Contents lists available at ScienceDirect Chemico-Biological Interactions journal homepage: www.elsevier.com/locate/chembioint Flavocoxid attenuates airway inflammation in ovalbumin-induced mouse asthma model Rania R. Abdеlaziz * , Mohammеd kh Еlmahdy, Ghada M. Suddеk Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt ARTICLE INFO Keywords: Ovalbumin IL-13 Flavocoxid Bеclomеthasonе Airway inflammation ABSTRACT Asthma is a common airways inflammatory disease. This study provides evidence on the efficacy of flavocoxid against ovalbumin (OVA)-induced allergic airways inflammation in a mouse model of asthma. Airway in- flammation was induced by intrapеritonеal injection of 10 mg ovalbumin (OVA) on day zero and day 7 followed by OVA challenge starting from 14th day to 16th day. Beclomethasone; a standard anti-inflammatory agent was selected as a drug in asthma. Flavocoxid (20 mg/kg, i. p.) was administered on day zero till 16th day followed by OVA challenge. At the end of the study, lung weight index, bronchoalveolar lavage fluid (BALF) content of total and differential WBCs, interleukin-13(IL-13), in addition to lung tissue nitrate/nitrite (NO) and oxidative stress biomarkers were measured. Also, histological and immunohistochemical analysis were conducted. Daily i. p. injection of flavocoxid (20 mg/kg) significantly improved airway inflammation. Inflammatory cells in BALF, malondialdehyde (MDA), NO and IL-13 significantly declined with concomitant increase in superoxide dis- mutase (SOD) activity. Histopathological examination and immunohistochеmical staining of mast cells were correlated with observed biochemical improvements. Collectively, these results demonstrate that flavocoxid mitigates the allergic airway inflammation induced by ovalbumin through attenuation of IL-13, NO expressions and oxidative stress. 1. Introduction Asthma is a common allergic disease characterized by airways in- flammation [1]. It usually presents with recurrent symptoms including obstruction of airflow, bronchoconstriction, wheezing, cough, dyspnea and chest tightness episodes [2]. Symptoms may become worsen with exercise or at night [3]. The main pathological changes that highlight asthma are mucus overproduction, airway obstruction, and increased infiltration of inflammatory cells including mast cells, eosinophils and lymphocytes [4]. Ovalbumin (OVA) is one of the most important allergen, utilized to reproduce asthma in experimental models [5]. Overеxprеssion of nitric oxide, T-helper cytokines, oxidative damage and inflammatory cells accumulation usually characterize OVA-induced asthma in mice [6]. The major mechanism of OVA-induced asthma involves activation of Type II T helper (Th 2 ) derived cytokines as interleukin (IL)-4; IL-5 and IL-13, which induce inflammatory cells activation, recruitment and overproduction of mucus [7]. There is strong evidence that the exogenous and endogenous ni- trogen and reactive oxygen species play a crucial role in airway in- flammation and are the most determinants of asthma severity [8,9]. Glucocorticoids are considered gold standard in asthma treatment, despite its limited efficacy in reversing airway remodeling. Side effects of inhaled form of beclomethasone caused infections of airways and inflammatory throat, Cushing's syndrome, headache, cataract, super- infection, anaphylactic reactions and oral candidiasis. Long term ad- ministration induced adrenal insufficiency and mood or personality changes [10]. The combination of bronchodilators and glucocorticoids is still unable to control the main asthma symptoms [11], and results in multiple complications. SO, there is an important need for the identi- fication of effective therapies for the management of airway in- flammation in asthma. Dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) in- hibitors of which, flavocoxid has been reported to show promising re- sults in modulation of inflammation and attenuation of the dangerous leukotrienes (LTs) expression involved in a variety of pathological conditions such as asthma, cardiovascular complications, renal in- sufficiency, and gastric ulceration [12]. Flavocoxid contains natural flavonoids catеchin and baicalin [12,13]. Flavocoxid binds to blood albumin, onset of action is 2–2.5 h and its duration is 12 h. A small concentration of its both components (catеchin and baicalin) (< 10%) is metabolized by liver enzymes. Catechin is metabolized to https://doi.org/10.1016/j.cbi.2018.07.001 Received 4 May 2018; Received in revised form 25 June 2018; Accepted 1 July 2018 * Corresponding author. E-mail addresses: rania200582@yahoo.com, rania200582@mans.edu.eg (R.R. Abdеlaziz). Chemico-Biological Interactions 292 (2018) 15–23 Available online 02 July 2018 0009-2797/ © 2018 Elsevier B.V. All rights reserved. T