Investigation of Neuroprotective Potential of Anti-Diabetic Agents in Ischemic Brain Proteomics Through In-Silico Molecular Simulation Studies

Defective neurotransmission, impaired synaptic plasticity, and progressive neurodegeneration triggered by diabetes and stroke. The computational designing of a therapeutic agent, molecular dynamic (MD) simulation, and molecular docking are essential, along with streamlined and inexpensive techniques which enable the potential therapeutic targets for the novel drug discovery process in specific pathology. Molecular docking software such as AutoDock tool v1.5.6, PyRx v8.0, Discovery Studio Visualizer v19.1.0.18287, and PyMOL v2.3.1 has been used for virtual screening and identification of structural based molecular interactions. The 3D co-crystal structures of receptor/target therapeutic proteins (BCl-2, Caspase-3, Caspase-8, Caspase-9, IL6, MAPKERK, PI3K, TGF-beta, TNF-alpha, and ZO-1) with attached ligand were gained from the RCSB-PDB website in PDB format. The obtained structures comprise a ligand and a water molecule, which must be removed before docking from the receptor using Discovery Studio Visualizer and finally transformed into macromolecules by AutoDock Vina of PyRx. The active residues were recognized through previously published literature. In-Silico molecular simulation study of anti-diabetic agents with stroke and neurodegeneration-associated proteins gave a strong hypothesis to the neuroprotective actions of the anti-diabetic drugs. Moreover, higher binding energy with all biomarker proteins directs us of exerting strong therapeutic action of the selected class of anti-diabetic agents, i.e., voglibose, saxagliptin, repaglinide, and Dapagliflozin with BCl-2, Caspase-3, Caspase-8, Caspase-9, IL6, MAPK/ERK, PI3K, TGF-beta, TNF-alpha and ZO-1. The current study elucidates the strong anti-stroke potential of selected anti-diabetic agents and can claim a strong candidature as anti-stroke therapeutics in specific hyperglycemic conditions.