Thymoquinone attenuates IgE-mediated allergic response via pi3k-Akt-NFκB pathway and upregulation of the Nrf2-HO1 axis.

IgE-dependent reactions mediate the majority of allergic diseases. This study explores the effects of thymoquinone (Tq) on IgE-mediated allergic response in activated mast cells, basophils, and neutrophils. Tq treatment resulted in a dose-dependent decrease in levels of TNF-α and IL-4 in activated RBL-2H3 cells. Tq inhibited the degranulation of these cells with an IC50 value of 56.37 µM. Moreover, the compound suppressed basophil activation induced through FcεRI receptors with an IC50 value of 45.76 µM in heparinized human whole blood. Likewise, neutrophil migration and elastase activity were dose-dependently reduced. While Tq decreased the phosphorylation of Akt and NFκB in activated RBL-2H3 cells, it increased nuclear Nrf2 and HO-1 antioxidant proteins. Our results indicate that Tq possesses demonstrable activity in cellular models of IgE-mediated allergic reactions. PRACTICAL APPLICATIONS: The current study sheds light on the mechanistic pathways of Tq on IgE-based response in activated mast cells, basophils, and neutrophils. The output of this preclinical in vitro study may be translated into better chemotherapeutic applications of Tq and its analogs in the treatment of allergic inflammation. However, a detailed investigation of in vivo models is recommended.