title: Traditional Chinese medicine, Xue-Fu-Zhu-Yu decoction, potentiates tissue plasminogen activator against thromboembolic stroke in rats.
abstract: OBJECTIVE
  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.
  
  
  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)-1 α 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-1 α, 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-1 α 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.
authors.affiliation: Department of Surgery, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan.
authors.forename: Jie-Jen
authors.initials: JJ
authors.lastname: Lee
authors.forename: Wen-Hsien
authors.initials: WH
authors.lastname: Hsu
authors.forename: Ting-Lin
authors.initials: TL
authors.lastname: Yen
authors.forename: Nen-Chung
authors.initials: NC
authors.lastname: Chang
authors.forename: Yue-Jyun
authors.initials: YJ
authors.lastname: Luo
authors.forename: George
authors.initials: G
authors.lastname: Hsiao
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D013923:Thromboembolism / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000502:physiology*
chemical_list: D004365:Drugs, Chinese Herbal; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C513826:Xue-Fu-Zhu-Yu decoction; D052247:Nitric Oxide Synthase Type II; D010959:Tissue Plasminogen Activator; D053148:Caspase 3