Red peppers with moderate and severe pungency prevent the memory deficit and hepatic insulin resistance in diabetic rats with Alzheimer's disease

Background: Dementia induced by beta-amyloid accumulation impairs peripheral glucose homeostasis, but red pepper extract improves glucose homeostasis. We therefore evaluated whether long-term oral consumption of different red pepper extracts improves cognitive dysfunction and glucose homeostasis in type 2 diabetic rats with beta-amyloid-induced dementia. Methods: Male diabetic rats received hippocampal CA1 infusions of beta-amyloid (25-35) (AD) or beta-amyloid (35-25, non-plaque forming), at a rate of 3.6 nmol/day for 14 days (Non-AD). AD rats were divided into four dietary groups receiving either 1% lyophilized 70% ethanol extracts of either low, moderate and severe pungency red peppers (AD-LP, AD-MP, and AD-SP) or 1% dextrin (AD-CON) in Western diets (43% energy as fat). Results: The ascending order of control < LSP < MSP and SSP potentiated the phosphorylation of CREB and GSK and inhibited Tau phosphorylation in the hippocampus which in turn inhibited beta-amyloid accumulation. The inhibition by MP and SP reduced the memory deficit measured by passive avoidance test and water maze test. Furthermore, the accumulation of beta-amyloid induced glucose intolerance, although serum insulin levels were elevated during the late phase of oral glucose tolerance test (OGTT). All of the red pepper extracts prevented the glucose intolerance in AD rats. Consistent with OGTT results, during euglycemic hyperinulinemic clamp glucose infusion rates were lower in AD-CON than Non-AD-CON with no difference in whole body glucose uptake. Hepatic glucose output at the hyperinsulinemic state was increased in AD-CON. beta-amyloid accumulation exacerbated hepatic insulin resistance, but all red pepper extract treatments reversed the insulin resistance in AD rats. Conclusions: The extracts of moderate and severe red peppers were found to prevent the memory deficit and exacerbation of insulin resistance by blocking tau phosphorylation and beta-amyloid accumulation in diabetic rats with experimentally induced Alzheimer's-like dementia. These results suggest that red pepper consumption might be an effective intervention for preventing age-related memory deficit.