Original Article
 

Formulation and Evaluation of the Anti-inflammatory, Anti-oxidative, and Anti-remodelling Effects of the Niosomal Myrtenol on the Lungs of Asthmatic Rats

Abstract

Asthma is a common chronic allergic disease that affects a significant percentage of the world’s population. Niosomes are nanoparticles consisting of non-ionic surfactants that can be used for drug delivery. This research was designed to investigate the impacts of inhalation of simple and niosomal forms of myrtenol against adverse consequences of asthma in rats.
Asthma induction was performed via injection of ovalbumin, followed by its inhalation. Niosomes were created by a heating protocol, and their physicochemical features were evaluated. Forty-nine male Wistar rats were allotted into 7 groups (n=7 each): Control (CTL), vacant niosome (VN), Asthma, Asthma+VN, Asthma+SM (simple myrtenol), Asthma+NM (niosomal myrtenol), and Asthma+B (budesonide). Lung remodeling, serum immunoglobulin E (IgE), inflammatory  and cytokines, and antioxidant factors in the lung tissue and bronchoalveolar fluid (BALF), as well as), were evaluated.
The results showed that myrtenol-loaded niosomes had appropriate encapsulation efficiency, kinetic release, size, and zeta potential. The thickness of the epithelial cell layer in the lungs, as well as cell infiltration, fibrosis, IgE, reactive oxygen species, interleukin (IL)-6, and tumor nuclear factor alpha (TNF-α) levels, decreased significantly. In contrast, superoxide dismutase and glutathione peroxide activity increased significantly in the serum and BALF of the treated groups. The niosomal form of myrtenol revealed a higher efficacy than simple myrtenol and was similar to budesonide in ameliorating asthma indices. 
Inhalation of simple and niosomal forms of myrtenol improved the detrimental changes in the asthmatic lung. The niosomal form induced more prominent anti-asthmatic effects comparable to those of budesonide.

1. Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008;118(11):3546-56.
2. 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. Evid Based Complement Alternat Med. 2022;2022.
3. Fazlollahi MR, Najmi M, Fallahnezhad M, Sabetkish N, Kazemnejad A, Bidad K, et al. The prevalence of asthma in Iranian adults: The first national survey and the most recent updates. Clin Respir J. 2018;12(5):1872-81.
4. Brightling C, Berry M, Amrani Y. Targeting TNF-α: a novel therapeutic approach for asthma .J Allergy Clin Immunol. 2008;121(1):5-10.
5. O'Donnell S, O'Morain CA. Therapeutic benefits of budesonide in gastroenterology. Ther Adv Chronic Dis. 2010;1(4):177-86.
6. Iborra M, Álvarez-Sotomayor D, Nos P. Long-term safety and efficacy of budesonide in the treatment of ulcerative colitis. Clin Exp Gastroenterol. 2014:39-46.
7. Hamelmann E. The rationale for treating allergic asthma with anti-IgE. Eur Respir Rev. 2007;16(104):61-6.
8. Bagnasco D, Ferrando M, Varricchi G, Passalacqua G, Canonica GW. A critical evaluation of anti-IL-13 and anti-IL-4 strategies in severe asthma. Int Arch Allergy Immunol. 2016;170(2):122-31.
9. Lambrecht BN, Hammad H, Fahy JV. The Cytokines of Asthma. Immunity. 2019;50(4):975-91.
10. Nakagome K, Nagata M. Pathogenesis of airway inflammation in bronchial asthma. Auris Nasus Larynx. 2011;38(5):555-63.
11. Henricks PA, Nijkamp FP. Reactive oxygen species as mediators in asthma. Pulm Pharmacol Ther. 2001;14(6):409-20.
12. 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 Neurosci. 2021:1-13.
13. 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.
14. 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 Tradit Complement Med. 2022;12(6):599-607.
15. Motamedi S, Sheibani V, Rajizadeh MA, Esmaeilpour K, Sepehri G. The effects of co-administration of marijuana and methylphenidate on spatial learning and memory in male rats. Toxin Rev. 2019.
16. Bouzabata A, Casanova J, Bighelli A, Cavaleiro C, Salgueiro L, Tomi F. The genus Myrtus L. in Algeria: Composition and biological aspects of essential oils from M. communis and M. nivellei: A review. Chem Biodivers. 2016;13(6):672-80.
17. Alipour G, Dashti S, Hosseinzadeh H. Review of pharmacological effects of Myrtus communis L. and its active constituents. Phytother Res. 2014;28(8):1125-36.
18. Amiri K, Nasibi S, Mehrabani M, Nematollahi MH, Harandi MF. In vitro evaluation on the scolicidal effect of Myrtus communis L. and Tripleurospermum disciforme L. methanolic extracts. Exp Parasitol. 2019;199:111-5.
19. 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. Allergol Immunopathol. 2019;47(2):185-93.
20. Rajizadeh MA, Najafipour H, Fekr MS, Rostamzadeh F, Jafari E, Bejeshk MA, et al. Anti-inflammatory and anti-oxidative effects of myrtenol in the rats with allergic asthma. Iran J Pharm Res. 2019;18(3):1488.
21. Samareh Fekri M, Mandegary A, Sharififar F, Poursalehi HR, Nematollahi MH, Izadi A, et al. Protective effect of standardized extract of Myrtus communis L.(myrtle) on experimentally bleomycin-induced pulmonary fibrosis: biochemical and histopathological study. Drug Chem Toxicol. 2018;41(4):408-14.
22. Raeiszadeh M, Esmaeili-Tarzi M, Bahrampour-Juybari K, Nematollahi-Mahani S, Pardakhty A, Nematollahi M, et al. Evaluation the effect of Myrtus communis L. extract on several underlying mechanisms involved in wound healing: An in vitro study. S Afr J Bot. 2018;118:144-50.
23. Dolovich MB, Ahrens RC, Hess DR, Anderson P, Dhand R, Rau JL, et al. Device selection and outcomes of aerosol therapy: evidence-based guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology. Chest. 2005;127(1):335-71.
24. Knudsen KB, Northeved H, Ek PK, Permin A, Gjetting T, Andresen TL, et al. In vivo toxicity of cationic micelles and liposomes. Nanomedicine. 2015;11(2):467-77.
25. Nematollahi MH, Torkzadeh-Mahanai M, Pardakhty A, Ebrahimi Meimand HA, Asadikaram G. Ternary complex of plasmid DNA with NLS-Mu-Mu protein and cationic niosome for biocompatible and efficient gene delivery: a comparative study with protamine and lipofectamine. Artif Cells Nanomed Biotechnol. 2018;46(8):1781-91.
26. Thabet Y, Elsabahy M, Eissa NG. Methods for preparation of niosomes: A focus on thin-film hydration method. Methods. 2022;199:9-15.
27. Maleki G, Bahrami Z, Woltering EJ, Khorasani S. A Review of Patents on" Mozafari Method" as a Green Technology for Manufacturing Bioactive Carriers. 2022.
28. Terzano C, Allegra L, Alhaique F, Marianecci C, Carafa M. Non-phospholipid vesicles for pulmonary glucocorticoid delivery. Eur J Pharm Biopharm. 2005;59(1):57-62.
29. Mohamad Saimi NI, Salim N, Ahmad N, Abdulmalek E, Abdul Rahman MB. Aerosolized Niosome Formulation Containing Gemcitabine and Cisplatin for Lung Cancer Treatment: Optimization, Characterization and In Vitro Evaluation. Pharmaceutics. 2021;13(1).
30. Basiri L, Rajabzadeh G, Bostan A. α-Tocopherol-loaded niosome prepared by heating method and its release behavior. Food chem. 2017;221:620-8.
31. Harandi H, Falahati-Pour SK, Mahmoodi M, Faramarz S, Maleki H, Nasab FB, et al. Nanoliposomal formulation of pistachio hull extract: preparation, characterization and anti-cancer evaluation through Bax/Bcl2 modulation. Molecular biology reports. 2022:1-9.
32. Barani M, Mirzaei M, Torkzadeh-Mahani M, Lohrasbi-Nejad A, Nematollahi MH. A new formulation of hydrophobin-coated niosome as a drug carrier to cancer cells. Mater Sci Eng C. 2020;113:110975.
33. Du W, Su J, Ye D, Wang Y, Huang Q, Gong X. Pinellia ternata attenuates mucus secretion and airway inflammation after inhaled corticosteroid withdrawal in COPD rats. Am J Chin Med. 2016;44(05):1027-41.
34. Vanacker NJ, Palmans E, Kips JC, Pauwels RA. Fluticasone inhibits but does not reverse allergen-induced structural airway changes. Am J Respir Crit Care Med. 2001;163(3):674-9.
35. 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. 2023:1-13.
36. Hrvačić B, Bošnjak B, Tudja M, Mesić M, Merćep M. Applicability of an ultrasonic nebulization system for the airways delivery of beclomethasone dipropionate in a murine model of asthma. Pharm Res. 2006;23(8):1765-75.
37. 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 Ther Med. 2013;6(5):1251-8.
38. Okrit F, Chantranuwatana P, Werawatganon D, Chayanupatkul M, Sanguanrungsirikul S. Changes of vitamin D receptors (VDR) and MAPK activation in cytoplasmic and nuclear fractions following exposure to cigarette smoke with or without filter in rats. Heliyon. 2021;7(1):e05927.
39. Hübner R-H, Gitter W, Eddine El Mokhtari N, Mathiak M, Both M, Bolte H, et al. Standardized quantification of pulmonary fibrosis in histological samples. Biotechniques. 2008;44(4):507-17.
40. Bejeshk MA, Beik A, Aminizadeh AH, Salimi F, Bagheri F, Sahebazzamani M, et al. Perillyl alcohol (PA) mitigates inflammatory, oxidative, and histopathological consequences of allergic asthma in rats. Naunyn Schmiedebergs Arch Pharmacol. 2023:1-11.
41. Ge X, Wei M, He S, Yuan W-E. Advances of non-ionic surfactant vesicles (niosomes) and their application in drug delivery. Pharmaceutics. 2019;11(2):55.
42. Barani M, Sangiovanni E, Angarano M, Rajizadeh MA, Mehrabani M, Piazza S, et al. Phytosomes as innovative delivery systems for phytochemicals: a comprehensive review of literature. Int J Nanomedicine. 2021;16:6983.
43. Shilakari Asthana G, Sharma PK, Asthana A. In vitro and in vivo evaluation of niosomal formulation for controlled delivery of clarithromycin. Scientifica. 2016;2016.
44. Gulati N, Chellappan DK, MacLoughlin R, Dua K, Dureja H. Inhaled nano-based therapeutics for inflammatory lung diseases: Recent advances and future prospects. Life sci. 2021;285:119969.
45. Wong J-Y, Yin Ng Z, Mehta M, Shukla SD, Panneerselvam J, Madheswaran T, et al. Curcumin-loaded niosomes downregulate mRNA expression of pro-inflammatory markers involved in asthma: an in vitro study. Nanomedicine. 2020;15(30):2955-70.
46. Berry M, Brightling C, Pavord I, Wardlaw AJ. TNF-α in asthma. Curr Opin Pharmacol. 2007;7(3):279-82.
47. Rincon M, Irvin CG. Role of IL-6 in asthma and other inflammatory pulmonary diseases. Int J Biol Sci. 2012;8(9):1281.
48. Mujoriya R, Bodla RB, Dhamande K, Patle L. Niosomal drug delivery system: The magic bullet. J Appl Pharm Sci. 2011(Issue):20-3.
49. Marianecci C, Rinaldi F, Mastriota M, Pieretti S, Trapasso E, Paolino D, et al. Anti-inflammatory activity of novel ammonium glycyrrhizinate/niosomes delivery system: human and murine models. J Control Release. 2012;164(1):17-25.
50. Barnes PJ. Reactive oxygen species and airway inflammation. Free Radic Biol Med. 1990;9(3):235-43.
51. Holgate ST. Asthma and allergy--disorders of civilization? QJM. 1998;91(3):171-84.
52. Humbert M, Bousquet J, Bachert C, Palomares O, Pfister P, Kottakis I, et al. IgE-mediated multimorbidities in allergic asthma and the potential for omalizumab therapy. J Allergy Clin Immunol: In Practice. 2019;7(5):1418-29.
53. Jackson DJ, Humbert M, Hirsch I, Newbold P, Garcia Gil E. Ability of serum IgE concentration to predict exacerbation risk and benralizumab efficacy for patients with severe eosinophilic asthma. Adv Ther. 2020;37:718-29.
54. Royce SG, Cheng V, Samuel CS, Tang ML. The regulation of fibrosis in airway remodeling in asthma. Mol Cell Endocrinol. 2012;351(2):167-75.
55. Méndez-Enríquez E, Hallgren J. Mast Cells and Their Progenitors in Allergic Asthma. Front Immunol. 2019;10:821.
56. Gevaert P, Wong K, Millette LA, Carr TF. The role of IgE in upper and lower airway disease: more than just allergy! Clin Rev Allergy Immunol. 2022;62(1):200-15.
57. Méndez-Enríquez E, Hallgren J. Mast cells and their progenitors in allergic asthma. Front immunol. 2019;10:821.
58. van der Veen TA, de Groot LE, Melgert BN. The different faces of the macrophage in asthma. Curr Opin Pulm Med. 2020;26(1):62.
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IssueVol 22 No 3 (2023) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijaai.v22i3.13054
Keywords
Allergic asthma Inflammation Histopathological changes Niosomes myrtenol Oxidative stress

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Rajizadeh MA, Nematollahi MH, Jafari E, Bejeshk MA, Mehrabani M, Rostamzadeh F, Samareh fekri M, Najafipour H. Formulation and Evaluation of the Anti-inflammatory, Anti-oxidative, and Anti-remodelling Effects of the Niosomal Myrtenol on the Lungs of Asthmatic Rats. Iran J Allergy Asthma Immunol. 2023;22(3):265-280.