Rosmarinic acid affects immunological and inflammatory mediator levels and restores lung pathological features in asthmatic rats
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Keywords
Rosmarinic acid, Immunological mediators, Lung pathology, Asthmatic rats, Ovalbumin
Abstract
Background: The effects of rosmarinic acid (RA) on immunological and inflammatory mediator levels in bronchoalveolar lavage fluid (BALF) as well as lung pathological changes in asthmatic rats were investigated.
Methods: The levels of IFN-, IL-4, IFN-/IL-4 ratio, IgE, PLA2, and total protein (TP) in BALF and pathological changes in the lung were evaluated in control group (C), asthma group (sensitized to ovalbumin) (A), asthma groups treated with RA and dexamethasone.
Results: Compared to the control group, asthmatic rats showed increased levels of IL-4, IgE, PLA2, and TP as well as all pathological scores with decreased levels of IFN-γ and IFN-γ/IL-4 ratio (P < 0.05 to P < 0.001). The levels of IL-4, IgE, PLA2, and TP significantly reduced in groups treated with all concentrations of RA compared to asthma group (P < 0.001 for all cases). IFN-γ was significantly decreased in groups treated with two lower concentrations of RA but IFN-γ/IL-4 ratio was increased in groups treated with two higher concentrations of RA compared to asthma group (P < 0.05 to P < 0.001). Treatment with all doses of RA led to significant improvement in pathological scores in asthmatic animals (P < 0.05 to P < 0.001). Most measured parameters were also significantly improved in dexamethasone-treated animals (P < 0.01 to P < 0.001) but IFN-γ/IL-4 ratio and the scores of interstitial fibrosis, bleeding and epithelial damage did not change in this group.
Conclusion: The results indicated a preventive effect for RA on immunological and inflammatory mediators as well as lung pathological changes in asthmatic rats which were comparable or even more potent than that of dexamethasone.
References
2. Education NA, on the Diagnosis TEP, of Asthma M. Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma. 2007.
3. Levine SJ, Wenzel SE. Narrative review: the role of Th2 immune pathway modulation in the treatment of severe asthma and its phenotypes. Ann Intern Med. 2010;152:232-7.
4. Chung F. Anti-inflammatory cytokines in asthma and allergy: interleukin-10, interleukin-12, interferon-. Mediators Inflamm. 2001;10:51-9.
5. Deo SS, Mistry KJ, Kakade AM, Niphadkar PV. Role played by Th2 type cytokines in IgE mediated allergy and asthma. Lung India. 2010;27:66-71.
6. Boskabady MH, Jalali S, Yahyazadeh N, Boskabady M. Carvacrol attenuates serum levels of total protein, phospholipase A2 and histamine in asthmatic guinea pig. Avicenna J Phytomed. 2016;6:636-42.
7. Shakeri F, Boskabady MH. Anti-inflammatory, antioxidant, and immunomodulatory effects of curcumin in ovalbumin-sensitized rat. BioFactors. 2017;43:567-76.
8. Bowton DL, Dmitrienko AA, Israel E, Zeiher BG, Sides GD. Impact of a soluble phospholipase A2 inhibitor on inhaled allergen challenge in subjects with asthma. J Asthma. 2005;42:65-71.
9. Burrows B, Martinez FD, Halonen M, Barbee RA, Cline MG. Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med. 1989;320:271-7.
10. Turner H, Kinet JP. Signalling through the high-affinity IgE receptor FcRI. Nature. 1999;402:24-30.
11. Barrios RJ, Kheradmand F, Batts LK, Corry DB. Asthma: pathology and pathophysiology. Arch Pathol Lab Med. 2006;130:447-51.
12. Shifren A, Witt C, Christie C, Castro M. Mechanisms of remodeling in asthmatic airways. J Allergy. 2012;2012:1-12.
13. Shekarchi M, Hajimehdipoor H, Saeidnia S, Gohari AR, Hamedani MP. Comparative study of rosmarinic acid content in some plants of Labiatae family. Pharmacogn Mag. 2012;8:37-41.
14. Stansbury J. Rosmarinic acid as a novel agent in the treatment of allergies and asthma. J Restor Med. 2014;3:121-6.
15. Ekambaram SP, Perumal SS, Balakrishnan A, Marappan N, Gajendran SS, Viswanathan V. Antibacterial synergy between rosmarinic acid and antibiotics against methicillin-resistant Staphylococcus aureus. J Intercult Ethnopharmacol. 2016;5:358-63.
16. Rocha J, Eduardo-Figueira M, Barateiro A, Fernandes A, Brites D, Bronze R, et al. Anti-inflammatory effect of rosmarinic acid and an extract of rosmarinus officinalis in rat models of local and systemic inflammation. Basic Clin Pharmacol Toxicol. 2015;116:398-413.
17. Yun SY, Hur YG, Kang MA, Lee J, Ahn C, Won J. Synergistic immunosuppressive effects of rosmarinic acid and rapamycin in vitro and in vivo1. Transplant. 2003;75:1758-60.
18. Liang Z, Xu Y, Wen X, Nie H, Hu T, Yang X, et al. Rosmarinic acid attenuates airway inflammation and hyperresponsiveness in a murine model of asthma. Molecules. 2016;21:1-15.
19. Eftekhar N, Moghimi A, Boskabady MH. Prophylactic effect of rosmarinic acid on tracheal responsiveness, white blood cell count and oxidative stress markers in lung lavage of sensitized rats. Pharmacol Rep. 2017;1:1-19.
20. Cuzzocrea S, Thiemermann C, Salvemini D. Potential therapeutic effect of antioxidant therapy in shock and inflammation. Curr Med Chem. 2004;11:1147-62.
21. Naito Y, Takano H, Yoshikawa T. Oxidative stress-related molecules as a therapeutic target for inflammatory and allergic diseases. Curr Drug Targets Inflamm Allergy. 2005;4: 511-5.
22. Shakeri F, Soukhtanloo M, Boskabady MH. The effect of hydroethanolic 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 Med Sci. 2017;20:155-65.
23. Boskabady M, Tabatabaee A, Byrami G. The effect of the extract of Crocus sativus and its constituent safranal, on lung pathology and lung inflammation of ovalbumin sensitized guinea-pigs. Phytomed. 2012;19:904-11.
24. Boskabady MH, Tabatabaee A, Jalali S. Potential effect of the extract of Zataria multiflora and its constituent, carvacrol, on lung pathology, total and differential WBC, IgE and eosinophil peroxidase levels in sensitized guinea pigs. J Funct Foods. 2014;11:49-61.
25. Sanbongi C, Takano H, Osakabe N, Sasa N, Natsume M, Yanagisawa R, et al. Rosmarinic acid in perilla extract inhibits allergic inflammation induced by mite allergen, in a mouse model. Clin Exp Allergy. 2004;34:971-7.
26. Liang Z, Nie H, Xu Y, Peng J, Zeng Y, Wei Y, et al. Therapeutic effects of rosmarinic acid on airway responses in a murine model of asthma. Int J Immunopharmacol. 2016;41:90-7.
27. Costa RS, Carneiro TCB, Cerqueira-Lima AT, Queiroz NV, Alcântara-Neves NM, Pontes-de-Carvalho LC, et al. Ocimum gratissimum Linn. and rosmarinic acid, attenuate eosinophilic airway inflammation in an experimental model of respiratory allergy to Blomia tropicalis. Int J Immunopharmacol. 2012;13:126-34.
28. Chu X, Ci X, He J, Jiang L, Wei M, Cao Q, et al. Effects of a natural prolyl oligopeptidase inhibitor, rosmarinic acid, on lipopolysaccharide-induced acute lung injury in mice. Molecules. 2012;17:3586-98.
29. Ticli FK, Hage LI, Cambraia RS, Pereira PS, Magro ÂJ, Fontes MR, et al. Rosmarinic acid, a new snake venom phospholipase A2 inhibitor from Cordia verbenacea (Boraginaceae): antiserum action potentiation and molecular interaction. Toxicon. 2005;46:318-27.
30. Rossi AG, Sawatsky DA. The resolution of inflammation. Inflammopharmacology. 2008;16:100-2.
31. Walsh GM, McDougall CM. The resolution of airway inflammation in asthma and chronic obstructive pulmonary disease. In: The Resolution of Inflammation. Springer; 2008. p. 159-91.
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