Inhibitory activity of narirutin on RBL-2H3 cells degranulation

Abstract

Context: It is an efficient strategy to apply inhibition of mast cell degranulation for evaluating anti-allergic effects of compounds. Previous works confirmed that narirutin had anti–allergic activity in OVA induced allergic asthma murine model. However, the mechanism is not clear. Objective: Here, inhibitory mechanism of narirutin on RBL-2H3 cells degranulation was investigated. Materials and methods: Cell viability was analyzed by CCK-8 kits, cell degranulation was analyzed by ELISA methods, morphology and ultrastructure of cells was observed by atomic force microscopy, intracellular Ca 2+ concentration was measured by fluorescence microscopre, mRNA expression were measured by PCR, and signaling pathways were measured by WB. Results: The results showed that narirutin have no direct effects on mRNA expression of FcεRI subunit. However, it inhibited Ca2+ influx by suppressing the phosphorylation of Syk, LAT and PLCγ1 signaling pathway transduction. Subsequently, the inhibition of Ca2+ influx directly leads to NF-κB signaling pathway transduction decreased. Narirutin can also suppress the phosphorylation of MAPK signaling pathways by decreasing the expression of P-p38, P-ERK and P-JNK, inhibit the synergistic effect for Ca2+ influx, and then reduce the release of IL-4, TNF-α, histamine and β-HEX. Conclusion: Our study suggested that the inhibitory mechanism of narirutin on RBL-2H3 cells degranulation could be related to regulate MAPK, NF-κB and Tyrosine kinase signaling pathway.