Cryptotanshinone inhibits IgE-mediated degranulation through inhibition of spleen tyrosine kinase and tyrosine-protein kinase phosphorylation in mast cells

Abstract

Atopic dermatitis (AD) is a type of chronic skin inflammation and one of the most common relapsing allergic diseases, which presents with a severe rash and itchy skin lesions. The pathogenesis of AD is primarily associated with hyper-activated mast cells, which makes them an effective treatment target. After cross-linking the antigen/immunoglobulin (Ig) E complex binds to its high affinity receptor Fc epsilon Rl on the surface of mast cells. The cells subsequently secrete excessive pro-inflammatory mediators, including histamine and cytokines, which lead to pruritus and immune cell infiltration in the skin lesions. The present study screened natural compounds that have an inhibitory effect on IgE/antigen-mediated secretory activity. It was revealed that cryptotanshinone (CRT), a natural compound extracted from Salvia miltiorrhiza Bunge, had inhibitory effects on the IgE/antigen complex. The underlying mechanism by which CRT exerted an anti-allergy/inflammatory function was investigated using rat basophilic leukaemia (RBL) cells for degranulation assays and a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD Balb/c mouse model for in vivo study. CRT effectively mitigated the secretion of pro-inflammatory cytokines, including tumor necrosis factor-alpha and interleukin 1 beta, as well as immune cell infiltration into skin lesions in a mouse model of AD-like skin disease induced by dinitrochlorobenzene. The inhibitory effect of CRT on IgE-mediated mast cell degranulation was mediated by the inhibition of tyrosine kinase-dependent degranulation signalling pathways involving spleen tyrosine kinase and Lyn. The present study revealed CRT as an inhibitor of mast cell degranulation. Therefore, CRT may be considered for development as a therapeutic drug to treat IgE-mediated skin diseases.