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Nigella sativa (N. sativa) seed had been used traditionally due to several pharmacological effects. The updated experimental and clinical effects of N. sativa and its constituents on respiratory, allergic and immunologic disorders are provided in this comprehensive review article. Various databases including PubMed, Science Direct and Scopus were used. The preventive effects of N. sativa on pulmonary diseases were mainly due to its constituents such as thymoquinone, thymol, carvacrol and alpha-hederin. Extracts and constituents of N. sativa showed the relaxant effect, with possible mechanisms indicating its bronchodilatory effect in obstructive pulmonary diseases. In experimental animal models of different respiratory diseases, the preventive effect of various extracts and constituents of N. sativa was demonstrated by mechanisms such as antioxidant, immunomodulatory and antiinflammatory effects. Bronchodilatory and preventive effects of the plant and its components on asthma, COPD and lung disorders due to exposure to noxious agents as well as on allergic and immunologic disorders were also shown in the clinical studies. Various extracts and constituents of N. sativa showed pharmacological and therapeutic effects on respiratory, allergic and immunologic disorders indicating possible remedy effect of that the plant and its effective substances in treating respiratory, allergic and immunologic diseases., (© 2021 John Wiley & Sons, Ltd.)

Our previous studies demonstrated the preventive effect of Nigella sativa extract on asthma and water-soluble substances of this extract, especially its methanol fraction were responsible for this relaxation on contracted tracheal chains of guinea pigs. For the first time, the present study has been conducted to determine the main constituents of its methanolic extract. Four constituents of 20%-methanolic fraction, consisting of two flavonoids (20-20% and 21-20% fractions) and two polysaccharides (1-20% and 2-20% fractions), were purified by analytical and preparative HPLC. The relaxant effects of four cumulative concentrations of each constituent (50, 100, 150 and 200 mg/lit) in comparison with saline (1 ml) as negative control and four cumulative concentrations of theophylline (0.2, 0.4, 0.6 and 0.8 mM) as positive control were examined on methacholine-precontracted guinea pig tracheal chains (n=6). All concentrations of theophylline and most concentrations of 20-20, 21-20 fractions showed significant relaxant effects compared to that of saline. 20-20 fraction (Comferol diglucoside) was the most potent bronchodilator. Their relaxant effects were lower than that of theophylline. Polysaccharides (1-20, 2-20 fractions) did not have any relaxant effects compared to that of saline. These results revealed that two flavonoids of 20%-methanolic fraction of Nigella sativa were its main relaxant constituents.

Several different pharmacological effects have been described for Nigella sativa (Siah-Daneh), including an anti-inflammatory effect. In the present study, the effect of the extract of N. sativa on lung pathology and blood interleukin-4 (IL-4) and interferon-γ (IFN-γ) of sensitized guinea pigs was examined. Three groups (n=8 for each group) of guinea pigs sensitized to ovalbumin (OA) were given drinking water alone, and drinking water containing low and high concentrations of the plant extract, respectively. The animals of the control group (n=8) were treated with saline instead of OA and were given drinking water. The pathological changes of the lung, including infiltration of eosinophils and lymphocytes, local epithelial necrosis, the presence of oedema, thickening of the basement membrane, smooth muscle layer hypertrophy, mucosal secretion, and the presence of mucosal plug, and blood IL-4 and IFN-γ of sensitized guinea pigs were evaluated. The lungs of the sensitized group showed significant pathological changes (P<0.001). Blood IL-4 and IFN-γ were increased in sensitized animals compared to the controls (P<0.01 and P<0.001, respectively). Treatment of sensitized animals with the extract led to a significant decrease in pathological changes of the lung (P<0.01 to P<0.001), except for the oedema in the sensitized group treated with low concentration of the extract, but an increased IFN-γ. These results confirm a preventive effect of N. sativa extract on lung inflammation of sensitized guinea pigs.

Objective: To examine the preventive effect of a hydro-ethanolic extract of Nigella sativa on the tracheal responsiveness and white blood cell count in the lung lavage fluid of sensitized guinea pigs., Methods: Three groups of guinea pigs sensitized to intraperitoneally injected and inhaled ovalbumin were given drinking water alone (group S), drinking water containing a low concentration of N. sativa extract (group S+LNS) or drinking water containing a high concentration of N. sativa extract (group S+HNS). The tracheal responses of control animals (group C) and the three groups of sensitized guinea pigs (n = 7 for all groups) to methacholine were measured by the assessment of the tracheal smooth muscle response to increasing concentrations of methacholine, and the effective concentration causing 50% of the maximum response (EC50) was determined. Tracheal responses to 0.1% ovalbumin and white blood cell counts in the lung lavage fluid were also examined., Results: The tracheal response of the group S guinea pigs to both methacholine and ovalbumin was significantly higher than the response of the controls (p<0.01 for both cases). The tracheal responses of the S+LNS and S+HNS groups to both methacholine and ovalbumin were significantly decreased compared to those of the S group (p<0.05 to p<0.01). The total white blood cell and eosinophil counts in the lung lavage fluid of group S were significantly higher than those of group C (p<0.01). The white blood cell counts in both treated groups showed significant improvements (p<0.01 for both cases)., Conclusions: These results demonstrate the preventive effect of the N. sativa extract on the tracheal response and lung inflammation in sensitized guinea pigs.

In previous studies, the relaxant, anticholinergic (functional antagonism) and antihistaminic, effects of Nigella sativa have been demonstrated on guinea pig tracheal chains. In the present study, the prophylactic effect of thymoquinone (one of the constituents of Nigella sativa) on tracheal responsiveness and white blood cell (WBC) count in lung lavage of sensitized guinea pigs was examined. Four groups of sensitized guinea pigs to ovalbumin (OA) were given drinking water alone (group S), drinking water containing low or high concentrations of thymoquinone (S + LTQ and S + HTQ groups) or inhaled fluticasone propionate (FP 250 microg) twice a day (positive control group) (n = 7, for all groups). Tracheal responses of control and four groups of sensitized animals to methacholine at an effective concentration causing 50 % of maximum response (EC(50) M) were measured. Tracheal responses to 0.1 % OA, relative to contraction induced by 10 microM methacholine were also examined. Total WBC and its differential count in lung lavage were also measured. The tracheal responsiveness to methacholine, OA and WBC of S guinea pigs was significantly higher than those of controls (p < 0.001 for all cases). Tracheal responsiveness in S + LTQ, S + HTQ, and FP groups to both methacholine (p < 0.05 to p < 0.001) and OA (p < 0.001 for all cases) was significantly decreased compared to that of the S group. Total WBC was also decreased in all experimental groups compared to that of the S group (p < 0.001 for all groups). There was an increase in eosinophils and a decrease in neutrophils, lymphocytes and monocytes in the S animals compared to the controls (p < 0.001 for all cases). Treatment with both concentrations of thymoquinone and FP variably improved differential WBC count changes compared to the S animals (nonsignificant to p < 0.001). The improvement in tracheal responsiveness, total WBC, eosinophils and lymphocytes changes in the S animals treated with both concentrations of TQ were significantly greater than those of FP (p < 0.05 to p < 0.001). These results showed a preventive effect of thymoquinone, one constituent of N. sativa, on tracheal responsiveness and inflammatory cells of lung lavage of sensitized guinea pigs which was comparable or even greater than that of the inhaled steroid., (Georg Thieme Verlag KG Stuttgart-New York.)

The relaxant effects of four cumulative concentrations of n-hexane, dichloromethane, methanol and aqueous fractions of N. sativa (0.8, 1.2, 1.6 and 2.0 g%) in comparison with saline as negative control and four cumulative concentrations of theophylline (0.2, 0.4, 0.6 and 0.8 mM) were examined by their relaxant effects on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1) and 10 microM methacholine (group 2). In group 1, all concentrations of only theophylline showed significant relaxant effects. However, in group 2, all concentrations of theophylline and methanol fraction, 1.2, 1.6 and 2.0 g% concentrations of dichloromethane and 1.2 and 2.0 g% concentrations of n-hexane fractions showed significant relaxant effects compared to that of saline. In addition, in group 1, the relaxant effect of most concentrations of all fractions except the low concentration (0.8 g%) of dichloromethane and methanol fraction were significantly less than those of theophylline. The relaxant effect of different concentrations of methanol and dichloromethane fraction and 1.2, 1.6 and 2.0 g% concentrations of n-hexane fraction were significantly greater in group 2 compared to group 1 experiments. There were significant positive correlations between the relaxant effects and concentrations for all fractions (except aqucous fraction) in group 2 and for theophylline in both groups but a negative correlation for n-hexane, dichloromethane and methanol fractions in group 1. The results showed relaxant effect of most fractions from N. sativa on tracheal chains of guinea pigs which was more potent for methanol and dichloromethane fractions.