Abstract

Quercetin is one of the most ubiquitous bioflavonoids in foods of plant origin. Although quercetin is generally considered to provide protection against oxidative injury and inflammation, recent studies have demonstrated that its cytoprotective effects occur within a narrow concentration range. We attempted to examine the concentration-dependent effect on proliferation and inflammation in the primary culture of rat aortic smooth muscle cells. We demonstrate that quercetin inhibited [3H]thymidine incorporation into rat aortic smooth muscle cells only at concentrations ≦50 μM in a concentration-dependent manner. Nevertheless, quercetin, at concentrations ≧100 μM, reduced cell viability; this was further characterized as being due to apoptosis, which occurred through the proteolytic activation of pro-caspase-3. Additionally, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) substantially increased in rat aortic smooth muscle cells exposed to 100 μM quercetin, results which differ from observations by others and ourselves of cells exposed to ≦50 μM quercetin. Unlike P-JNK and P-p38, the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/ERK2) was not significantly affected by the concentration-dependent effects of quercetin. Surprisingly, the adverse effects of higher concentrations of quercetin could be ameliorated by adding the antioxidants, catalase, and N-acetylcysteine (NAC). Furthermore, the electrophoretic mobility shift assay (EMSA) showed that rat aortic smooth muscle cells exposed to quercetin at concentrations of ≦50 μM caused concentration-dependent inhibition of nuclear factor kappa B (NF-κB) activity, whereas concentrations of ≧100 μM resulted in increased NF-κB binding activity. We demonstrate for the first time that quercetin at low concentrations has antiproliferative and antiinflammatory effects, but at concentrations of ≧100 μM, is likely to induce the opposite effects on rat aortic smooth muscle cells.

Original languageEnglish
Pages (from-to)41-48
Number of pages8
JournalEuropean Journal of Pharmacology
Volume496
Issue number1
DOIs
Publication statusPublished - Aug 2 2004

Fingerprint

Quercetin
Smooth Muscle Myocytes
NF-kappa B
Phosphorylation
Inflammation
Edible Plants
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Acetylcysteine
Electrophoretic Mobility Shift Assay
p38 Mitogen-Activated Protein Kinases
Flavonoids
Caspase 3
Catalase
Thymidine
Cell Survival
Anti-Inflammatory Agents
Phosphotransferases
Antioxidants

Keywords

  • Aortic smooth muscle cell
  • c-Jun N-terminal kinase
  • Extracellular signal-regulated kinase
  • Mitogen-activated protein kinase
  • Quercetin
  • rat

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

@article{89e5aed4fa83439aaa3db1ddceda3ed3,
title = "Concentration-dependent differential effects of quercetin on rat aortic smooth muscle cells",
abstract = "Quercetin is one of the most ubiquitous bioflavonoids in foods of plant origin. Although quercetin is generally considered to provide protection against oxidative injury and inflammation, recent studies have demonstrated that its cytoprotective effects occur within a narrow concentration range. We attempted to examine the concentration-dependent effect on proliferation and inflammation in the primary culture of rat aortic smooth muscle cells. We demonstrate that quercetin inhibited [3H]thymidine incorporation into rat aortic smooth muscle cells only at concentrations ≦50 μM in a concentration-dependent manner. Nevertheless, quercetin, at concentrations ≧100 μM, reduced cell viability; this was further characterized as being due to apoptosis, which occurred through the proteolytic activation of pro-caspase-3. Additionally, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) substantially increased in rat aortic smooth muscle cells exposed to 100 μM quercetin, results which differ from observations by others and ourselves of cells exposed to ≦50 μM quercetin. Unlike P-JNK and P-p38, the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/ERK2) was not significantly affected by the concentration-dependent effects of quercetin. Surprisingly, the adverse effects of higher concentrations of quercetin could be ameliorated by adding the antioxidants, catalase, and N-acetylcysteine (NAC). Furthermore, the electrophoretic mobility shift assay (EMSA) showed that rat aortic smooth muscle cells exposed to quercetin at concentrations of ≦50 μM caused concentration-dependent inhibition of nuclear factor kappa B (NF-κB) activity, whereas concentrations of ≧100 μM resulted in increased NF-κB binding activity. We demonstrate for the first time that quercetin at low concentrations has antiproliferative and antiinflammatory effects, but at concentrations of ≧100 μM, is likely to induce the opposite effects on rat aortic smooth muscle cells.",
keywords = "Aortic smooth muscle cell, c-Jun N-terminal kinase, Extracellular signal-regulated kinase, Mitogen-activated protein kinase, Quercetin, rat",
author = "Shih, {Chun Ming} and Heng Lin and Liang, {Yu Chih} and Lee, {Wen Sen} and Bi, {Wei Fung} and Juan, {Shu Hui}",
year = "2004",
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language = "English",
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journal = "European Journal of Pharmacology",
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T1 - Concentration-dependent differential effects of quercetin on rat aortic smooth muscle cells

AU - Shih, Chun Ming

AU - Lin, Heng

AU - Liang, Yu Chih

AU - Lee, Wen Sen

AU - Bi, Wei Fung

AU - Juan, Shu Hui

PY - 2004/8/2

Y1 - 2004/8/2

N2 - Quercetin is one of the most ubiquitous bioflavonoids in foods of plant origin. Although quercetin is generally considered to provide protection against oxidative injury and inflammation, recent studies have demonstrated that its cytoprotective effects occur within a narrow concentration range. We attempted to examine the concentration-dependent effect on proliferation and inflammation in the primary culture of rat aortic smooth muscle cells. We demonstrate that quercetin inhibited [3H]thymidine incorporation into rat aortic smooth muscle cells only at concentrations ≦50 μM in a concentration-dependent manner. Nevertheless, quercetin, at concentrations ≧100 μM, reduced cell viability; this was further characterized as being due to apoptosis, which occurred through the proteolytic activation of pro-caspase-3. Additionally, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) substantially increased in rat aortic smooth muscle cells exposed to 100 μM quercetin, results which differ from observations by others and ourselves of cells exposed to ≦50 μM quercetin. Unlike P-JNK and P-p38, the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/ERK2) was not significantly affected by the concentration-dependent effects of quercetin. Surprisingly, the adverse effects of higher concentrations of quercetin could be ameliorated by adding the antioxidants, catalase, and N-acetylcysteine (NAC). Furthermore, the electrophoretic mobility shift assay (EMSA) showed that rat aortic smooth muscle cells exposed to quercetin at concentrations of ≦50 μM caused concentration-dependent inhibition of nuclear factor kappa B (NF-κB) activity, whereas concentrations of ≧100 μM resulted in increased NF-κB binding activity. We demonstrate for the first time that quercetin at low concentrations has antiproliferative and antiinflammatory effects, but at concentrations of ≧100 μM, is likely to induce the opposite effects on rat aortic smooth muscle cells.

AB - Quercetin is one of the most ubiquitous bioflavonoids in foods of plant origin. Although quercetin is generally considered to provide protection against oxidative injury and inflammation, recent studies have demonstrated that its cytoprotective effects occur within a narrow concentration range. We attempted to examine the concentration-dependent effect on proliferation and inflammation in the primary culture of rat aortic smooth muscle cells. We demonstrate that quercetin inhibited [3H]thymidine incorporation into rat aortic smooth muscle cells only at concentrations ≦50 μM in a concentration-dependent manner. Nevertheless, quercetin, at concentrations ≧100 μM, reduced cell viability; this was further characterized as being due to apoptosis, which occurred through the proteolytic activation of pro-caspase-3. Additionally, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) substantially increased in rat aortic smooth muscle cells exposed to 100 μM quercetin, results which differ from observations by others and ourselves of cells exposed to ≦50 μM quercetin. Unlike P-JNK and P-p38, the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/ERK2) was not significantly affected by the concentration-dependent effects of quercetin. Surprisingly, the adverse effects of higher concentrations of quercetin could be ameliorated by adding the antioxidants, catalase, and N-acetylcysteine (NAC). Furthermore, the electrophoretic mobility shift assay (EMSA) showed that rat aortic smooth muscle cells exposed to quercetin at concentrations of ≦50 μM caused concentration-dependent inhibition of nuclear factor kappa B (NF-κB) activity, whereas concentrations of ≧100 μM resulted in increased NF-κB binding activity. We demonstrate for the first time that quercetin at low concentrations has antiproliferative and antiinflammatory effects, but at concentrations of ≧100 μM, is likely to induce the opposite effects on rat aortic smooth muscle cells.

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