title: Neuroprotection of Gueichih-Fuling-Wan on cerebral ischemia/ reperfusion injury in streptozotocin-induced hyperglycemic rats via the inhibition of the cellular apoptosis pathway and neuroinflammation.
abstract: BACKGROUND
  Risks of stroke link with complications of hyperglycemia. Gueichih-Fuling-Wan (GFW), according to Chinese Medical Code literature, has the promotion of blood circulation and attenuates the swollen plot. Recent pharmacological studies have pointed out its efficacy in patients with cerebral ischemia or diabetes. Therefore, this study determined whether GFW has the protection against cerebral ischemia/ reperfusion (I/R) injury in streptozotocin (STZ)-induced hyperglycemic rats and LPS-induced inflammation in BV-2 microglial cells.
  
  
  METHODS
  Extracts of GFW were filtered and frozen to dry for use. Hyperglycemia was induced by intraperitoneal injection of 70 mg/kg STZ. Fourteen days after STZ injection, GFW (1, 2 and 4 g/kg) was orally administered once daily for seven days. Rats were subjected to cerebral ischemia/reperfusion and sacrificed for infarction analysis and neuronal apoptosis detection twenty-one days after STZ injection. MTT assay was used for cell viability; nitrite quantification and western blot analysis of iNOS and COX-2 were used to explore the effects of GFW on LPS-induced inflammation in BV-2 microglial cells.
  
  
  RESULTS
  GFW significantly ameliorated cerebral infarction while dosage was more than 1 g/kg (by 38.03% at 2 g/kg and 52.44% at 4 g/kg), and attenuated neurological deficits by 23.48% (at 2 g/kg) and 47.25% (at 4 g/kg). Furthermore, GFW (2, 4 g/kg) notably decreased TUNEL- and cleaved caspase-3-positive cells in the immunohistochemical stain (P < 0.01 and P < 0.001, respectively). GFW remarkably increased in Bcl-2 and decreased in caspase-3 and Bax/Bcl-2 ratio protein expressions by Western blot. GFW (0.25, 0.5, 1 mg/ ml) significantly reduced LPS-induced NO production in BV-2 microglial cells. And GFW attenuated iNOS and COX-2 expression in LPS-treated BV-2 cells.
  
  
  CONCLUSIONS
  In summary, GFW has good bioactivities to protect cerebral I/R injury in hyperglycemic rats, which might be due to inhibition of cellular apoptosis and neuroinflammation.
authors.affiliation: Department of Pharmacology, China Medical University, 404, Taichung, Taiwan. yfchen@mail.cmu.edu.tw.|Department of Pharmacy, China Medical University Hospital, 404, Taichung, Taiwan. yfchen@mail.cmu.edu.tw.
authors.forename: Yuh-Fung
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, China Medical University, 404, Taichung, Taiwan.
authors.forename: Kuo-Jen
authors.initials: KJ
authors.lastname: Wu
authors.affiliation: Department of Neurology, China Medical University, 404, Taichung, Taiwan.|Department of Neurology, China Medical University Hospital, 404, Taichung, Taiwan.
authors.forename: Wei-Shih
authors.initials: WS
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, China Medical University Hospital, 404, Taichung, Taiwan.|Department of Pharmacy, China Medical University, 404, Taichung, Taiwan.
authors.forename: Yow-Wen
authors.initials: YW
authors.lastname: Hsieh
authors.affiliation: Department of Pharmacology, China Medical University, 404, Taichung, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, China Medical University Hospital, 404, Taichung, Taiwan.
authors.forename: Huei-Yann
authors.initials: HY
authors.lastname: Tsai
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, 413, Taichung, Taiwan.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Lee
keywords: Cellular Apoptosis; Cerebral Ischemia/ Reperfusion Injury; Gueichih-Fuling-Wan; Hyperglycemia; Neuroinflammation