Abstract

A B S T R A C T Nigella sativa L. has been used in folk medicine for treatment of many diseases. Thymoquinone (TQ), a main constituent of its oil and seeds, has shown promising medicinal properties in the treatment and prevention of various diseases. The present study aims to investigate the potential effect of TQ on airway-induced hypersensitivity. Ovalbumin (OVA) sensitization and challenge in guinea pig tracheal muscle preparation were used in order to investigate the anti-asthmatic activity of TQ. To study the effect of TQ on acute lung injury, lipopolysaccharide (LPS) - induced lung injury method was used. In addition, rat peritoneal mast cells (RPMCs) were collected to investigate the release of histamine from these cells. Furthermore, to study the anti-allergic activity of TQ, the systemic anaphylactic shock technique induced by compound 48/80 was performed. Pretreatment with TQ (3 mg/kg, i.p.) for 5 days prior to ovalbumin sensitization showed a marked decrease in the response of the tracheal spirals to acetylcholine and histamine, as spasmogens in a cumulative dose response–curve. TQ (8mg/kg, i.p.) prevented most of the pathological detrimental changes that occurred in response to the endotoxin LPS as the inflammatory cells infiltration, lipid peroxidation (LP), glutathione depletion (GSH), tumor necrosis factor-alpha (TNF- α) and interlukin-1 beta (IL-1β) levels in both boronchoalevolar lavage fluid (BALF) and lung tissue homogenates. Sensitization of rats induced a significant increase in the histamine release from RPMCs which is inhibited by pretreatment with TQ (8 mg/ kg, i.p.). Similarly, pretreatment of mice with TQ (50 and 100 mg/kg), 1hr prior to injection of compound 48/80 (8mg/kg, i.p.) significantly inhibited the % of mortality of mice following the systemic anaphylactic reaction. Considering the anti-asthmatic, anti-inflammatory, antioxidant and anti-allergic activities of TQ reported in this study, one can conclude that TQ could be of therapeutic potentials in treating various diseases associated with airway-induced hypersensitivity.

Highlights

  • Asthma is a common chronic disorder of the airways characterized by airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation (Busse and Lemanske, 2001)

  • Pretreatment of the sensitized guinea pigs with TQ showed a significant decrease in the response of the tracheal spirals to histamine and acetylcholine compared to that produced with sensitized animals

  • The relaxant, anticholinergic and antihistaminic, effects of Nigella sativa have been demonstrated on guinea pig tracheal chains (Boskabady and Shahabi, 1997; Boskabadi and Shiravi, 2000)

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Summary

Introduction

Asthma is a common chronic disorder of the airways characterized by airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation (Busse and Lemanske, 2001). Inflammation has a central role in the pathophysiology of asthma. It involves an interaction of many cell types and multiple mediators with the airways that eventually results in the characteristic features of the disease (O’Byrne, 2009). Many inflammatory cells, including eosinophils, mast cells, macrophages and neutrophils, are involved in the pathogenesis of airway inflammation in asthma (Kelly et al, 1998). These cells produce more reactive oxygen species (ROS) (Cluzel et al, 1987) that affect airway smooth muscles and simulate histamine release from mast cells (Adler et al, 1990).

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