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

作者：Lee Fei Peng; Shih Chwen Ming; Shen Hsin Yi; Chen Chien Ming; Chen Chi Ming; Ko Wun Chang^*

来源：European Journal of Pharmacology, 2010, 635(1-3): 198-203.

DOI：10.1016/j.ejphar.2010.02.055

• Ayanin
• Allergic asthma
• Airway hyperresponsiveness
• Cytokine
• Phosphodiesterase inhibitor
• PDE4(H)/PDE4(L) ratio

In recent in vitro reports, the IC50 value of ayanin (quercetin-3,7,4'-O-trimethylether) was 2.2 mu M 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 mu mol/kg, orally (p.o.)) dose-dependently and significantly attenuated the enhanced pause (P-enh) 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)-alpha in bronchoalveolar lavage fluid of these mice. However, at 100 mu mol/kg, it significantly enhanced the level of interferon (IFN)-gamma. In addition, ayanin (30-100 mu mol/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 IgG(2a) 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.

• 出版日期2010-6-10
• 单位河北医科大学