Abstract

Chuanxiong is a Chinese herb that has been used widely in China to treat vascular disorders. 2,3,5,6-Tetramethylpyrazine (TMP) is one of the major components purified from chuanxiong. Many studies have demonstrated that TMP is effective in the treatment of cardiovascular diseases. However, the mechanism of action by which TMP exerts relaxation in vascular vessels remains unclear. Endothelin (ET)-1 is a potent vasopressor synthesised by endothelial cells both in culture and in vivo. The aims of the present study were to test the hypothesis that TMP may alter strain-induced ET-1 secretion and to identify the putative underlying signalling pathways in endothelial cells. We showed that TMP inhibits strain-induced ET-1 secretion. 2,3,5,6-Tetramethylpyrazine also inhibits the strain-induced formation of reactive oxygen species (ROS) and phosphorylation of extracellular signal-regulated kinases (ERK) 1/2. Furthermore, pretreating cells with TMP or the anti-oxidant N-acetyl-cysteine decreased strain-induced increases in ET-1 secretion and ERK1/2 phosphorylation. Using a reporter gene assay, TMP and N-acetyl-cysteine were demonstrated to also attenuate the strain-induced activity of the activator protein-1 reporter. In summary, we have demonstrated, for the first time, that TMP inhibits strain-induced ET-1 gene expression, in part by interfering with the ERK1/2 pathway via attenuation of ROS formation. Thus, the present study provides important new insights into the molecular pathways that may contribute to the proposed beneficial effects of TMP in the vascular system.

Original languageEnglish
Pages (from-to)536-540
Number of pages5
JournalClinical and Experimental Pharmacology and Physiology
Volume32
Issue number7
Publication statusPublished - Jul 2005

Fingerprint

Endothelin-1
Blood Vessels
Cysteine
Reactive Oxygen Species
Endothelial Cells
Phosphorylation
tetramethylpyrazine
Mitogen-Activated Protein Kinase 3
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase 1
Transcription Factor AP-1
Reporter Genes
Oxidants
China
Cardiovascular Diseases
Gene Expression

Keywords

  • Endothelial cells
  • Endothelin-1
  • Extracellular signal-regulated kinases 1/2
  • Reactive oxygen species
  • Strain
  • Tetramethylpyrazine

ASJC Scopus subject areas

  • Physiology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Inhibition of cyclic strain-induced endothelin-1 secretion by tetramethylpyrazine. / Bi, Wei Fung; Yang, Hung Yu; Liu, Ju Chi; Cheng, Tzu Hurng; Chen, Cheng Hsien; Shih, Chun Ming; Lin, Heng; Wang, Tze Che; Lian, Wei Shiung; Chen, Jin Jer; Chiu, Heng Cheng; Chang, Nen Chung.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 32, No. 7, 07.2005, p. 536-540.

Research output: Contribution to journalArticle

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abstract = "Chuanxiong is a Chinese herb that has been used widely in China to treat vascular disorders. 2,3,5,6-Tetramethylpyrazine (TMP) is one of the major components purified from chuanxiong. Many studies have demonstrated that TMP is effective in the treatment of cardiovascular diseases. However, the mechanism of action by which TMP exerts relaxation in vascular vessels remains unclear. Endothelin (ET)-1 is a potent vasopressor synthesised by endothelial cells both in culture and in vivo. The aims of the present study were to test the hypothesis that TMP may alter strain-induced ET-1 secretion and to identify the putative underlying signalling pathways in endothelial cells. We showed that TMP inhibits strain-induced ET-1 secretion. 2,3,5,6-Tetramethylpyrazine also inhibits the strain-induced formation of reactive oxygen species (ROS) and phosphorylation of extracellular signal-regulated kinases (ERK) 1/2. Furthermore, pretreating cells with TMP or the anti-oxidant N-acetyl-cysteine decreased strain-induced increases in ET-1 secretion and ERK1/2 phosphorylation. Using a reporter gene assay, TMP and N-acetyl-cysteine were demonstrated to also attenuate the strain-induced activity of the activator protein-1 reporter. In summary, we have demonstrated, for the first time, that TMP inhibits strain-induced ET-1 gene expression, in part by interfering with the ERK1/2 pathway via attenuation of ROS formation. Thus, the present study provides important new insights into the molecular pathways that may contribute to the proposed beneficial effects of TMP in the vascular system.",
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author = "Bi, {Wei Fung} and Yang, {Hung Yu} and Liu, {Ju Chi} and Cheng, {Tzu Hurng} and Chen, {Cheng Hsien} and Shih, {Chun Ming} and Heng Lin and Wang, {Tze Che} and Lian, {Wei Shiung} and Chen, {Jin Jer} and Chiu, {Heng Cheng} and Chang, {Nen Chung}",
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T1 - Inhibition of cyclic strain-induced endothelin-1 secretion by tetramethylpyrazine

AU - Bi, Wei Fung

AU - Yang, Hung Yu

AU - Liu, Ju Chi

AU - Cheng, Tzu Hurng

AU - Chen, Cheng Hsien

AU - Shih, Chun Ming

AU - Lin, Heng

AU - Wang, Tze Che

AU - Lian, Wei Shiung

AU - Chen, Jin Jer

AU - Chiu, Heng Cheng

AU - Chang, Nen Chung

PY - 2005/7

Y1 - 2005/7

N2 - Chuanxiong is a Chinese herb that has been used widely in China to treat vascular disorders. 2,3,5,6-Tetramethylpyrazine (TMP) is one of the major components purified from chuanxiong. Many studies have demonstrated that TMP is effective in the treatment of cardiovascular diseases. However, the mechanism of action by which TMP exerts relaxation in vascular vessels remains unclear. Endothelin (ET)-1 is a potent vasopressor synthesised by endothelial cells both in culture and in vivo. The aims of the present study were to test the hypothesis that TMP may alter strain-induced ET-1 secretion and to identify the putative underlying signalling pathways in endothelial cells. We showed that TMP inhibits strain-induced ET-1 secretion. 2,3,5,6-Tetramethylpyrazine also inhibits the strain-induced formation of reactive oxygen species (ROS) and phosphorylation of extracellular signal-regulated kinases (ERK) 1/2. Furthermore, pretreating cells with TMP or the anti-oxidant N-acetyl-cysteine decreased strain-induced increases in ET-1 secretion and ERK1/2 phosphorylation. Using a reporter gene assay, TMP and N-acetyl-cysteine were demonstrated to also attenuate the strain-induced activity of the activator protein-1 reporter. In summary, we have demonstrated, for the first time, that TMP inhibits strain-induced ET-1 gene expression, in part by interfering with the ERK1/2 pathway via attenuation of ROS formation. Thus, the present study provides important new insights into the molecular pathways that may contribute to the proposed beneficial effects of TMP in the vascular system.

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KW - Endothelin-1

KW - Extracellular signal-regulated kinases 1/2

KW - Reactive oxygen species

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