Identifying a potential dietary non-pharmacological treatment to prevent cerebrovascular damage in Alzheimer’s disease is crucial for alleviating cognitive decline in older adults and enhancing quality of life. This study featured the combined supplementation of soy lecithin (SL) and soy isoflavones (SIF), using in vivo animal models, in vitro vascular ring preparation, and cell studies to investigate the potential advantages and mechanisms of SL combined with SIF on cognitive function and cerebrovascular health from multiple perspectives. The results show that Aβ can significantly induce learning and memory impairment in rats, as well as pathological changes in brain blood vessels, exacerbating damage to cerebral vasodilation function and subsequently reducing cerebral blood flow in the brain. The above-mentioned phenomena induced by Aβ can be significantly improved by the combined intervention of SL and SIF. Further research has revealed that the combined intervention of SL and SIF can reverse the downregulation of the PI3K/PIP3/PDK-1/Akt/eNOS signaling pathway and phosphorylated protein expression induced by Aβ in rat brain vascular tissues and bEND.3 cells. Silencing PDK-1 expression in bEND.3 cells showed that the upregulation effect of SL and SIF on Akt and eNOS disappeared. Here we find that prophylactically supplementation with SL in conjunction with SIF appears to effectively activate the PI3K/PIP3/PDK-1/Akt/eNOS pathway within cerebral vascular. This activation improves cerebrovascular vasodilation, offering potential protective effects for both cerebral vascular health and cognitive function.
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