Comparative proteomic analysis of cerebral cortex revealed neuroprotective mechanism of esculentoside A on Alzheimer's disease

Esculentoside A (EsA), isolated from phytolacca esculenta, is a saponin showing neuroprotective effect in the mouse models of Alzheimer's disease (AD). To investigate its action target and underlying mechanism, this study used the proteomics technique of isobaric tags for relative and absolute quantification (iTRAQ) to analyze the differentially expressed proteins (DEPs) in the cerebral cortex of EsA-treated and untreated triple-transgenic 3 × Tg-AD model mice. Proteomic comparison revealed 250, 436, and 903 DEPs in three group pairs, i.e. AD/Wild-type (WT), AD+5 mg/kg EsA/AD, AD+10 mg/kg EsA/AD, respectively. Among them 28 DEPs were commonly shared by three group pairs, and 25 of them showed reversed expression levels in the diseased group under the treatment of both doses of EsA. Bioinformatics analysis revealed that these DEPs were mainly linked to metabolism, synapses, apoptosis, learning and memory. EsA treatment restored the expression of these proteins, including amyloid precursor protein (APP), cathepsin B (Cstb), 4-aminobutyrate aminotransferase (Abat), 3-phosphoinositide-dependent protein kinase-1 (PDK1), carnitine palmitoyltransferase1 (Cpt1) and synaptotagmin 17 (Syt17), thereby ameliorated the spatial learning and memory of AD mice. Collectively, this study reveals for the first time the profound effect of EsA on the cerebral cortex of AD mice, which might be a potential therapeutic agent for the treatment of AD.