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

Abstract

BackgroundDementia induced by β-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 β-amyloid-induced dementia.MethodsMale diabetic rats received hippocampal CA1 infusions of β-amyloid (25–35) (AD) or β-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).ResultsThe 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 β-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 β-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. β-amyloid accumulation exacerbated hepatic insulin resistance, but all red pepper extract treatments reversed the insulin resistance in AD rats.ConclusionsThe extracts of moderate and severe red peppers were found to prevent the memory deficit and exacerbation of insulin resistance by blocking tau phosphorylation and β-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.

Capsaicin reduces Alzheimer-associated tau changes in the hippocampus of type 2 diabetes rats

“…In our present study, deficiency of brain impaired insulin signaling pathway was found in the brain of T2D rats, which is consistent with our previous findings that showing impaired brain insulin signaling pathway in individuals with type 2 diabetes [ 9 , 12 ]. Proteins involved in insulin signaling pathway was up-regulated in T2D+CAP group compared to T2D rats, which is also consistent with a recent study showed that the administration of extracts of red peppers restored insulin signaling pathway and prevented tau hyperphosphorylation and β-amyloid accumulation in a rat model of T2D combined with β-amyloid-induced dementia [ 43 ]. Studies suggested that calcium influx triggered PI3K/AKT signaling pathway in several tissues [ 44 – 46 ].…”

The potential value of capsaicin in modulating cognitive functions in a rat model of streptozotocin-induced Alzheimer’s disease

“…Behavioral alterations were monitored after 2 weeks from the STZ infusion (versus the negative controls in group I) using passive avoidance (short-term memory) [64] and Morris water maze (MWM) (spatial memory) tests [50] to examine for the development of Alzheimer's model. Rats with retention latency less than 300 s were studied by further subdivision of rats into 2 groups as follows: STZ-induced AD, capsaicin untreated group, where ten rats were treated by intragastric infusion of the vehicle (0.9% saline) for 47 days, served as positive controls (group II); STZ-induced AD, capsaicin treated group, where ten rats were treated with capsaicin, 10 mg/kg BW in 0.2 ml saline, and 0.1% ethanol by intragastric infusion for 47 days (group III) [30,78]. Flow chart and the experimental design are shown in Fig.…”

The central role of heat shock factor 1 in synaptic fidelity and memory consolidation

“…Curcumin activates HSF1 (Teiten et al 2009) and augments memory function (Zhang et al 2015a). Capsaicin activates calcium channels (TRPV) and thereby activates HSF1 (Bromberg et al 2013) and improves cognitive function while blocking tau phosphorylation and β-amyloid accumulation in a diabetic-dementia animal model (Yang et al 2015).…”