Potential advantages of Chinese medicine Taohong Siwu Decoction (桃红四物汤) combined with tissue-plasminogen activator for alleviating middle cerebral artery occlusion-induced embolic stroke in rats

Ting Lin Yen, Eng Thiam Ong, Kuan Hung Lin, Chao Chien Chang, Thanasekaran Jayakumar, Song Chow Lin, Tsorng Han Fong, Joen Rong Sheu

Research output: Contribution to journalArticle

Abstract

Objective: To investigate whether combination treatment with Taohong Siwu Decoction (桃红四物汤, TSD) and recombinant tissue-type plasminogen activator (rt-PA) potentiate in reducing infarct volume and alleviate thromboembolic stroke in an in vivo rat model.

Method: Adult male Wistar rats were subjected to embolic middle cerebral artery occlusion (MCAO) and treated with rt-PA (4 and 8 mg/kg) alone (n=5), TSD [0.7 g/(kg·day)] alone (n=5), combination of rt-PA and TSD, 24 h after stroke. Rats were sacrificed at 14 days after treatment and lesion volumes were measured. To investigate the underlying mechanism of neuroprotective effect of the combination treatment, cleaved caspase-3, tumor necrosis factor alpha (TNF-α), hypoxia-inducible factor (HIF)-1α, and inducible nitric oxide synthase (iNOS) immunostaining were performed.

Results: Combination treatment significantly reduced infarct volume of cerebral ischemic regions compared with treatment of rt-PA and TSD alone and that of the saline control group (P

Conclusions: A combination of low-dose rt-PA and TSD after embolic stroke reduced infarct volume, improved cerebral blood flow and provided neuroprotection and these effects were associated with reduction of apoptosis and attenuation of HIF-1α, TNF-α and iNOS expression. These results provide a positive contribution to better understand the therapeutic value of the combination of TSD with rt-PA in ischemic stroke and may support further clinical evaluation.

Original languageEnglish
JournalChinese Journal of Integrative Medicine
DOIs
Publication statusAccepted/In press - Sep 24 2014

Fingerprint

Middle Cerebral Artery Infarction
Tissue Plasminogen Activator
Stroke
Medicine
Hypoxia-Inducible Factor 1
Nitric Oxide Synthase Type II
Cerebrovascular Circulation
Neuroprotective Agents
Caspase 3
Wistar Rats
Tumor Necrosis Factor-alpha
Apoptosis
Control Groups

Keywords

  • caspase-3
  • Chinese medicine
  • hypoxia-induced factor-1α
  • inducible nitric oxide synthase
  • rats
  • recombinant tissuse-type plasminogen activator
  • Taohong Siwu Decoction
  • thromboembolic stroke
  • tumor necrosis factor α

ASJC Scopus subject areas

  • Complementary and alternative medicine
  • Pharmacology (medical)

Cite this

@article{5229168a7705449790c7aae78b908cc6,
title = "Potential advantages of Chinese medicine Taohong Siwu Decoction (桃红四物汤) combined with tissue-plasminogen activator for alleviating middle cerebral artery occlusion-induced embolic stroke in rats",
abstract = "Objective: To investigate whether combination treatment with Taohong Siwu Decoction (桃红四物汤, TSD) and recombinant tissue-type plasminogen activator (rt-PA) potentiate in reducing infarct volume and alleviate thromboembolic stroke in an in vivo rat model.Method: Adult male Wistar rats were subjected to embolic middle cerebral artery occlusion (MCAO) and treated with rt-PA (4 and 8 mg/kg) alone (n=5), TSD [0.7 g/(kg·day)] alone (n=5), combination of rt-PA and TSD, 24 h after stroke. Rats were sacrificed at 14 days after treatment and lesion volumes were measured. To investigate the underlying mechanism of neuroprotective effect of the combination treatment, cleaved caspase-3, tumor necrosis factor alpha (TNF-α), hypoxia-inducible factor (HIF)-1α, and inducible nitric oxide synthase (iNOS) immunostaining were performed.Results: Combination treatment significantly reduced infarct volume of cerebral ischemic regions compared with treatment of rt-PA and TSD alone and that of the saline control group (PConclusions: A combination of low-dose rt-PA and TSD after embolic stroke reduced infarct volume, improved cerebral blood flow and provided neuroprotection and these effects were associated with reduction of apoptosis and attenuation of HIF-1α, TNF-α and iNOS expression. These results provide a positive contribution to better understand the therapeutic value of the combination of TSD with rt-PA in ischemic stroke and may support further clinical evaluation.",
keywords = "caspase-3, Chinese medicine, hypoxia-induced factor-1α, inducible nitric oxide synthase, rats, recombinant tissuse-type plasminogen activator, Taohong Siwu Decoction, thromboembolic stroke, tumor necrosis factor α",
author = "Yen, {Ting Lin} and Ong, {Eng Thiam} and Lin, {Kuan Hung} and Chang, {Chao Chien} and Thanasekaran Jayakumar and Lin, {Song Chow} and Fong, {Tsorng Han} and Sheu, {Joen Rong}",
year = "2014",
month = "9",
day = "24",
doi = "10.1007/s11655-014-1847-x",
language = "English",
journal = "Chinese Journal of Integrative Medicine",
issn = "1672-0415",
publisher = "Chinese Journal of Integrated Traditional and Western Medicine Press",

}

TY - JOUR

T1 - Potential advantages of Chinese medicine Taohong Siwu Decoction (桃红四物汤) combined with tissue-plasminogen activator for alleviating middle cerebral artery occlusion-induced embolic stroke in rats

AU - Yen, Ting Lin

AU - Ong, Eng Thiam

AU - Lin, Kuan Hung

AU - Chang, Chao Chien

AU - Jayakumar, Thanasekaran

AU - Lin, Song Chow

AU - Fong, Tsorng Han

AU - Sheu, Joen Rong

PY - 2014/9/24

Y1 - 2014/9/24

N2 - Objective: To investigate whether combination treatment with Taohong Siwu Decoction (桃红四物汤, TSD) and recombinant tissue-type plasminogen activator (rt-PA) potentiate in reducing infarct volume and alleviate thromboembolic stroke in an in vivo rat model.Method: Adult male Wistar rats were subjected to embolic middle cerebral artery occlusion (MCAO) and treated with rt-PA (4 and 8 mg/kg) alone (n=5), TSD [0.7 g/(kg·day)] alone (n=5), combination of rt-PA and TSD, 24 h after stroke. Rats were sacrificed at 14 days after treatment and lesion volumes were measured. To investigate the underlying mechanism of neuroprotective effect of the combination treatment, cleaved caspase-3, tumor necrosis factor alpha (TNF-α), hypoxia-inducible factor (HIF)-1α, and inducible nitric oxide synthase (iNOS) immunostaining were performed.Results: Combination treatment significantly reduced infarct volume of cerebral ischemic regions compared with treatment of rt-PA and TSD alone and that of the saline control group (PConclusions: A combination of low-dose rt-PA and TSD after embolic stroke reduced infarct volume, improved cerebral blood flow and provided neuroprotection and these effects were associated with reduction of apoptosis and attenuation of HIF-1α, TNF-α and iNOS expression. These results provide a positive contribution to better understand the therapeutic value of the combination of TSD with rt-PA in ischemic stroke and may support further clinical evaluation.

AB - Objective: To investigate whether combination treatment with Taohong Siwu Decoction (桃红四物汤, TSD) and recombinant tissue-type plasminogen activator (rt-PA) potentiate in reducing infarct volume and alleviate thromboembolic stroke in an in vivo rat model.Method: Adult male Wistar rats were subjected to embolic middle cerebral artery occlusion (MCAO) and treated with rt-PA (4 and 8 mg/kg) alone (n=5), TSD [0.7 g/(kg·day)] alone (n=5), combination of rt-PA and TSD, 24 h after stroke. Rats were sacrificed at 14 days after treatment and lesion volumes were measured. To investigate the underlying mechanism of neuroprotective effect of the combination treatment, cleaved caspase-3, tumor necrosis factor alpha (TNF-α), hypoxia-inducible factor (HIF)-1α, and inducible nitric oxide synthase (iNOS) immunostaining were performed.Results: Combination treatment significantly reduced infarct volume of cerebral ischemic regions compared with treatment of rt-PA and TSD alone and that of the saline control group (PConclusions: A combination of low-dose rt-PA and TSD after embolic stroke reduced infarct volume, improved cerebral blood flow and provided neuroprotection and these effects were associated with reduction of apoptosis and attenuation of HIF-1α, TNF-α and iNOS expression. These results provide a positive contribution to better understand the therapeutic value of the combination of TSD with rt-PA in ischemic stroke and may support further clinical evaluation.

KW - caspase-3

KW - Chinese medicine

KW - hypoxia-induced factor-1α

KW - inducible nitric oxide synthase

KW - rats

KW - recombinant tissuse-type plasminogen activator

KW - Taohong Siwu Decoction

KW - thromboembolic stroke

KW - tumor necrosis factor α

UR - http://www.scopus.com/inward/record.url?scp=84908538302&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908538302&partnerID=8YFLogxK

U2 - 10.1007/s11655-014-1847-x

DO - 10.1007/s11655-014-1847-x

M3 - Article

JO - Chinese Journal of Integrative Medicine

JF - Chinese Journal of Integrative Medicine

SN - 1672-0415

ER -