| Description: |
3-O-Methylquercetin is a selective and competitive PDE3/PDE4 inhibitor, and inhibits PDE3 than PDE4 with a low K(m) value; it inhibits total cAMP- and cGMP-phosphodiesterase (PDE) of guinea pig trachealis at low concentrations. 3-O-Methylquercetin has antiviral, anti-inflammatory and bronchodilating effects, and has the potential for use in the treatment of asthma at a dose without affecting blood pressure. |
| Targets: |
cAMP | PDE | IL Receptor | TNF-α | NOS | NO | Antifection |
| In vitro: |
| Pharmazie. 2009 Nov;64(11):726-30. | | Development of topical nanoemulsions containing quercetin and 3-O-methylquercetin.[Pubmed: 20099516] | This study describes the physico-chemical properties and the skin permeation profile of quercetin (Q) and 3-O-Methylquercetin (MQ) from lipid nanoemulsions.
METHODS AND RESULTS:
Formulations composed of octyldodecanol, egg lecithin, water (NE) and cetyl trimethyl ammonium bromide (CNE) were obtained by spontaneous emulsification. This procedure yielded monodisperse nanoemulsions exhibiting a mean droplet size of approximately 200-300 nm. Nanoemulsions were further characterized in terms of zeta-potential, surface tension, and morphology by transmission electron microscopy. The amount of flavonoids incorporated into nanoemulsions reached nearly 100% (at 1 mg/mL). The permeation studies were carried out using ear pig skin mounted in Franz diffusion cells.
CONCLUSIONS:
The overall results have shown a slow permeation profile of both Q and 3-O-Methylquercetin from nanoemulsions. However, a higher permeation flux rate of flavonoids from CNE (approximately 0.2 microg/cm2/h) as compared to NE (approximately 0.08 microg/cm2/h) was observed, showing the effect of the positively charged surface of CNE on this parameter.
Such results open interesting perspectives for the topical administration of the flavonoids Q and 3-O-Methylquercetin. | | Planta Med. 2003 Apr;69(4):310-5. | | 3-O-methylquercetin more selectively inhibits phosphodiesterase subtype 3.[Pubmed: 12709896] | 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. Therefore we were interested in investigating the inhibitory effect of 3-O-Methylquercetin on various PDE isozymes from guinea pig lungs and hearts.
METHODS AND RESULTS:
Isolated guinea pig lungs and hearts were homogenized and centrifuged. The supernatant was chromatographed over a column of Q-sepharose, and eluted with various concentrations of NaCl. In the following order, PDE subtypes 1, 5, 2, 4 from lungs, and 3 from hearts were separated. The IC 50 values of 3-O-Methylquercetin on these isozymes were 31.9, 86.9, 18.6, 28.5 and 1.6 microM, respectively. 3-O-Methylquercetin (10-100 microM) non-competitively inhibited PDE2, but competitively inhibited PDE4. 3-O-Methylquercetin (1-10 microM) also competitively inhibited PDE3. However, 3-O-Methylquercetin (10-100 microM) did not competitively inhibit PDE1 and 5, although it had a tendency to competitively inhibit PDE1 at concentrations of 10 - 30 microM. The present results showed that K i value of 3-O-Methylquercetin was similar to that of milrinone in PDE3, and was not significantly different from that of Ro 20 - 1724 in PDE4, respectively.
CONCLUSIONS:
In conclusion, 3-O-Methylquercetin was revealed to be a selective and competitive PDE3/PDE4 inhibitor, although its inhibitory effect on PDE4 was not potent. Therefore, 3-O-Methylquercetin may have a potential in the treatment of asthma beside its antiviral activity. |
|
| In vivo: |
| Planta Med. 2004 Dec;70(12):1123-7. | | Suppressive effects of 3-O-methylquercetin on ovalbumin-induced airway hyperresponsiveness.[Pubmed: 15643544] | 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-O-Methylquercetin 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.
METHODS AND RESULTS:
3-O-Methylquercetin (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-O-Methylquercetin (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-O-Methylquercetin (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-O-Methylquercetin (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-O-Methylquercetin nor milrinone significantly affected baseline beating rate in the right atria. 3-O-Methylquercetin (3-30 micromol/kg, i. p.) did not significantly affect systolic pressure in conscious mice.
CONCLUSIONS:
In conclusion, 3-O-Methylquercetin 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. |
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