Inhibitory effects of β-asarone on lncRNA BACE1-mediated induction of autophagy in a model of Alzheimer’s disease

The primary aim of this study was to examine the correlation between the formation of Aβ plaques and autophagy, which is regulated by β-asarone and the lncRNA BACE1-AS. Additionally, the study sought to explore potential targets of the drug in inhibiting the deposition of toxic AD-related proteins and restoring impaired mitochondrial and autophagic functions. SHY5Y cells were utilized to construct a stable Alzheimer's disease (AD) model, followed by the utilization of interference and overexpression lentiviruses targeting BACE1-AS to establish a cell model. The cells were categorized into five groups, including a normal group, siRNA/BACE1 group, and β-asarone group. The fluorescence quantitative PCR technique was employed to assess the disparity in BACE1 mRNA expression, while changes in immunofluorescence (IF) were observed to determine the stable interference titre and action time of the lentiviruses. Additionally, western blotting (WB) and fluorescence quantitative PCR were employed to evaluate the expression of proteins and mRNAs associated with AD and autophagy. The findings demonstrated a significant elevation in BACE1 expression levels in brain tissue among individuals with AD compared to those without the condition. Moreover, the results indicated that the introduction of β-asarone led to an increase in the expression of the BACE1-AS gene in the cell group transfected with plasmid H12732. Furthermore, it was observed that β-asarone enhanced the expression levels of shRNA and BACE1 after 72 h. In contrast, β-asarone suppressed the expression of PS1, Aβ, BACE1, APP, and p62, while promoting the expression of syn, LC3 I/II, and Beclin-1. Based on these findings, it can be concluded that β-Asarone exerts a comprehensive influence on the expression of proteins associated with AD and synaptic function. β-Asarone exhibits the potential to mitigate Aβ deposition by impeding the expression of lncBACE1, thereby facilitating autophagy through the suppression of BACE1's inhibitory impact on autophagy. This complements the self-enhancing effect of autophagy.