Downregulation of leukotriene biosynthesis by thymoquinone attenuates airway inflammation in a mouse model of allergic asthma.
Chronic airway inflammation is a key feature of bronchial asthma. Leukotrienes are potent inflammatory mediators that play a role in the pathophysiology of asthma, and their levels are elevated in the airways in response to allergen challenge. We examined the anti-inflammatory effect of thymoquinone (TQ), the active principle in the volatile oil of Nigella sativa seeds, on leukotriene (LT) biosynthesis in a mouse model of allergic asthma. Mice sensitized and challenged with ovalbumin (OVA) antigen had an increased amounts of leukotriene B4 and C4, Th2 cytokines, and eosinophils in bronchoalveolar lavage (BAL) fluid. In addition, there was also a marked increase in lung tissue eosinophilia and goblet cell numbers. Administration of TQ before OVA challenge inhibited 5-lipoxygenase, the main enzyme in leukotriene biosynthesis, expression by lung cells and significantly reduced the levels of LTB4 and LTC4. This was accompanied by a marked decrease in Th2 cytokines and BAL fluid and lung tissue eosinophilia, all of which are characteristics of airway inflammation. These results demonstrate the anti-inflammatory effect of TQ in experimental asthma.
El Gazzar
Mohamed
M
Department of Medicine, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Denver, CO 80262, USA. mohamed.elgazzar@uchsc.edu
El Mezayen
Rabab
R
Nicolls
Mark R
MR
Marecki
John C
JC
Dreskin
Stephen C
SC
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001249:Asthma / Q000473:pathology*; D016227:Benzoquinones / Q000737:chemistry*; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006967:Hypersensitivity / Q000473:pathology; D007249:Inflammation; D015289:Leukotrienes / Q000096:biosynthesis*; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D031881:Nigella sativa / Q000378:metabolism
D016227:Benzoquinones; D016207:Cytokines; D015289:Leukotrienes; D001094:Arachidonate 5-Lipoxygenase; C003466:thymoquinone