Original article

BioMedicine

, 6:21

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Yuh-Fung ChenAffiliated withDepartment of Pharmacology, China Medical UniversityDepartment of Pharmacy, China Medical University Hospital Email author 
  • , Kuo-Jen WuAffiliated withDepartment of Pharmacology, China Medical University
  • , Wei-Shih HuangAffiliated withDepartment of Neurology, China Medical UniversityDepartment of Neurology, China Medical University Hospital
  • , Yow-Wen HsiehAffiliated withDepartment of Pharmacy, China Medical University HospitalDepartment of Pharmacy, China Medical University
  • , Yu-Wen WangAffiliated withDepartment of Pharmacology, China Medical University
  • , Huei-Yann TsaiAffiliated withDepartment of Pharmacy, China Medical University Hospital
  • , Ming-Ming LeeAffiliated withDepartment of Health and Nutrition Biotechnology, Asia University, Taichung

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.

Keywords:

Gueichih-Fuling-Wan Cerebral Ischemia/ Reperfusion Injury Hyperglycemia Cellular Apoptosis Neuroinflammation