Title:Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies
Volume: 20
Issue: 3
Author(s): Pooja Shah, Vishal Chavda, Snehal Patel*, Shraddha Bhadada and Ghulam Md. Ashraf
Affiliation:
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmadabad, Gujarat, 382 481,India
Keywords:
Cerebrovascular disease, hyperglycemia, focal ischemia, vascular damage, voglibose, stroke.
Abstract: Background: Postprandial hyperglycemia considered to be a major risk factor for
cerebrovascular complications.
Objective: The current study was designed to elucidate the beneficial role of voglibose via in-silico in
vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone
type 2 diabetes.
Materials and Methods: In-Silico molecular docking and virtual screening were carried out with the
help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the
results of docking studies, in-vivo investigation was carried out for possible neuroprotective action.
T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after
induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks,
diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery,
neurological deficits were determined. The blood was collected for the determination of serum
glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct
volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels,
and aldose reductase activity.
Results: In-silico docking studies showed good docking binding score for stroke associated proteins,
which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study,
pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels.
Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the
difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced
significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+
ATPase, oxidative stress, and aldose reductase activity in brain homogenate.
Conclusion: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo
induced stroke, animal model outcomes support the strong anti-stroke signature for possible
neuroprotective therapeutics.
