Pre-Exposure of Voglibose Exerts Cerebroprotective Effects Through Attenuating Activation of The Polyol Pathway and Inflammation

Abstract

Chronic hyperglycemia induces activation of the polyol-sorbitol pathway, which is a major contributor to microvascular complications like stroke. The current study was designed to elucidate the therapeutic role of α-glucose inhibitor in chronic hyperglycemia-induced impaired polyol pathway and associated micro-complications. Male albino-Wistar rats (200–250 g) were treated with voglibose 10 mg kg−1 day−1/p.o. for 2 weeks before middle cerebral artery occlusion; 72 hr after surgery, neurological score was evaluated and blood was collected for the assessment of various serum biochemical parameters like CRP, CK-MB, LDH, lipid profile, and blood glucose levels. In the end, brain samples were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ATPase activity oxidative stress-related parameters, aldose reductase activity, and gene expression studies. Results from the present study indicate that pre-treatment with voglibose showed significant improvement in lipid parameters but did not impact glucose levels. Voglibose has shown a statistically significant (p < .05) reduction in neurological score and brain infarct volume, and the difference in brain hemisphere weight as compared to the disease control group. Voglibose significantly (p < .05) improve all biochemical parameters and reduced Na+-K+ATPase and aldose reductase activity. Moreover, voglibose produced a significant reduction in oxidative stress and down-regulation of TNF-α and BCl-2 gene expression which reduces the risk of factors related to stroke. In conclusion, the pleiotropic effect of voglibose on cerebrovascular complications may be due to inhibition of aldose reductase or anti-inflammatory pathways.