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.
Highlights
IntroductionAtherosclerosis in the carotid and vertebrobasilar artery causing cerebral infarction is the chief cause of stroke worldwide [1]
Atherosclerosis in the carotid and vertebrobasilar artery causing cerebral infarction is the chief cause of stroke worldwide [1].Stroke, the leading cause of and disability and death, is a multifactor disease that forms a possible end state for diabetes, atherosclerosis, and hypertension [2]
Diabetes alters central nervous system dysfunction associated with cognitive change and function abnormality, which increases the performance of reactive oxygen species and inflammatory mediators, and spawns neuronal apoptosis and neurodegeneration after reperfusion injury
Summary
Atherosclerosis in the carotid and vertebrobasilar artery causing cerebral infarction is the chief cause of stroke worldwide [1]. Diabetes alters central nervous system dysfunction associated with cognitive change and function abnormality, which increases the performance of reactive oxygen species and inflammatory mediators, and spawns neuronal apoptosis and neurodegeneration after reperfusion injury. It would exacerbate the likelihood of stroke damage [10,11,12]. Recent studies show that GFW had the neuroprotective effect against cerebral ischemia in rats [31], and ameliorated memory deficits and neuronal apoptosis in streptozotocin-induced hyperglycemic rodents [32]. This study explored the neuroprotective mechanism of GFW in STZ-induced hyperglycemic rats with an ischemia/reperfusion brain injury in vivo and LPS-induced inflammation in BV-2 microglial cells in vitro
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
