Effects of safflower yellow on cholesterol levels in serum and brain tissue of APP/PS1 mice
Effects of safflower yellow on cholesterol levels in serum and brain tissue of APP/PS1 mice
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DOI：
10.1007/s11011-021-00680-0
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发表时间：
2021-02-06
影响因子：
3.6
通讯作者：
Hu, Yanli
中科院分区：
文献类型：
--
作者：
Du, Chao;Hou, Jiawei;Hu, Yanli
阿尔茨海默病（AD）是一种侵袭性神经退行性疾病，与认知能力下降、记忆力、语言和视觉空间协调障碍相关，最终导致基本功能完全丧失。高胆固醇血症在AD及其相关疾病的发病机制中起重要作用。红花黄色素（SY）是从红花中分离得到的一种天然查尔酮化合物，具有抗氧化和减肥作用。以往的研究表明，SY对各种AD模型动物的学习记忆均有明显改善作用。在蛋白质组学技术的早期阶段，我们发现痴呆大鼠胆固醇合成限速酶甲羟戊酸脱羧酶（MVD）异常增高，SY治疗后MVD表达水平降低。我们推测SY可能通过影响胆固醇代谢而改善AD小鼠的学习记忆能力。本研究的目的是评估SY调节胆固醇代谢和改善痴呆的作用。检测APP/PS1小鼠脑内β淀粉样蛋白（A β）斑块面积及各项血液生化和分子生物学指标。通过行为学实验发现APP/ PS1小鼠与野生型小鼠相比有明显的学习记忆障碍（P < 0.01）。SY（30 mg/kg）治疗1个月可显著改善APP/PS1小鼠的学习记忆能力（P < 0.01）。结果表明，SY能降低血清总胆固醇（TC）和甘油三酯（TG），升高高密度脂蛋白（HDL）水平。HE染色显示SY对APP/PS1小鼠肝组织的影响（P < 0.05和P < 0.01）。结果表明，SY可降低脑皮质MVD和载脂蛋白E 4（APOE 4）的表达（P < 0.05和P < 0.01）。综上所述，SY能有效地控制血清和脑胆固醇，改变肝组织的变性。SY通过降低血清、皮质和皮质胆固醇改善阿尔茨海默病。
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-beta (A beta) 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.