Objective: To investigate the antidepressant
effect
and potential mechanism of the Chufan Yishen Formula (CFYS) through
network pharmacology, molecular docking, and experimental verification. Methods: The active ingredients and their target genes of
CFYS were identified through Traditional Chinese Medicine Systems
Pharmacology (TCMSP) and TCM-ID. We obtained the differentially expressed
genes in patients with depression from the GEO database and screened
out the genes intersecting with the target genes of CFYS to construct
the PPI network. The key pathways were selected through STRING and
KEGG. Then, molecular docking and experimental verification were performed. Results: A total of 113 effective components and 195 target
genes were obtained. After intersecting the target genes with the
differentially expressed genes in patients with depression, we obtained
37 differential target genes, among which HMOX1, VEGFA, etc., were
the key genes. After enriching the differential target genes by KEGG,
we found that the “chemical carcinogenesis-reactive oxygen
species” pathway was the key pathway for the CFYS antidepressant
effect. Besides, VEGFA might be a key marker for depression. Experimental
verification found that CFYS could significantly improve the behavioral
indicators of rats with depression models, including improving the
antioxidant enzyme activity and increasing VEGFA levels. The results
are consistent with the network pharmacology analysis. Conclusions: CFYS treatment for depression is a multicomponent, multitarget,
and multipathway complex process, which may mainly exert an antidepressant
effect by improving the neuron antioxidant stress response and regulating
VEGFA levels.