Sea-buckthorn flavonoids alleviate high-fat and high-fructose diet-induced cognitive impairment by inhibiting insulin resistance and neuroinflammation.

Sea-buckthorn flavonoids (SF) have been used as functional food components for their bioactive potential on preventing metabolic complications caused by diet, such as obesity and inflammation. However, the protective effect of SF on cognitive function is not fully clear. In this study, a high-fat and high-fructose diet (HFFD)-induced obese mice model was treated with SF 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 HFFD-fed mice. SF significantly prevented HFFD-induced neuronal loss and memory impairment in behavioral tests. Additionally, SF also suppressed 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, SF is a potential nutraceutical to prevent high-energy density diet-induced cognitive impairments which could be possibly explained by its mediating effects on insulin signaling and inflammatory responses in brain.