Sayyed_2026_Nutr.Neurosci__1

BACKGROUND: Erucic acid (EA), a monounsaturated omega-9 fatty acid derived from Raphanus sativus L. seeds, has antioxidant and anti-inflammatory properties. This study investigated its neuroprotective effects against streptozotocin (STZ)-induced diabetes-associated cognitive dysfunction in rats. METHODS: Male Wistar rats were randomly assigned to five groups: normal control, STZ control (60 mg/kg), STZ + EA (10 mg/kg), STZ + EA (20 mg/kg), and EA (20 mg/kg) per se. EA was administered orally for 38 days. Blood glucose and body weight were measured before STZ administration and at the end of the study. Cognitive function was assessed using the Y-maze and Morris water maze (MWM). Cholinergic function, oxidative stress, neurotransmitters, inflammatory mediators, apoptosis, and cellular energy status were evaluated biochemically, and hippocampal histopathology was performed. RESULTS: EA treatment significantly reduced hyperglycemia and attenuated diabetes-induced body weight loss. EA improved spontaneous alternation in the Y-maze and spatial learning and memory in the MWM, reducing escape latency and increasing target-quadrant time. EA decreased acetylcholinesterase activity while increasing choline acetyltransferase activity, restored antioxidant defenses, and reduced MDA, ROS, and NO levels. It also normalized neurotransmitter levels, suppressed TNF-alpha, IL-1beta, IL-6, NF-kappaB, and caspase-3, increased IL-10, and improved the ATP/ADP ratio. Histopathology demonstrated preservation of hippocampal neuronal architecture. CONCLUSIONS: EA ameliorated diabetes-associated cognitive dysfunction by improving learning and memory, preserving cholinergic neurotransmission, reducing oxidative stress and neuroinflammation, inhibiting neuronal apoptosis, and restoring cellular energy metabolism. These findings support the therapeutic potential of EA for managing cognitive impairment associated with diabetes.