Investigation of the Effect of Quercetin on Neurological Alterations During Type 2 Diabetes Mellitus in Swiss Albino Mice

Abstract

Diabetes mellitus (DM) is a complex progressive metabolic disorder arising from variety of pathogenic mechanisms, genetic or environmental, resulting in hyperglycemia. Hyperglycemia leads to both acute symptoms and chronic abnormalities, amongst which neuropathy, is one of the major causes of morbidity. In the present study, we screened 267 natural molecules for their antidiabetic potential and associated neurological complications through docking studies, followed by in-vitro assays. Our results demonstrated quercetin to be most efficient molecule and hence we further investigated its potential to modulate type II diabetes (T2DM) and associated neurological complications in animal model of experimental diabetes by using multiple low dose streptozotocin (STZ) injection in Swiss albino mice. Further, to get a better insight into the mechanism of quercetin action, we induced insulin resistant state in mice by subjecting them to 21 day chromic unpredicted stress (CUS) and investigated the neuromodulatory effect of quercetin treatment. Diabetes was allowed to progress for 8 weeks during which animals were treated with 15 mg/kg quercetin and 5 mg/kg rosiglitazone. STZ treated animals showed steady increase in the blood glucose levels, development of glucose intolerance and insulin resistance (IR). Diabetic animals were highly anxious, depressed and showed marked learning and memory dysfunction. Quercetin and rosiglitazone treatment improved hyperglycemia, glucose intolerance, attenuated IR and behavioral dysfunction. Behavioral deficits in diabetic animals may be attributed to hyperglycemia mediated enhanced hippocampal oxidative stress, neurodegeneration and impaired neuronal insulin signaling, which were attenuated by quercetin and rosiglitazone treatment. newlineFurther, CUS induced pre-diabetic state, IR and behavioral dysfunctions in mice, which were associated with enhanced hippocampal oxidative stress, neurodegeneration and impaired hippocampal insulin signaling. Quercetin treatment (30 mg/kg; po; od) during CUS impro