Curcumenol Inhibits Mast Cells Activation in Ovalbumin-Induced Anaphylaxis Model Mice through Modulation of the Fc Epsilon Receptor I Signaling Pathway.

Abstract

Curcumenol, a sesquiterpene isolated from Curcuma zedoaria, has a variety of therapeutic effects, such as neuroprotective, antitumor and hepatoprotective effects. This study elucidates whether curcumenol can inhibit ovalbumin (OVA)-induced allergic reactions in a mouse and monoclonal anti-2,4,6-dinitrophenyl (DNP)-immunoglobulin (IgE)/bovine serum albumin (BSA)-mediated allergic reactions in mouse bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia cells (RBL-2H3). IgE-mediated passive cutaneous anaphylaxis and ovalbumin (OVA)-induced anaphylaxis mouse models were performed. β-hexosaminidase release and mast cell degranulation were analyzed in vitro. Western blot analyses were performed to validate the effect of curcumenol on FcεRI signaling pathway. Molecular docking analysis were performed to evaluate curcumenol and tyrosine kinase interaction. Curcumenol alleviated OVA-induced anaphylactic allergic symptoms by increasing rectal temperature in a dosedependent manner. In addition, it reduced the levels of plasma histamine, IgE, and interleukin-4 in mouse model. Curcumenol inhibited IgE-BSA-stimulated β-hexosaminidase release and mast cell degranulation in a dose-dependent manner in BMMCs and RBL-2H3. Curcumenol also inhibited the activation of Src family tyrosine kinases (Fyn and Lyn) and the downstream spleen tyrosine kinase (Syk) in the FcεRI signaling pathway in BMMCs. Furthermore, curcumenol suppressed the activation of Akt, PLCγ1, and mitogen-activated protein kinase signaling. Molecular docking analysis revealed that curcumenol could bind to Fyn and Lyn kinases, thereby suppressing Src family tyrosine kinase signaling. This study suggests that curcumenol inhibits IgE-mediated allergic reactions by suppressing the activation Lyn and Fyn Src family kinases in OVA-challenged model animals. Therefore, curcumenol could be used as an effective alternative therapeutic for allergic diseases.