Tetramethylpyrazine suppresses HIF-1α, TNF-α, and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats

Yi Chang, George Hsiao, Seu Hwa Chen, Yi Cheng Chen, Jiing Han Lin, Kuang Hung Lin, Duen Suey Chou, Joen Rong Sheu

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Abstract

Aim: To examine the detailed mechanisms underlying the inhibitory effect of tetramethylpyrazine (TMPZ) in inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAO) in rats. Methods: MCAO-induced focal cerebral ischemia in rats was used in this study. The hypoxia-inducible factor-1α (HIF-1α), activation of caspase-3, and TNF-α mRNA transcription in ischemic regions were detected by immunoblotting and RT-PCR, respectively. Anti-oxidative activity was investigated using a thiobarbituric acid-reactive substance (TBARS) test in rat brain homogenate preparations. Results: We showed the statistical results of the infarct areas of solvent- and TMPZ (20 mg/kg)-treated groups at various distances from the frontal pole in MCAO-induced focal cerebral ischemia in rats. Treatment with TMPZ (20 mg/kg) markedly reduced the infarct area in all regions, especially in the third to fifth sections. MCAO-induced focal cerebral ischemia was associated with increases in HIF-1α and the activation of caspase-3, as well as TNF-α transcription in ischemic regions. These expressions were markedly inhibited by treatment with TMPZ (20 mg/kg). However, TMPZ (0.5-5 mmol/L) did not significantly inhibit TBARS reaction in rat brain homogenates. Conclusion: The neuroprotective effect of TMPZ may be mediated at least by a portion of the inhibition of HIF-1α and TNF-α activations, followed by the inhibition of apoptosis formation (active caspase-3), resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, TMPZ treatment may represent an ideal approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders.

Original languageEnglish
Pages (from-to)327-333
Number of pages7
JournalActa Pharmacologica Sinica
Volume28
Issue number3
DOIs
Publication statusPublished - Mar 2007

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Hypoxia-Inducible Factor 1
Middle Cerebral Artery Infarction
Brain Ischemia
Caspase 3
Rats
Brain
Thiobarbituric Acid Reactive Substances
Chemical activation
Transcription
Reperfusion Injury
Brain Injuries
Neuroprotective Agents
tetramethylpyrazine
Immunoblotting
Poles
Apoptosis
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Caspase-3
  • HIF-1α
  • Middle cerebral artery occlusion
  • Tetramethylpyrazine
  • Thiobarbituric acid-reactive substance
  • TNF-α

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmacology

Cite this

@article{e4d30ddd434443e1acc802469936823e,
title = "Tetramethylpyrazine suppresses HIF-1α, TNF-α, and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats",
abstract = "Aim: To examine the detailed mechanisms underlying the inhibitory effect of tetramethylpyrazine (TMPZ) in inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAO) in rats. Methods: MCAO-induced focal cerebral ischemia in rats was used in this study. The hypoxia-inducible factor-1α (HIF-1α), activation of caspase-3, and TNF-α mRNA transcription in ischemic regions were detected by immunoblotting and RT-PCR, respectively. Anti-oxidative activity was investigated using a thiobarbituric acid-reactive substance (TBARS) test in rat brain homogenate preparations. Results: We showed the statistical results of the infarct areas of solvent- and TMPZ (20 mg/kg)-treated groups at various distances from the frontal pole in MCAO-induced focal cerebral ischemia in rats. Treatment with TMPZ (20 mg/kg) markedly reduced the infarct area in all regions, especially in the third to fifth sections. MCAO-induced focal cerebral ischemia was associated with increases in HIF-1α and the activation of caspase-3, as well as TNF-α transcription in ischemic regions. These expressions were markedly inhibited by treatment with TMPZ (20 mg/kg). However, TMPZ (0.5-5 mmol/L) did not significantly inhibit TBARS reaction in rat brain homogenates. Conclusion: The neuroprotective effect of TMPZ may be mediated at least by a portion of the inhibition of HIF-1α and TNF-α activations, followed by the inhibition of apoptosis formation (active caspase-3), resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, TMPZ treatment may represent an ideal approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders.",
keywords = "Caspase-3, HIF-1α, Middle cerebral artery occlusion, Tetramethylpyrazine, Thiobarbituric acid-reactive substance, TNF-α",
author = "Yi Chang and George Hsiao and Chen, {Seu Hwa} and Chen, {Yi Cheng} and Lin, {Jiing Han} and Lin, {Kuang Hung} and Chou, {Duen Suey} and Sheu, {Joen Rong}",
year = "2007",
month = "3",
doi = "10.1111/j.1745-7254.2007.00514.x",
language = "English",
volume = "28",
pages = "327--333",
journal = "Acta Pharmacologica Sinica",
issn = "1671-4083",
publisher = "Nature Publishing Group",
number = "3",

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TY - JOUR

T1 - Tetramethylpyrazine suppresses HIF-1α, TNF-α, and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats

AU - Chang, Yi

AU - Hsiao, George

AU - Chen, Seu Hwa

AU - Chen, Yi Cheng

AU - Lin, Jiing Han

AU - Lin, Kuang Hung

AU - Chou, Duen Suey

AU - Sheu, Joen Rong

PY - 2007/3

Y1 - 2007/3

N2 - Aim: To examine the detailed mechanisms underlying the inhibitory effect of tetramethylpyrazine (TMPZ) in inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAO) in rats. Methods: MCAO-induced focal cerebral ischemia in rats was used in this study. The hypoxia-inducible factor-1α (HIF-1α), activation of caspase-3, and TNF-α mRNA transcription in ischemic regions were detected by immunoblotting and RT-PCR, respectively. Anti-oxidative activity was investigated using a thiobarbituric acid-reactive substance (TBARS) test in rat brain homogenate preparations. Results: We showed the statistical results of the infarct areas of solvent- and TMPZ (20 mg/kg)-treated groups at various distances from the frontal pole in MCAO-induced focal cerebral ischemia in rats. Treatment with TMPZ (20 mg/kg) markedly reduced the infarct area in all regions, especially in the third to fifth sections. MCAO-induced focal cerebral ischemia was associated with increases in HIF-1α and the activation of caspase-3, as well as TNF-α transcription in ischemic regions. These expressions were markedly inhibited by treatment with TMPZ (20 mg/kg). However, TMPZ (0.5-5 mmol/L) did not significantly inhibit TBARS reaction in rat brain homogenates. Conclusion: The neuroprotective effect of TMPZ may be mediated at least by a portion of the inhibition of HIF-1α and TNF-α activations, followed by the inhibition of apoptosis formation (active caspase-3), resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, TMPZ treatment may represent an ideal approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders.

AB - Aim: To examine the detailed mechanisms underlying the inhibitory effect of tetramethylpyrazine (TMPZ) in inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAO) in rats. Methods: MCAO-induced focal cerebral ischemia in rats was used in this study. The hypoxia-inducible factor-1α (HIF-1α), activation of caspase-3, and TNF-α mRNA transcription in ischemic regions were detected by immunoblotting and RT-PCR, respectively. Anti-oxidative activity was investigated using a thiobarbituric acid-reactive substance (TBARS) test in rat brain homogenate preparations. Results: We showed the statistical results of the infarct areas of solvent- and TMPZ (20 mg/kg)-treated groups at various distances from the frontal pole in MCAO-induced focal cerebral ischemia in rats. Treatment with TMPZ (20 mg/kg) markedly reduced the infarct area in all regions, especially in the third to fifth sections. MCAO-induced focal cerebral ischemia was associated with increases in HIF-1α and the activation of caspase-3, as well as TNF-α transcription in ischemic regions. These expressions were markedly inhibited by treatment with TMPZ (20 mg/kg). However, TMPZ (0.5-5 mmol/L) did not significantly inhibit TBARS reaction in rat brain homogenates. Conclusion: The neuroprotective effect of TMPZ may be mediated at least by a portion of the inhibition of HIF-1α and TNF-α activations, followed by the inhibition of apoptosis formation (active caspase-3), resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, TMPZ treatment may represent an ideal approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders.

KW - Caspase-3

KW - HIF-1α

KW - Middle cerebral artery occlusion

KW - Tetramethylpyrazine

KW - Thiobarbituric acid-reactive substance

KW - TNF-α

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U2 - 10.1111/j.1745-7254.2007.00514.x

DO - 10.1111/j.1745-7254.2007.00514.x

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JO - Acta Pharmacologica Sinica

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SN - 1671-4083

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