Traditional Chinese medicine, Xue-Fu-Zhu-Yu decoction, potentiates tissue plasminogen activator against thromboembolic stroke in rats

Jie Jen Lee, Wen Hsien Hsu, Ting Lin Yen, Nen Chung Chang, Yue Jyun Luo, George Hsiao, Joen Rong Sheu

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Aim of this study: The Xue-Fu-Zhu-Yu decoction (XFZYD) is a well-known traditional Chinese medicine for treating cardiovascular diseases. The therapeutic effects of this XFZYD have been well documented especially in treating of atherosclerosis and hyperlipidemia. Since this decoction can induce endothelial progenitor cell angiogenesis, it can provide experimental evidence for the treatment of ischemic diseases. Patients who are admitted to the hospital with acute ischemic stroke are initially considered candidates for the recombinant tissue plasminogen activator (rt-PA). However, rt-PA therapy is still lesser than ideal due to its major side effect of hemorrhaging. Therefore, medical research has been devoted to finding an alternative and/or complementary therapy for ischemic stroke. In the present study, we evaluated the protective effect of the combination of XFZYD with or without rt-PA in a rat model of thromboembolic stroke. Materials and methods: A cerebral thromboembolic stroke animal model and immunoblotting analysis were used to assess the effects of XFZYD and rt-PA. Results: Treatment with rt-PA (8 mg/kg) or XFZYD (1.5 and 3.0 g/kg/day) alone showed slight reductions in the infarct volume compared to solvent-treated rats. However, XFZYD (1.5 and 3.0 g/kg/day) obviously potentiated rt-PA-mediated reduction in the infarct volume in cerebral ischemic regions. In addition, treatment with rt-PA significantly reduced both tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) but not hypoxia-inducible factor (HIF)-1α or active caspase-3 expressions in ischemic regions, whereas treatment with XFZYD (3.0 g/kg/day) significantly reduced all of these protein expressions in ischemic regions. Moreover, treatment with XFZYD (1.5 and 3.0 g/kg/day) obviously potentiated rt-PA-mediated reductions in TNF-α, iNOS, HIF-1α, and active caspase-3 expressions. Conclusions: Results of this study suggest that XFZYD potentiated rt-PA-mediated neuroprotection against thromboembolic stroke in rats. This neuroprotection is probably mediated by the inhibition of HIF-1α and TNF-α, followed by the inhibition of inflammatory responses (i.e., iNOS) and apoptosis (active caspase-3). These results provide a better understanding of the scientific validation of the therapeutic value of the combination of XFZYD with rt-PA in ischemic stroke.

Original languageEnglish
Pages (from-to)824-830
Number of pages7
JournalJournal of Ethnopharmacology
Volume134
Issue number3
DOIs
Publication statusPublished - Apr 12 2011

Fingerprint

Chinese Traditional Medicine
Tissue Plasminogen Activator
Stroke
Hypoxia-Inducible Factor 1
Nitric Oxide Synthase Type II
Caspase 3
Tumor Necrosis Factor-alpha
Complementary Therapies
Therapeutics
Xue-Fu-Zhu-Yu decoction
Therapeutic Uses
Hyperlipidemias
Immunoblotting
Biomedical Research
Atherosclerosis
Cardiovascular Diseases
Animal Models
Apoptosis

Keywords

  • Caspase-3
  • HIF-1α
  • iNOS
  • Thromboembolic stroke
  • TNF-α
  • Xue-Fu-Zhu-Yu decoction

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Traditional Chinese medicine, Xue-Fu-Zhu-Yu decoction, potentiates tissue plasminogen activator against thromboembolic stroke in rats. / Lee, Jie Jen; Hsu, Wen Hsien; Yen, Ting Lin; Chang, Nen Chung; Luo, Yue Jyun; Hsiao, George; Sheu, Joen Rong.

In: Journal of Ethnopharmacology, Vol. 134, No. 3, 12.04.2011, p. 824-830.

Research output: Contribution to journalArticle

@article{4cc0969fc94b47cdba8b7516d9f2237c,
title = "Traditional Chinese medicine, Xue-Fu-Zhu-Yu decoction, potentiates tissue plasminogen activator against thromboembolic stroke in rats",
abstract = "Aim of this study: The Xue-Fu-Zhu-Yu decoction (XFZYD) is a well-known traditional Chinese medicine for treating cardiovascular diseases. The therapeutic effects of this XFZYD have been well documented especially in treating of atherosclerosis and hyperlipidemia. Since this decoction can induce endothelial progenitor cell angiogenesis, it can provide experimental evidence for the treatment of ischemic diseases. Patients who are admitted to the hospital with acute ischemic stroke are initially considered candidates for the recombinant tissue plasminogen activator (rt-PA). However, rt-PA therapy is still lesser than ideal due to its major side effect of hemorrhaging. Therefore, medical research has been devoted to finding an alternative and/or complementary therapy for ischemic stroke. In the present study, we evaluated the protective effect of the combination of XFZYD with or without rt-PA in a rat model of thromboembolic stroke. Materials and methods: A cerebral thromboembolic stroke animal model and immunoblotting analysis were used to assess the effects of XFZYD and rt-PA. Results: Treatment with rt-PA (8 mg/kg) or XFZYD (1.5 and 3.0 g/kg/day) alone showed slight reductions in the infarct volume compared to solvent-treated rats. However, XFZYD (1.5 and 3.0 g/kg/day) obviously potentiated rt-PA-mediated reduction in the infarct volume in cerebral ischemic regions. In addition, treatment with rt-PA significantly reduced both tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) but not hypoxia-inducible factor (HIF)-1α or active caspase-3 expressions in ischemic regions, whereas treatment with XFZYD (3.0 g/kg/day) significantly reduced all of these protein expressions in ischemic regions. Moreover, treatment with XFZYD (1.5 and 3.0 g/kg/day) obviously potentiated rt-PA-mediated reductions in TNF-α, iNOS, HIF-1α, and active caspase-3 expressions. Conclusions: Results of this study suggest that XFZYD potentiated rt-PA-mediated neuroprotection against thromboembolic stroke in rats. This neuroprotection is probably mediated by the inhibition of HIF-1α and TNF-α, followed by the inhibition of inflammatory responses (i.e., iNOS) and apoptosis (active caspase-3). These results provide a better understanding of the scientific validation of the therapeutic value of the combination of XFZYD with rt-PA in ischemic stroke.",
keywords = "Caspase-3, HIF-1α, iNOS, Thromboembolic stroke, TNF-α, Xue-Fu-Zhu-Yu decoction",
author = "Lee, {Jie Jen} and Hsu, {Wen Hsien} and Yen, {Ting Lin} and Chang, {Nen Chung} and Luo, {Yue Jyun} and George Hsiao and Sheu, {Joen Rong}",
year = "2011",
month = "4",
day = "12",
doi = "10.1016/j.jep.2011.01.033",
language = "English",
volume = "134",
pages = "824--830",
journal = "Journal of Ethnopharmacology",
issn = "0378-8741",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

TY - JOUR

T1 - Traditional Chinese medicine, Xue-Fu-Zhu-Yu decoction, potentiates tissue plasminogen activator against thromboembolic stroke in rats

AU - Lee, Jie Jen

AU - Hsu, Wen Hsien

AU - Yen, Ting Lin

AU - Chang, Nen Chung

AU - Luo, Yue Jyun

AU - Hsiao, George

AU - Sheu, Joen Rong

PY - 2011/4/12

Y1 - 2011/4/12

N2 - Aim of this study: The Xue-Fu-Zhu-Yu decoction (XFZYD) is a well-known traditional Chinese medicine for treating cardiovascular diseases. The therapeutic effects of this XFZYD have been well documented especially in treating of atherosclerosis and hyperlipidemia. Since this decoction can induce endothelial progenitor cell angiogenesis, it can provide experimental evidence for the treatment of ischemic diseases. Patients who are admitted to the hospital with acute ischemic stroke are initially considered candidates for the recombinant tissue plasminogen activator (rt-PA). However, rt-PA therapy is still lesser than ideal due to its major side effect of hemorrhaging. Therefore, medical research has been devoted to finding an alternative and/or complementary therapy for ischemic stroke. In the present study, we evaluated the protective effect of the combination of XFZYD with or without rt-PA in a rat model of thromboembolic stroke. Materials and methods: A cerebral thromboembolic stroke animal model and immunoblotting analysis were used to assess the effects of XFZYD and rt-PA. Results: Treatment with rt-PA (8 mg/kg) or XFZYD (1.5 and 3.0 g/kg/day) alone showed slight reductions in the infarct volume compared to solvent-treated rats. However, XFZYD (1.5 and 3.0 g/kg/day) obviously potentiated rt-PA-mediated reduction in the infarct volume in cerebral ischemic regions. In addition, treatment with rt-PA significantly reduced both tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) but not hypoxia-inducible factor (HIF)-1α or active caspase-3 expressions in ischemic regions, whereas treatment with XFZYD (3.0 g/kg/day) significantly reduced all of these protein expressions in ischemic regions. Moreover, treatment with XFZYD (1.5 and 3.0 g/kg/day) obviously potentiated rt-PA-mediated reductions in TNF-α, iNOS, HIF-1α, and active caspase-3 expressions. Conclusions: Results of this study suggest that XFZYD potentiated rt-PA-mediated neuroprotection against thromboembolic stroke in rats. This neuroprotection is probably mediated by the inhibition of HIF-1α and TNF-α, followed by the inhibition of inflammatory responses (i.e., iNOS) and apoptosis (active caspase-3). These results provide a better understanding of the scientific validation of the therapeutic value of the combination of XFZYD with rt-PA in ischemic stroke.

AB - Aim of this study: The Xue-Fu-Zhu-Yu decoction (XFZYD) is a well-known traditional Chinese medicine for treating cardiovascular diseases. The therapeutic effects of this XFZYD have been well documented especially in treating of atherosclerosis and hyperlipidemia. Since this decoction can induce endothelial progenitor cell angiogenesis, it can provide experimental evidence for the treatment of ischemic diseases. Patients who are admitted to the hospital with acute ischemic stroke are initially considered candidates for the recombinant tissue plasminogen activator (rt-PA). However, rt-PA therapy is still lesser than ideal due to its major side effect of hemorrhaging. Therefore, medical research has been devoted to finding an alternative and/or complementary therapy for ischemic stroke. In the present study, we evaluated the protective effect of the combination of XFZYD with or without rt-PA in a rat model of thromboembolic stroke. Materials and methods: A cerebral thromboembolic stroke animal model and immunoblotting analysis were used to assess the effects of XFZYD and rt-PA. Results: Treatment with rt-PA (8 mg/kg) or XFZYD (1.5 and 3.0 g/kg/day) alone showed slight reductions in the infarct volume compared to solvent-treated rats. However, XFZYD (1.5 and 3.0 g/kg/day) obviously potentiated rt-PA-mediated reduction in the infarct volume in cerebral ischemic regions. In addition, treatment with rt-PA significantly reduced both tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) but not hypoxia-inducible factor (HIF)-1α or active caspase-3 expressions in ischemic regions, whereas treatment with XFZYD (3.0 g/kg/day) significantly reduced all of these protein expressions in ischemic regions. Moreover, treatment with XFZYD (1.5 and 3.0 g/kg/day) obviously potentiated rt-PA-mediated reductions in TNF-α, iNOS, HIF-1α, and active caspase-3 expressions. Conclusions: Results of this study suggest that XFZYD potentiated rt-PA-mediated neuroprotection against thromboembolic stroke in rats. This neuroprotection is probably mediated by the inhibition of HIF-1α and TNF-α, followed by the inhibition of inflammatory responses (i.e., iNOS) and apoptosis (active caspase-3). These results provide a better understanding of the scientific validation of the therapeutic value of the combination of XFZYD with rt-PA in ischemic stroke.

KW - Caspase-3

KW - HIF-1α

KW - iNOS

KW - Thromboembolic stroke

KW - TNF-α

KW - Xue-Fu-Zhu-Yu decoction

UR - http://www.scopus.com/inward/record.url?scp=79954419856&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79954419856&partnerID=8YFLogxK

U2 - 10.1016/j.jep.2011.01.033

DO - 10.1016/j.jep.2011.01.033

M3 - Article

C2 - 21315142

AN - SCOPUS:79954419856

VL - 134

SP - 824

EP - 830

JO - Journal of Ethnopharmacology

JF - Journal of Ethnopharmacology

SN - 0378-8741

IS - 3

ER -