Investigation of the Effect of Rutin on Type II Diabetes Mellitus Associated Neurological Complications

Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by chronic, consistent andprolonged hyperglycemia. Diabetes is associated with neurological complications likeneurodegeneration, cognitive decline, dementia and even disorders like Alzheimer s andParkinson s. Our previous work elucidated a high quantity of rutin in Urtica dioica leaf extract,which showed pronounced neuroprotection against diabetes and depression. So, we aimed toexplore the neuroprotective effects of rutin against type 2 diabetes (T2DM) mellitus associatedneurological complications. We further aim to identify the role of insulin signaling in brainduring T2DM and the effect of rutin treatment on it. newlineOur first objective was to study the neurological complications of chronic diabetes and the effectof rutin in it. Diabetes was induced using multiple low dose of streptozotocin (STZ), and treatedwith 100 mg/kg rutin for 2 months. STZ treatment led to significant hyperglycemia, glucoseintolerance and hypoinsulinemia. Diabetic animals were observed to be depressed, anxious, andshowed pronounced learning and memory deficits. These behavioral deficits were attributed tohippocampal neurodegeneration and impaired hippocampal insulin signaling. Rutin treatmentimproved hyperglycemia, glucose intolerance, attenuated hypoinsulinemia and behavioraldysfunction, and upregulated the hippocampal insulin signaling. In conclusion, rutin halts andameliorates the progression of diabetes and associated neurological complications. newlineTo better mimic the natural way of diabetes induction, our next objective was to develop aninsulin resistant state, as observed in T2DM. For this we employed a 21 day chronic unpredictedstress (CUS) induced depression paradigm, along with rutin treatment (100 mg/kg; po; od). CUSinduced pre-diabetes, insulin resistance (IR) and glucose intolerance along with similarbehavioral dysfunctions. Molecular underpinnings included hippocampal neurodegeneration andIR.