3-O-methylquercetin more selectively inhibits phosphodiesterase subtype 3

Wun Chang Ko, Mei Chun Chen, Sheng Hao Wang, Ya Hsin Lai, Jun Hao Chen, Chun Nan Lin

Research output: Contribution to journalArticle

28 Citations (Scopus)

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. Therefore we were interested in investigating the inhibitory effect of 3-MQ on various PDE isozymes from guinea pig lungs and hearts. Isolated guinea pig lungs and hearts were homogenized and centrifuged. The supematant 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 IC50 values of 3-MQ on these isozymes were 31.9, 86.9, 18.6, 28.5 and 1.6 μM, respectively. 3-MQ (10-100 μM) non-competitively inhibited PDE2, but competitively inhibited PDE4. 3-MQ (1-10 μM) also competitively inhibited PDE3. However, 3-MQ (10-100 μM) did not competitively inhibit PDE1 and 5, although it had a tendency to competitively inhibit PDE1 at concentrations of 10-30 μM. The present results showed that Ki value of 3-MQ was similar to that of milrinone in PDE3, and was not significantly different from that of Ro 20-1724 in PDE4, respectively. In conclusion, 3-MQ was revealed to be a selective and competitive PDE3/PDE4 inhibitor, although its inhibitory effect on PDE4 was not potent. Therefore, 3-MQ may have a potential in the treatment of asthma beside its antiviral activity.

Original languageEnglish
Pages (from-to)310-315
Number of pages6
JournalPlanta Medica
Volume69
Issue number4
DOIs
Publication statusPublished - Apr 1 2003

Fingerprint

Phosphoric Diester Hydrolases
guinea pigs
lungs
heart
asthma
isozymes
Rhamnus
Rhamnaceae
constipation
traditional medicine
agarose
inhibitory concentration 50
Taiwan
Guinea Pigs
inflammation
Lung
Isoenzymes
neoplasms
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
Asthma

Keywords

  • 3-O-Methylquercetin
  • Guinea pig
  • Isozymes
  • Phosphodiesterase
  • Rhamnaceae
  • Rhamnus nakaharai

ASJC Scopus subject areas

  • Plant Science
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Ko, W. C., Chen, M. C., Wang, S. H., Lai, Y. H., Chen, J. H., & Lin, C. N. (2003). 3-O-methylquercetin more selectively inhibits phosphodiesterase subtype 3. Planta Medica, 69(4), 310-315. https://doi.org/10.1055/s-2003-38874

3-O-methylquercetin more selectively inhibits phosphodiesterase subtype 3. / Ko, Wun Chang; Chen, Mei Chun; Wang, Sheng Hao; Lai, Ya Hsin; Chen, Jun Hao; Lin, Chun Nan.

In: Planta Medica, Vol. 69, No. 4, 01.04.2003, p. 310-315.

Research output: Contribution to journalArticle

Ko, WC, Chen, MC, Wang, SH, Lai, YH, Chen, JH & Lin, CN 2003, '3-O-methylquercetin more selectively inhibits phosphodiesterase subtype 3', Planta Medica, vol. 69, no. 4, pp. 310-315. https://doi.org/10.1055/s-2003-38874
Ko, Wun Chang ; Chen, Mei Chun ; Wang, Sheng Hao ; Lai, Ya Hsin ; Chen, Jun Hao ; Lin, Chun Nan. / 3-O-methylquercetin more selectively inhibits phosphodiesterase subtype 3. In: Planta Medica. 2003 ; Vol. 69, No. 4. pp. 310-315.
@article{4a85adc03c4840fdb9af8653b00e390f,
title = "3-O-methylquercetin more selectively inhibits phosphodiesterase subtype 3",
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. Therefore we were interested in investigating the inhibitory effect of 3-MQ on various PDE isozymes from guinea pig lungs and hearts. Isolated guinea pig lungs and hearts were homogenized and centrifuged. The supematant 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 IC50 values of 3-MQ on these isozymes were 31.9, 86.9, 18.6, 28.5 and 1.6 μM, respectively. 3-MQ (10-100 μM) non-competitively inhibited PDE2, but competitively inhibited PDE4. 3-MQ (1-10 μM) also competitively inhibited PDE3. However, 3-MQ (10-100 μM) did not competitively inhibit PDE1 and 5, although it had a tendency to competitively inhibit PDE1 at concentrations of 10-30 μM. The present results showed that Ki value of 3-MQ was similar to that of milrinone in PDE3, and was not significantly different from that of Ro 20-1724 in PDE4, respectively. In conclusion, 3-MQ was revealed to be a selective and competitive PDE3/PDE4 inhibitor, although its inhibitory effect on PDE4 was not potent. Therefore, 3-MQ may have a potential in the treatment of asthma beside its antiviral activity.",
keywords = "3-O-Methylquercetin, Guinea pig, Isozymes, Phosphodiesterase, Rhamnaceae, Rhamnus nakaharai",
author = "Ko, {Wun Chang} and Chen, {Mei Chun} and Wang, {Sheng Hao} and Lai, {Ya Hsin} and Chen, {Jun Hao} and Lin, {Chun Nan}",
year = "2003",
month = "4",
day = "1",
doi = "10.1055/s-2003-38874",
language = "English",
volume = "69",
pages = "310--315",
journal = "Planta Medica",
issn = "0032-0943",
publisher = "Georg Thieme Verlag",
number = "4",

}

TY - JOUR

T1 - 3-O-methylquercetin more selectively inhibits phosphodiesterase subtype 3

AU - Ko, Wun Chang

AU - Chen, Mei Chun

AU - Wang, Sheng Hao

AU - Lai, Ya Hsin

AU - Chen, Jun Hao

AU - Lin, Chun Nan

PY - 2003/4/1

Y1 - 2003/4/1

N2 - 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-MQ on various PDE isozymes from guinea pig lungs and hearts. Isolated guinea pig lungs and hearts were homogenized and centrifuged. The supematant 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 IC50 values of 3-MQ on these isozymes were 31.9, 86.9, 18.6, 28.5 and 1.6 μM, respectively. 3-MQ (10-100 μM) non-competitively inhibited PDE2, but competitively inhibited PDE4. 3-MQ (1-10 μM) also competitively inhibited PDE3. However, 3-MQ (10-100 μM) did not competitively inhibit PDE1 and 5, although it had a tendency to competitively inhibit PDE1 at concentrations of 10-30 μM. The present results showed that Ki value of 3-MQ was similar to that of milrinone in PDE3, and was not significantly different from that of Ro 20-1724 in PDE4, respectively. In conclusion, 3-MQ was revealed to be a selective and competitive PDE3/PDE4 inhibitor, although its inhibitory effect on PDE4 was not potent. Therefore, 3-MQ may have a potential in the treatment of asthma beside its antiviral activity.

AB - 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-MQ on various PDE isozymes from guinea pig lungs and hearts. Isolated guinea pig lungs and hearts were homogenized and centrifuged. The supematant 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 IC50 values of 3-MQ on these isozymes were 31.9, 86.9, 18.6, 28.5 and 1.6 μM, respectively. 3-MQ (10-100 μM) non-competitively inhibited PDE2, but competitively inhibited PDE4. 3-MQ (1-10 μM) also competitively inhibited PDE3. However, 3-MQ (10-100 μM) did not competitively inhibit PDE1 and 5, although it had a tendency to competitively inhibit PDE1 at concentrations of 10-30 μM. The present results showed that Ki value of 3-MQ was similar to that of milrinone in PDE3, and was not significantly different from that of Ro 20-1724 in PDE4, respectively. In conclusion, 3-MQ was revealed to be a selective and competitive PDE3/PDE4 inhibitor, although its inhibitory effect on PDE4 was not potent. Therefore, 3-MQ may have a potential in the treatment of asthma beside its antiviral activity.

KW - 3-O-Methylquercetin

KW - Guinea pig

KW - Isozymes

KW - Phosphodiesterase

KW - Rhamnaceae

KW - Rhamnus nakaharai

UR - http://www.scopus.com/inward/record.url?scp=0037616054&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037616054&partnerID=8YFLogxK

U2 - 10.1055/s-2003-38874

DO - 10.1055/s-2003-38874

M3 - Article

C2 - 12709896

AN - SCOPUS:0037616054

VL - 69

SP - 310

EP - 315

JO - Planta Medica

JF - Planta Medica

SN - 0032-0943

IS - 4

ER -