Background: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder increasingly associated with central nervous system complications, including cognitive decline and hippocampal neurodegeneration. Oxidative stress is a primary mechanism underlying this neuronal damage. Flavonoids, such as eriodictyol, are natural compounds known for their potent antioxidant properties. This study aimed to investigate the neuroprotective effects of eriodictyol against biochemical and histopathological abnormalities in the hippocampus of fructose/streptozotocin (F-STZ)-induced diabetic rats.

Methods: T2DM was induced in male Wistar rats using a high-fructose diet (10% w/v) for two weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg). Diabetic rats were treated with eriodictyol (50 mg/kg) orally for 45 days. At the end of the treatment, glycemic parameters (blood glucose, HbA1c), hippocampal markers of oxidative stress (lipid peroxidation, protein carbonyls, reduced glutathione), antioxidant enzyme activities (SOD, GR), acetylcholinesterase (AChE), and Na$^+/K^+$-ATPase were assessed. Hippocampal tissues were also processed for histopathological examination using H&E staining.

Results: The F-STZ-induced diabetic rats exhibited significant hyperglycemia, increased hippocampal oxidative stress markers, and depleted antioxidant defenses. This was accompanied by aberrant AChE and Na$^+/K^+$-ATPase activities and severe neuronal damage in the hippocampal CA1 region. Eriodictyol administration significantly (P < 0.05) ameliorated hyperglycemia, reversed the oxidative stress markers, and restored the activity of antioxidant and membrane-bound enzymes towards normal levels. Histopathological analysis confirmed that eriodictyol treatment markedly preserved the structural integrity of hippocampal neurons.

Conclusion: The findings suggest that eriodictyol exerts a potent neuroprotective effect in the diabetic rat hippocampus. This protection is likely mediated by its ability to improve glycemic control and mitigate oxidative stress, thereby preserving neuronal function and structure. Eriodictyol represents a promising natural therapeutic candidate for preventing or treating diabetic neurological complications.

Eriodictyol, Type 2 Diabetes, Hippocampus, Neuroprotection

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