Abstract
Although mulberry fruit has various beneficial effects, its effect on diabetes-related dementia remains unknown. We investigated whether the ethyl acetate fraction of ethanolic extract of mulberry fruit (MFE) could alleviate biochemical and behavioral deficits in alloxan-induced diabetic mice. In the diabetic mice, MFE considerably abolished multiple deficits, e.g., body weight reduction; water and food intake increase; and hyperglycemia, hyperlipidemia, hypoinsulinism, and hypertrophy of the liver, kidneys, spleen, and brain. A 200 mg/kg MFE dose reduced malondialdehyde levels and improved antioxidant enzyme activity in the liver, kidney, and brain tissues. MFE attenuated hyperglycemia-induced memory impairments and acetylcholine deprivation, protected neuronal cells in CA1 and CA3 regions via p-CREB/BDNF pathway activation, and reduced amyloid-β precursor protein and p-Tau expressions in the brain tissue. In conclusion, MFE exerts antidiabetic and neuroprotective effects by upregulating antioxidative activities and p-CREB/BDNF pathway in chronic diabetes. Therefore, MFE may be used as a therapeutic agent for diabetes and diabetic neurodegenerative diseases.
Highlights
The prevalence of diabetes, a chronic metabolic disorder characterized by persistent hyperglycemia, has been consistently increasing over the past few decades, becoming a global epidemic in modern society [1]
MFE inhibited amyloid-β precursor protein (APP) and phosphorylated Tau (p-Tau) expression and increased Brain-derived neurotrophic factor (BDNF) and pCREB expression in the brain tissues of alloxan-treated mice. These findings suggest that MFE regulates both the activation of the p-cAMP response element-binding protein C-reactive protein (CRP) (CREB)/BDNF pathway and expression of the Alzheimer-related markers, APP and Tau, in diabetic dementia
These results suggest that MFE contributes to reduction in diabetic complications, such as diabetic dementia and renal failure, by regulating hyperglycemia in diabetes
Summary
The prevalence of diabetes, a chronic metabolic disorder characterized by persistent hyperglycemia, has been consistently increasing over the past few decades, becoming a global epidemic in modern society [1]. The progression of diabetes causes various complications, such as hypertension, hyperglycemia, hyperlipidemia, renal disorder, vascular diseases, and neurodegeneration [2]. Neurodegeneration is recognized as a cause of cognitive impairment observed in diabetic individuals [3]. Controlling hyperglycemia in patients with diabetes is important for preventing complications. Oxidative stress is the principal mechanism of many diabetic complications because of its active role in cellular injury in both neuronal and vascular cells [4]. Tau protein is hyperphosphorylated in diabetic mouse models and may underlie neuronal death [7]
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