Ellagic acid protects against diabetes-associated behavioral deficits in rats: Possible involved mechanisms.

AIMS: Diabetes mellitus (DM), a chronic metabolic disease, is associated with behavioral deficits. It has been suggested that ellagic acid (EA), a natural polyphenol compound, has potent anti-diabetic, anti-inflammatory, and neuroprotective properties. The present study was aimed to explore the potential protective effects of EA against diabetes-associated behavioral deficits and verified possible involved mechanisms.

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METHODS

Fifty adult male Wistar rats were randomly divided into five groups: i.e., CON: normal rats treated with vehicle (5 ml/kg/day; P.O.), EA: normal rats treated with EA (50 mg/kg/day; P.O.), STZ: diabetic rats treated with vehicle (5 ml/kg/day; P.O.), STZ + INS: diabetic rats treated with insulin (6 IU/rat/day; S.C.), STZ + EA: diabetic rats treated with EA (50 mg/kg/day; P.O.). All the groups were under treatment for eight consecutive weeks. During the seventh and eighth weeks, behavioral functions of the rats were assessed by commonly used behavioral tests. Subsequently, pro- and anti-inflammatory cytokines, neurotrophic factors, and also histological changes were evaluated in both cerebral cortex and hippocampus of the rats.

KEY FINDINGS: Chronic EA treatment attenuated anxiety/depression-like behaviors, improved exploratory/locomotor activities, and ameliorated cognitive deficits in diabetic rats. These results were accompanied by decreased blood glucose levels, modulation of inflammation status, improved neurotrophic support, and amelioration of neuronal loss in diabetic rats. In some aspects, treatment with EA was even more effective than insulin therapy.

SIGNIFICANCE: The current work's data confirms that EA could potentially serve as a novel, promising, and accessible protective agent against diabetes-associated behavioral deficits, owing to its anti-hyperglycemic, anti-inflammatory, and neurotrophic properties.