BMC Complement Med Ther. 2024 Jun 8;24(1):222. doi: 10.1186/s12906-024-04527-w.

ABSTRACT

CONTEXT: Bu-shen-yi-jing-fang (BSYJF) has been reported to reduce amyloid-β (Aβ)_1-42 deposition in the brain of APP/PS1 mice and ameliorate cognitive function. However, its neuroprotective mechanism remains unclear.

OBJECTIVE: This study aims to investigate whether BSYJF exerts a protective effect on Aβ_1-42-induced oxidative stress injury and explore its possible mechanism.

MATERIALS AND METHODS: The platform databases TCMSP, Swiss, TTD, DrugBank, and GeneCards were used to mine the targets of Alzheimer’s disease (AD) and BSYJF. The platform databases STRING and Metascape were used to build the interaction network of the target protein, and Cytoscape software was used to analyze this network and screen out the key pathways. Aβ_1-42-treated SKNMC cells were established to verify the mechanism of BSYJF and the key proteins. The downstream proteins and antioxidants as well as apoptosis and ferroptosis of the PI3K/AKT/Nrf2 signaling pathway were validated using an in vitro SKNMC cell model experiment. The expression levels of related proteins were detected using Western blotting. Flow cytometry and immunofluorescence staining were used to analyze apoptosis and ferroptosis.

RESULTS: Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis considered the key signal pathways, mainly involving the PI3K/AKT signaling pathway. Experimental validation demonstrated that BSYJF treatment markedly increased the activity of the PI3K/AKT pathway, which could exert anti-AD effects.

CONCLUSIONS: Our data provided compelling evidence that the protective effects of BSYJF might be associated with their regulation of the PI3K/AKT/Nrf2 signaling pathway. These studies offered a potential therapy for natural herbal medicine treatment of AD.

PMID:38851758 | DOI:10.1186/s12906-024-04527-w