Rhamnan Sulfate from the Seaweed <em>Monostroma nitidum</em> May Improve Cognitive Impairment Caused by Hyperglycemia

Rhamnan sulfate (RS), extracted from the seaweed Monostroma nitidum, suppresses vascular endothelial inflammation and arteriosclerosis, decreases blood glucose levels, and improves blood lipid metabolism and the intestinal environment. We investigated whether RS improves diabetic brain dysfunction using a hyperglycemic mouse model induced by pretreatment with nicotinamide and streptozotocin followed by oral administration of a high-fat diet and maltodextrin (MD) for 4 months. RS was administered in a 1% MD solution at doses of 100, 300, and 1,000 mg/kg of mouse body weight. Administration of RS to hyperglycemic mice significantly reduced blood glucose levels and showed a tendency to improve memory function in behavioral pharmacological tests using spontaneous locomotor activity, the rotarod test, and eight-arm maze test. Brain histopathological analysis showed that RS significantly reduced the atrophy of the neuronal layers in each region of the hippocampus compared to the untreated hyperglycemic controls. RS also significantly suppressed TNF-α expression and microglial activation in the brain, and showed a tendency to reduce the accumulation of advanced glycation end products in the brain. These results suggest that RS intake suppresses inflammation in the brain and alleviates the cognitive impairment associated with hyperglycemic diabetes.