Investigation of anti diabetic agents in hyperglycemic brain insult and associated cognitive decline

Abstract

Diabetes is a chronic metabolic disorder and affects the multiple system of human body. The newlineepidemiologic number of diabetes associated systemic complications are more in number than newlineany other disease in the world population. Diabetes is associated with variety of set of morbid newlinecomplications like ischemia, vascular dementia and cognitive decline. The diabetics have newlineimpaired metabolic functions which may lead to cerebrovascular, cardiovascular and newlineneuropsychiatric disorders. Since past few decades, research is on going with some class of antidiabetic newlineagents such as biguanides, sulfonylureas, thiazolidinediones for their neuroprotective newlineproperties, but nowork has been reported with GLP-1 analogues, and#945;-glucosidase inhibitors, SGL2 newlineinhibitors and DPP4 inhibitors for diabetes associated brain insult and cognitive newlinedecline.Therefore, the objective of our study wasto analyses such anti-diabetic class of drugs for newlineneuroprotective action who exert a strict hyperglycemic control. We have selected voglibose, newlinesaxagliptin, repaglinide and dapagliflozin and screened using in-silico molecular docking with newlineproteins which are linked through various mechanisms associated with hyperglycemia and newlineneurodegeneration.Further, we performed in-vitro cell line studies for their neuroprotective newlineeffect. Thereafter, we aimed to develop anin-vitromodel of Zebrafishwhich can re-produce and newlinemimic the action and pathophysiology of strokesimilartohuman being. Zebrafish exerts very newlinesimilar genetic similarities and also can be useful for diabetes associated stroke research. newlineTherefore, we developed a chemical induced stroke model which can induce similar pattern and newlinepathophysiology of stroke comparing to rodents. Moreover, we also screened all anti-diabetic newlinedrugs anti-stroke potential through this induction model. Add on, we observed cognitive newlineimprovement in all-anti diabetic drug treated fishes. After this evaluation, we evaluated diabetes newlineassociated stress and cognitive decline through UCMS induced stress model in adult zebrafish. newlineThe adult fishes we