Mulberry Fruit Prevents Diabetes and Diabetic Dementia by Regulation of Blood Glucose through Upregulation of Antioxidative Activities and CREB/BDNF Pathway in Alloxan-Induced Diabetic Mice

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-beta 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.