Suppressive effects of 3-O-methylquercetin on ovalbumin-induced airway hyperresponsiveness.
Rhamnus nakaharai Hayata (Rhamnaceae) has been used as a folk medicine in Taiwan for treating constipation, inflammation, tumors, and asthma. 3-O-Methylquercetin (3-MQ), a main constituent of the plant, has been reported to inhibit total cAMP- and cGMP-phosphodiesterase (PDE) of guinea pig trachealis at low concentrations. 3-MQ has been also reported to more selectively inhibit PDE3 than PDE4 with a low K(m) value. Therefore we were interested in investigating its suppressive effects on ovalbumin (OVA)-induced airway hyperresponsiveness in vivo and in vitro. 3-MQ (3-30 micromol/kg, i. p.) significantly suppressed the enhanced pause (Penh) value induced by aerosolized methacholine (50 mg/mL) in sensitized mice after secondary allergen challenge. 3-MQ (3-30 micromol/kg, i. p.) also significantly suppressed total inflammatory cells, macrophages, neutrophils, and eosinophils, but not lymphocytes. In addition, 3-MQ (3 micromol/kg, i. p.) significantly decreased the secretion of TNF-alpha, and at the highest dose (30 micromol/kg, i. p.) even decreased the secretions of IL-4, IL-5, and TNF-alpha. 3-MQ (1-10 microM) as well as Ro 20-1724 (3-30 microM), a selective PDE4 inhibitor, significantly attenuated OVA (100 microg/mL)-induced contractions. 3-MQ (30 microM) as well as milrinone (1-10 microM), a selective PDE3 inhibitor, significantly enhanced baseline contractions in isolated guinea pig left and right atria. However, neither 3-MQ nor milrinone significantly affected baseline beating rate in the right atria. 3-MQ (3-30 micromol/kg, i. p.) did not significantly affect systolic pressure in conscious mice. In conclusion, 3-MQ has both anti-inflammatory and bronchodilating effects, and has the potential for use in the treatment of asthma at a dose without affecting blood pressure.
Ko
Wun-Chang
WC
Graduate Institute of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC. wc_ko@tmu.edu.tw
Shih
Chwen-Ming
CM
Chen
Mei-Chun
MC
Lai
Ya-Hsin
YH
Chen
Jun-Hao
JH
Chen
Chien-Ming
CM
Lin
Chun-Nan
CN
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D031955:Rhamnus
D001993:Bronchodilator Agents; D010726:Phosphodiesterase Inhibitors; C047368:3-methylquercetin; D010047:Ovalbumin; D011794:Quercetin