Suppressive Effects of 3-O-Methylquercetin on Ovalbumin-Induced Airway Hyperresponsiveness

Abstract

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.

Stereoselective activity of 2-(4-amino-3-chloro-5- trifluomethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride to improve the pulmonary function in asthma

“…The contractions of the spontaneously beating right atria were measured according to the method described by Ko et al (10), which was slightly modified. Subsequent to the baseline contraction of the spontaneously beating right atria becoming stable, the contractile tension was assessed in response to the cumulative addition of (-)SPFF, (±)SPFF and (+)SPFF in final concentrations ranging from 10…”

Anti-inflammatory activity of quercetin and isoquercitrin in experimental murine allergic asthma

“…Previous reports have described several fl avonoids that have potent anti-allergic effects in murine models of asthma [12][13][14]. Quercetin, a fl avonoid found in Abstract.…”

Effect of Enzymatically Modified Isoquercitrin, a Flavonoid, on Symptoms of Japanese Cedar Pollinosis: A Randomized Double-Blind Placebo-Controlled Trial

“…Furthermore, an epidemiologic study found that a higher intake of flavonoids was associated with a lower incidence of asthma [44]. In experimental models, oral administration of flavonoids has been demonstrated to prevent allergic diseases including asthma, anaphylaxis, food allergies and atopic dermatitis [16, 17,32,33,34,35,36,37]. This study showed that the ocular symptoms were reduced in the EMIQ group.…”

“…We and others have shown that some kinds of flavonoids including apigenin, fisetin, luteolin and quercetin suppress the expression of Th2-type (IL-4, IL-5 and IL-13) [13, 14], proinflammatory cytokines [31] and CD40 ligand [15] in basophils or in mast cells. In addition to these in vitro antiallergic activities, studies with allergic animal models have demonstrated that flavonoids exert preventative and therapeutic effects by modifying Th2-type cytokine expression and suppressing IgE elevation [16, 17,32,33,34,35,36,37]. In our study we measured the serum levels of cytokines and chemokines before and after the study but found no significant reduction in Th2 cytokines (IL-4, IL-5 and IL-13), chemokines (eotaxin) or IgE concentration as a result of EMIQ intake except for TARC (fig.…”