Baihe Extracts Reduce the Activation and Apoptosis of Microglia in the Hippocampus of Mice with Depression-like Behaviors by Downregulating MYC

The purpose of our investigation is to identify the potential effects and key molecular targets of Baihe extracts in depression treatment. Network meta-analysis was applied for the synthesis of efficacy outcomes of fluoxetine and three traditional Chinese medicine Baihe prescriptions in depression. Depression-related target genes were screened using "GeneCards" database and "Comparative Toxicogenomics Database (CTD)". The major active components and targets of Baihe were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The identified depression-related genes and the target genes of Baihe were intersected, an interaction network was constructed using the "String" database, and key target genes were determined based on their degree value. Functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) profiles was performed using the "ClusterProfiler" R package. A mouse model with depression-like behaviors was constructed to verify the putative roles of the in silico identified key genes. Microglia were isolated from the mouse hippocampus, and the effects of Baihe extract-containing serum on microglia activation and apoptosis by targeting the key genes were examined in vitro. The meta-analysis results revealed no obvious differences in depression treatment efficacy between fluoxetine and the three Baihe prescriptions, suggesting Baihe extracts as a safe and effective alternative treatment for depression. Using network pharmacology and bioinformatics analysis, Baihe extracts were found to modulate depression by regulating 15 key genes, with MYC as the key gene. Subsequent animal experiments demonstrated that Baihe extracts reduced depression-related behavior, microglial activation, and inflammatory mediator release in mice by inhibiting MYC. Serum containing Baihe extracts could inhibit the activation of microglia and the release of inflammatory mediators by downregulating MYC. In summary, Baihe extracts were found to diminish MYC expression to reduce microglial activation and inflammatory factor release, thereby exerting antidepressant effects.