Effect of Alpha-Hederin, the active constituent of Nigella sativa, on miRNA-126, IL-13 mRNA levels and inflammation of lungs in ovalbumin-sensitized male rats

Document Type: Original Research Article

Authors

1 Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

2 Medical Education Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of molecular medicine, School of advanced medical sciences, Tabriz University of Medical Sciences, Tabriz, Iran

4 Department of basic sciences, College of veterinary medicine, Tabriz branch, Islamic Azad University, Tabriz, Iran

5 Department of Physiology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

6 Tuberculosis and lung diseases research center, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Objectives: In previous studies the therapeutic effects of Nigella sativa have been demonstrated on asthmatic animals. In the present study, the preventive effect of single dose of alpha-hederin, its active constituent, has been evaluated on lung inflammation and some inflammatory mediators in lungs of ovalbumin sensitized rat in order to elicit its mechanism.
Materials and methods: Forty rats were randomly grouped in 4 groups; control (C), sensitized (S), sensitized pretreated groups with thymoquinone (3 mg/kg i.p., S+TQ) and alpha-hederin (0.02 mg/kg i.p., S+AH). Levels of IL-13 mRNA and miRNA-126 in lung tissue and its pathological changes in each group were assessed.
Results: Elevated levels of miRNA-126, IL-13 mRNA and pathological changes were observed in the sensitized group compared to the control group (pConclusion: The results suggested that alpha-hederin had preventive effect on sensitized rats like thymoquinone. It may intervene in miRNA-126 expression, which consequently could interfere with IL-13 secretion pathway leading to a reduction in inflammatory responses.

Keywords

Main Subjects


Abd El Aziz AE, El Sayed NS, Mahran LG. 2011. Anti-asthmatic and anti-allergic effects of thymoquinone on airway-induced hypersensitivity in experimental animals. J Appl Pharm Sci, 1: 109-117.

Alipour MR, Khamaneh AM, Yousefzadeh N, Mohammad-nejad D, Soufi FG. 2013. Upregulation of microRNA-146a was not accompanied by downregulation of pro-inflammatory markers in diabetic kidney. Mol Biol Rep, 40: 6477-6483.

Al-JawadFH, Al-Razzuqi RAM, Hashim HM, Ismael AH. 2012. Broncho-relaxant activity of Nigella sativa versus anthemisnobilis in chronic bronchial asthma; a comparative study of efficacy. IOSR J Pharmac, 2: 81-83.

Angulo M, Lecuona E, Sznajder JI. 2012. Role of MicroRNAs in lung disease. Archivos de Bronconeumología (English Edition), 48: 325-330.

Barnes PJ. 2001. Th2 cytokines and asthma: an introduction. Respir Res, 2: 64-65.

Boskabady MH, Aslani MR. 2005. Possible relaxant effects of thymoquinone on guinea pig tracheal chains. Iran Biomed J, 9: 123-128.

Boskabady MH, Mohsenpoor N, Takaloo L. 2010. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomedicine, 17: 707-713.

Bosnjak B, Stelzmueller B, Erb KJ, Epstein MM. 2011. Treatment of allergic asthma: modulation of Th2 cells and their responses. Respir Res, 12: 114.

Collison A, Herbert C, Siegle, J. Mattes, P. S. Foster and R. K. Kumar. 2011b. Altered expression of microRNA in the airway wall in chronic asthma: miR-126 as a potential therapeutic target. BMC pulmonary medicine, 11: 29.

Collison A, Mattes J, Plank M, Foster PS. 2011a. Inhibition of house dust mite–induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment. J Allergy  Clin Immunol, 128: 160-167. e4.

Gepdiremen A, Mshvildadze V, Süleyman H, Elias R. 2005. Acute anti-inflammatory activity of four saponins isolated from ivy: alpha-hederin, hederasaponin-C, hederacolchiside-E and hederacolchiside-F in carrageenan-induced rat paw edema. Phytomedicine, 12: 440-444.

Greene CM, Gaughan KP. 2013. microRNAs in asthma: potential therapeutic targets. Curr Opin Pulm Med, 19:66–72.

Grünig G, Corry DB, Reibman J, Wills-Karp M. 2012. Interleukin 13 and the evolution of asthma therapy. Am J Clin Exp Immunol, 1: 20.

Hocaoglu AB, Karaman O, Erge DO, Erbil G, Yilmaz O, Kivcak B, Bagriyanik A, Uzuner N. 2012. Effect of hedera helix on lung histopathology in chronic asthma. Iran J Allergy, Asthma Immunol, 11: 316-323.

Hosseinzadeh H, Eskandari M, Ziaee T. 2008. Antitussive effect of thymoquinone, a constituent of Nigella sativa seeds, in guinea pigs. Pharmacologyonline, 2: 480-484.

Keyhanmanesh R, Boskabady MH, Khamneh S, Doostar Y. 2010. Effect of thymoquinone on the lung pathology and cytokine levels of ovalbumin-sensitized guinea pigs. Pharmacol rep, 62: 910-916.

Keyhanmanesh R, Gholamnezhad Z, Boskabady MH. 2014b. The relaxant effect of Nigella sativa on smooth muscles, its possible mechanisms and clinical applications. Iran J Basic Med Sci, 17: 939-949.

Keyhanmanesh R, Pejman L, Omrani H, Mirzamohammadi Z, Shahbazfar AA. 2014a. The effect of single dose of thymoquinone, the main constituents of Nigella sativa, in guinea pig model of asthma. BioImpacts, 4: 75.

Kumar M, Ahmad T, Sharma A, Mabalirajan U, Kulshreshtha A, Agrawal A, et al. 2011. Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immunol,128:1077–1085.

Mattes J, Collison A, Plank M, Phipps S, Foster PS. 2009. Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease. Proc Nat Acad Sci, 106: 18704-18709.

May R, Monk P, Cohen E, Manuel D, Dempsey F, Davis N, Dodd A, Corkill D, Woods J, Joberty-Candotti C, Conroy L, Koentgen F, Martin E, Wilson R, Brennan N, Powell J, Anderson I. 2011. Preclinical development of CAT-354, an IL-13-neutralising antibody, for the treatment of severe uncontrolled asthma. Br J Pharmacol, 166: 177-93.

Oglesby IK, Mc Elvaney NG, Greene CM. 2010. MicroRNAs in inflammatory lung disease-master regulators or target practice? Respiratory research, 11: 148.

Rad MK, Neamati A, Boskabady MH, Mahdavi-Shahri N, Mahmoudabady M. 2012. The preventive effect of Brassica napus L. oil on pathophysiological changes of respiratory system in experimental asthmatic rat.Avicenna J

 Phytomed, 3: 56-63.

Rooney S, Ryan M. 2005. Modes of action of alpha-hederin and thymoquinone, active constituents of Nigella sativa, against HEp-2 cancer cells. Anticancer res, 25: 4255-4259.

Saadat S, Mohammadi M, Fallahi M, keyhanmanesh R, Aslani MR. 2015.The protective effect of α-hederin, the active constituent of Nigella sativa, on tracheal responsiveness and lung inflammation in ovalbumin sensitized guinea pigs. J Physiol Sci, 65: 285-92.

Tsitsiou E, Williams AE, Moschos SA, Patel K, Rossios C, Jiang, X, Adams O, Macedo P, Booton R, Gibeon D, Chung KF, Lindsay MA. 2012. Transcriptome analysis shows activation of circulatingCD81 T cells in patients with severe asthma. American Academy of Allergy, Asthma Immunol, 129(1): 96-103.

Wolf A, Gosens R , Meurs H, Häberlein H. 2011. Pre-treatment with α-hederin increases β-adrenoceptor mediated relaxation of airway smooth muscle. Phytomedicine, 18: 214-218.

Yang M, Mattes J. 2008. Discovery, biology and therapeutic potential of RNA interference, microRNA and antagomirs. Pharmacol  therap, 117: 94-104.