Ayanin, a non-selective phosphodiesterase 1–4 inhibitor, effectively suppresses ovalbumin-induced airway hyperresponsiveness without affecting xylazine/ketamine-induced anesthesia

In recent in vitro reports, the IC50 value of ayanin (quercetin-3,7,4′-O-trimethylether) was 2.2 μM for inhibiting interleukin (IL)-4 production from purified basophils, and its therapeutic ratio was > 19. Therefore, we were interested in investigating the effects on ovalbumin induced airway hyperresponsiveness in vivo, and to clarify its potential for treating asthma. Ayanin (30–100 μmol/kg, orally (p.o.)) dose-dependently and significantly attenuated the enhanced pause (Penh) value induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including IL-2, IL-4, IL-5, and tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid of these mice. However, at 100 μmol/kg, it significantly enhanced the level of interferon (IFN)-γ. In addition, ayanin (30–100 μmol/kg, p.o.) dose-dependently and significantly suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and bronchoalveolar lavage fluid, and enhanced the IgG2a level in serum of these mice. In the present results, ayanin did not affect xylazine/ketamine-induced anesthesia, suggesting that ayanin has few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, the above results suggest that ayanin may have the potential for use in treating allergic asthma.