Combining network pharmacology and bioinformatics approaches to explore the molecular mechanism of Erdong Nourishing Heart oral solution in the treatment of anxiety disorders

Abstract

Background

Erdong Nourishing Heart oral solution (EDYX) is a traditional in-hospital formula used for the clinical treatment of anxiety disorders at the Shanghai Mental Health Center; however, its active medicinal components and mechanisms of action remain unexplored.

Methods

Active compounds of EDYX and their corresponding targets were identified using the TCMSP, Symmap, and Herb databases. Data intersecting the targets of EDYX and anxiety disorders were obtained from the GeneCards, OMIM, and CTD databases.We take the intersecting targets of EDYX and anxiety disorders to construct a PPI network and a ingredient-disease-target network.Network parameters were analyzed systematically using Cytoscape software, deriving the core targets and key components of EDYX's mechanism.Molecular docking methods assessed and verified interactions between core targets and key components, while the reliability of drug targets was confirmed using the GEO dataset.

Findings

A total of 59 active compounds and 3574 corresponding pharmacotherapeutic targets were identified for EDYX, while 6894 targets relevant to anxiety disorders were also screened. Systematic analysis of 1587 potential common targets between EDYX and anxiety disorders revealed core components of EDYX, including polyphenolic compounds such as quercetin, stigmasterol, and γ-sitosterol, and core targets such as TP53,SRC,AKT1,CXCL8 and CXCR4. Pathway enrichment analysis suggested that EDYX potentially inhibits neuroinflammation, enhances cell proliferation and metabolism, and alleviates anxiety by modulating signaling pathways including JUN-STAT, MAPK-NK-κB, PI3K-AKT-mTOR, and neuroactive ligand-receptor interactions.The results of molecular docking showed that the docking scores of JUN and EP300 target proteins with the key compounds were significantly lower than the other proteins, which may be the potential binding targets of EDYX for the treatment of Anxiety. The results of GEO database validation indicated that MMP8 and FOSB may be potential impact genes for EDYX treatment of Anxiety.

Conclusions

EDYX is a Chinese medicine compound preparation with multi-component, multi-target, and multi-pathway antidepressant efficacy, which is expected to be a powerful choice for the future adjuvant treatment of Anxiety.Further molecular experiments are required to verify the molecular mechanism of EDYX and its active ingredients, providing a theoretical basis for clinical application.