Investigation of the Effect of Stinging Nettle Extract on Neurological Alterations during Comorbidity of Depression and Type 2 Diabetes

Abstract

Clinically depression and diabetes are comorbid. Diabetes makes the symptoms of depression worse. Depression reduces overall physical and mental health not only by increasing the risk for diabetes but making diabetic symptoms worse. Both depression and diabetes are the risk factor for cognitive impairment. Cholinergic system autophagy ATG insulin signaling pathway and sonic hedgehog Shh pathway are involved in many regulatory processes including learning and memory. Stinging nettle Urtica dioica UD extract has been claimed for its beneficial effects against depression diabetes and cognition. The present study was performed to evaluate whether chronic unpredictable mild stress CUMS or diabetes mediated cognitive deficit is associated with dysfunction in cholinergic system ATG insulin signaling and Shh pathway. In addition standardized UD extract was used to evaluate its effect on CUMS or diabetes mediated neuronal dysfunction. Rosiglitazone fluoxetine and St. John s wort were used as standard drugs for comparison. CUMS 3 weeks and multiple dose of streptozotocin STZ 50 mgkg i.p. for 5 consecutive days resulted in depressive like behaviour cognitive impairments and hypolocomotion in mice. CUMS induced insulin resistance and hypercorticosteronemia in mice. CUMS and diabetes impaired insulin signaling pathway ATG and muscarinic cholinergic system in the hippocampus. In addition CUMS impaired Smoothened SmoGlioma associated oncogene1 Gli1 pathway in the hippocampus. CUMS and diabetes downregulated muscarinic cholinergic receptor4 mAChR4 expression in striatum but not in hippocampus. Both CUMS and diabetes were associated with oxidative stress inflammation and apoptosis. Chronic UD treatment 50 mgkg p.o. significantly reverted CUMS and diabetes mediated cognitive impairment depressive like behaviour and insulin resistance. UD reduced hypercorticosteronemia in stressed mice. Chronic UD administration modulated insulin signaling pathway ATG and muscarinic cholinergic system in the hippocampus of chronically stressed and