Crocetin inhibits mast cell-dependent immediate-type allergic reactions through Ca2+/PLC/IP3 and TNF pathway

Crocetin is a kind of glycocone naturally occurring in Crocus sativus L.. It is an active metabolite produced by biohydrolysis of Crocus sativus L.. Crocetin has anti-cardiovascular diseases and antioxidant effects, but its antiallergic effect has not been reported. In this study, the inhibitory effect of crocetin on immunoglobulin E (IgE)mediated allergic reaction and the mechanism of action were investigated. The passive cutaneous anaphylaxis (PCA) was used to elucidate the anti-allergic effects of crocetin in vivo. Degranulation assay, calcium imaging, and cytokine release assay were to evaluate the anti-allergic effect of crocetin in vitro. We found that crocetin IgEmediated RBL -2H3 cell degranulation and allergy both in vitro and in vivo. The TNF pathway was inhibited by crocetin in our RNA-seq sequences, Furthermore, crocetin inhibits IgE-mediated calcium influx, and PLC / IP3 phosphorylation in RBL -2H3 cells. Our findings suggested that crocetin revealed prominent anti-allergy activity through TNF and Ca2+/PLC/IP3 pathway.