Sea-Buckthorn Flavonoids Alleviate High-Fat and High-Fructose Diet-Induced Cognitive Impairment by Inhibiting Insulin Resistance and Neuroinflammation

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.