Anti-inflammatory and anti-remodeling effects of myrtenol in the lungs of asthmatic rats: Histopathological and biochemical findings
Main Article Content
Keywords
Experimental asthma, Myrtenol, Oxidative stress, Interleukins, Histopathology
Abstract
Introduction: Asthma is a chronic inflammatory disease of the airways. In this study, we evaluated the anti-inflammatory effects of myrtenol on the inflammatory indices in the pulmonary parenchyma and airways and on the inflammatory and oxidative indices of the bronchoalveolar lavage fluid (BALF) of asthmatic rats.
Methods: The allergic asthma was induced by sensitization (two weeks) followed by the inhalation of ovalbumin (four weeks). Animals were divided into two main groups: (1) Histopathology, and (2) measurement of inflammatory and oxidative biomarkers in the BALF. Each main group was subdivided into four subgroups: Control, Asthma, Asthma + Dexamethasone and Asthma + Myrtenol. (−)-Myrtenol (50 mg/kg) or Dexamethasone (2.5 mg/kg) was administered intraperitoneally once a day for one week, at the end of the inhalation period. On day 50, lung histopathologic parameters and inflammatory indices in BALF including INF-, IL 10, IL-1, and TNF-α and oxidative stress biomarkers (MDA, SOD, and GPX) were measured.
Result: In the Asthma group, leukocyte infiltration, the thickness of smooth muscle and epithelium of airways wall and the number of goblet cells increased. Myrtenol reduced all of the above-mentioned indices except the epithelium thickness. It also inhibited the increase in BALF ILβ-1, TNF-α and MDA and increased the levels of INF-γ, IL-10 and SOD.
Conclusion: Our results suggest that myrtenol reduced damage caused by experimental asthma by reducing the inflammatory indices, normalizing the level of interleukins and balancing oxidative stress in the lungs. It also prevented airway remodeling. Myrtenol may be suggested as a potent herbal medicine for the treatment of allergic asthma.
References
2. Lin R, Liu X, Meng Y, Xu M, Guo J. Effects of Laminaria japonica polysaccharides on airway inflammation of lungs in an asthma mouse model. Multidiscip Respir Med. 2015;10:20.
3. Girodet P-O, Ozier A, Bara I, de Lara J-MT, Marthan R, Berger P. Airway remodeling in asthma: new mechanisms and potential for pharmacological intervention. Pharmacol Ther. 2011;130:325-37.
4. Bloemen K, Verstraelen S, Van Den Heuvel R, Witters H, Nelissen I, Schoeters G. The allergic cascade: review of the most important molecules in the asthmatic lung. Immunol Lett. 2007;113:6-18.
5. Al-Muhsen S, Johnson JR, Hamid Q. Remodeling in asthma. J Allergy Clin Immunol. 2011;128:451-62.
6. Sharafkhaneh A, Velamuri S, Badmaev V, Lan C, Hanania N. The potential role of natural agents in treatment of airway inflammation. Ther Adv Respir Dis. 2007;1:105-20.
7. Pezhmanmehr M, Dastan D, Ebrahimi S, Hadian J. Essential oil constituents of leaves and fruits of Myrtus communis L. from Iran. Planta Med. 2009;75:PJ164.
8. 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;13:672-80.
9. Silva RO, Salvadori MS, Sousa FBM, Santos MS, Carvalho NS, Sousa DP, et al. Evaluation of the anti-inflammatory and antinociceptive effects of myrtenol, a plant-derived monoterpene alcohol, in mice. Flavour Fragr J. 2014;29:184-92.
10. Sepici A, Gürbüz I, C¸evik C, Yesilada E. Hypoglycaemic effects of myrtle oil in normal and alloxan-diabetic rabbits. J Ethnopharmacol. 2004;93(2-3):311-8.
11. Aleksic V, Knezevic P. Antimicrobial and antioxidative activity of extracts and essential oils of Myrtus communis L. Microbiol Res. 2014;169:240-54.
12. Clark AM. Natural products as a resource for new drugs. Pharm Res. 1996;13:1133-41.
13. Poursalehi HR, Samareh Fekri M, Sharififar F, Mandegari A, Izadi A, Mahmoodi R, et al. Early and late preventive effect of Nigella sativa on the bleomycin-induced pulmonary fibrosis in rats: an experimental study. Avicenna J Phytomed. 2018:1-11.
14. Samareh Fekri M, Poursalehi HR, Mandegary A, Sharififar F, Mahmoodi R, Izadi A, et al. The effect of methanol extract of fennel on bleomycin-induced pulmonary fibrosis in rats. J Kerman Univ Med Sci. 2015:470-83.
15. Samareh Fekri M, Mandegary A, Sharififar F, Poursalehi HR, Nematollahi MH, Izadi A, Mehdipour M, 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. 2018:1-7.
16. Zuo L, Otenbaker NP, Rose BA, Salisbury KS. Molecular mechanisms of reactive oxygen species-related pulmonary inflammation and asthma. Mol Immunol. 2013;56(1-2):57-63.
17. Nadeem A, Siddiqui N, Alharbi NO, Alharbi MM. Airway and systemic oxidant-antioxidant dysregulation in asthma: a possible scenario of oxidants spillover from lung into blood. Pulm Pharmacol Ther. 2014;29:31-40.
18. Van Toan N, Hanh TT. Retracted article: Improved treatment of asthma by using natural sources of antioxidants. Springerplus. 2013;2:278.
19. Sepici-Dincel A, Ac¸ıkgöz ¸,S Cevik C, Sengelen M, Yes¸ilada E. Effects of in vivo antioxidant enzyme activities of myrtle oil in normoglycaemic and alloxan diabetic rabbits. J Ethnopharmacol. 2007;110:498-503.
20. Moreira MRC, Salvadori MGDSS, de Almeida AAC, de Sousa DP, Jordán J, Satyal P, et al. Anxiolytic-like effects and mechanism of (−) myrtenol: a monoterpene alcohol. Neurosci Lett. 2014;579:119-24.
21. Mehta AA, Mahajan S. Role of cytokines in pathophysiology of asthma. Iran J Pharmacol Ther. 2006;5:1-10.
22. Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008;118:3546-56.
23. Tang M, Kemp A, Varigos G. IL-4 and interferon-gamma production in children with atopic disease. Clin Exp Immunol. 1993;92:120-4.
24. Borish L. IL-10: evolving concepts. J Allergy Clin Immunol. 1998;101:293-7.
25. Halonen M, Martinez F. A deficient capacity to produce interferon-gamma: is it a risk for asthma and allergies? Clin Exp Allergy. 1997;27:1234-6.
26. 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;163:674-9.
27. Arora P, Ansari S, Najmi AK, Anjum V, Ahmad S. Investigation of anti-asthmatic potential of dried fruits of Vitis vinifera L. in animal model of bronchial asthma. Allergy Asthma Clin Immunol. 2016;12:42.
28. Hocaoglu AB, Karaman O, Erge DO, Erbil G, Yilmaz O, Bagriyanik A, et al. Glycyrrhizin and long-term histopathologic changes in a murine model of asthma. Curr Ther Res Clin Exp. 2011;72:250-61.
29. Mohammadian M, Boskabady MH, Kashani IR, Jahromi GP, Omidi A, Nejad AK, et al. Effect of bone marrow-derived mesenchymal stem cells on lung pathology and inflammation in ovalbumin-induced asthma in mouse. Iran J Basic Med Sci. 2016;19:55.
30. Zosky G, Sly P. Animal models of asthma. Clin Exp Allergy. 2007;37:973-88.
31. Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma: from bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med. 2000;161:1720-45.
32. Bradding P. Asthma: eosinophil disease, mast cell disease, or both? Allergy Asthma Clin Immunol. 2008;4:84.
33. Gomes BS, Neto BP, Lopes EM, Cunha FV, Araújo AR, Wanderley CW, et al. Anti-inflammatory effect of the monoterpene myrtenol is dependent on the direct modulation of neutrophil migration and oxidative stress. Chem Biol Interact. 2017;273:73-81.
34. Bogdan C. Nitric oxide and the immune response. Nat Immunol. 2001;2:907.
35. Behr J, Maier K, Degenkolb B, Krombach F, Vogelmeier C. Antioxidative and clinical effects of high-dose Nacetylcysteine in fibrosing alveolitis: adjunctive therapy to maintenance immunosuppression. Am J Respir Crit Care Med. 1997;156:1897-901.
36. Comhair SA, Erzurum SC. Redox control of asthma: molecular mechanisms and therapeutic opportunities. Antioxid Redox Signal. 2010;12:93-124.
37. Pretolani M, Goldman M. IL-10: a potential therapy for allergic inflammation? Immunol Today. 1997;18:277-80.
38. Koulis A, Robinson D. The anti-inflammatory effects of interleukin-10 in allergic disease. Clin Exp Allergy. 2000;30:747.
39. Davoine F, Lacy P. Eosinophil cytokines, chemokines, and growth factors: emerging roles in immunity. Front Immunol. 2014;5:570.
40. Joubert P, Hamid Q. Role of airway smooth muscle in airway remodeling. J Allergy Clin Immunol. 2005;116:713-6.