Combination of Alpinia Oxyphylla Fructus and Schisandra Chinensis Fructus ameliorates aluminum-induced Alzheimer's disease via reducing BACE1 expression

Being the most common form of dementia, Alzheimer's disease (AD) has a series of modifiable risk factors, including metal ions represented by aluminium. Aluminium (Al) exhibits its neurotoxic effects, especially mainly by affecting amyloid-β protein (Aβ) aggregation and Tau hyperphosphorylation. As reported in our previous study, the combination of Alpinia Oxyphylla Fructus and Schisandra Chinensis Fructus (AS) had a neuroprotective effect. This study aimed to evaluate the anti-AD effect of AS and the mechanism by which AS reduces the neurotoxic effect of Al. Firstly, we used aluminium-maltol (Al(mal)3) to construct a mouse model of AD and performed oral administration of AS, followed by behavioral experiments, and we collected the mouse brain for immunohistochemistry analysis. In vivo results showed that AS significantly improved Al-induced cognitive decline in mice, and reduced the levels of Aβ1–42 and P-Tau in the brain, which further proved the anti-AD effect of AS. Then, in order to explore the mechanism by which AS reduced Aβ1–42, Al-induced PC12 cells were used for the in vitro experiments. Compared with other ratios, the ratio of Alpinia Oxyphylla Fructus: Schisandra Chinensis Fructus (AO:SC) = 1:2 could better improve the cell viability and reduce the Aβ1–42 level. According to western blot and quantitative real-time polymerase chain reaction (qPCR) results, AS ameliorated the pathological process by downregulating the expression of β-secretase (BACE1), rather than by reducing the expression of amyloid precursor protein (APP) or Tau. These results suggest that AS ameliorated Al-induced AD by affecting the expression of BACE1 and reducing the level of Aβ1–42, thereby exerting a neuroprotective effect. Combined with previous studies, this study shows that AS has potential for further research and development in AD treatment.