European Archives of Oto-Rhino-Laryngology

, Volume 276, Issue 2, pp 407–415 | Cite as

The amendatory effect of hesperidin and thymol in allergic rhinitis: an ovalbumin-induced rat model

  • Korhan KilicEmail author
  • Muhammed Sedat Sakat
  • Serkan Yildirim
  • Fatih Mehmet Kandemir
  • Mustafa Sitki Gozeler
  • Muhammed Bahaeddin Dortbudak
  • Sefa Kucukler



Allergic rhinitis is an immunoglobulin-E (Ig-E)-mediated response driven by type 2 helper T cells. Hesperidin and thymol are biological agents that possess antioxidant and anti-inflammatory characteristics. The purpose of this study was to investigate the effects of hesperidin and thymol in rats with ovalbumin-induced allergic rhinitis.


Thirty adult Sprague–Dawley rats were randomly assigned into five groups, each containing six animals. The first group constituted the negative control group, while the remaining groups were exposed to an ovalbumin-induced model of allergic rhinitis. In the provocation stage, 4 mL/kg saline was administered to the positive control group, 10 mg/kg desloratadine to the reference group, 100 mg/kg hesperidin to the hesperidin group, and 20 mg/kg thymol to the thymol group, all by gastric lavage for 7 days. Nasal symptoms were scored on day 22. Rats were then sacrificed, and intracardiac blood specimens were collected to measure plasma total Ig-E, IL-5, IL-13, total antioxidant capacity (TAC), and total oxidant status (TOS) levels. Nasal tissues were extracted for histopathological and immunochemical examination.


Nasal symptom scores were highest in the positive control group, while hesperidin and thymol ameliorated these symptoms to the same extent as desloratadine. Ig-E, IL-5, IL-13, and TOS levels increased, while TAC levels decreased significantly in the allergic rhinitis group compared to the other groups. Significant improvement in these parameters was observed in both the hesperidin and thymol groups. At histopathological and immunohistochemical examination of the nasal cavity, severe allergic inflammation and severe TNF-α expression was determined in rats from the allergic rhinitis group. Mild inflammatory changes and mild TNF-α expression were observed in all three treatment groups.


Both hesperidin and thymol were effective in suppressing allergic symptoms and inflammation in the treatment of allergic rhinitis.


Hesperidin Thymol Ovalbumin Allergic rhinitis Immunoglobulin-E 



This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This study was performed in accordance with the PHS Policy on Human Care and Use of Laboratory Animals, the NIH Guide for the Care and Use of Laboratory Animals, and the Animal Welfare Act (7 U.S.C. et seq.); the animal use protocol was approved by the local Animal Experiments ethical committee.


  1. 1.
    Greiner AN, Hellings PW, Rotiroti G, Scadding GK (2011) Allergic rhinitis. Lancet 378:2112–2122CrossRefPubMedGoogle Scholar
  2. 2.
    Li C, Fu Y, Wang Y et al (2017) Mesenchymal stromal cells ameliorate acute allergic rhinitis in rats. Cell Biochem Funct 35:420–425CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ulusoy S, Ayan NN, Dinc ME, Is A, Bicer C, Erel O (2016) A new oxidative stress marker for thiol-disulphide homeostasis in seasonal allergic rhinitis. Am J Rhinol Allergy 30:53–57CrossRefPubMedGoogle Scholar
  4. 4.
    Garg A, Garg S, Zaneveld LJ, Singla AK (2001) Chemistry and pharmacology of the citrus bioflavonoid hesperidin. Phytother Res 15:655–669CrossRefPubMedGoogle Scholar
  5. 5.
    Yeh MH, Kao ST, Hung CM, Liu CJ, Lee KH, Yeh CC (2009) Hesperidin inhibited acetaldehyde-induced matrix metalloproteinase-9 gene expression in human hepatocellular carcinoma cells. Toxicol Lett 184:204–210CrossRefPubMedGoogle Scholar
  6. 6.
    Park SH, Park EK, Kim DH (2005) Passive cutaneous anaphylaxis-inhibitory activity of flavanones from Citrus unshiu and Poncirus trifoliata. Planta Med 71:24–27CrossRefPubMedGoogle Scholar
  7. 7.
    Aeschbach R, Loliger J, Scott BC et al (1994) Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and hydroxytyrosol. Food Chem Toxicol 32:31–36CrossRefPubMedGoogle Scholar
  8. 8.
    Kwon HI, Jeong NH, Jun SH et al (2018) Thymol attenuates the worsening of atopic dermatitis induced by Staphylococcus aureus membrane vesicles. Int Immunopharmacol 59:301–309CrossRefPubMedGoogle Scholar
  9. 9.
    Senturk E, Yildirim YS, Dogan R et al (2018) Assessment of the effectiveness of cyclosporine nasal spray in an animal model of allergic rhinitis. Eur Arch Otorhinolaryngol 275:117–124CrossRefPubMedGoogle Scholar
  10. 10.
    Wen WD, Yuan F, Wang JL, Hou YP (2007) Botulinum toxin therapy in the ovalbumin-sensitized rat. Neuroimmunomodulation 14:78–83CrossRefPubMedGoogle Scholar
  11. 11.
    Erel O (2005) A new automated colorimetric method for measuring total oxidant status. Clin Biochem 38:1103–1111CrossRefPubMedGoogle Scholar
  12. 12.
    Erel O (2004) A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 37:277–285CrossRefPubMedGoogle Scholar
  13. 13.
    Sagit M, Polat H, Gurgen SG, Berk E, Guler S, Yasar M (2017) Effectiveness of quercetin in an experimental rat model of allergic rhinitis. Eur Arch Otorhinolaryngol 274:3087–3095CrossRefPubMedGoogle Scholar
  14. 14.
    Tatar A, Yayla M, Kose D, Halici Z, Yoruk O, Polat E (2016) The role of endothelin-1 and endothelin receptor antagonists in allergic rhinitis inflammation:ovalbumin-induced rat model. Rhinology 54:266–272CrossRefPubMedGoogle Scholar
  15. 15.
    Günel C, Demirci B, Eryılmaz A et al (2016) Inhibitory effect of Pycnogenol(®) on airway inflammation in ovalbumin-induced allergic rhinitis. Balkan Med J 33:620–626CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Yman L (2001) Standardization of in vitro methods. Allergy 56:70–74CrossRefPubMedGoogle Scholar
  17. 17.
    Caglayan C, Temel Y, Kandemir FM, Yildirim S, Kucukler S (2018) Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. Environ Sci Pollut Res Int. (Epub ahead of print) PubMedCrossRefGoogle Scholar
  18. 18.
    Chen B, Qu S, Li M et al (2017) Effects of 1,25-dihydroxyvitamin D3 in an ovalbumin-induced allergic rhinitis model. Int Immunopharmacol 47:182–189CrossRefPubMedGoogle Scholar
  19. 19.
    Yu S, Zhao C, Che N, Jing L, Ge R (2017) Hydrogen-rich saline attenuates eosinophil activation in a guinea pig model of allergic rhinitis via reducing oxidative stress. J Inflamm (Lond) 14:1CrossRefGoogle Scholar
  20. 20.
    Emin O, Hasan A, Aysegul D, Rusen D (2012) Total antioxidant status and oxidative stress and their relationship to total IgE levels and eosinophil counts in children with allergic rhinitis. J Investig Allergol Clin Immunol 22:188–192PubMedGoogle Scholar
  21. 21.
    Parhiz H, Roohbakhsh A, Soltani F, Rezaee R, Iranshahi M (2015) Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: an updated review of their molecular mechanisms and experimental models. Phytother Res 29:323–331CrossRefPubMedGoogle Scholar
  22. 22.
    Kim SH, Kim BK, Lee YC (2011) Antiasthmatic effects of hesperidin, a potential Th2 cytokine antagonist, in a mouse model of allergic asthma. Mediat Inflamm 2011:485402Google Scholar
  23. 23.
    Wei D, Ci X, Chu X, Wei M, Hua S, Deng X (2012) Hesperidin suppresses ovalbumin-induced airway inflammation in a mouse allergic asthma model. Inflammation 35:114–121CrossRefPubMedGoogle Scholar
  24. 24.
    Kandemir FM, Ozkaraca M, Küçükler S, Caglayan C, Hanedan B (2017) Preventive effects of hesperidin on diabetic nephropathy induced by streptozotocin via modulating TGF-β1 and oxidative DNA damage. Toxin Rev. CrossRefGoogle Scholar
  25. 25.
    Selmi S, Rtibi K, Grami D, Sebai H, Marzouki L (2017) Protective effects of orange (Citrus sinensis L.) peel aqueous extract and hesperidin on oxidative stress and peptic ulcer induced by alcohol in rat. Lipids Health Dis 16:152CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Riella KR, Marinho RR, Santos JS, Pereira-Filho RN, Cardoso JC, Albuquerque-Junior RL et al. (2012) Anti-inflammatory and cicatrizing activities of thymol, a monoterpene of the essential oil from Lippia gracilis, in rodents. J Ethnopharmacol 143:656–663CrossRefPubMedGoogle Scholar
  27. 27.
    El-Sayed el-SM, Mansour AM, Abdul-Hameed MS (2016) Thymol and carvacrol prevent doxorubicin-induced cardiotoxicity by abrogation of oxidative stress, inflammation, and apoptosis in rats. J Biochem Mol Toxicol 30:37–44CrossRefGoogle Scholar
  28. 28.
    Ku CM, Lin JY (2013) Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1/Th2 cytokine secretion profiles using murine primary splenocytes. Food Chem 141:1104–1113CrossRefPubMedGoogle Scholar
  29. 29.
    Nagoor Meeran MF, Jagadeesh GS, Selvaraj P (2015) Thymol attenuates inflammation in isoproterenol induced myocardial infarcted rats by inhibiting the release of lysosomal enzymes and downregulating the expressions of proinflammatory cytokines. Eur J Pharmacol 754:153–161CrossRefPubMedGoogle Scholar
  30. 30.
    Güvenç M, Cellat M, Gökçek İ, Yavaş İ, Yurdagül Özsoy Ş (2018) Effects of thymol and carvacrol on sperm quality and oxidant/antioxidant balance in rats. Arch Physiol Biochem 25:1–8CrossRefGoogle Scholar
  31. 31.
    Zhou E, Fu Y, Wei Z, Yu Y, Zhang X, Yang Z (2014) Thymol attenuates allergic airway inflammation in ovalbumin (OVA)-induced mouse asthma. Fitoterapia 96:131–137CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of OtorhinolaryngologyAtaturk University, Faculty of MedicineErzurumTurkey
  2. 2.Department of PathologyAtaturk University, Faculty of VeterinaryErzurumTurkey
  3. 3.Department of BiochemistryAtaturk University, Faculty of VeterinaryErzurumTurkey

Personalised recommendations