Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies.
Animals
Cerebrovascular Disorders
/ complications
Computer Simulation
Diabetes Mellitus, Experimental
/ drug therapy
Diabetes Mellitus, Type 2
/ blood
Disease Models, Animal
Drug Evaluation, Preclinical
Humans
Hyperglycemia
/ complications
Infarction, Middle Cerebral Artery
Inositol
/ analogs & derivatives
Lipids
/ blood
Molecular Docking Simulation
Neuroprotective Agents
/ pharmacology
Nitric Oxide
/ blood
Rats
Risk Factors
Sodium-Potassium-Exchanging ATPase
/ genetics
Software
Stroke
/ drug therapy
User-Computer Interface
Cerebrovascular disease
focal ischemia
hyperglycemia
stroke
vascular damage
voglibose
Journal
Current gene therapy
ISSN: 1875-5631
Titre abrégé: Curr Gene Ther
Pays: United Arab Emirates
ID NLM: 101125446
Informations de publication
Date de publication:
2020
2020
Historique:
received:
02
10
2019
revised:
28
05
2020
accepted:
14
07
2020
entrez:
15
10
2020
pubmed:
16
10
2020
medline:
19
8
2021
Statut:
ppublish
Résumé
Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. 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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 33054705
pii: CGT-EPUB-108471
doi: 10.2174/1566523220999200726225457
doi:
Substances chimiques
Lipids
0
Neuroprotective Agents
0
Nitric Oxide
31C4KY9ESH
Inositol
4L6452S749
Sodium-Potassium-Exchanging ATPase
EC 7.2.2.13
voglibose
S77P977AG8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
223-235Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.