Original Article

The Alleviating Impacts of Quercetin on Inflammation and Oxidant-antioxidant Imbalance in Rats with Allergic Asthma


Asthma is an inflammatory disease of the airways. We assessed the anti-inflammatory and antioxidative impacts of quercetin, a plant derivative, on inflammatory and oxidative indices in lung tissue and serum of rats with asthma.Asth
ma was induced by ovalbumin. Rats were divided into 4 groups: control, asthma+vehicle (Receieved normal saline), asthma+dexamethasone, and asthma+quercetin. After asthma induction, quercetin (50 mg/kg) and dexamethasone (2.5 mg/kg) were injected intraperitoneally once daily for 1 week. On day 50, lung histopathology indices; inflammatory factors; tissue gene expression, including GATA Binding Protein 3 (Gata-3), Tbx21 (T-bet), Transforming growth factor-β (TGF-β), Il10 (IL-10), Il1b (IL-1β), Il6 (IL-6), Acta2 (α-SMA), and Tnf (TNF-α); and oxidative stress indices (malondialdehyde [MDA], catalase [CAT], glutathione peroxidase [GPX], superoxide dismutase [SOD], and total antioxidant capacity [TAC]) in tissue and serum, were evaluated.
The results showed that quercetin reduced Gata3, Tnf, Tgfb1, Il1b, and Acta2 gene expression and increased Tbx21 gene expression following asthma. Quercetin also improved oxidative stress by decreasing MDA levels and increasing TAC, CAT, SOD, and GPX levels in serum and lung tissue. Furthermore, quercetin decreased IL6 and TNFα levels and increased IL10 levels in lung tissue after asthma was treated with quercetin.
Quercetin ameliorates oxidative stress and inflammation caused by asthma, especially at the tissue level. Therefore, quercetin can be considered a potent antiasthmatic agent.

1. Huang W-C, Fang L-W, Liou C-J. Corrigendum: Phloretin Attenuates Allergic Airway Inflammation and Oxidative Stress in Asthmatic Mice. Front Immunol. 2020;11:2221.
2. Varmaghani M, Farzadfar F, Sharifi F, Rashidian A, Moin M, Moradi-Lakeh M, et al. Prevalence of asthma, COPD, and chronic bronchitis in Iran: a systematic review and meta-analysis. Iranian J Allergy, Asthma Immunol. 2016:93-104.
3. Qu J, Li Y, Zhong W, Gao P, Hu C. Recent developments in the role of reactive oxygen species in allergic asthma. J Thoracic Dis. 2017;9(1):E32.
4. Zhang N, Deng C, Zhang X, Zhang J, Bai C. Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in allergic asthmatic mice. Asthma Res Practice. 2018;4(1):1-9.
5. Huang W-C, Liu C-Y, Shen S-C, Chen L-C, Yeh K-W, Liu S-H, et al. Protective effects of licochalcone A improve airway hyper-responsiveness and oxidative stress in a mouse model of asthma. Cells. 2019;8(6):617.
6. Denner DR, Doeing DC, Hogarth DK, Dugan K, Naureckas ET, White SR. Airway inflammation after bronchial thermoplasty for severe asthma. Ann American Thoracic Society. 2015;12(9):1302-9.
7. Rajizadeh MA, Najafipour H, Fekr MS, Rostamzadeh F, Jafari E, Bejeshk MA, et al. Anti-inflammatory and antioxidative effects of myrtenol in the rats with allergic asthma. Iran J Pharmaceutical Res. 2019;18(3):1488.
8. Gubernatorova EO, Gorshkova EA, Namakanova OA, Zvartsev RV, Hidalgo J, Drutskaya MS, et al. Non-redundant functions of IL-6 produced by macrophages and dendritic cells in allergic airway inflammation. Front Immunol. 2018;9:2718.
9. Shim HJ, Park S-Y, Kwon H-S, Song W-J, Kim T-B, Moon K-A, et al. Oxidative stress modulates the expression pattern of peroxiredoxin-6 in peripheral blood mononuclear cells of asthmatic patients and bronchial epithelial cells. Allergy Asthma Immunol Res. 2020;12(3):523-36.
10. Laxmi V, Gupta R, Bhattacharya SK, Ray A, Gulati K. Inhibitory effects of sildenafil and tadalafil on inflammation, oxidative stress and nitrosative stress in animal model of bronchial asthma. Pharmacol Rep. 2019;71(3):517-21.
11. Doustimotlagh AH, Dehpour AR, Nourbakhsh M, Golestani A. Alteration in membrane protein, antioxidant status and hexokinase activity in erythrocytes of CCl4-induced cirrhotic rats. Acta Medica Iranica. 2014:795-803.
12. Choo CYW, Yeh K-W, Huang J-L, Su K-W, Tsai M-H, Hua M-C, et al. Oxidative stress is associated with atopic indices in relation to childhood rhinitis and asthma. J Microbiol Immunol Infection. 2021;54(3):466-73.
13. Garavaglia ML, Giustarini D, Colombo G, Reggiani F, Finazzi S, Calatroni M, et al. Blood Thiol Redox State in Chronic Kidney Disease. Int J Mol Sci. 2022;23(5):2853.
14. Rajizadeh MA, Aminizadeh AH, Esmaeilpour K, Bejeshk MA, Sadeghi A, Salimi F. Investigating the effects of Citrullus colocynthis on cognitive performance and anxiety-like behaviors in STZ-induced diabetic rats. Int J Neuroscience. 2021:1-13.
15. Bejeshk MA, Aminizadeh AH, Rajizadeh MA, Khaksari M, Lashkarizadeh M, Shahrokhi N, et al. The effect of combining basil seeds and gum Arabic on the healing process of experimental acetic acid-induced ulcerative colitis in rats. J Traditional Complementary Med. 2022;12(6):599-607.
16. Amirazodi M, Mehrabi A, Rajizadeh MA, Bejeshk MA, Esmaeilpour K, Daryanoosh F, et al. The effects of combined resveratrol and high intensity interval training on the hippocampus in aged male rats: An investigation into some signaling pathways related to mitochondria. Iran J Basic Med Sci. 2022;25(2):254.
17. Anand David AV, Arulmoli R, Parasuraman S. Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid. Pharmacogn Rev. 2016;10(20):84-9.
18. Tang S-M, Deng X-T, Zhou J, Li Q-P, Ge X-X, Miao L. Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects. Biomed Pharmacotherapy. 2020;121:109604.
19. Yang Y-G, Tian W-M, Zhang H, Li M, Shang Y-X. Nerve growth factor exacerbates allergic lung inflammation and airway remodeling in a rat model of chronic asthma. Exp Therapeutic Med. 2013;6(5):1251-8.
20. Bejeshk MA, Pourghadamyari H, Najafipour H, Eftekhari M, Mottaghipisheh J, Omidifar N, et al. The Hydroalcoholic Extract of Nasturtium officinale Reduces Lung Inflammation and Oxidative Stress in an Ovalbumin-Induced Rat Model of Asthma. Evidence-Based Complementary and Alternative Medicine. 2022.
21. Bejeshk MA, Aminizadeh AH, Jafari E, Motamedi S, Zangiabadi I, Ghasemi A, et al. Myrtenol Ameliorates Recognition Memories’ Impairment and Anxiety-Like Behaviors Induced by Asthma by Mitigating Hippocampal Inflammation and Oxidative Stress in Rats. Neuroimmunomodulation. 2023:42-54.
22. Ilić S, Stojiljković N, Veljković M, Veljković S, Stojanović G. Protective effect of quercetin on cisplatin-induced nephrotoxicity in rats. Facta Universitatis Series: Medicine and Biology. 2014;16(2):71-5.
23. Sadeghi H, Azarmehr N, Razmkhah F, Sadeghi H, Danaei N, Omidifar N, et al. The hydroalcoholic extract of watercress attenuates protein oxidation, oxidative stress, and liver damage after bile duct ligation in rats. J Cell Biochem. 2019;120(9):14875-84.
24. Doustimotlagh AH, Kokhdan EP, Vakilpour H, Khalvati B, Barmak MJ, Sadeghi H, et al. Protective effect of Nasturtium officinale R. Br and quercetin against cyclophosphamide-induced hepatotoxicity in rats. Molecular Biol Rep. 2020;47(7):5001-12.
25. Khaldi T, Chekchaki N, Boumendjel M, Taibi F, Abdellaoui M, Messarah M, et al. Ameliorating effects of Nigella sativa oil on aggravation of inflammation, oxidative stress and cytotoxicity induced by smokeless tobacco extract in an allergic asthma model in Wistar rats. Allergologia et Immunopathologia. 2018;46(5):472-81.
26. Bejeshk M, Fekri MS, Najafipour H, Rostamzadeh F, Jafari E, Rajizadeh M, et al. Anti-inflammatory and anti-remodeling effects of myrtenol in the lungs of asthmatic rats: Histopathological and biochemical findings. Allergologia et Immunopathologia. 2019;47(2):185-93.
27. Balestra AC, Sandy CM, Ramalho F, Júnior AAJ, Contini SHT, Crevelin EJ, et al. Aqueous Pyrostegia venusta (Ker Gawl.) Miers extract attenuates allergen-induced asthma in a mouse model via an antioxidant mechanism. J Asthma. 2021;58(6):808-18.
28. Rajizadeh MA, Esmaeilpour K, Motamedy S, Borzadaranb FM, Sheibani V. Cognitive impairments of sleep-deprived ovariectomized (OVX) female rats by voluntary exercise. Basic Clin Neuroscience. 2020;11(5):573.
29. Bejeshk M-A, Joukar S, Shahouzehi B, Asadi-shekari M, Rajizadeh M, Raji-amirhasani A, et al. Combinatorial effect of lower extremity blood flow restriction and low intensity endurance exercise on aorta of old male rats: Histomorphological and molecular approach. Artery Res. 2018;24:22-31.
30. Berry M, Brightling C, Pavord I, Wardlaw AJ. TNF-α in asthma. Curr Opin Pharmacol. 2007;7(3):279-82.
31. Zare D, Rajizadeh MA, Maneshian M, Jonaidi H, Sheibani V, Asadi-Shekaari M, et al. Inhibition of protease-activated receptor 1 (PAR1) ameliorates cognitive performance and synaptic plasticity impairments in animal model of Alzheimer’s diseases. Psychopharmacology. 2021;238(6):1645-56.
32. Brightling C, Berry M, Amrani Y. Targeting TNF-α: a novel therapeutic approach for asthma. J Allergy Clin Immunol. 2008;121(1):5-10.
33. Matera MG, Calzetta L, Cazzola M. TNF-α inhibitors in asthma and COPD: we must not throw the baby out with the bath water. Pulmonary Pharmacol Therapeutics. 2010;23(2):121-8.
34. Rincon M, Irvin CG. Role of IL-6 in asthma and other inflammatory pulmonary diseases. Int J Biol sci. 2012;8(9):1281.
35. Wood LG, Shivappa N, Berthon BS, Gibson PG, Hebert JR. Dietary inflammatory index is related to asthma risk, lung function and systemic inflammation in asthma. Clin Exp Allergy. 2015;45(1):177-83.
36. Peters MC, McGrath KW, Hawkins GA, Hastie AT, Levy BD, Israel E, et al. Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts. lancet Resp Med. 2016;4(7):574-84.
37. Neveu WA, Allard JL, Raymond DM, Bourassa LM, Burns SM, Bunn JY, et al. Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function. Respi Res. 2010;11(1):1-10.
38. Coomes S, Kannan Y, Pelly V, Entwistle L, Guidi R, Perez-Lloret J, et al. CD4+ Th2 cells are directly regulated by IL-10 during allergic airway inflammation. Mucosal immunol. 2017;10(1):150-61.
39. Wong C, Ho C, Ko F, Chan C, Ho A, Hui D, et al. Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-γ, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin Expe Immunol. 2001;125(2):177-83.
40. Sánchez‐Ovando S, Baines KJ, Barker D, Wark PA, Simpson JL. Six gene and TH2 signature expression in endobronchial biopsies of participants with asthma. Immunity Inflamm Dis. 2020;8(1):40-9.
41. Min Y-D, Choi C-H, Bark H, Son H-Y, Park H-H, Lee S, et al. Quercetin inhibits expression of inflammatory cytokines through attenuation of NF-κB and p38 MAPK in HMC-1 human mast cell line. Inflammation Res. 2007;56(5):210-5.
42. Zhu S, Wang H, Zhang J, Yu C, Liu C, Sun H, et al. Antiasthmatic activity of quercetin glycosides in neonatal asthmatic rats. 3 Biotech. 2019;9(5):1-9.
43. Sozmen SC, Karaman M, Micili SC, Isik S, Bagriyanik A, Ayyildiz ZA, et al. Effects of quercetin treatment on epithelium-derived cytokines and epithelial cell apoptosis in allergic airway inflammation mice model. Iran J Allergy Asthma Immunol. 2016:487-97.
44. Heiran H, Ahmadi M, Rahbarghazi R, Mir‐ershadi F, Delkhosh A, Khaksar M, et al. C‐Kit+ progenitors restore rat asthmatic lung function by modulation of T‐bet and GATA‐3 expression. Exp Physiol. 2020;105(9):1623-33.
45. Aierken A, Xu P. Bacterial respiratory tract inflammation in neonatal rat model is attenuated by benzofuran through inhibition of GATA3. Microbial pathogenesis. 2018;125:313-7.
46. Halwani R, Al-Muhsen S, Al-Jahdali H, Hamid Q. Role of transforming growth factor–β in airway remodeling in asthma. American journal of respiratory cell and molecular biology. 2011;44(2):127-33.
47. Yan Y, Liu L, Dou Z, Xu Y, Yan X. Soufeng Yuchuan decoction mitigates the ovalbumin-induced lung damage in a rat model of asthma. Biomed Pharmacotherapy. 2020;125:109933.
48. Ge Y, Cheng R, Sun S, Zhang S, Li L, Jiang J, et al. Fangxiao Formula alleviates airway inflammation and remodeling in rats with asthma via suppression of transforming growth factor-β/Smad3 signaling pathway. Biomed Pharmacotherapy. 2019;119:109429.
49. Lee ES, Lee HE, Shin JY, Yoon S, Moon JO. The flavonoid quercetin inhibits dimethylnitrosamine‐induced liver damage in rats. J pharmacy pharmacol. 2003;55(8):1169-74.
50. Lai P-B, Zhang L, Yang L-Y. Quercetin ameliorates diabetic nephropathy by reducing the expressions of transforming growth factor-β1 and connective tissue growth factor in streptozotocin-induced diabetic rats. Renal failure. 2012;34(1):83-7.
51. Wu Z, Luo F, Wang Z, Liu X, Liu C, Wang W, et al. Expression of alpha-SMA mRNA in the lung tissue of rat with asthma. Sichuan da xue xue bao Yi xue ban= Journal of Sichuan University Medical Science Edition. 2003;34(2):330-2.
52. Ren X-B, Liu C-T, Zhu T. Investigation of effect of bicuculline on expression of alpha-smooth muscle actin and airway remodeling in asthmatic mice. Sichuan da xue xue bao Yi xue ban= Journal of Sichuan University Medical Science Edition. 2010;41(4):626-9.
53. Kanter M. Protective effect of quercetin on liver damage induced by chronic toluene exposure in rats. Toxicology and Industrial Health. 2012;28(6):483-91.
54. Al-Harbi NO, Nadeem A, Al-Harbi MM, Imam F, Al-Shabanah OA, Ahmad SF, et al. Oxidative airway inflammation leads to systemic and vascular oxidative stress in a murine model of allergic asthma. Int Immunopharmacol. 2015;26(1):237-45.
55. Nadeem A, Raj HG, Chhabra SK. Increased oxidative stress in acute exacerbations of asthma. J Asthma. 2005;42(1):45-50.
56. Yang T, Luo F, Shen Y, An J, Li X, Liu X, et al. Quercetin attenuates airway inflammation and mucus production induced by cigarette smoke in rats. Int Immunopharmacol. 2012;13(1):73-81.
57. 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.
58. Gerin F, Sener U, Erman H, Yilmaz A, Aydin B, Armutcu F, et al. The effects of quercetin on acute lung injury and biomarkers of inflammation and oxidative stress in the rat model of sepsis. Inflammation. 2016;39(2):700-5.
59. Shakeri F, Soukhtanloo M, Boskabady MH. The effect of hydro-ethanolic extract of Curcuma longa rhizome and curcumin on total and differential WBC and serum oxidant, antioxidant biomarkers in rat model of asthma. Iran J Basic Me Sci. 2017;20(2):155.
60. Ezz-Eldin YM, Aboseif AA, Khalaf MM. Potential anti-inflammatory and immunomodulatory effects of carvacrol against ovalbumin-induced asthma in rats. Life sciences. 2020;242:117222.
61. Zemmouri H, Sekiou O, Ammar S, El Feki A, Bouaziz M, Messarah M, et al. Urtica dioica attenuates ovalbumin-induced inflammation and lipid peroxidation of lung tissues in rat asthma model. Pharmaceutical biol. 2017;55(1):1561-8.
62. Cellat M, Kuzu M, İşler CT, Etyemez M, Dikmen N, Uyar A, et al. Tyrosol improves ovalbumin (OVA)-induced asthma in rat model through prevention of airway inflammation. Naunyn-Schmiedeberg's Archives of Pharmacology. 2021;394(10):2061-75.
63. Karadogan B, Beyaz S, Gelincik A, Buyukozturk S, Arda N. Evaluation of oxidative stress biomarkers and antioxidant parameters in allergic asthma patients with different level of asthma control. J Asthma. 2020:1-15.
64. Kim HJ, Kim A, Herath KHINM, Mihindukulasooriya SP, Jeon Y-J, Kim HJ, et al. Antioxidant potential of Sargassum horneri extracts in the liver of mice with PM-induced asthma. Korean J Food Sci Technol. 2021;53(5):535-43.
65. Boots AW, Veith C, Albrecht C, Bartholome R, Drittij M-J, Claessen SM, et al. The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice. BMC Pulmonary Med. 2020;20(1):1-16.
66. da Silva Araújo NP, de Matos NA, Leticia Antunes Mota S, Farias de Souza AB, Dantas Cangussú S, Cunha Alvim de Menezes R, et al. Quercetin attenuates acute lung injury caused by cigarette smoke both in vitro and in vivo. J Chronic Obstructive Pulmonary Dis. 2020;17(2):205-14.
67. Seyedrezazadeh E, Kolahian S, Shahbazfar AA, Ansarin K, Pour Moghaddam M, Sakhinia M, et al. Effects of the Flavanone combination Hesperetin‐Naringenin, and Orange and Grapefruit Juices, on Airway inflammation and Remodeling in a murine asthma model. Phytotherapy Res. 2015;29(4):591-8.
68. Shi Y, Dai J, Liu H, Li R-R, Sun P-L, Du Q, et al. Naringenin inhibits allergen-induced airway inflammation and airway responsiveness and inhibits NF-κB activity in a murine model of asthma. Canadian J Physiol Pharmacol. 2009;87(9):729-35.
69. Lee M, Kim S, Kwon O-K, Oh S-R, Lee H-K, Ahn K. Anti-inflammatory and antiasthmatic effects of resveratrol, a polyphenolic stilbene, in a mouse model of allergic asthma. Int Immunopharmacol. 2009;9(4):418-24.
70. Jafarinia M, Sadat Hosseini M, Fazel N, Fathi F, Ganjalikhani Hakemi M, Eskandari N. Quercetin with the potential effect on allergic diseases. Allergy Asthma Clin Immunol. 2020;16(1):1-11.
IssueVol 22 No 2 (2023) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijaai.v22i2.12675
Asthma Inflammation Oxidative stress Quercetin

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Rajizadeh MA, Bejeshk MA, Doustimotlagh AH, Najafipour H, Eftekhari M, Mahmoodi M, Azizi M, Rostamabadi F, Pourghadamyari H. The Alleviating Impacts of Quercetin on Inflammation and Oxidant-antioxidant Imbalance in Rats with Allergic Asthma. Iran J Allergy Asthma Immunol. 2023;22(2):138-149.