Inhibitory mechanisms of tetramethylpyrazine in middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats

George Hsiao, Yi Cheng Chen, Jiing Han Lin, Kuang Hung Lin, Duen Suey Chou, Chien-Huang Lin, Joen Rong Sheu

研究成果: 雜誌貢獻文章

35 引文 (Scopus)

摘要

Tetramethylpyrazine (TMPZ) is an active ingredient isolated from a commonly used Chinese herb, Ligusticum wallichii Franchat, which has long been used in China for the treatment of vascular diseases. In the present study, TMPZ significantly attenuated middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats. Administration of TMPZ at 10 and 20 mg/kg produced concentration-dependent reductions in infarct size compared to that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in both nitrotyrosine and inducible nitric oxide synthase (iNOS) expression in ischemic regions. The expressions of nitrotyrosine and iNOS were markedly inhibited by TMPZ (20 mg/kg) treatment. Furthermore, TMPZ (100-250 μM) concentration-dependently inhibited respiratory bursts in human neutrophils stimulated by fMLP (800 nM) and PMA (320 nM). TMPZ (100-250 μM) also significantly inhibited neutrophil migration stimulated by fMLP (800 nM) and LTB4 (160 nM). An electron spin resonance (ESR) method was used to further study the scavenging activity of TMPZ on free radicals formed in human neutrophils. TMPZ (100 and 200 μM) greatly reduced the ESR signal intensity of hydroxyl radical formation. In conclusion, we demonstrate a neuroprotective effect of TMPZ in MCAO-induced focal cerebral ischemia in vivo. TMPZ mediates at least part of the free radical-scavenging activity and inhibits neutrophil activation, 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.
原文英語
頁(從 - 到)411-417
頁數7
期刊Planta Medica
72
發行號5
DOIs
出版狀態已發佈 - 四月 2006

指紋

Middle Cerebral Artery Infarction
ischemia
Brain Ischemia
arteries
Rats
neutrophils
rats
infarction
electron paramagnetic resonance spectroscopy
Ligusticum
brain
neuroprotective effect
vascular diseases
Neutrophils
hydroxyl radicals
active ingredients
Scavenging
Electron Spin Resonance Spectroscopy
Nitric Oxide Synthase Type II
Reperfusion Injury

ASJC Scopus subject areas

  • Plant Science
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

引用此文

@article{4a971e0d9e3c4722812701eda1051155,
title = "Inhibitory mechanisms of tetramethylpyrazine in middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats",
abstract = "Tetramethylpyrazine (TMPZ) is an active ingredient isolated from a commonly used Chinese herb, Ligusticum wallichii Franchat, which has long been used in China for the treatment of vascular diseases. In the present study, TMPZ significantly attenuated middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats. Administration of TMPZ at 10 and 20 mg/kg produced concentration-dependent reductions in infarct size compared to that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in both nitrotyrosine and inducible nitric oxide synthase (iNOS) expression in ischemic regions. The expressions of nitrotyrosine and iNOS were markedly inhibited by TMPZ (20 mg/kg) treatment. Furthermore, TMPZ (100-250 μM) concentration-dependently inhibited respiratory bursts in human neutrophils stimulated by fMLP (800 nM) and PMA (320 nM). TMPZ (100-250 μM) also significantly inhibited neutrophil migration stimulated by fMLP (800 nM) and LTB4 (160 nM). An electron spin resonance (ESR) method was used to further study the scavenging activity of TMPZ on free radicals formed in human neutrophils. TMPZ (100 and 200 μM) greatly reduced the ESR signal intensity of hydroxyl radical formation. In conclusion, we demonstrate a neuroprotective effect of TMPZ in MCAO-induced focal cerebral ischemia in vivo. TMPZ mediates at least part of the free radical-scavenging activity and inhibits neutrophil activation, 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 = "Free radicals, Inducible nitric oxide synthase, Middle cerebral artery occlusion (MCAO), Neutrophil activation, Nitrotyrosine, TMPZ",
author = "George Hsiao and Chen, {Yi Cheng} and Lin, {Jiing Han} and Lin, {Kuang Hung} and Chou, {Duen Suey} and Chien-Huang Lin and Sheu, {Joen Rong}",
year = "2006",
month = "4",
doi = "10.1055/s-2005-917242",
language = "English",
volume = "72",
pages = "411--417",
journal = "Planta Medica",
issn = "0032-0943",
publisher = "Georg Thieme Verlag",
number = "5",

}

TY - JOUR

T1 - Inhibitory mechanisms of tetramethylpyrazine in middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats

AU - Hsiao, George

AU - Chen, Yi Cheng

AU - Lin, Jiing Han

AU - Lin, Kuang Hung

AU - Chou, Duen Suey

AU - Lin, Chien-Huang

AU - Sheu, Joen Rong

PY - 2006/4

Y1 - 2006/4

N2 - Tetramethylpyrazine (TMPZ) is an active ingredient isolated from a commonly used Chinese herb, Ligusticum wallichii Franchat, which has long been used in China for the treatment of vascular diseases. In the present study, TMPZ significantly attenuated middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats. Administration of TMPZ at 10 and 20 mg/kg produced concentration-dependent reductions in infarct size compared to that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in both nitrotyrosine and inducible nitric oxide synthase (iNOS) expression in ischemic regions. The expressions of nitrotyrosine and iNOS were markedly inhibited by TMPZ (20 mg/kg) treatment. Furthermore, TMPZ (100-250 μM) concentration-dependently inhibited respiratory bursts in human neutrophils stimulated by fMLP (800 nM) and PMA (320 nM). TMPZ (100-250 μM) also significantly inhibited neutrophil migration stimulated by fMLP (800 nM) and LTB4 (160 nM). An electron spin resonance (ESR) method was used to further study the scavenging activity of TMPZ on free radicals formed in human neutrophils. TMPZ (100 and 200 μM) greatly reduced the ESR signal intensity of hydroxyl radical formation. In conclusion, we demonstrate a neuroprotective effect of TMPZ in MCAO-induced focal cerebral ischemia in vivo. TMPZ mediates at least part of the free radical-scavenging activity and inhibits neutrophil activation, 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 - Tetramethylpyrazine (TMPZ) is an active ingredient isolated from a commonly used Chinese herb, Ligusticum wallichii Franchat, which has long been used in China for the treatment of vascular diseases. In the present study, TMPZ significantly attenuated middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats. Administration of TMPZ at 10 and 20 mg/kg produced concentration-dependent reductions in infarct size compared to that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in both nitrotyrosine and inducible nitric oxide synthase (iNOS) expression in ischemic regions. The expressions of nitrotyrosine and iNOS were markedly inhibited by TMPZ (20 mg/kg) treatment. Furthermore, TMPZ (100-250 μM) concentration-dependently inhibited respiratory bursts in human neutrophils stimulated by fMLP (800 nM) and PMA (320 nM). TMPZ (100-250 μM) also significantly inhibited neutrophil migration stimulated by fMLP (800 nM) and LTB4 (160 nM). An electron spin resonance (ESR) method was used to further study the scavenging activity of TMPZ on free radicals formed in human neutrophils. TMPZ (100 and 200 μM) greatly reduced the ESR signal intensity of hydroxyl radical formation. In conclusion, we demonstrate a neuroprotective effect of TMPZ in MCAO-induced focal cerebral ischemia in vivo. TMPZ mediates at least part of the free radical-scavenging activity and inhibits neutrophil activation, 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 - Free radicals

KW - Inducible nitric oxide synthase

KW - Middle cerebral artery occlusion (MCAO)

KW - Neutrophil activation

KW - Nitrotyrosine

KW - TMPZ

UR - http://www.scopus.com/inward/record.url?scp=33645999403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645999403&partnerID=8YFLogxK

U2 - 10.1055/s-2005-917242

DO - 10.1055/s-2005-917242

M3 - Article

C2 - 16557454

AN - SCOPUS:33645999403

VL - 72

SP - 411

EP - 417

JO - Planta Medica

JF - Planta Medica

SN - 0032-0943

IS - 5

ER -