in an ovalbumin-induced rat model of airway hypersensitivity. Inflammopharmacology 1:3. https://doi.org/10.1007/s10787-021-00798-8
Boskabady MH, Kaveh M, Shakeri F et al (2019) Alpha-linolenic acid ameliorates bronchial asthma features in ovalbumin-sensitized rats. J Pharm Pharmacol 71:1089–1099. https://doi.org/10.1111/jphp.13094
Bu Y, Rho S, Kim J et al (2007) Neuroprotective effect of tyrosol on transient focal cerebral ischemia in rats. Neurosci Lett 414:218–221. https://doi.org/10.1016/j.neulet.2006.08.094
Chan CK, Lin TC, Huang YA et al (2016) The modulation of Th2 immune pathway in the immunosuppressive effect of human umbilical cord mesenchymal stem cells in a murine asthmatic model. Inflamm Res 65:795–801. https://doi.org/10.1007/s00011-016-0961-y
Chandramohan R, Pari L (2016) Anti-inflammatory effects of tyrosol in streptozotocin-induced diabetic Wistar rats. J Funct Foods 27:17–28. https://doi.org/10.1016/j.jff.2016.08.043
Chandramohan R, Pari L, Rathinam A, Sheikh BA (2015) Tyrosol, a phenolic compound, ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats. Chem Biol Interact 229:44–54. https://doi.org/10.1016/j.cbi.2015.01.026
Chandramohan R, Saravanan S, Pari L (2017) Beneficial effects of tyrosol on altered glycoprotein components in streptozotocin-induced diabetic rats. Pharm Biol 55:1631–1637. https://doi.org/10.1080/13880209.2017.1315603
Chen W, Sivaprasad U, Gibson AM et al (2013) IL-13 receptor α2 contributes to development of experimental allergic asthma. J Allergy Clin Immunol 132:951-958.e6. https://doi.org/10.1016/j.jaci.2013.04.016
Chiappara G, Gagliardo R, Siena A et al (2001) Airway remodelling in the pathogenesis of asthma. Curr Opin Allergy Clin Immunol 1:85–93
Dalouchi F, Falak R, Bakhshesh M et al (2021) Human amniotic membrane mesenchymal stem cell-conditioned medium reduces inflammatory factors and fibrosis in ovalbumin-induced asthma in mice. Exp Physiol 106:544–554. https://doi.org/10.1113/EP088911
Di Benedetto R, Varì R, Scazzocchio B et al (2007) Tyrosol, the major extra virgin olive oil compound, restored intracellular antioxidant defences in spite of its weak antioxidative effectiveness. Nutr Metab Cardiovasc Dis 17:535–545. https://doi.org/10.1016/j.numecd.2006.03.005
Eftekhar N, Moghimi A, Mohammadian Roshan N et al (2019) Immunomodulatory and anti-inflammatory effects of hydro-ethanolic extract of Ocimum basilicum leaves and its effect on lung pathological changes in an ovalbumin-induced rat model of asthma. BMC Complement Altern Med 19:349. https://doi.org/10.1186/s12906-019-2765-4
Elaidy SM, Essawy SS, Hussain MA et al (2018) Modulation of the IL-23/IL-17 axis by fenofibrate ameliorates the ovalbumin/lipopolysaccharide-induced airway inflammation and bronchial asthma in rats. Naunyn Schmiedebergs Arch Pharmacol 391:309–321. https://doi.org/10.1007/s00210-017-1459-z
Ezz-Eldin YM, Aboseif AA, Khalaf MM (2020) Potential anti-inflammatory and immunomodulatory effects of carvacrol against ovalbumin-induced asthma in rats. Life Sci 242:117222. https://doi.org/10.1016/j.lfs.2019.117222
Fitó M, Covas MI, Lamuela-Raventós RM et al (2000) Protective effect of olive oil and its phenolic compounds against low density lipoprotein oxidation. Lipids 35:633–638. https://doi.org/10.1007/s11745-000-0567-1
Guan Y, Shen HJ, Shen J et al (2019) Anti-allergic activities of 5,7-dimethoxy-3,4′-dihydroxyflavone via inhalation in rat allergic models. Eur J Pharmacol 848:55–61. https://doi.org/10.1016/j.ejphar.2019.01.046
Güvenç M, Cellat M, Gökçek İ et al (2020) Tyrosol prevents AlCl3 induced male reproductive damage by suppressing apoptosis and activating the Nrf-2/HO-1 pathway. Andrologia 52:e13499. https://doi.org/10.1111/and.13499
Güvenç M, Cellat M, Özkan H et al (2019) Protective effects of tyrosol against DSS-induced ulcerative colitis in rats. Inflammation 42:1680–1691. https://doi.org/10.1007/s10753-019-01028-8
Hanna DA, Khalaf MM, Abo-Saif AA (2019) Polydatin protects against ovalbumin-induced bronchial asthma in rats; involvement of urocortin and surfactant-D expression. Immunopharmacol Immunotoxicol 41:403–412. https://doi.org/10.1080/08923973.2018.1536985
Innes Asher M, García-Marcos L, Pearce NE, Strachan DP (2020) Trends in worldwide asthma prevalence. Eur Respir J 56.https://doi.org/10.1183/13993003.02094-2020
Irwin RS, Richardson ND (2006) Side effects with inhaled corticosteroids: the physician’s perception. Chest 130:41–53. https://doi.org/10.1378/chest.130.1_suppl.41S
Je I-G, Kim D-S, Kim S-W et al (2015) Tyrosol suppresses allergic inflammation by inhibiting the activation of phosphoinositide 3-kinase in mast cells. PLoS One 10:e0129829. https://doi.org/10.1371/journal.pone.0129829
Jiang J, Mehrabi Nasab E, Athari SM, Athari SS (2021) Effects of vitamin E and selenium on allergic rhinitis and asthma pathophysiology. Respir Physiol Neurobiol 286:103614. https://doi.org/10.1016/j.resp.2020.103614
Kaplan A, Mitchell PD, Cave AJ et al (2020) Effective asthma management: is it time to let the AIR out of SABA? J Clin Med 9:921. https://doi.org/10.3390/jcm9040921
Kim YY, Hur G, Lee SW et al (2020) AGK2 ameliorates mast cell-mediated allergic airway inflammation and fibrosis by inhibiting FcεRI/TGF-β signaling pathway. Pharmacol Res 159:105027. https://doi.org/10.1016/j.phrs.2020.105027
Kim YY, Lee S, Kim MJ et al (2017) Tyrosol attenuates lipopolysaccharide-induced acute lung injury by inhibiting the inflammatory response and maintaining the alveolar capillary barrier. Food Chem Toxicol 109:526–533. https://doi.org/10.1016/j.fct.2017.09.053
Kuzu M, Kandemir FM, Yildirim S et al (2018) Morin attenuates doxorubicin-induced heart and brain damage by reducing oxidative stress, inflammation and apoptosis. Biomed Pharmacother 106:443–453. https://doi.org/10.1016/j.biopha.2018.06.161
Kuzu M, Yıldırım S, Kandemir FM et al (2019) Protective effect of morin on doxorubicin-induced hepatorenal toxicity in rats. Chem Biol Interact 308:89–100. https://doi.org/10.1016/j.cbi.2019.05.017
Lin LJ, Lin CC, Wang S Der, et al (2012) The immunomodulatory effect of You-Gui-Wan on Dermatogoides-pteronyssinus-induced asthma. Evidence-based Complement Altern Med 2012.https://doi.org/10.1155/2012/476060
Lin LJ, Wu CJ, Der WS, Te KS (2020) Qi-Wei-Du-Qi-Wan and its major constituents exert an anti-asthmatic effect by inhibiting mast cell degranulation. J Ethnopharmacol 254:112406. https://doi.org/10.1016/j.jep.2019.112406
Liou C-J, Chen Y-L, Yu M-C et al (2020) Sesamol alleviates airway hyperresponsiveness and oxidative stress in asthmatic mice. Antioxidants 9:295. https://doi.org/10.3390/antiox9040295
Liu Y, Zhang B, Zhang T et al (2020) Effect of NF-κB signal pathway on mucus secretion induced by atmospheric PM2.5 in asthmatic rats. Ecotoxicol Environ Saf 190:110094. https://doi.org/10.1016/j.ecoenv.2019.110094
Louis R, Lau LCK, Bron AO et al (2000) The relationship between airways inflammation and asthma severity. Am J Respir Crit Care Med 161:9–16. https://doi.org/10.1164/ajrccm.161.1.9802048
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with pholin phenol reagent. J Biol Chem 193:265–275
Ma C, Zou L, Xia Y et al (2019) Extracts of Coleus forskohlii relieves cough and asthma symptoms via modulating inflammation and the extracellular matrix. J Cell Biochem 120:9648–9655. https://doi.org/10.1002/jcb.28243
Mäkelä MJ, Kanehiro A, Borish L et al (2000) IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization. Proc Natl Acad Sci U S A 97:6007–6012. https://doi.org/10.1073/pnas.100118997
Martínez-Martos JM, Mayas MD, Carrera P et al (2014) Phenolic compounds oleuropein and hydroxytyrosol exert differential effects on glioma development via antioxidant defense systems. J Funct Foods 11:221–234. https://doi.org/10.1016/j.jff.2014.09.006
Maslan J, Mims JW (2014) What is asthma? Pathophysiology, demographics, and health care costs. Otolaryngol Clin North Am 47:13–22. https://doi.org/10.1016/j.otc.2013.09.010
Mattiuzzi C, Lippi G (2020) Worldwide asthma epidemiology: insights from the Global Health Data Exchange database. Int Forum Allergy Rhinol 10:75–80. https://doi.org/10.1002/alr.22464
Menzella F, Ruggiero P, Galeone C et al (2020) Significant improvement in lung function and asthma control after benralizumab treatment for severe refractory eosinophilic asthma. Pulm Pharmacol Ther 64:101966. https://doi.org/10.1016/j.pupt.2020.101966
Migliorati G, Nicoletti I, Nocentini G et al (1994) Dexamethasone and interleukins modulate apoptosis of murine thymocytes and peripheral T-lymphocytes. Pharmacol Res 30:43–52. https://doi.org/10.1016/1043-6618(94)80086-3
Myou S, Leff AR, Myo S et al (2003) Blockade of inflammation and airway hyperresponsiveness in immune-sensitized mice by dominant-negative phosphoinositide 3-kinase-TAT. J Exp Med 198:1573–1582. https://doi.org/10.1084/jem.20030298
Nader MA, El-Awady MS, Shalaby AA, El-Agamy DS (2012) Sitagliptin exerts anti-inflammatory and anti-allergic effects in ovalbumin-induced murine model of allergic airway disease. Naunyn Schmiedebergs Arch Pharmacol 385:909–919. https://doi.org/10.1007/s00210-012-0772-9
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358. https://doi.org/10.1016/0003-2697(79)90738-3
Parlar A, Arslan SO (2020) CB2 agonist (AM1241) improving effect on ovalbumin-induced asthma in rats. Iran J Pharm Res 19:3–17. https://doi.org/10.22037/ijpr.2019.1101002
Périz M, Pérez-Cano FJ, Rodríguez-Lagunas MJ et al (2020) Development and characterization of an allergic asthma rat model for interventional studies. Int J Mol Sci 21:3841. https://doi.org/10.3390/ijms21113841
Peterson JD, Herzenberg LA, Vasquez K, Waltenbaugh C (1998) Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. Proc Natl Acad Sci U S A 95:3071–3076. https://doi.org/10.1073/pnas.95.6.3071
Plotnikov MB, Plotnikova TM (2021) Tyrosol as a neuroprotector: strong effects of a “weak” antioxidant. Curr Neuropharmacol 19:434–448. https://doi.org/10.2174/1570159x18666200507082311
Pourmehdi A, Sakhaei Z, Alirezaei M, Dezfoulian O (2020) Betaine effects against asthma-induced oxidative stress in the liver and kidney of mice. Mol Biol Rep 47:5729–5735. https://doi.org/10.1007/s11033-020-05620-2
Rahman I, Biswas SK, Kode A (2006) Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol 533:222–239. https://doi.org/10.1016/j.ejphar.2005.12.087
Rajizadeh MA, Najafipour H, Fekri MS et al (2019) Anti-inflammatory and anti-oxidative effects of myrtenol in the rats with allergic asthma. Iran J Pharm Res 18:1488–1498. https://doi.org/10.22037/ijpr.2019.1100749
Regele R (2000) The pathology of asthma: brief review. In: Immunopharmacology. Elsevier, pp 257–262
Rodríguez-Morató J, Boronat A, Kotronoulas A et al (2016) Metabolic disposition and biological significance of simple phenols of dietary origin: hydroxytyrosol and tyrosol. Drug Metab Rev 48:218–236. https://doi.org/10.1080/03602532.2016.1179754
Russell RJ, Brightling CE (2017) Pathogenesis of asthma: implications for precision medicine. Clin Sci 131:1723–1735
Saikumar Jayalatha AK, Hesse L, Ketelaar ME et al (2021) The central role of IL-33/IL-1RL1 pathway in asthma: from pathogenesis to intervention. Pharmacol Ther 225:107847. https://doi.org/10.1016/j.pharmthera.2021.107847
Selzman CH, McIntyre RC, Shames BD et al (1998) Interleukin-10 inhibits human vascular smooth muscle proliferation. J Mol Cell Cardiol 30:889–896. https://doi.org/10.1006/jmcc.1998.0642
Smith K, Mrozek J, Simonton S et al (1997) Prolonged partial liquid ventilation using conventional and high-frequency ventilatory techniques: gas exchange and lung pathology in an animal model of respiratory. Crit Care Med 25:1888–1897
Stern J, Pier J, Litonjua AA (2020) Asthma epidemiology and risk factors. Semin Immunopathol 42:5–15
Sun L-Z, Elsayed S, Aasen TB et al (2010) Comparison between ovalbumin and ovalbumin peptide 323–339 responses in allergic mice: humoral and cellular aspects. Scand J Immunol 71:329–335. https://doi.org/10.1111/j.1365-3083.2010.02382.x
Sussan TE, Gajghate S, Chatterjee S et al (2015) Nrf2 reduces allergic asthma in mice through enhanced airway epithelial cytoprotective function. Am J Physiol Cell Mol Physiol 309:27–36. https://doi.org/10.1152/ajplung.00398.2014
Tanaka H, Masuda T, Tokuoka S et al (2001) The effect of allergen-induced airway inflammation on airway remodeling in a murine model of allergic asthma. Inflamm Res 50:616–624. https://doi.org/10.1007/PL00000243
Thakur VR, Khuman V, Beladiya JV et al (2019) An experimental model of asthma in rats using ovalbumin and lipopolysaccharide allergens. Heliyon 5:e02864. https://doi.org/10.1016/j.heliyon.2019.e02864
Tiwari M, Dwivedi UN, Kakkar P (2014) Tinospora cordifolia extract modulates COX-2, iNOS, ICAM-1, pro-inflammatory cytokines and redox status in murine model of asthma. J Ethnopharmacol 153:326–337. https://doi.org/10.1016/j.jep.2014.01.031
Tuck KL, Hayball PJ (2002) Major phenolic compounds in olive oil: metabolism and health effects. J Nutr Biochem 13:636–644. https://doi.org/10.1016/S0955-2863(02)00229-2
Türk E, Güvenç M, Cellat M, et al (2020) Zingerone protects liver and kidney tissues by preventing oxidative stress, inflammation, and apoptosis in methotrexate-treated rats. Drug Chem Toxicol 1–12.https://doi.org/10.1080/01480545.2020.1804397
Wang W, Xia Y, Yang B et al (2017) Protective effects of tyrosol against LPS-induced acute lung injury via inhibiting NF-κB and AP-1 activation and activating the HO-1/Nrf2 pathways. Biol Pharm Bull 40:583–593. https://doi.org/10.1248/bpb.b16-00756
Westergaard CG, Porsbjerg C, Backer V (2015) Emerging corticosteroid agonists for the treatment of asthma. Expert Opin Emerg Drugs 20:653–662. https://doi.org/10.1517/14728214.2015.1061503
Whitehead GS, Grasman KA, Kimmel EC (2003) Lung function and airway inflammation in rats following exposure to combustion products of carbon-graphite/epoxy composite material: comparison to a rodent model of acute lung injury. Toxicology 183:175–197. https://doi.org/10.1016/S0300-483X(02)00542-5
Yan S, Ci X, Chen N et al (2011) Anti-inflammatory effects of ivermectin in mouse model of allergic asthma. Inflamm Res 60:589–596. https://doi.org/10.1007/s00011-011-0307-8
Yang CH, Tian JJ, Ko WS et al (2019) Oligo-fucoidan improved unbalance the Th1/Th2 and Treg/Th17 ratios in asthmatic patients: an ex vivo study. Exp Ther Med 17:3–10. https://doi.org/10.3892/etm.2018.6939
Yosri H, Elkashef WF, Said E, Gameil NM (2017) Crocin modulates IL-4/IL-13 signaling and ameliorates experimentally induced allergic airway asthma in a murine model. Int Immunopharmacol 50:305–312. https://doi.org/10.1016/j.intimp.2017.07.012
Zhong Z, Umemura A, Sanchez-Lopez E et al (2016) NF-κB restricts inflammasome activation via elimination of damaged mitochondria. Cell 164:896–910. https://doi.org/10.1016/j.cell.2015.12.057
Zhu S, Wang H, Zhang J et al (2019) Antiasthmatic activity of quercetin glycosides in neonatal asthmatic rats. 3 Biotech 9:189. https://doi.org/10.1007/s13205-019-1618-7
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MC conceived and designed the research. MK, CTİ, ME, ND, AU, İG, ET and MG conducted the experiments. MG analysed the data. MK, MC and CTİ wrote the manuscript. All authors read and approved the manuscript. All data were generated in-house, and no paper mill was used.
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Cellat, M., Kuzu, M., İşler, C.T. et al. Tyrosol improves ovalbumin (OVA)-induced asthma in rat model through prevention of airway inflammation. Naunyn-Schmiedeberg's Arch Pharmacol 394, 2061–2075 (2021). https://doi.org/10.1007/s00210-021-02117-y
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DOI: https://doi.org/10.1007/s00210-021-02117-y