研究发现，口服沙棘黄酮（0.06％和0.31％ w/w，混饲）可显着降低高脂和高果糖饮食喂养小鼠的体重增加和胰岛素抵抗。在行为测试中，沙棘黄酮类化合物可有效预防高脂和高果糖饮食诱导的神经元缺失和记忆障碍。此外，沙棘黄酮类化合物还通过增加突触后致密蛋白95（PSD-95）的表达来抑制高脂和高果糖饮食诱导的突触功能障碍和神经元损伤。此外，沙棘黄酮处理激活了ERK/CREB/BDNF和IRS-1/AKT通路，并灭活NF-κB信号及其下游炎性介质表达。总之，沙棘黄酮类化合物是一种潜在的营养保健品，可预防高能量密度饮食引起的认知障碍，这可能是由于其对胰岛素信号和大脑炎症反应的调节作用。
ABSTRACT
Sea-Buckthorn Flavonoids Alleviate High-Fat and High-Fructose Diet-Induced Cognitive Impairment by Inhibiting Insulin Resistance and Neuroinflammation
Aiziguli Mulatia, Shaobo Maa, Hongbo Zhanga, Bo Rena, Beita Zhaoa, Luanfeng Wanga, Xiaoning Liua, Tong Zhaoa, Svetlana Kamanovaa, Ali Tahir Sairb, Zhigang Liua,b, Xuebo Liua
a Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, 712100 China
b Department of Food Science, Cornell University, Ithaca, New York 14850, United States
Sea-buckthorn flavonoids (SFs) have been used as functional food components for their bioactive potential in preventing metabolic complications caused by diet, such as obesity and inflammation. However, the protective effect of SFs on cognitive functions is not fully clear. In this study, a high-fat and high-fructose diet (HFFD)-induced obese mice model was treated with SFs for 14 weeks. It was found that the oral SF administration (0.06% and 0.31% w/w, mixed in diet) significantly reduced bodyweight gain and insulin resistance in the HFFD-fed mice. SFs significantly prevented HFFD-induced neuronal loss and memory impairment in behavioral tests. Additionally, SFs also suppressed the HFFD-induced synaptic dysfunction and neuronal damages by increasing the protein expressions of PSD-95. Furthermore, SF treatment activated the ERK/CREB/BDNF and IRS-1/AKT pathways and inactivated the NF-κB signaling and its downstream inflammatory mediator expressions. In conclusion, SFs are a potential nutraceutical to prevent high-energy density diet-induced cognitive impairments, which could be possibly explained by their mediating effects on insulin signaling and inflammatory responses in the brain.
