Alzheimer's disease (AD) is an aggressive neurodegenerative disease associated with cognitive decline, memory, language, and visual-spatial coordination disorders that eventually lead to complete loss of basic function. Hypercholesterolemia plays an important role in the pathogenesis of AD and its related diseases. Safflower yellow (SY) is a natural chalcone compound isolated from safflower, which has the effect of antioxidation and weight loss. Previous studies have shown that SY has a significant improvement in learning and memory in various AD model animals. In the early stage of proteomic technology, we found that the cholesterol synthesis rate-limiting enzyme Mevalonate decarboxylase (MVD) was abnormally high in dementia rats, and the expression level of MVD decreased after SY treatment. We speculated that SY may improve the learning and memory ability of AD mice by affecting cholesterol metabolism. The purpose of this study was to evaluate the effect of SY on regulating cholesterol metabolism and improving dementia. The area of amyloid-β (Aβ) plaque in the brain of APP/PS1 mice and various blood biochemical and molecular biological indexes was detected. Through behavioral experiments, we found that APP/ PS1 mice had significant learning and memory impairment compared with wild type mice(P < 0.01). SY (30 mg/kg) treatment for 1 month can significantly improve the learning and memory ability of APP/PS1 mice (P < 0.01). Our results showed that SY decreased serum Total cholesterol (TC) and Triglyceride (TG) and increased the level of High-density lipoprotein (HDL). HE staining obscured that SY affect the changes of liver tissue in APP/PS1 mice (P < 0.05 and P < 0.01). We found that SY reduced the expression of MVD and Apolipoprotein E (APOE4) in the cortex (P < 0.05 and P < 0.01). In summary, SY can effectively control cholesterol in serum and brain and change the degeneration of liver tissue. SY improves Alzheimer's disease by lowering serum, cortex and cortical cholesterol.
Keywords: Alzheimer’s disease; Amyloid-β; Cholesterol; Lipid metabolism; Safflower yellow.