Effect of gastrodin against cognitive impairment and neurodegeneration in APP/PS1 mice via regulating gut microbiota–gut–brain axis

Gastrodin (Gas) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of Gas against cognitive impairment via regulating gut microbiota. APPswe/PSEN1dE9 transgenic (APP/PS1) mice were treated intragastrically with Gas for 4 weeks, and then cognitive deficits, deposits of amyloid-β (Aβ) and phosphorylation of tau were analyzed. The expression levels of insulin-like growth factor-1 (IGF-1) pathway-related proteins, such as cAMP response element-binding protein (CREB), were detected. Meanwhile, gut microbiota composition was evaluated. Our results showed that Gas treatment significantly improved cognitive deficits and Aβ deposition in APP/PS1 mice. Moreover, Gas treatment increased the level of Bcl-2 and decreased level of Bax and ultimately inhibited neuronal apoptosis. Gas treatment markedly increased the expression levels of IGF-1 and CREB in APP/PS1 mice. Moreover, Gas treatment improved abnormal composition and structure of gut microbiota in APP/PS1 mice. These findings revealed that Gas actively participated in regulating the IGF-1 pathway to inhibit neuronal apoptosis via the gut–brain axis and that it can be considered a new therapeutic strategy against Alzheimer’s disease.