Abstract
There is accumulating evidence showing that hyperglycemia conditions like diabetes possess a greater risk of impairment to the neuronal system because high glucose levels exacerbate oxidative stress, accumulation of amyloid-beta peptides, and mitochondrial dysfunction, and impair cognitive functions and cause neurodegeneration conditions like Alzheimer’s diseases. Due to the extensive focus on pharmacological intervention to prevent neuronal cells’ impairment induced by hyperglycemia, the underlying molecular mechanism that links between Diabetes and Alzheimer’s is still lacking. Given this, the present study aimed to evaluate the protective effect of piperine on streptozotocin (STZ) induced hyperglycemia and candidate gene expression. In the present study, rats were divided into four groups: control (Vehicle only), diabetic control (STZ only), piperine treated (20 mg/kg day, i.p), and sitagliptin (Positive control) treated. The memory function was assessed by Morris water maze and probe test. After treatment, biochemical parameters such as HOMA index and lipid profile were estimated in the serum, whereas histopathology was evaluated in pancreatic and brain tissue samples. Gene expression studies were done by real-time PCR technique. Present data indicated that piperine caused significant memory improvement as compared to diabetic (STZ) control. The assessment of HOMA indices in serum samples showed that piperine and sitagliptin (positive control, PC) caused significant alterations of insulin resistance, β cell function, and insulin sensitivity. Assessment of brain and pancreas histopathology shows significant improvement in tissue architecture in piperine and sitagliptin treated groups compared to diabetic control. The gene expression profile in brain tissue shows significantly reduced BACE1, PSEN1, APAF1, CASPASE3, and CATALASE genes in the piperine and sitagliptin (PC) treated groups compared to Diabetic (STZ) control. The present study demonstrated that piperine not only improves memory in diabetic rats but also reduces the expression of specific AD-related genes that can help design a novel strategy for therapeutic intervention at the molecular level.
Highlights
There is growing evidence showing a link between Diabetes mellitus (DM) and Alzheimer’s disease (AD)
The PC12 cells were pre-treated with piperine, followed by H2O2 induction to determine the protective effect of piperine against H2O2 induced oxidative stress
At 1 μM final concentration of piperine, 99.39 ± 4.70% percentage of viability was observed as compared to the negative control (H2O2 only) (Figure 2A), showing that piperine significantly protected PC12 cells against H2O2 induced oxidative stress (p < 0.01)
Summary
There is growing evidence showing a link between Diabetes mellitus (DM) and Alzheimer’s disease (AD). There is accumulating evidence showing that hyperglycemia conditions like diabetes possess a greater risk of impairment to the neuronal system (GonzálezReyes et al, 2016; Pruzin et al, 2018; Rojas-carranza et al, 2018) because high glucose levels exacerbate oxidative stress, accumulation of amyloid-beta peptides, and mitochondrial dysfunction, and impair cognitive functions, and cause neurodegeneration conditions like Alzheimer’s diseases (Macauley et al, 2015; Gaspar et al, 2016; Kim et al, 2016; Rom et al, 2018; Silzer and Phillips, 2018). STZ uptake by pancreatic β cells is detrimental for β cells as STZ causes the generation of reactive oxygen species (ROS) (Vessal et al, 2003) It results in cognitive impairment, glucose metabolism dysfunction, oxidative stress, and phosphorylation of tau protein resulting in neuronal cell death, a hallmark feature of AD (Salkovic-Petrisic et al, 2013; Moreira-Silva et al, 2018)
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