Network Pharmacology-Based and Experimental Identification of the Effects of Paeoniflorin on Major Depressive Disorder

Objective: Major depressive disorder (MDD) is one of the most common psychiatric disorders, the diagnosis and treatment of MDD are major clinical issues. However, there is a lack of effective biomarkers and drugs diagnosis and therapeutics of MDD. In the present study, bioinformatics analysis combined with an experimental verification strategy was used to identify biomarkers and paeoniflorin targets for MDD diagnosis and treatment. Methods: Based on network pharmacology, we obtained potential targets and pathways of paeoniflorin as an antidepressant through multiple databases. We then constructed a protein-protein interaction network and performed enrichment analyses. According to the results, we performed in vivo and in vitro experimental validation. Results: The results showed that paeoniflorin may exert an antidepressant effect by regulating cell inflammation, synaptic function, NF-κB signaling pathway, and intestinal inflammation. Conclusion: NPM1, HSPA8, HSPA5, HNRNPU, and TNF are the targets of paeoniflorin treatment. In addition, we demonstrated that paeoniflorin inhibits inflammatory cytokine production via the p38MAPK/NF-κB pathway and has neuroprotective effects on the synaptic structure. Our findings provide valuable evidence for the diagnosis and treatment of MDD.