Inhibitory Effect of Fraxin on Mast Cell-Mediated Anaphylaxis

Mast cells plays a key role in the immediate-type hypersensitivity. Fraxin, the active constituent isolated from Cortex Fraxini, has been known to have anti-inflammatory capacity. However, the effects of fraxin in mast cell-mediated ana-phylactic reaction have not been fully shown. Therefore, the in vivo anti-anaphylactic activity of fraxin was evaluated using rodent models of anaphylaxis. Additionally, we assessed the mechanism underlying the mast cell stabilizing effect of fraxin, with a specific focus on histamine release from rat peritoneal mast cells (RPMC). Systemic anaphylaxis-like reaction, plasma histamine levels, and ear swelling response were attenuated in mice treated with fraxin. Fraxin also suppressed passive systemic and cutaneous anaphylaxis. Furthermore, fraxin dose-dependently blocked histamine release from RPMC evoked by histamine liberators or the antigen-antibody reaction, which is in agreement with in vivo findings. To elucidate the mechanism of action of fraxin, both calcium influx and intracellular cAMP content in RPMC were assessed. In RPMC stimulated by compound 48/ 80 or ionophore A23187, fraxin decreased calcium uptake into the cells. Moreover, fraxin increased the intracellular cAMP level and significantly prevented compound 48/80-induced cAMP reduction in RPMC. Taken together, the inhibition of histamine release by fraxin appears to be mediated partly through the suppression of calcium uptake as well as the augmentation of cAMP levels. In conclusions, the clinical application of fraxin in the immediate-type hypersensitivity may be feasible.