Protective mechanism of soy extracted isoflavones genistein against apoptosis using network pharmacology

Abstract

Objective: This study aimed to predict the action targets of genistein (GEN) in apoptosis using network pharmacology and to explore their potential multitarget and multipathway mechanisms. Additionally, a key Alzheimer’s disease signal pathway, which is one of the apoptosis-related signal pathways of GEN, was verified in vitro. Methods: The potential targets of GEN were selected after searching the PubChem database. Apoptosis-related targets were selected after searching the Genecards database, whereas the main targets of GEN and apoptosis were selected after searching the Venny 2.1.0 database. The protein-protein interaction map of the GEN anti-apoptosis protein interaction network was constructed using the STRING database software, and the core targets were analyzed using the Cyto-scape 3.8.2. Jingdu Encyclopedia of Gene and Genome (Kyoto Encyclopedia of Genes and Genomes, KEGG) and Gene Ontology (GO) were used for pathway enrichment analysis. An apoptosis model of PC12 cells induced by Aβ25-35 was developed, and the signal pathways predicted by network pharmacology were selected to verify the effect of GEN on apoptosis-related targets using PCR, western blotting, and spectrophotometry. Results: A total of 59 GEN-related targets and 791 apoptotic targets were discovered, including 31 common targets of GEN and apoptosis. GO and KEGG enrichment analysis showed that Alzheimer’s disease-related pathways could be analyzed in the target pathway network. GEN offers protection against Aβ25-35-induced apoptosis via reducing Aβ25-35-induced phosphorylation of c-Jun N-terminal kinase (JNK) activation, which then inhibits the JNK-dependent Fas-apoptotic pathway. Conclusion: The effect of GEN in apoptosis is characterized by a multitarget and multipathway coordination. This study predicted the key targets of GEN and apoptosis and highlighted the signal pathways related to Alzheimer’s disease. This information, combined with experimental verification, may provide a useful basis for the study of the molecular mechanisms of traditional Chinese medicine in the treatment of Alzheimer’s disease.

Keywords

• Network pharmacology
• Alzheimer’s disease
• Soy isoflavones
• Genistein
• Cell apoptosis