Exploring the differences in efficacy and mechanisms of Schisandra chinensis and its processed products in treating Alzheimer's disease based on UPLC-Q-TOF-MS/MS, network pharmacology, and experimental validation.

内容摘要

This study aims to elucidate the efficacy differences and underlying mechanisms of Schisandra chinensis (SC) and its processed products against Alzheimer's disease (AD). A total of 39 compounds were identified from SC and its processed products through UPLC-Q-TOF-MS/MS in both positive and negative ion modes. Multivariate statistical analysis revealed significant differences in chemical composition among the various processed products, with schisandrol A, epigomisin O, and angeloylgomisin O identified as key significantly differential components. Based on the identified compounds, potential targets were predicted via Swiss Target Prediction, which were then intersected with AD targets from the GeneCards and OMIM databases to construct a protein-protein interaction (PPI) network of "SC-AD" intersection targets. Enrichment analysis indicated that the core mechanism of its anti-AD effect involves the regulation of the PI3K/AKT signaling pathway. Experimental validation was conducted using the Aβ25-35-induced HT22 cell injury model and a D-galactose combined with scopolamine-induced AD mouse model. The results demonstrated that SC and its processed products significantly improved the behavioral performance of AD mice, alleviated pathological damage in brain tissue, and reduced pro-inflammatory factor levels. Furthermore, they upregulated AKT protein expression and inhibited mTOR protein expression. Notably, the regulatory effects of the processed products on these indicators were significantly superior to those of the raw products. In conclusion, both SC and its processed products can ameliorate AD by activating the PI3K/AKT pathway, with the effect significantly enhanced post-processing. This mechanism may be associated with the regulation of the PI3K/AKT signaling pathway.