TY - JOUR
T1 - Ayanin, a non-selective phosphodiesterase 1-4 inhibitor, effectively suppresses ovalbumin-induced airway hyperresponsiveness without affecting xylazine/ketamine-induced anesthesia
AU - Lee, Fei Peng
AU - Shih, Chwen Ming
AU - Shen, Hsin Y.
AU - Chen, Chien Ming
AU - Chen, Chi Ming
AU - Ko, Wun-Chang
PY - 2010/6
Y1 - 2010/6
N2 - In recent in vitro reports, the IC50 value of ayanin (quercetin-3,7,4′-O-trimethylether) was 2.2μM 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 (30-100μmol/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 100μmol/kg, it significantly enhanced the level of interferon (IFN)-γ. In addition, ayanin (30-100μmol/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.
AB - In recent in vitro reports, the IC50 value of ayanin (quercetin-3,7,4′-O-trimethylether) was 2.2μM 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 (30-100μmol/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 100μmol/kg, it significantly enhanced the level of interferon (IFN)-γ. In addition, ayanin (30-100μmol/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.
KW - Airway hyperresponsiveness
KW - Allergic asthma
KW - Ayanin
KW - Cytokine
KW - PDE4/PDE4 ratio
KW - Phosphodiesterase inhibitor
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U2 - 10.1016/j.ejphar.2010.02.055
DO - 10.1016/j.ejphar.2010.02.055
M3 - Article
C2 - 20307524
AN - SCOPUS:77952323268
SN - 0014-2999
VL - 635
SP - 198
EP - 203
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -